Clinical Management of Dilated Cardiomyopathy



Evolving concepts in dilated cardiomyopathyMerlo M1, Cannatà A1, Gobbo M1, Stolfo D1, Elliott PM2, Sinagra G11Cardiovascular Department “Ospedali Riuniti” and University of Trieste, Trieste, Italy2Centre for Heart Muscle Disease, Institute of Cardiological Sciences, University College London and St. Bartholomew’s Hospital, London, United KingdomConflicts of interest: NoneCorresponding author:Prof. Gianfranco Sinagra, MDCardiovascular Department, “Ospedali Riuniti” and University of Trieste, Trieste, ItalyVia P. Valdoni 7, 34100, Trieste, Italy,Tel: +39 040 399 4865Fax: +39 040 399 4878E-mail: gianfranco.sinagra@asuits.sanita.fvg.itTotal Word Count: 3000Abstract: 130AbstractDilated cardiomyopathy (DCM) represents a particular etiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few comorbidities. The prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the red-flag integrated approach to the disease, early diagnosis through systematic familial screening, and the concept of DCM as a dynamic disease requiring constant optimization of medical and non-pharmacological evidence-based treatments. However, some important issues in clinical management remain unresolved, such as the role of cardiac magnetic resonance for diagnosis and risk categorization and the interaction between genotype and clinical phenotype, and arrhythmic risk stratification. This review provides a comprehensive survey of these and other emerging issues in the clinical management of DCM, providing where possible practical recommendations.List of abbreviationsCMRCardiac magnetic resonanceCRTCardiac resynchronization therapyDCMDilated cardiomyopathyICDImplantable cardiac defibrillator LBBBLeft bundle branch blockLGELate gadolinium enhancementLVLeft ventricleLVRRLeft ventricular reverse remodelingRVRight ventricleSCDSudden cardiac death BackgroundDilated Cardiomyopathy (DCM) is a heart muscle disease characterized by left ventricular (LV) or biventricular dilation and systolic dysfunction in the absence of either pressure or volume overload or coronary artery disease sufficient to explain the dysfunction ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/ehm342", "ISBN" : "0195-668X (Print)\r0195-668x", "PMID" : "17916581", "abstract" : "In biology, classification systems are used to promote understanding and systematic discussion through the use of logical groups and hierarchies. In clinical medicine, similar principles are used to standardise the nomenclature of disease. For more than three decades, heart muscle diseases have been classified into primary or idiopathic myocardial diseases (cardiomyopathies) and secondary disorders that have similar morphological appearances, but which are caused by an identifiable pathology such as coronary artery disease or myocardial infiltration (specific heart muscle diseases). In this document, The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases presents an update of the existing classification scheme. The aim is to help clinicians look beyond generic diagnostic labels in order to reach more specific diagnoses.", "author" : [ { "dropping-particle" : "", "family" : "Elliott", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersson", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arbustini", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bilinska", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cecchi", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubourg", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhl", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maisch", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKenna", "given" : "W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monserrat", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankuweit", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rapezzi", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seferovic", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavazzi", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur Heart J", "edition" : "2007/10/06", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "language" : "eng", "note" : "Elliott, Perry\nAndersson, Bert\nArbustini, Eloisa\nBilinska, Zofia\nCecchi, Franco\nCharron, Philippe\nDubourg, Olivier\nKuhl, Uwe\nMaisch, Bernhard\nMcKenna, William J\nMonserrat, Lorenzo\nPankuweit, Sabine\nRapezzi, Claudio\nSeferovic, Petar\nTavazzi, Luigi\nKeren, Andre\nJournal Article\nEngland\nEur Heart J. 2008 Jan;29(2):270-6. 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Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/eurheartj/ehv727", "ISSN" : "1522-9645 (Electronic)", "PMID" : "26792875", "abstract" : "In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.", "author" : [ { "dropping-particle" : "", "family" : "Pinto", "given" : "Yigal M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Perry M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arbustini", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler", "given" : "Yehuda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anastasakis", "given" : "Aris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bohm", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duboc", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gimeno", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groote", "given" : "Pascal", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imazio", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heymans", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klingel", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komajda", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Limongelli", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linhart", "given" : "Ales", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mogensen", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moon", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pieper", "given" : "Petronella G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seferovic", "given" : "Petar M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schueler", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zamorano", "given" : "Jose L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caforio", "given" : "Alida L P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European heart journal", "id" : "ITEM-3", "issue" : "23", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "language" : "eng", "page" : "1850-1858", "publisher-place" : "England", "title" : "Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(1\u20133)", "manualFormatting" : "(1\u20133)", "plainTextFormattedCitation" : "(1\u20133)", "previouslyFormattedCitation" : "(1\u20133)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(1–3). Although previously considered as a rare and orphan disease, contemporary estimates for the prevalence of DCM range from 1/2500 up to 1/250 people ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrcardio.2013.105", "ISSN" : "1759-5010 (Electronic)", "PMID" : "23900355", "abstract" : "Remarkable progress has been made in understanding the genetic basis of dilated cardiomyopathy (DCM). Rare variants in >30 genes, some also involved in other cardiomyopathies, muscular dystrophy, or syndromic disease, perturb a diverse set of important myocardial proteins to produce a final DCM phenotype. Large, publicly available datasets have provided the opportunity to evaluate previously identified DCM-causing mutations, and to examine the population frequency of sequence variants similar to those that have been observed to cause DCM. The frequency of these variants, whether associated with dilated or hypertrophic cardiomyopathy, is greater than estimates of disease prevalence. This mismatch might be explained by one or more of the following possibilities: that the penetrance of DCM-causing mutations is lower than previously thought, that some variants are noncausal, that DCM prevalence is higher than previously estimated, or that other more-complex genomics underlie DCM. Reassessment of our assumptions about the complexity of the genomic and phenomic architecture of DCM is warranted. Much about the genomic basis of DCM remains to be investigated, which will require comprehensive genomic studies in much larger cohorts of rigorously phenotyped probands and family members than previously examined.", "author" : [ { "dropping-particle" : "", "family" : "Hershberger", "given" : "Ray E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedges", "given" : "Dale J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morales", "given" : "Ana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Cardiology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "language" : "eng", "page" : "531-547", "publisher-place" : "England", "title" : "Dilated cardiomyopathy: the complexity of a diverse genetic architecture.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(4)", "plainTextFormattedCitation" : "(4)", "previouslyFormattedCitation" : "(4)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(4). Commonly, the onset of the disease occurs in the 3rd or 4th decade of life with a 3:1 male to female predominance. By time the patients are diagnosed, they often have severe contractile dysfunction and remodeling of the ventricles, reflecting a long period of asymptomatic silent disease progression. However, implementation of optimal pharmacological and non-pharmacological treatment has dramatically improved the prognosis of DCM ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ejhf.16", "ISBN" : "1388-9842", "PMID" : "24464640", "abstract" : "AIMS: ACE-inhibitors, beta-blockers, implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) improved prognosis of heart failure. We sought to analyse the long-term prognostic impact of evidence-based integrated therapeutic strategies in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: From 1978 to 2007, 853 IDCM patients (45 +/- 15 years, 72% males) were enrolled and classified as follows: Group 1, 110 patients (12.8%) enrolled during 1978-1987; Group 2, 376 patients (44.1%) enrolled during 1988-1997; Group 3, 367 patients (43.1%) enrolled during 1998-2007. ACE-inhibitors/angiotensin receptor blockers were administered in 34%, 93%, and 93% (P <0.001), and beta-blockers in 11%, 82%, and 86% (P <0.001) in Groups 1, 2, and 3, respectively; ICDs were implanted in 2%, 14%, and 13% (P = 0.005); mean time to device implantation was lower in Group 3. At 8 years, heart transplant (HTx)-free survival rates were 55%, 71%, and 87% in Groups 1, 2, and 3, respectively (P <0.001). Similar progressive improvement was found for pump-failure death (DHF)/HTx, while survival free from sudden death (SD) was significantly improved only in Group 3. Multivariable models considering competing risk indicated early diagnosis (i.e. a baseline less advanced disease stage) and tailored medical therapy (HR 0.44, CI 95% 0.19-0.98) as independent protectors against DHF/HTx. Concerning SD, lower left ventricular ejection fraction emerged as a predictor, while ICD was the only therapy with a protective role (HR 0.08, CI 95% 0.01-0.61). Treatment with digitalis emerged as a predictor of both DHF/HTx and SD. CONCLUSIONS: An effective management and evidence-based integrated therapeutic approach progressively and significantly improved the long-term prognosis of IDCM during the last three decades.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Heart Fail", "edition" : "2014/01/28", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "language" : "eng", "note" : "1879-0844\nMerlo, Marco\nPivetta, Alberto\nPinamonti, Bruno\nStolfo, Davide\nZecchin, Massimo\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nEngland\nEur J Heart Fail. 2014 Mar;16(3):317-24. doi: 10.1002/ejhf.16. Epub 2013 Dec 14.", "page" : "317-324", "title" : "Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(5)", "plainTextFormattedCitation" : "(5)", "previouslyFormattedCitation" : "(5)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(5) with an estimated survival free from death or heart transplantation up to 85% at 10 years ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2010.11.030", "ISBN" : "0735-1097", "PMID" : "21435516", "abstract" : "OBJECTIVES: The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Tailored medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. METHODS: We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of >/=10 U or a left ventricular ejection fraction of >/=50% and a decrease in indexed left ventricular end-diastolic diameter of >/=10% or indexed left ventricular end-diastolic diameter of >/=33 mm/m(2) at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 +/- 53 months; there were 55 deaths (23%) and 32 HTx (13%). RESULTS: LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. CONCLUSIONS: LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pyxaras", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Coll Cardiol", "edition" : "2011/03/26", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "language" : "eng", "note" : "1558-3597\nMerlo, Marco\nPyxaras, Stylianos A\nPinamonti, Bruno\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nUnited States\nJ Am Coll Cardiol. 2011 Mar 29;57(13):1468-76. doi: 10.1016/j.jacc.2010.11.030.", "page" : "1468-1476", "title" : "Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.amjcard.2011.10.033", "ISSN" : "1879-1913 (Electronic)", "PMID" : "22176998", "abstract" : "To assess the proportion and long-term outcomes of patients with idiopathic dilated cardiomyopathy and potential indications for implantable cardioverter-defibrillator before and after optimization of medical treatment, 503 consecutive patients with idiopathic dilated cardiomyopathy were evaluated from 1988 to 2006. A total of 245 patients (49%) satisfied the \"Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) criteria,\" defined as a left ventricular ejection fraction of </=0.35 and New York Heart Association (NYHA) class II-III on registration. Among these, 162 (group A) were re-evaluated 5.4 +/- 2 months later with concurrent beta-blockers and angiotensin-converting enzyme inhibitor use. Of the 162 patients, 50 (31%) still had \"SCD-HeFT criteria\" (group A1), 109 (67%) had an improved left ventricular ejection fraction and/or New York Heart Association class (group A2), and 3 (2%) were in NYHA class IV. Of the 227 patients without baseline \"SCD-HeFT criteria\" (left ventricular ejection fraction >0.35 or NYHA class I), 125 were evaluated after 5.5 +/- 2 months. Of these 227 patients, 13 (10%) developed \"SCD-HeFT criteria\" (group B1), 111 (89%) remained without \"SCD-HeFT criteria\" (group B2), and 1 (1%) had worsened to NYHA class IV. The 10-year mortality/heart transplantation and sudden death/sustained ventricular arrhythmia rate was 57% and 37% in group A1, 23% and 20% in group A2 (p <0.001 for mortality/heart transplantation and p = 0.014 for sudden death/sustained ventricular arrhythmia vs group A1), 45% and 41% in group B1 (p = NS vs group A1), 16% and 14% in group B2 (p = NS vs group A2), respectively. In conclusion, two thirds of patients with idiopathic dilated cardiomyopathy and \"SCD-HeFT criteria\" at presentation did not maintain implantable cardioverter-defibrillator indications 3 to 9 months later with optimal medical therapy. Their long-term outcome was excellent, similar to that observed for patients who had never met the \"SCD-HeFT criteria.\"", "author" : [ { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lutman", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregori", "given" : "Dario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serdoz", "given" : "Laura Vitali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bardari", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnani", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proclemer", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of cardiology", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "3" ] ] }, "language" : "eng", "page" : "729-735", "publisher-place" : "United States", "title" : "How can optimization of medical treatment avoid unnecessary implantable cardioverter-defibrillator implantations in patients with idiopathic dilated cardiomyopathy presenting with \"SCD-HeFT criteria?\".", "type" : "article-journal", "volume" : "109" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6, 7)", "plainTextFormattedCitation" : "(6, 7)", "previouslyFormattedCitation" : "(6, 7)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6, 7). Moreover, the lower prevalence of co-morbidities when compared to most patients with other forms of systolic LV dysfunction suggests that individuals with DCM tend to have fewer non-cardiovascular events ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ejhf.16", "ISBN" : "1388-9842", "PMID" : "24464640", "abstract" : "AIMS: ACE-inhibitors, beta-blockers, implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) improved prognosis of heart failure. We sought to analyse the long-term prognostic impact of evidence-based integrated therapeutic strategies in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: From 1978 to 2007, 853 IDCM patients (45 +/- 15 years, 72% males) were enrolled and classified as follows: Group 1, 110 patients (12.8%) enrolled during 1978-1987; Group 2, 376 patients (44.1%) enrolled during 1988-1997; Group 3, 367 patients (43.1%) enrolled during 1998-2007. ACE-inhibitors/angiotensin receptor blockers were administered in 34%, 93%, and 93% (P <0.001), and beta-blockers in 11%, 82%, and 86% (P <0.001) in Groups 1, 2, and 3, respectively; ICDs were implanted in 2%, 14%, and 13% (P = 0.005); mean time to device implantation was lower in Group 3. At 8 years, heart transplant (HTx)-free survival rates were 55%, 71%, and 87% in Groups 1, 2, and 3, respectively (P <0.001). Similar progressive improvement was found for pump-failure death (DHF)/HTx, while survival free from sudden death (SD) was significantly improved only in Group 3. Multivariable models considering competing risk indicated early diagnosis (i.e. a baseline less advanced disease stage) and tailored medical therapy (HR 0.44, CI 95% 0.19-0.98) as independent protectors against DHF/HTx. Concerning SD, lower left ventricular ejection fraction emerged as a predictor, while ICD was the only therapy with a protective role (HR 0.08, CI 95% 0.01-0.61). Treatment with digitalis emerged as a predictor of both DHF/HTx and SD. CONCLUSIONS: An effective management and evidence-based integrated therapeutic approach progressively and significantly improved the long-term prognosis of IDCM during the last three decades.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Heart Fail", "edition" : "2014/01/28", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "language" : "eng", "note" : "1879-0844\nMerlo, Marco\nPivetta, Alberto\nPinamonti, Bruno\nStolfo, Davide\nZecchin, Massimo\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nEngland\nEur J Heart Fail. 2014 Mar;16(3):317-24. doi: 10.1002/ejhf.16. Epub 2013 Dec 14.", "page" : "317-324", "title" : "Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(5)", "plainTextFormattedCitation" : "(5)", "previouslyFormattedCitation" : "(5)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(5). These improved outcomes are paralleled by a higher rate of LV reverse remodeling (LVRR) with optimal pharmacological and non-pharmacological treatments ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ejhf.16", "ISBN" : "1388-9842", "PMID" : "24464640", "abstract" : "AIMS: ACE-inhibitors, beta-blockers, implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) improved prognosis of heart failure. We sought to analyse the long-term prognostic impact of evidence-based integrated therapeutic strategies in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: From 1978 to 2007, 853 IDCM patients (45 +/- 15 years, 72% males) were enrolled and classified as follows: Group 1, 110 patients (12.8%) enrolled during 1978-1987; Group 2, 376 patients (44.1%) enrolled during 1988-1997; Group 3, 367 patients (43.1%) enrolled during 1998-2007. ACE-inhibitors/angiotensin receptor blockers were administered in 34%, 93%, and 93% (P <0.001), and beta-blockers in 11%, 82%, and 86% (P <0.001) in Groups 1, 2, and 3, respectively; ICDs were implanted in 2%, 14%, and 13% (P = 0.005); mean time to device implantation was lower in Group 3. At 8 years, heart transplant (HTx)-free survival rates were 55%, 71%, and 87% in Groups 1, 2, and 3, respectively (P <0.001). Similar progressive improvement was found for pump-failure death (DHF)/HTx, while survival free from sudden death (SD) was significantly improved only in Group 3. Multivariable models considering competing risk indicated early diagnosis (i.e. a baseline less advanced disease stage) and tailored medical therapy (HR 0.44, CI 95% 0.19-0.98) as independent protectors against DHF/HTx. Concerning SD, lower left ventricular ejection fraction emerged as a predictor, while ICD was the only therapy with a protective role (HR 0.08, CI 95% 0.01-0.61). Treatment with digitalis emerged as a predictor of both DHF/HTx and SD. CONCLUSIONS: An effective management and evidence-based integrated therapeutic approach progressively and significantly improved the long-term prognosis of IDCM during the last three decades.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Heart Fail", "edition" : "2014/01/28", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "language" : "eng", "note" : "1879-0844\nMerlo, Marco\nPivetta, Alberto\nPinamonti, Bruno\nStolfo, Davide\nZecchin, Massimo\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nEngland\nEur J Heart Fail. 2014 Mar;16(3):317-24. doi: 10.1002/ejhf.16. Epub 2013 Dec 14.", "page" : "317-324", "title" : "Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jacc.2010.11.030", "ISBN" : "0735-1097", "PMID" : "21435516", "abstract" : "OBJECTIVES: The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Tailored medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. METHODS: We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of >/=10 U or a left ventricular ejection fraction of >/=50% and a decrease in indexed left ventricular end-diastolic diameter of >/=10% or indexed left ventricular end-diastolic diameter of >/=33 mm/m(2) at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 +/- 53 months; there were 55 deaths (23%) and 32 HTx (13%). RESULTS: LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. CONCLUSIONS: LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pyxaras", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Coll Cardiol", "edition" : "2011/03/26", "id" : "ITEM-2", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "language" : "eng", "note" : "1558-3597\nMerlo, Marco\nPyxaras, Stylianos A\nPinamonti, Bruno\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nUnited States\nJ Am Coll Cardiol. 2011 Mar 29;57(13):1468-76. doi: 10.1016/j.jacc.2010.11.030.", "page" : "1468-1476", "title" : "Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.amjcard.2011.10.033", "ISSN" : "1879-1913 (Electronic)", "PMID" : "22176998", "abstract" : "To assess the proportion and long-term outcomes of patients with idiopathic dilated cardiomyopathy and potential indications for implantable cardioverter-defibrillator before and after optimization of medical treatment, 503 consecutive patients with idiopathic dilated cardiomyopathy were evaluated from 1988 to 2006. A total of 245 patients (49%) satisfied the \"Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) criteria,\" defined as a left ventricular ejection fraction of </=0.35 and New York Heart Association (NYHA) class II-III on registration. Among these, 162 (group A) were re-evaluated 5.4 +/- 2 months later with concurrent beta-blockers and angiotensin-converting enzyme inhibitor use. Of the 162 patients, 50 (31%) still had \"SCD-HeFT criteria\" (group A1), 109 (67%) had an improved left ventricular ejection fraction and/or New York Heart Association class (group A2), and 3 (2%) were in NYHA class IV. Of the 227 patients without baseline \"SCD-HeFT criteria\" (left ventricular ejection fraction >0.35 or NYHA class I), 125 were evaluated after 5.5 +/- 2 months. Of these 227 patients, 13 (10%) developed \"SCD-HeFT criteria\" (group B1), 111 (89%) remained without \"SCD-HeFT criteria\" (group B2), and 1 (1%) had worsened to NYHA class IV. The 10-year mortality/heart transplantation and sudden death/sustained ventricular arrhythmia rate was 57% and 37% in group A1, 23% and 20% in group A2 (p <0.001 for mortality/heart transplantation and p = 0.014 for sudden death/sustained ventricular arrhythmia vs group A1), 45% and 41% in group B1 (p = NS vs group A1), 16% and 14% in group B2 (p = NS vs group A2), respectively. In conclusion, two thirds of patients with idiopathic dilated cardiomyopathy and \"SCD-HeFT criteria\" at presentation did not maintain implantable cardioverter-defibrillator indications 3 to 9 months later with optimal medical therapy. Their long-term outcome was excellent, similar to that observed for patients who had never met the \"SCD-HeFT criteria.\"", "author" : [ { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lutman", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregori", "given" : "Dario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serdoz", "given" : "Laura Vitali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bardari", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnani", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proclemer", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of cardiology", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "3" ] ] }, "language" : "eng", "page" : "729-735", "publisher-place" : "United States", "title" : "How can optimization of medical treatment avoid unnecessary implantable cardioverter-defibrillator implantations in patients with idiopathic dilated cardiomyopathy presenting with \"SCD-HeFT criteria?\".", "type" : "article-journal", "volume" : "109" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(5\u20137)", "plainTextFormattedCitation" : "(5\u20137)", "previouslyFormattedCitation" : "(5\u20137)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(5–7).In spite of this therapeutic success, emerging evidence suggests that some patients remain vulnerable to sudden cardiac death (SCD) and refractory heart failure (HF) requiring heart transplant or mechanical circulatory support ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2010.11.030", "ISBN" : "0735-1097", "PMID" : "21435516", "abstract" : "OBJECTIVES: The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Tailored medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. METHODS: We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of >/=10 U or a left ventricular ejection fraction of >/=50% and a decrease in indexed left ventricular end-diastolic diameter of >/=10% or indexed left ventricular end-diastolic diameter of >/=33 mm/m(2) at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 +/- 53 months; there were 55 deaths (23%) and 32 HTx (13%). RESULTS: LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. CONCLUSIONS: LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pyxaras", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Coll Cardiol", "edition" : "2011/03/26", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "language" : "eng", "note" : "1558-3597\nMerlo, Marco\nPyxaras, Stylianos A\nPinamonti, Bruno\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nUnited States\nJ Am Coll Cardiol. 2011 Mar 29;57(13):1468-76. doi: 10.1016/j.jacc.2010.11.030.", "page" : "1468-1476", "title" : "Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "manualFormatting" : "(7)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7). This review highlights some important concepts in the clinical management of DCM patients such as the possible LVRR under therapy, the need of a continuous individualized long-term follow-up, the role of genetic testing. Some unresolved issues such as the arrhythmic stratification or the genotype-phenotype correlation are also discussed, highlighting potential strategies for diagnosing and treating high risk sub-sets of patients with DCM throughout the whole natural history of the disease.1 - The cornerstones of clinical management of DCM at diagnosis: aetiological characterization and early diagnosis1.1 Reversible causes of dilated cardiomyopathyWhile there is a general appreciation that DCM can be caused by many different disease processes, in everyday clinical practice it is often considered under the catch-all heading of “non-ischaemic HF” with reduced ejection fraction. However, the concept that DCM represents a family of diseases characterized by complex interactions between environment and genetic predisposition is gaining prominence as the clinical impact of a precise diagnosis is better appreciated ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2015.07.023", "ISSN" : "1558-3597 (Electronic)", "PMID" : "26383716", "abstract" : "BACKGROUND: The multifactorial pathogenesis leading to dilated cardiomyopathy (DCM) makes stratification difficult. The recent MOGE(S) (morphofunctional, organ involvement, genetic or familial, etiology, stage) classification addresses this issue. OBJECTIVES: The purpose of this study was to investigate the applicability and prognostic relevance of the MOGE(S) classification in patients with DCM. METHODS: This study used patients from the Maastricht Cardiomyopathy Registry in the Netherlands and excluded patients with ischemic, valvular, hypertensive, and congenital heart disease. All other patients underwent a complete diagnostic work-up, including genetic evaluation and endomyocardial biopsy. RESULTS: A total of 213 consecutive patients with DCM were included: organ involvement was demonstrated in 35 (16%) and genetic or familial DCM in 70 (33%) patients, including 16 (8%) patients with a pathogenic mutation. At least 1 cause was found in 155 (73%) patients, of whom 48 (23%) had more than 1 possible cause. Left ventricular reverse remodeling was more common in patients with nongenetic or nonfamilial DCM than in patients with genetic or familial DCM (40% vs. 25%; p = 0.04). After a median follow-up of 47 months, organ involvement and higher New York Heart Association functional class were associated with adverse outcome (p < 0.001 and p = 0.02, respectively). Genetic or familial DCM per se was of no prognostic significance, but when it was accompanied by additional etiologic-environmental factors such as significant viral load, immune-mediated factors, rhythm disturbances, or toxic triggers, a worse outcome was revealed (p = 0.03). A higher presence of MOGE(S) attributes (>/=2 vs. </=1 attributes) showed an adverse outcome (p = 0.007). CONCLUSIONS: The MOGE(S) classification in DCM is applicable, and each attribute or the gene-environment interaction is associated with outcome. Importantly, the presence of multiple attributes was a strong predictor of adverse outcome. Finally, adaptation of the MOGE(S) involving multiple possible etiologies is recommended.", "author" : [ { "dropping-particle" : "", "family" : "Hazebroek", "given" : "Mark R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moors", "given" : "Suzanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dennert", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijngaard", "given" : "Arthur", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krapels", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoos", "given" : "Marije", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verdonschot", "given" : "Job", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merken", "given" : "Jort J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vries", "given" : "Bart", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolffs", "given" : "Petra F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crijns", "given" : "Harry J G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner-La Rocca", "given" : "Hans-Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heymans", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "language" : "eng", "page" : "1313-1323", "publisher-place" : "United States", "title" : "Prognostic Relevance of Gene-Environment Interactions in Patients With Dilated Cardiomyopathy: Applying the MOGE(S) Classification.", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/ejhf.464", "ISSN" : "1879-0844 (Electronic)", "PMID" : "26763891", "abstract" : "AIM: Dilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long-term outcome has yet been established. Myocardial tenascin-C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long-term outcome in DCM. METHODS AND RESULTS: One hundred and twenty-three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC-positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area >/=2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9 months after endomyocardial biopsy, the low TNC group was associated with decreased LV end-diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P < 0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR = 1.347, P = 0.032). CONCLUSIONS: Increased myocardial TNC expression was associated with worse LV remodeling and long-term outcome in DCM.", "author" : [ { "dropping-particle" : "", "family" : "Yokokawa", "given" : "Tetsuro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugano", "given" : "Yasuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakayama", "given" : "Takafumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagai", "given" : "Toshiyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsuyama", "given" : "Taka-Aki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohta-Ogo", "given" : "Keiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Yoshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishibashi-Ueda", "given" : "Hatsue", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakatani", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuda", "given" : "Satoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeishi", "given" : "Yasuchika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Hisao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anzai", "given" : "Toshihisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of heart failure", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2016", "4" ] ] }, "language" : "eng", "page" : "375-385", "publisher-place" : "England", "title" : "Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8, 9)", "plainTextFormattedCitation" : "(8, 9)", "previouslyFormattedCitation" : "(8, 9)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8, 9). The term idiopathic DCM is often used in clinical practice and in some series represents 20-30% of non-ischaemic HF. However, the approach to a patient with non-ischaemic DCM rarely seeks reversible factors other than hypertension, valve disease and congenital heart disease (Figure 1) Examples of commonly overlooked or underappreciated reversible triggers for left ventricular (LV) dysfunction include sustained supraventricular arrhythmias or very frequent ventricular ectopic beats which can lead to tachycardia-induced cardiomyopathy; substance abuse (e.g. alcohol, cocaine); acute emotional stress or chemotherapies that cause catecholamine or toxin-induced cardiomyopathies; and systemic autoimmune disorders (e.g. Churg-Strauss syndrome and sarcoidosis). The new-onset of HF with LV dysfunction occurring during pregnancy or during the post-partum period could identify a peripartum cardiomyopathy. Confirmation of an active myocarditis as the cause of recent onset severe HF (Figure 2) is particularly important as it may require investigations, such as endomyocardial biopsy, that are rarely performed in some health care settings ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anzini", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira L", "given" : "Naveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bussani", "given" : "Rossana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finocchiaro", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartunek", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mayo Clinic Proc", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Myocarditis in clinical practice. A clinical approach to myocarditis.", "type" : "article-journal", "volume" : "[In Press]" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(10)", "plainTextFormattedCitation" : "(10)", "previouslyFormattedCitation" : "(10)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(10). Accordingly, a comprehensive integrated approach, including third level diagnostic tools, should be systematically implemented in clinical practice in order to remove every possible reversible cause through specific therapeutic intervention (Table 1). This issue appears essential to promote left ventricular reverse remodeling (LVRR) and subsequent outcome improvement. 1.2 Identification of genetic causes of DCM (Figure 3)When obvious acquired factors have been excluded, a genetic basis for DCM becomes more likely, particularly when there is a family history of disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0195-668X (Print)\r0195-668x", "PMID" : "10099905", "author" : [ { "dropping-particle" : "", "family" : "Mestroni", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maisch", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKenna", "given" : "W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwartz", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocco", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tesson", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richter", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilke", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komajda", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur Heart J", "edition" : "1999/04/01", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "language" : "eng", "note" : "Mestroni, L\nMaisch, B\nMcKenna, W J\nSchwartz, K\nCharron, P\nRocco, C\nTesson, F\nRichter, A\nWilke, A\nKomajda, M\nGuideline\nJournal Article\nPractice Guideline\nResearch Support, Non-U.S. Gov't\nReview\nEngland\nEur Heart J. 1999 Jan;20(2):93-102.", "page" : "93-102", "title" : "Guidelines for the study of familial dilated cardiomyopathies. 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Familial screening should be systematically performed to obtain an early diagnosis in relatives as this facilitates prompt prophylactic therapy in early or preclinical disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurjhf/hfq093", "ISSN" : "1879-0844", "author" : [ { "dropping-particle" : "", "family" : "Moretti", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregori", "given" : "Dario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Heart Failure", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2010", "9", "1" ] ] }, "page" : "922-927", "title" : "Prognostic impact of familial screening in dilated cardiomyopathy", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(11)", "plainTextFormattedCitation" : "(11)", "previouslyFormattedCitation" : "(11)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(11). Importantly, a negative family history does not rule out a genetic form of DCM as de novo mutations can be responsible for sporadic forms. Genetic forms of DCM are also suggested by the presence of clinical traits, sometimes referred to as diagnostic red-flags (Table 2) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/ehs397", "ISSN" : "1522-9645 (Electronic)", "PMID" : "23211230", "abstract" : "In 2008, The ESC Working Group on Myocardial and Pericardial Diseases proposed an updated classification of cardiomyopathies based on morphological and functional phenotypes and subcategories of familial/genetic and non-familial/non-genetic disease. In this position statement, we propose a framework for the clinical approach to diagnosis in cardiomyopathies based on the recognition of diagnostic 'red flags' that can be used to guide rational selection of specialized tests including genetic analysis. The basic premise is that the adoption of a cardiomyopathy-specific mindset which combines conventional cardiological assessment with non-cardiac and molecular parameters increases diagnostic accuracy and thus improves advice and treatment for patients and families.", "author" : [ { "dropping-particle" : "", "family" : "Rapezzi", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arbustini", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caforio", "given" : "Alida L P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gimeno-Blanes", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helio", "given" : "Tiina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linhart", "given" : "Ales", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mogensen", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Yigal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ristic", "given" : "Arsen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seggewiss", "given" : "Hubert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavazzi", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Perry M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European heart journal", "id" : "ITEM-1", "issue" : "19", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "language" : "eng", "page" : "1448-1458", "publisher-place" : "England", "title" : "Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(12)", "plainTextFormattedCitation" : "(12)", "previouslyFormattedCitation" : "(12)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(12). Rare, but important signs and symptoms that suggest specific forms of multisystem disease or specific genotypes are abnormal skin pigmentation, skeletal myopathy and neurosensory disorders (e.g. deafness, blindness) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/ehs397", "ISSN" : "1522-9645 (Electronic)", "PMID" : "23211230", "abstract" : "In 2008, The ESC Working Group on Myocardial and Pericardial Diseases proposed an updated classification of cardiomyopathies based on morphological and functional phenotypes and subcategories of familial/genetic and non-familial/non-genetic disease. In this position statement, we propose a framework for the clinical approach to diagnosis in cardiomyopathies based on the recognition of diagnostic 'red flags' that can be used to guide rational selection of specialized tests including genetic analysis. 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A position statement from the ESC Working Group on Myocardial and Pericardial Diseases.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(12)", "plainTextFormattedCitation" : "(12)", "previouslyFormattedCitation" : "(12)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(12). In most epidemiological studies, the proportion of patients with genetically determined DCM is substantially underestimated due to variable clinical presentation, incomplete disease penetrance and the lack of specific phenotypes. However, contemporary series using genetic screening suggest that up to 40% of DCM is genetically determined ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrcardio.2013.105", "ISSN" : "1759-5010 (Electronic)", "PMID" : "23900355", "abstract" : "Remarkable progress has been made in understanding the genetic basis of dilated cardiomyopathy (DCM). Rare variants in >30 genes, some also involved in other cardiomyopathies, muscular dystrophy, or syndromic disease, perturb a diverse set of important myocardial proteins to produce a final DCM phenotype. Large, publicly available datasets have provided the opportunity to evaluate previously identified DCM-causing mutations, and to examine the population frequency of sequence variants similar to those that have been observed to cause DCM. The frequency of these variants, whether associated with dilated or hypertrophic cardiomyopathy, is greater than estimates of disease prevalence. This mismatch might be explained by one or more of the following possibilities: that the penetrance of DCM-causing mutations is lower than previously thought, that some variants are noncausal, that DCM prevalence is higher than previously estimated, or that other more-complex genomics underlie DCM. Reassessment of our assumptions about the complexity of the genomic and phenomic architecture of DCM is warranted. Much about the genomic basis of DCM remains to be investigated, which will require comprehensive genomic studies in much larger cohorts of rigorously phenotyped probands and family members than previously examined.", "author" : [ { "dropping-particle" : "", "family" : "Hershberger", "given" : "Ray E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedges", "given" : "Dale J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morales", "given" : "Ana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Cardiology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "language" : "eng", "page" : "531-547", "publisher-place" : "England", "title" : "Dilated cardiomyopathy: the complexity of a diverse genetic architecture.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(4)", "plainTextFormattedCitation" : "(4)", "previouslyFormattedCitation" : "(4)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(4). Most patients with familial DCM have autosomal dominant inheritance, but X-linked, autosomal recessive and maternal transmission (as in mitochondrial disorders) are recognized in isolated cardiac disease and in the context of multiorgan syndromes. So far, more than 50 genes encoding for sarcomeric proteins, cytoskeleton, nuclear envelope, sarcolemma, ion channels and intercellular junctions have been implicated in DCM. The most common is TTN (encoding for titin) which is estimated to cause or contribute to approximately 15-25% of familial DCM, according to different series ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/ehv727", "ISSN" : "1522-9645 (Electronic)", "PMID" : "26792875", "abstract" : "In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.", "author" : [ { "dropping-particle" : "", "family" : "Pinto", "given" : "Yigal M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Perry M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arbustini", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler", "given" : "Yehuda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anastasakis", "given" : "Aris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bohm", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duboc", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gimeno", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groote", "given" : "Pascal", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imazio", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heymans", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klingel", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komajda", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Limongelli", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linhart", "given" : "Ales", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mogensen", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moon", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pieper", "given" : "Petronella G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seferovic", "given" : "Petar M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schueler", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zamorano", "given" : "Jose L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caforio", "given" : "Alida L P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European heart journal", "id" : "ITEM-1", "issue" : "23", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "language" : "eng", "page" : "1850-1858", "publisher-place" : "England", "title" : "Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/ejhf.673", "ISSN" : "1879-0844 (Electronic)", "PMID" : "27813223", "abstract" : "AIMS: Truncating titin mutations (tTTN) occur in 25% of dilated cardiomyopathy (DCM) cases, but the phenotype and severity of disease they cause have not yet been systematically studied. We studied whether tTTN variants are associated with a clinically distinguishable form of DCM. METHODS AND RESULTS: We compared clinical data on DCM probands and relatives with a tTTN mutation (n = 45, n = 73), LMNA mutation (n = 28, n = 29), and probands who tested negative for both genes [idiopathic DCM (iDCM); n = 60]. Median follow-up was at least 2.5 years in each group. TTN subjects presented with DCM at higher age than LMNA subjects (probands 47.9 vs. 40.4 years, P = 0.004; relatives 59.8 vs. 47.0 years, P = 0.01), less often developed LVEF <35% [probands hazard ratio (HR) 0.38, P = 0.002], had higher age of death (probands 70.4 vs. 59.4 years, P < 0.001; relatives 74.1 vs. 58.4 years, P = 0.008), and had better composite outcome (malignant ventricular arrhythmia, heart transplantation, or death; probands HR 0.09, P < 0.001; relatives HR 0.21, P = 0.02) than LMNA subjects and iDCM subjects (HR 0.36, P = 0.07). An LVEF increase of at least 10% occurred in 46.9% of TTN subjects after initiation of standard heart failure treatment, while this only occurred in 6.5% of LMNA subjects (P < 0.001) and 18.5% of iDCM subjects (P = 0.02). This was confirmed in families with co-segregation, in which the 10% point LVEF increase occurred in 55.6% of subjects (P = 0.003 vs. LMNA, P = 0.079 vs. iDCM). CONCLUSIONS: This study shows that tTTN-associated DCM is less severe at presentation and more amenable to standard therapy than LMNA mutation-induced DCM or iDCM.", "author" : [ { "dropping-particle" : "", "family" : "Jansweijer", "given" : "Joeri A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwhof", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Russo", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoorntje", "given" : "Edgar T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jongbloed", "given" : "Jan D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lekanne Deprez", "given" : "Ronald H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Postma", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bronk", "given" : "Marieke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rijsingen", "given" : "Ingrid A W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haij", "given" : "Simone", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biagini", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haelst", "given" : "Paul L", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijngaarden", "given" : "Jan", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berg", "given" : "Maarten P", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilde", "given" : "Arthur A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mannens", "given" : "Marcel M A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boer", "given" : "Rudolf A", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spaendonck-Zwarts", "given" : "Karin Y", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tintelen", "given" : "J Peter", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Yigal M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of heart failure", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2017", "4" ] ] }, "language" : "eng", "page" : "512-521", "publisher-place" : "England", "title" : "Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/eurheartj/ehu301", "ISSN" : "1522-9645 (Electronic)", "PMID" : "25163546", "abstract" : "AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. CONCLUSION: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. 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Another important cluster of genes involved in DCM pathogenesis includes cytoskeleton genes (DES, DMD, FLNC, NEXN, LDB3). Of note, the DMD gene (encoding for dystrophin) is involved in muscular dystrophy patients and X-linked familial DCM in the absence of overt skeletal muscle disease (4). Although ECG findings in DCM are generally non-specific, DMD-related DCM may represent an exception as it is frequently characterized by a posterolateral or inferolateral “pseudonecrosis” pattern. Echocardiographic and cardiac magnetic resonance (CMR) evaluations usually reveal posterolateral akinesia with late gadolinium enhanced (LGE)-based myocardial scar. Mutations in the DES gene (encoding for desmin) cause skeletal myopathy, cardiac disease with variable cardiomyopathy phenotypes including DCM and restrictive cardiomyopathy or a combination of the two ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/CIRCULATIONAHA.106.646778", "ISSN" : "1524-4539 (Electronic)", "PMID" : "17325244", "abstract" : "BACKGROUND: Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known. METHODS AND RESULTS: Denaturing high-performance liquid chromatography was used to screen DES for mutations in 116 DCM families from the Familial Dilated Cardiomyopathy Registry and in 309 subjects with DCM from the Beta-Blocker Evaluation of Survival Trial (BEST). DES mutations were transfected into SW13 and human smooth muscle cells and neonatal rat cardiac myocytes, and the effects on cytoskeletal desmin network architecture were analyzed with confocal microscopy. Five novel missense DES mutations, including the first localized to the highly conserved 1A domain, were detected in 6 subjects (1.4%). Transfection of DES mutations in the 2B domain severely disrupted the fine intracytoplasmic staining of desmin, causing clumping of the desmin protein. A tail domain mutation (Val459Ile) showed milder effects on desmin cytoplasmic network formation and appears to be a low-penetrant mutation restricted to black subjects. CONCLUSIONS: The prevalence of DES mutations in DCM is between 1% and 2%, and mutations in the 1A helical domain, as well as the 2B rod domain, are capable of causing a DCM phenotype. The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM.", "author" : [ { "dropping-particle" : "", "family" : "Taylor", "given" : "Matthew R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slavov", "given" : "Dobromir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ku", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carniel", "given" : "Elisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haubold", "given" : "Kurt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boucek", "given" : "Mark M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferguson", "given" : "Debra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graw", "given" : "Sharon L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Xiao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavanaugh", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sucharov", "given" : "Carmen C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Long", "given" : "Carlin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bristow", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavori", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2007", "3" ] ] }, "language" : "eng", "page" : "1244-1251", "publisher-place" : "United States", "title" : "Prevalence of desmin mutations in dilated cardiomyopathy.", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ejheart.2005.11.003", "ISSN" : "1388-9842 (Print)", "PMID" : "16376610", "abstract" : "BACKGROUND: Primary desminopathies are caused by desmin gene [DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study. AIMS: To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects. METHODS AND RESULTS: Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [DES and alphaB-crystallin (CRYAB)] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon-intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative. CONCLUSIONS: A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical.", "author" : [ { "dropping-particle" : "", "family" : "Arbustini", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasotti", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pilotto", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pellegrini", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grasso", "given" : "Maurizia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Previtali", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Repetto", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellini", "given" : "Ornella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azan", "given" : "Gaetano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaffino", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campana", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piccolo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vigano", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavazzi", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of heart failure", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "8" ] ] }, "language" : "ENG", "page" : "477-483", "publisher-place" : "England", "title" : "Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(15, 16)", "manualFormatting" : "(15,16)", "plainTextFormattedCitation" : "(15, 16)", "previouslyFormattedCitation" : "(15, 16)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(15,16).Mutations in the LMNA gene (encoding Lamin A/C) are a cause of familial DCM characterized by cardiac conduction disturbances (atrioventricular block) with elevated serum creatine kinase levels and in some cases skeletal muscle involvement (limb-girdle or Emery-Dreifuss muscular dystrophy) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2011.08.078", "ISSN" : "1558-3597 (Electronic)", "PMID" : "22281253", "abstract" : "OBJECTIVES: The purpose of this study was to determine risk factors that predict malignant ventricular arrhythmias (MVA) in Lamin A/C (LMNA) mutation carriers. BACKGROUND: LMNA mutations cause a variety of clinical phenotypes, including dilated cardiomyopathy and conduction disease. Many LMNA mutation carriers have a poor prognosis, because of a high frequency of MVA and progression to end-stage heart failure. However, it is unclear how to identify mutation carriers that are at risk for MVA. METHODS: In this multicenter cohort of 269 LMNA mutation carriers, we evaluated risk factors for MVA, defined as sudden cardiac death, resuscitation, and appropriate implantable cardioverter-defibrillator (ICD) treatment. RESULTS: In a median follow-up period of 43 months (interquartile range: 17 to 101 months), 48 (18%) persons experienced a first episode of MVA: 11 persons received successful cardiopulmonary resuscitation, 25 received appropriate ICD treatment, and 12 persons died suddenly. Independent risk factors for MVA were nonsustained ventricular tachycardia, left ventricular ejection fraction <45% at the first clinical contact, male sex, and non-missense mutations (ins-del/truncating or mutations affecting splicing). MVA occurred only in persons with at least 2 of these risk factors. There was a cumulative risk for MVA per additional risk factor. CONCLUSIONS: Carriers of LMNA mutations with a high risk of MVA can be identified using these risk factors. This facilitates selection of LMNA mutation carriers who are most likely to benefit from an ICD.", "author" : [ { "dropping-particle" : "", "family" : "Rijsingen", "given" : "Ingrid A W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arbustini", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Perry M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mogensen", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hermans-van Ast", "given" : "Johanna F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooi", "given" : "Anneke J", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tintelen", "given" : "J Peter", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berg", "given" : "Maarten P", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pilotto", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasotti", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jenkins", "given" : "Sharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rowland", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aslam", "given" : "Uzma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilde", "given" : "Arthur A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perrot", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankuweit", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zwinderman", "given" : "Aeilko H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Yigal M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "language" : "eng", "page" : "493-500", "publisher-place" : "United States", "title" : "Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(17)", "plainTextFormattedCitation" : "(17)", "previouslyFormattedCitation" : "(17)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(17). Lamin A/C mutations also convey an increased risk of life threatening ventricular arrhythmias irrespective of the severity of LV dysfunction and dilation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2011.08.078", "ISSN" : "1558-3597 (Electronic)", "PMID" : "22281253", "abstract" : "OBJECTIVES: The purpose of this study was to determine risk factors that predict malignant ventricular arrhythmias (MVA) in Lamin A/C (LMNA) mutation carriers. BACKGROUND: LMNA mutations cause a variety of clinical phenotypes, including dilated cardiomyopathy and conduction disease. Many LMNA mutation carriers have a poor prognosis, because of a high frequency of MVA and progression to end-stage heart failure. However, it is unclear how to identify mutation carriers that are at risk for MVA. METHODS: In this multicenter cohort of 269 LMNA mutation carriers, we evaluated risk factors for MVA, defined as sudden cardiac death, resuscitation, and appropriate implantable cardioverter-defibrillator (ICD) treatment. RESULTS: In a median follow-up period of 43 months (interquartile range: 17 to 101 months), 48 (18%) persons experienced a first episode of MVA: 11 persons received successful cardiopulmonary resuscitation, 25 received appropriate ICD treatment, and 12 persons died suddenly. Independent risk factors for MVA were nonsustained ventricular tachycardia, left ventricular ejection fraction <45% at the first clinical contact, male sex, and non-missense mutations (ins-del/truncating or mutations affecting splicing). MVA occurred only in persons with at least 2 of these risk factors. There was a cumulative risk for MVA per additional risk factor. CONCLUSIONS: Carriers of LMNA mutations with a high risk of MVA can be identified using these risk factors. This facilitates selection of LMNA mutation carriers who are most likely to benefit from an ICD.", "author" : [ { "dropping-particle" : "", "family" : "Rijsingen", "given" : "Ingrid A W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arbustini", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Perry M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mogensen", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hermans-van Ast", "given" : "Johanna F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooi", "given" : "Anneke J", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tintelen", "given" : "J Peter", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berg", "given" : "Maarten P", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pilotto", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasotti", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jenkins", "given" : "Sharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rowland", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aslam", "given" : "Uzma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilde", "given" : "Arthur A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perrot", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankuweit", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zwinderman", "given" : "Aeilko H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Yigal M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "language" : "eng", "page" : "493-500", "publisher-place" : "United States", "title" : "Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(17)", "plainTextFormattedCitation" : "(17)", "previouslyFormattedCitation" : "(17)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(17). Other forms of DCM increasingly grouped under the heading of arrrhythmogenic cardiomyopathies are also characterized by a propensity to ventricular arrhythmia. These include disease caused by mutations in genes encoding desmosomal proteins which are classically linked to arrhythmogenic right ventricular cardiomyopathy but have now emerged as a cause of isolated DCM ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/CIRCGENETICS.110.937805", "ISSN" : "1942-3268 (Electronic)", "PMID" : "20716751", "abstract" : "BACKGROUND: Idiopathic dilated cardiomyopathy is a familial disorder in 25% to 50% of patients, but the genetic basis in the majority of cases remains unknown. Genes encoding desmosomal proteins, currently regarded as synonymous with another disorder, arrhythmogenic right ventricular cardiomyopathy, are known to cause left ventricular dysfunction, but their importance in unselected patients with unequivocal dilated cardiomyopathy is unknown. The objective of this study was to determine the prevalence of mutations in 5 desmosomal protein genes in patients with dilated cardiomyopathy. METHODS AND RESULTS: We studied 100 unrelated patients with idiopathic dilated cardiomyopathy consecutively referred to a dedicated cardiomyopathy unit. Patients underwent clinical evaluation, ECG, echocardiography, exercise testing, 24-hour ambulatory ECG monitoring, and mutation screening of 5 genes implicated in arrhythmogenic right ventricular cardiomyopathy: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. Of the 100 patients (mean age at evaluation, 46.8+/-13.8 years; range, 17.0 to 72.8 years; male sex, 63%), 5 were found to carry pathogenic desmosomal protein gene mutations. An additional 13 patients had sequence variants of uncertain pathogenic significance and were excluded from further comparative analysis. Patients harboring desmosomal gene mutations had a phenotype indistinguishable from the 82 noncarriers, with the exception of exercise-induced ventricular ectopy, which was more frequent in the desmosomal mutation carriers (P=0.033). None of the 5 carriers of desmosomal mutations fulfilled current diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy, but 1 had fibrofatty change in the left ventricle at autopsy. CONCLUSIONS: Heart failure caused by a dilated, poorly contracting left ventricle and arrhythmogenic right ventricular cardiomyopathy have been considered distinct clinicopathologic entities. This study suggests that both clinical presentations can be caused by mutations in desmosomal protein genes.", "author" : [ { "dropping-particle" : "", "family" : "Elliott", "given" : "Perry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Mahony", "given" : "Constantinos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syrris", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "Alison", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera Sorensen", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheppard", "given" : "Mary N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carr-White", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantazis", "given" : "Antonios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKenna", "given" : "William J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation. Cardiovascular genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "8" ] ] }, "language" : "eng", "page" : "314-322", "publisher-place" : "United States", "title" : "Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1161/JAHA.115.002149", "ISSN" : "2047-9980 (Electronic)", "PMID" : "26475296", "abstract" : "BACKGROUND: Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (AR-DCM). We investigated the phenotype and natural history of patients with AR-DCM. METHODS AND RESULTS: Two hundred eighty-five patients with a recent diagnosis of DCM (median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months). AR-DCM was defined by the presence of >/=1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (>/=5 beats, >/=150 bpm), >/=1000 premature ventricular contractions/24 hours, and >/=50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (SCD), sustained ventricular tachycardia (SVT), or ventricular fibrillation (VF). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for AR-DCM phenotype. AR-DCM subjects had a higher incidence of SCD/SVT/VF compared with non-AR-DCM patients (30.3% vs 17.6%, P=0.022), with no difference in the secondary end points. A family history of SCD/SVT/VF and the AR-DCM phenotype were statistically significant and cumulative predictors of SCD/SVT/VF. CONCLUSIONS: One-third of DCM patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow-up. A family history of ventricular arrhythmias in DCM predicts a poor prognosis and increased risk of SCD.", "author" : [ { "dropping-particle" : "", "family" : "Spezzacatene", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graw", "given" : "Sharon L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slavov", "given" : "Dobromir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salcedo", "given" : "Ernesto E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towbin", "given" : "Jeffrey A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saffitz", "given" : "Jeffrey E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "Frank I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zareba", "given" : "Wojciech", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "Matthew R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Heart Association", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "language" : "eng", "page" : "e002149", "publisher-place" : "England", "title" : "Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias.", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jacc.2008.09.019", "ISBN" : "0735-1097", "PMID" : "19095136", "abstract" : "OBJECTIVES: We sought to investigate the clinical-genetic profile of left-dominant arrhythmogenic cardiomyopathy (LDAC). BACKGROUND: In the absence of coronary disease and left ventricular (LV) systolic dysfunction, lateral T-wave inversion and arrhythmia of LV origin are often considered benign. Similarly, chest pain with enzyme release might be attributed to viral myocarditis. We hypothesized that these abnormalities might be manifestations of the \"left-dominant\" subtype of arrhythmogenic right ventricular cardiomyopathy. METHODS: The 42-patient cohort was established through clinical evaluation of individuals with unexplained (infero)lateral T-wave inversion, arrhythmia of LV origin, and/or proven LDAC/idiopathic myocardial fibrosis in the family. RESULTS: Patients presented from adolescence to age >80 years with arrhythmia or chest pain but not heart failure. Desmosomal mutations were identified in 8 of 24 families (15 of 33 patients). Magnetic resonance findings included LV late-enhancement in a subepicardial/midwall distribution, corresponding to fibrofatty replacement and fibrosis on histopathology. Fifty percent had previously been misdiagnosed with viral myocarditis, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy, or idiopathic ventricular tachycardia. Arrhythmic events included presentation with ventricular fibrillatory arrest in 1 patient and 2 instances of sudden cardiac death during follow-up. CONCLUSIONS: Arrhythmogenic cardiomyopathy is distinguished from DCM by a propensity towards arrhythmia exceeding the degree of ventricular dysfunction. The left-dominant subtype is under-recognized owing to misattribution to other disorders and lack of specific diagnostic criteria. Clinicians are alerted to the possibility of LDAC in patients of any age with unexplained arrhythmia of LV origin, (infero)lateral T-wave inversion, apparent DCM (with arrhythmic presentation), or myocarditis (chest pain and enzyme rise with unobstructed coronary arteries).", "author" : [ { "dropping-particle" : "", "family" : "Sen-Chowdhry", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syrris", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "S K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merrifield", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennell", "given" : "D J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKenna", "given" : "W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Coll Cardiol", "edition" : "2008/12/20", "id" : "ITEM-3", "issue" : "25", "issued" : { "date-parts" : [ [ "2008" ] ] }, "language" : "eng", "note" : "1558-3597\nSen-Chowdhry, Srijita\nSyrris, Petros\nPrasad, Sanjay K\nHughes, Sian E\nMerrifield, Robert\nWard, Deirdre\nPennell, Dudley J\nMcKenna, William J\nBritish Heart Foundation/United Kingdom\nJournal Article\nResearch Support, Non-U.S. Gov't\nUnited States\nJ Am Coll Cardiol. 2008 Dec 16;52(25):2175-87. doi: 10.1016/j.jacc.2008.09.019.", "page" : "2175-2187", "title" : "Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(18\u201320)", "plainTextFormattedCitation" : "(18\u201320)", "previouslyFormattedCitation" : "(18\u201320)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(18–20). Mutations of FLNC (encoding for filamin C) gene are more recently described as also associated to arrhythmogenic phenotypes of DCMs ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2016.09.927", "ISSN" : "1558-3597 (Electronic)", "PMID" : "27908349", "abstract" : "BACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.", "author" : [ { "dropping-particle" : "", "family" : "Ortiz-Genga", "given" : "Martin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuenca", "given" : "Sofia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dal Ferro", "given" : "Matteo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zorio", "given" : "Esther", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salgado-Aranda", "given" : "Ricardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Climent", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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}, { "dropping-particle" : "", "family" : "Lara-Pezzi", "given" : "Enrique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calvo-Iglesias", "given" : "Francisco E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nof", "given" : "Eyal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calo", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barriales-Villa", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gimeno-Blanes", "given" : "Juan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arad", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garcia-Pavia", "given" : "Pablo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monserrat", "given" : "Lorenzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2016", "12" ] ] }, "language" : "eng", "page" : "2440-2451", "publisher-place" : "United States", "title" : "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies.", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(21)", "plainTextFormattedCitation" : "(21)", "previouslyFormattedCitation" : "(21)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(21).Mutations in genes encoding for sarcomere (MYH7, ACTC1, TNNT2, MYH6 and MYBPC3) and sodium ion channels (RYR2 and SCN5A) may also be associated with DCM ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2010.09.084", "ISSN" : "1558-3597 (Electronic)", "PMID" : "21596231", "abstract" : "OBJECTIVES: The aim of this study was to discern the role of the cardiac voltage-gated sodium ion channel SCN5A in the etiology of dilated cardiomyopathy (DCM). BACKGROUND: Dilated cardiomyopathy associates with mutations in the SCN5A gene, but the frequency, phenotype, and causative nature of these associations remain the focus of ongoing investigation. METHODS: Since 1991, DCM probands and family members have been enrolled in the Familial Cardiomyopathy Registry and extensively evaluated by clinical phenotype. Genomic deoxyribonucleic acid samples from 338 individuals among 289 DCM families were obtained and screened for SCN5A mutations by denaturing high-performance liquid chromatography and sequence analysis. RESULTS: We identified 5 missense SCN5A mutations among our DCM families, including novel mutations E446K, F1520L, and V1279I, as well as previously reported mutations D1275N and R222Q. Of 15 SCN5A mutation carriers in our study, 14 (93%) manifested arrhythmia: supraventricular arrhythmia (13 of 15), including sick sinus syndrome (5 of 15) and atrial fibrillation (9 of 15), ventricular tachycardia (5 of 15), and conduction disease (9 of 15). CONCLUSIONS: Mutations in SCN5A were detected in 1.7% of DCM families. Two-thirds (6 of 9) of all reported DCM mutations in SCN5A localize to the highly conserved homologous S3 and S4 transmembrane segments, suggesting a shared mechanism of disruption of the voltage-sensing mechanism of this channel leading to DCM. Not surprisingly, SCN5A mutation carriers show a strong arrhythmic pattern that has clinical and diagnostic implications.", "author" : [ { "dropping-particle" : "", "family" : "McNair", "given" : "William P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "Matthew R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferguson", "given" : "Debra A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salcedo", "given" : "Ernesto E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slavov", "given" : "Dobromir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Xiao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldwell", "given" : "John H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-1", "issue" : "21", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "language" : "eng", "page" : "2160-2168", "publisher-place" : "United States", "title" : "SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism.", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(22)", "plainTextFormattedCitation" : "(22)", "previouslyFormattedCitation" : "(22)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(22) with current widely unknown genotype-phenotype correlations.1.3 Specific phenotypes of DCMRecently, a position statement of the European Society of Cardiology ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/ehv727", "ISSN" : "1522-9645 (Electronic)", "PMID" : "26792875", "abstract" : "In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. 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The latter could often be the result of an early diagnosis of DCM and a timely management, which in turn can lead to favourable long-term outcome. Nonetheless, association with specific features such as familial history of SCD in arrhythmic DCM and severe diastolic dysfunction or non-sustained ventricular arrhythmias in hypokinetic non-dilated cardiomyopathy, can indicate distinct genotypes with a less favorable course that require focused follow-up and more aggressive therapeutic strategies such as ICD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/JAHA.115.002149", "ISSN" : "2047-9980 (Electronic)", "PMID" : "26475296", "abstract" : "BACKGROUND: Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (AR-DCM). We investigated the phenotype and natural history of patients with AR-DCM. METHODS AND RESULTS: Two hundred eighty-five patients with a recent diagnosis of DCM (median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months). AR-DCM was defined by the presence of >/=1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (>/=5 beats, >/=150 bpm), >/=1000 premature ventricular contractions/24 hours, and >/=50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (SCD), sustained ventricular tachycardia (SVT), or ventricular fibrillation (VF). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for AR-DCM phenotype. AR-DCM subjects had a higher incidence of SCD/SVT/VF compared with non-AR-DCM patients (30.3% vs 17.6%, P=0.022), with no difference in the secondary end points. A family history of SCD/SVT/VF and the AR-DCM phenotype were statistically significant and cumulative predictors of SCD/SVT/VF. CONCLUSIONS: One-third of DCM patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow-up. A family history of ventricular arrhythmias in DCM predicts a poor prognosis and increased risk of SCD.", "author" : [ { "dropping-particle" : "", "family" : "Spezzacatene", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graw", "given" : "Sharon L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slavov", "given" : "Dobromir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salcedo", "given" : "Ernesto E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towbin", "given" : "Jeffrey A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saffitz", "given" : "Jeffrey E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "Frank I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zareba", "given" : "Wojciech", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "Matthew R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Heart Association", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "language" : "eng", "page" : "e002149", "publisher-place" : "England", "title" : "Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias.", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of heart failure", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "531-539", "title" : "Insights into Mildly Dilated Cardiomyopathy: temporal evolution and long-term prognosis", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(19, 23)", "plainTextFormattedCitation" : "(19, 23)", "previouslyFormattedCitation" : "(19, 23)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(19, 23). 2 - The cornerstones of clinical management of DCM during follow-up2.1 – DCM as dynamic disease: left ventricular reverse remodeling and the importance of follow-up DCM has long been considered to be an irreversible condition. However, in recent years several studies revealed that almost 40% of patients experience a significant LVRR when treated with evidence-based pharmacological and device treatments ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2010.11.030", "ISBN" : "0735-1097", "PMID" : "21435516", "abstract" : "OBJECTIVES: The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Tailored medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. METHODS: We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of >/=10 U or a left ventricular ejection fraction of >/=50% and a decrease in indexed left ventricular end-diastolic diameter of >/=10% or indexed left ventricular end-diastolic diameter of >/=33 mm/m(2) at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 +/- 53 months; there were 55 deaths (23%) and 32 HTx (13%). RESULTS: LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. CONCLUSIONS: LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pyxaras", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Coll Cardiol", "edition" : "2011/03/26", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "language" : "eng", "note" : "1558-3597\nMerlo, Marco\nPyxaras, Stylianos A\nPinamonti, Bruno\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nUnited States\nJ Am Coll Cardiol. 2011 Mar 29;57(13):1468-76. doi: 10.1016/j.jacc.2010.11.030.", "page" : "1468-1476", "title" : "Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZXJsbzwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl

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ADDIN EN.CITE.DATA . LVRR is one of the main determinants of prognosis in DCM and should be considered a major goal in approaching newly diagnosed cases. In the absence of specific treatments, the medical management of DCM is based largely on conventional therapy with ACE-inhibitors/angiotensin receptors blockers, beta-blockers and mineralcorticoid receptors antagonists ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ponikowski", "given" : "Piotr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voors", "given" : "Adriaan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anker", "given" : "Stefan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bueno", "given" : "H\u00e9ctor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cleland", "given" : "John G F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coats", "given" : "Andrew J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Volkmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Juanatey", "given" : "Jos\u00e9 Ram\u00f3n", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harjola", "given" : "Veli-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jankowska", "given" : "Ewa A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jessup", "given" : "Mariell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linde", "given" : "Cecilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nihoyannopoulos", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parissis", "given" : "John T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pieske", "given" : "Burkert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Jillian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosano", "given" : "Giuseppe M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruilope", "given" : "Luis M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruschitzka", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rutten", "given" : "Frans H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meer", "given" : "Peter", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Heart Journal", "id" : "ITEM-1", "issue" : "27", "issued" : { "date-parts" : [ [ "2016", "6", "8" ] ] }, "page" : "2129-2200", "title" : "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(24)", "plainTextFormattedCitation" : "(24)", "previouslyFormattedCitation" : "(24)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(24). In patients with LV dyssynchrony manifested by left bundle branch block (LBBB), cardiac resynchronization therapy (CRT) can induce LVRR, sometimes with normalization of LV size and systolic function ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2010.01.022", "ISSN" : "1558-3597 (Electronic)", "PMID" : "20413027", "abstract" : "OBJECTIVES: The purpose of this study was to describe the long-term course of left ventricular remodeling induced by cardiac resynchronization therapy (CRT), adjusting for the confounding effect of patient loss due to disease. BACKGROUND: Reverse remodeling has been identified as the primary mechanism of improved symptoms and outcome in heart failure patients. METHODS: A total of 313 consecutive patients who underwent CRT with available baseline echocardiograms and subsequent clinical and echocardiographic follow-up were included in the analysis. Long-term follow-up included all-cause mortality, heart transplantation, and implantation of a left ventricular assist device. Longitudinal data analysis of left ventricular end-systolic volume index (LVESVi) was performed to adjust for the confounding effect of patient loss during follow-up. RESULTS: Patients with uneventful survival had a lower baseline LVESVi (Delta = 8.6 ml/m(2), SE = 4.6 ml/m(2), p < 0.0001) and a decreased LVESVi by -0.11 ml/m(2)/day during first 6 months, whereas the LVESVi remained unchanged in patients with adverse events (p < 0.0001). Beyond 6 months, the LVESVi remained unchanged in patients with uneventful survival, whereas the LVESVi continued to increase in those with adverse events at a rate of 0.01 ml/m(2)/day (p < 0.0001). Predictors of reverse remodeling were nonischemic etiology, female sex, and a wider QRS duration (p < 0.0001, p = 0.014, and p = 0.001, respectively). In the majority of patients, 6 months indicates a break point after which reverse remodeling becomes significantly less pronounced. CONCLUSIONS: CRT patients with uneventful survival show a significant decrease in the LVSVi at 6 months and generally maintain this response in the long term. Those with adverse outcomes are characterized by left ventricular dilation despite CRT.", "author" : [ { "dropping-particle" : "", "family" : "Verhaert", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grimm", "given" : "Richard A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puntawangkoon", "given" : "Chirapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolski", "given" : "Kathy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "De", "given" : "Sabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilkoff", "given" : "Bruce L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Starling", "given" : "Randall C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "W H Wilson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "James D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Popovic", "given" : "Zoran B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "language" : "eng", "page" : "1788-1795", "publisher-place" : "United States", "title" : "Long-term reverse remodeling with cardiac resynchronization therapy: results of extended echocardiographic follow-up.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/europace/eut339", "ISSN" : "1532-2092 (Electronic)", "PMID" : "24189477", "abstract" : "AIMS: To evaluate the long-term changes of clinical and echocardiographic parameters, the incidence of cardiac events and parameters associated with late cardiac events in 'super-responders' to cardiac resynchronization therapy (CRT) with [CRT defibrillator (CRT-D)] or without defibrillator back-up. METHODS AND RESULTS: In all consecutive patients treated with CRT in two Italian centres (Trieste and Udine) with left ventricular ejection fraction (LVEF) </=0.35 at implantation (Timp) and LVEF > 0.50 1 and/or 2 years (Tnorm) after implantation, the long-term outcome and the evolution of echocardiographic parameters were assessed; factors associated with a higher risk of cardiac events, defined as hospitalization or death for heart failure (HF), sudden death, or CRT-D appropriate interventions, were also analysed. Among the 259 patients evaluated, 62 (24%) had LVEF >/= 0.50 at Tnorm (n = 44 with at 1 year, n = 18 at 2 years). During a mean follow-up of 68 +/- 30 months, one cardiac death (for HF) and eight cardiovascular events (two hospitalization for HF and six appropriate CRT-D interventions) occurred. At the last echo evaluation (Tfup) performed 51 +/- 26 months after Timp, LVEF was <0.50 in five patients (>0.45 in four of them). At univariable analysis, only LV end-systolic volume evaluated at Tfup was associated with a higher risk of cardiac events during follow-up. CONCLUSION: In 'super-responders' to CRT long-term outcome is excellent. However, cardiac events, mainly CRT-D appropriate interventions, can occur despite the persistence of LVEF > 0.50. Early identification of these patients is still an unsolved issue.", "author" : [ { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proclemer", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnani", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali-Serdoz", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Facchin", "given" : "Domenico", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muser", "given" : "Daniele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordio", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puggia", "given" : "Ilaria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proclemer", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Europace", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "language" : "ENG", "page" : "363-371", "publisher-place" : "England", "title" : "Long-term outcome of 'super-responder' patients to cardiac resynchronization therapy.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(25, 26)", "plainTextFormattedCitation" : "(25, 26)", "previouslyFormattedCitation" : "(25, 26)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(25, 26). Even when there is improvement in LV dysfunction, the potential for later decline in systolic function remains, despite uninterrupted treatment ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurjhf/hfq093", "ISSN" : "1879-0844", "author" : [ { "dropping-particle" : "", "family" : "Moretti", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregori", "given" : "Dario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Heart Failure", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2010", "9", "1" ] ] }, "page" : "922-927", "title" : "Prognostic impact of familial screening in dilated cardiomyopathy", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(11)", "plainTextFormattedCitation" : "(11)", "previouslyFormattedCitation" : "(11)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(11). This issue emphasizes the pivotal role not only of an accurate and complete initial diagnostic evaluation but also of continuous therapy and individualized, long-term surveillance in order to recognize and treat the first signs of late disease progression (Table 3, Figure 4).2.2 – Other markers of disease severity and progressionThe process of LVRR may take up to two years following diagnosis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2010.11.030", "ISBN" : "0735-1097", "PMID" : "21435516", "abstract" : "OBJECTIVES: The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Tailored medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. METHODS: We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of >/=10 U or a left ventricular ejection fraction of >/=50% and a decrease in indexed left ventricular end-diastolic diameter of >/=10% or indexed left ventricular end-diastolic diameter of >/=33 mm/m(2) at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 +/- 53 months; there were 55 deaths (23%) and 32 HTx (13%). RESULTS: LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. CONCLUSIONS: LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pyxaras", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Coll Cardiol", "edition" : "2011/03/26", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "language" : "eng", "note" : "1558-3597\nMerlo, Marco\nPyxaras, Stylianos A\nPinamonti, Bruno\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nUnited States\nJ Am Coll Cardiol. 2011 Mar 29;57(13):1468-76. doi: 10.1016/j.jacc.2010.11.030.", "page" : "1468-1476", "title" : "Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6). The following aspects have been demonstrated as influencing the course and the prognosis of the disease and the likelihood of LVRR in the early stages and should be hence systematically assessed:Right ventricular function at diagnosis, is an important prognostic feature in DCM ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/circulationaha.113.002518", "ISBN" : "0009-7322", "ISSN" : "1524-4539 (Electronic)", "PMID" : "23965488", "abstract" : "BACKGROUND: Cardiovascular magnetic resonance is the gold-standard technique for the assessment of ventricular function. Although left ventricular volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether cardiovascular magnetic resonance assessment of RV function has prognostic value in DCM. METHODS AND RESULTS: We prospectively studied 250 consecutive DCM patients with the use of cardiovascular magnetic resonance. RVSD, defined by RV ejection fraction</=45%, was present in 86 (34%) patients. During a median follow-up period of 6.8 years, there were 52 deaths, and 7 patients underwent cardiac transplantation. The primary end point of all-cause mortality or cardiac transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients without RVSD (49% versus 10%; hazard ratio, 5.90; 95% confidence interval [CI], 3.35-10.37; P<0.001). On multivariable analysis, RVSD remained a significant independent predictor of the primary end point (hazard ratio, 3.90; 95% CI, 2.16-7.04; P<0.001), as well as secondary outcomes of cardiovascular mortality or cardiac transplantation (hazard ratio, 3.35; 95% CI, 1.76-6.39; P<0.001), and heart failure death, heart failure hospitalization, or cardiac transplantation (hazard ratio, 2.70; 95% CI, 1.32-5.51; P=0.006). Assessment of RVSD improved risk stratification for all-cause mortality or cardiac transplantation (net reclassification improvement, 0.31; 95% CI 0.10-0.53; P=0.001). CONCLUSIONS: RVSD is a powerful, independent predictor of transplant-free survival and adverse heart failure outcomes in DCM. Cardiovascular magnetic resonance assessment of RV function is important in the evaluation and risk stratification of DCM patients.", "author" : [ { "dropping-particle" : "", "family" : "Gulati", "given" : "Ankur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ismail", "given" : "Tevfik F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jabbour", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alpendurada", "given" : "Francisco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guha", "given" : "Kaushik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ismail", "given" : "Nizar A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raza", "given" : "Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khwaja", "given" : "Jahanzaib", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Tristan D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morarji", "given" : "Kishen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liodakis", "given" : "Emmanouil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roughton", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wage", "given" : "Ricardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakrashi", "given" : "Tapesh C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Rakesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpenter", "given" : "John-Paul P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Stuart A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowie", "given" : "Martin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Assomull", "given" : "Ravi G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennell", "given" : "Dudley J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation", "edition" : "2013/08/24", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "language" : "eng", "note" : "From Duplicate 1 (The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy - Gulati, A; Ismail, T F; Jabbour, A; Alpendurada, F; Guha, K; Ismail, N A; Raza, S; Khwaja, J; Brown, T D; Morarji, K; Liodakis, E; Roughton, M; Wage, R; Pakrashi, T C; Sharma, R; Carpenter, J P; Cook, S A; Cowie, M R; Assomull, R G; Pennell, D J; Prasad, S K)\n\n1524-4539\nGulati, Ankur\nIsmail, Tevfik F\nJabbour, Andrew\nAlpendurada, Francisco\nGuha, Kaushik\nIsmail, Nizar A\nRaza, Sadaf\nKhwaja, Jahanzaib\nBrown, Tristan D H\nMorarji, Kishen\nLiodakis, Emmanouil\nRoughton, Michael\nWage, Ricardo\nPakrashi, Tapesh C\nSharma, Rakesh\nCarpenter, John-Paul\nCook, Stuart A\nCowie, Martin R\nAssomull, Ravi G\nPennell, Dudley J\nPrasad, Sanjay K\nJournal Article\nResearch Support, Non-U.S. Gov't\nUnited States\nCirculation. 2013 Oct 8;128(15):1623-33. doi: 10.1161/CIRCULATIONAHA.113.002518. Epub 2013 Aug 21.\n\nFrom Duplicate 2 (The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy - Gulati, Ankur; Ismail, Tevfik F; Jabbour, Andrew; Alpendurada, Francisco; Guha, Kaushik; Ismail, Nizar A; Raza, Sadaf; Khwaja, Jahanzaib; Brown, Tristan D H; Morarji, Kishen; Liodakis, Emmanouil; Roughton, Michael; Wage, Ricardo; Pakrashi, Tapesh C; Sharma, Rakesh; Carpenter, John-Paul P; Cook, Stuart A; Cowie, Martin R; Assomull, Ravi G; Pennell, Dudley J; Prasad, Sanjay K)\n\nFrom Duplicate 2 (The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy - Gulati, A; Ismail, T F; Jabbour, A; Alpendurada, F; Guha, K; Ismail, N A; Raza, S; Khwaja, J; Brown, T D; Morarji, K; Liodakis, E; Roughton, M; Wage, R; Pakrashi, T C; Sharma, R; Carpenter, J P; Cook, S A; Cowie, M R; Assomull, R G; Pennell, D J; Prasad, S K)\n\n1524-4539\nGulati, Ankur\nIsmail, Tevfik F\nJabbour, Andrew\nAlpendurada, Francisco\nGuha, Kaushik\nIsmail, Nizar A\nRaza, Sadaf\nKhwaja, Jahanzaib\nBrown, Tristan D H\nMorarji, Kishen\nLiodakis, Emmanouil\nRoughton, Michael\nWage, Ricardo\nPakrashi, Tapesh C\nSharma, Rakesh\nCarpenter, John-Paul\nCook, Stuart A\nCowie, Martin R\nAssomull, Ravi G\nPennell, Dudley J\nPrasad, Sanjay K\nJournal Article\nResearch Support, Non-U.S. Gov't\nUnited States\nCirculation. 2013 Oct 8;128(15):1623-33. doi: 10.1161/CIRCULATIONAHA.113.002518. Epub 2013 Aug 21.", "page" : "1623-1633", "publisher-place" : "United States", "title" : "The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(27)", "plainTextFormattedCitation" : "(27)", "previouslyFormattedCitation" : "(27)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(27). The recovery of right ventricular function under therapy is frequent and can already be observed at 6 months. It precedes LVRR, and is emerging as an early therapeutic target and an independent prognostic predictor ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jcmg.2016.01.027", "ISSN" : "1876-7591 (Electronic)", "PMID" : "27344413", "abstract" : "OBJECTIVES: In this study, we analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). BACKGROUND: RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. METHODS: From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of >/=72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. RESULTS: At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). CONCLUSIONS: Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF throughout regular follow-up conferred additive long-term prognostic value to the baseline evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gobbo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Losurdo", "given" : "Pasquale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anzini", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JACC. Cardiovascular imaging", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "language" : "ENG", "page" : "1034-1042", "title" : "The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(28)", "plainTextFormattedCitation" : "(28)", "previouslyFormattedCitation" : "(28)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(28). Improvement in right ventricular function is also described in CRT recipients as a secondary expression of haemodynamic improvement very early after resynchronization, with consequently favourable survival rates ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.amjcard.2015.01.549", "ISSN" : "0002-9149", "PMID" : "25721482", "abstract" : "The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 +/- 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poli", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabris", "given" : "Enrico", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Cardiology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "7", "21" ] ] }, "language" : "eng", "note" : "From Duplicate 1 (Early Improvement of Functional Mitral Regurgitation in Patients With Idiopathic Dilated Cardiomyopathy - Stolfo, Davide; Merlo, Marco; Pinamonti, Bruno; Poli, Stefano; Gigli, Marta; Barbati, Giulia; Fabris, Enrico; Di Lenarda, Andrea; Sinagra, Gianfranco)\n\ndoi: 10.1016/j.amjcard.2015.01.549", "page" : "1137-1143", "publisher" : "Elsevier", "publisher-place" : "United States", "title" : "Early Improvement of Functional Mitral Regurgitation in Patients With Idiopathic Dilated Cardiomyopathy", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(29)", "plainTextFormattedCitation" : "(29)", "previouslyFormattedCitation" : "(29)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(29). In contrast, the development of right ventricular dysfunction during long term follow-up is an expression of structural progression of the disease and portends a negative outcome ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jcmg.2016.01.027", "ISSN" : "1876-7591 (Electronic)", "PMID" : "27344413", "abstract" : "OBJECTIVES: In this study, we analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). BACKGROUND: RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. METHODS: From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of >/=72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. RESULTS: At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). CONCLUSIONS: Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF throughout regular follow-up conferred additive long-term prognostic value to the baseline evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gobbo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Losurdo", "given" : "Pasquale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anzini", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JACC. Cardiovascular imaging", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "language" : "ENG", "page" : "1034-1042", "title" : "The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(28)", "plainTextFormattedCitation" : "(28)", "previouslyFormattedCitation" : "(28)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(28).Functional mitral regurgitation conveys important prognostic implications. Moderate to severe mitral regurgitation at diagnosis or persistent despite optimal medical treatment or CRT is associated with poorer outcomes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/pace.12731", "ISSN" : "1540-8159", "author" : [ { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tonet", "given" : "Elisabetta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pacing and Clinical Electrophysiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015", "11", "1" ] ] }, "page" : "1287-1296", "title" : "Acute Hemodynamic Response to Cardiac Resynchronization in Dilated Cardiomyopathy: Effect on Late Mitral Regurgitation", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.amjcard.2015.01.549", "ISSN" : "0002-9149", "PMID" : "25721482", "abstract" : "The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 +/- 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poli", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabris", "given" : "Enrico", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Cardiology", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "7", "21" ] ] }, "language" : "eng", "note" : "From Duplicate 1 (Early Improvement of Functional Mitral Regurgitation in Patients With Idiopathic Dilated Cardiomyopathy - Stolfo, Davide; Merlo, Marco; Pinamonti, Bruno; Poli, Stefano; Gigli, Marta; Barbati, Giulia; Fabris, Enrico; Di Lenarda, Andrea; Sinagra, Gianfranco)\n\ndoi: 10.1016/j.amjcard.2015.01.549", "page" : "1137-1143", "publisher" : "Elsevier", "publisher-place" : "United States", "title" : "Early Improvement of Functional Mitral Regurgitation in Patients With Idiopathic Dilated Cardiomyopathy", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(29, 30)", "plainTextFormattedCitation" : "(29, 30)", "previouslyFormattedCitation" : "(29, 30)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(29, 30). Patients with DCM and haemodynamically important mitral regurgitation may require invasive therapeutic strategies such as percutaneous repair of the mitral valve, mechanical circulatory support or even heart transplantation.LBBB is a frequent ECG marker at diagnosis and is negatively associated with the likelihood of LVRR ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2010.11.030", "ISBN" : "0735-1097", "PMID" : "21435516", "abstract" : "OBJECTIVES: The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Tailored medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. METHODS: We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of >/=10 U or a left ventricular ejection fraction of >/=50% and a decrease in indexed left ventricular end-diastolic diameter of >/=10% or indexed left ventricular end-diastolic diameter of >/=33 mm/m(2) at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 +/- 53 months; there were 55 deaths (23%) and 32 HTx (13%). RESULTS: LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. CONCLUSIONS: LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pyxaras", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Coll Cardiol", "edition" : "2011/03/26", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "language" : "eng", "note" : "1558-3597\nMerlo, Marco\nPyxaras, Stylianos A\nPinamonti, Bruno\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nUnited States\nJ Am Coll Cardiol. 2011 Mar 29;57(13):1468-76. doi: 10.1016/j.jacc.2010.11.030.", "page" : "1468-1476", "title" : "Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6). Importantly the development of new LBBB during follow-up is a strong independent prognostic predictor of all-cause mortality ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/europace/euu016", "ISSN" : "1532-2092 (Electronic)", "PMID" : "24550348", "abstract" : "AIMS: Left bundle branch block (LBBB) is commonly associated with heart failure. We evaluated the prevalence, incidence, and impact of LBBB on long-term outcome in young patients with heart failure affected by idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We included 608 patients with DCM from the Heart Muscle Disease Registry of Trieste in this retrospective analysis. At baseline electrocardiogram (ECG), 189 patients (31.1%) had LBBB. The patients with baseline LBBB had a significantly higher mortality rate than the patients without LBBB (38.6 vs. 27.9%, P = 0.002) at the univariate analysis. After a multiple covariate adjustment, the baseline LBBB was not associated with a significantly increased risk of death [hazard ratio (HR) 1.27, 95% confidence interval (CI): 0.88-1.81, P = 0.2]. Forty-seven (11.2%) patients without LBBB at baseline ECG developed LBBB during follow-up. Among these, the mortality rate was 49 vs. 25% in patients without new-onset LBBB (P = 0.001). New-onset LBBB was a strong and independent predictor of all-cause mortality (HR 3.18, 95% CI: 1.90-5.31, P < 0.001) at multivariate analysis. CONCLUSION: After correcting for potential confounders, new-onset LBBB was found to be associated with an increased risk of all-cause mortality. The management of patients with new-onset LBBB may need to be more aggressive, possibly including early cardiac resynchronization therapy/implantable cardioverter-defibrillator therapy.", "author" : [ { "dropping-particle" : "", "family" : "Aleksova", "given" : "Aneta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carriere", "given" : "Cosimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitrella", "given" : "Giancarlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Europace", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2014", "10" ] ] }, "language" : "eng", "page" : "1450-1459", "publisher-place" : "England", "title" : "New-onset left bundle branch block independently predicts long-term mortality in patients with idiopathic dilated cardiomyopathy: data from the Trieste Heart Muscle Disease Registry.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(31)", "plainTextFormattedCitation" : "(31)", "previouslyFormattedCitation" : "(31)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(31). Importantly CRT has been reduced the risk induced by LBBB, specifically in DCM patients (25, 26) and should timely considered after LBBB development during follow-up.The onset of atrial fibrillation during the follow-up is a sign of structural progression of the disease and negatively impacts on the prognosis of these patients, despite effective treatments ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3121/cmr.2010.908", "ISSN" : "1554-6179 (Electronic)", "PMID" : "20682760", "abstract" : "OBJECTIVE: There is a paucity and inconsistency of data regarding the natural history of patients affected by idiopathic dilated cardiomyopathy (IDCM) and atrial fibrillation (AF). We examined the prognostic implications of AF in a subset of patients with IDCM. METHODS: We analyzed the data of 539 patients with IDCM enrolled in the Heart Muscle Disease Registry of Trieste. RESULTS: At baseline, 52 (9.6%) of 539 patients had AF. There was no difference in survival of patients with either AF or sinus rhythm at enrollment (P = .28). During long-term follow-up (90 +/- 58 months), AF was detected on ECG/ECG-Holter monitoring in 28 (5.7%) of 487 patients in sinus rhythm at baseline. Predictors of new onset of AF at multivariate analysis were a more dilated left atrium (OR 1.35, 95% CI 1.06-1.72; P = .01) and a lower left ventricle ejection fraction (for 10% decrease, OR 2.41, 95% CI 1.24-4.69, P = .016). Patients developing AF had higher mortality/heart transplantation rate compared to patients who maintained sinus rhythm during follow-up (P < .001). At multivariate analysis, new onset AF (HR 3.67, 95% CI 2.07-6.5; P < .001) in the first three years after diagnosis, but not baseline AF, was found to be independently associated with a worse outcome. CONCLUSIONS: Atrial fibrillation is relatively frequent in patients with IDCM. The early development of AF during follow-up, but not its presence at baseline, is associated with poor survival.", "author" : [ { "dropping-particle" : "", "family" : "Aleksova", "given" : "Aneta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sabbadini", "given" : "Gastone", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitrella", "given" : "Giancarlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical medicine & research", "id" : "ITEM-1", "issue" : "3-4", "issued" : { "date-parts" : [ [ "2010", "12" ] ] }, "language" : "eng", "page" : "142-149", "publisher-place" : "United States", "title" : "Impact of atrial fibrillation on outcome of patients with idiopathic dilated cardiomyopathy: data from the Heart Muscle Disease Registry of Trieste.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(32)", "plainTextFormattedCitation" : "(32)", "previouslyFormattedCitation" : "(32)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(32). The implications of these observations are that a multiparametric approach to diagnosis and long-term follow-up, not limited to the left ventricular systolic function and size alone, appear essential in order to improve the quality of clinical management of DCM patients (Figure 5). 3 – Specific aspects in clinical management of DCM3.1 - Re-classification of DCM during long-term follow-upModern management of HF has increased the survival rates of DCM and has resulted in long periods of clinical stability ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ejhf.16", "ISBN" : "1388-9842", "PMID" : "24464640", "abstract" : "AIMS: ACE-inhibitors, beta-blockers, implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) improved prognosis of heart failure. We sought to analyse the long-term prognostic impact of evidence-based integrated therapeutic strategies in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: From 1978 to 2007, 853 IDCM patients (45 +/- 15 years, 72% males) were enrolled and classified as follows: Group 1, 110 patients (12.8%) enrolled during 1978-1987; Group 2, 376 patients (44.1%) enrolled during 1988-1997; Group 3, 367 patients (43.1%) enrolled during 1998-2007. ACE-inhibitors/angiotensin receptor blockers were administered in 34%, 93%, and 93% (P <0.001), and beta-blockers in 11%, 82%, and 86% (P <0.001) in Groups 1, 2, and 3, respectively; ICDs were implanted in 2%, 14%, and 13% (P = 0.005); mean time to device implantation was lower in Group 3. At 8 years, heart transplant (HTx)-free survival rates were 55%, 71%, and 87% in Groups 1, 2, and 3, respectively (P <0.001). Similar progressive improvement was found for pump-failure death (DHF)/HTx, while survival free from sudden death (SD) was significantly improved only in Group 3. Multivariable models considering competing risk indicated early diagnosis (i.e. a baseline less advanced disease stage) and tailored medical therapy (HR 0.44, CI 95% 0.19-0.98) as independent protectors against DHF/HTx. Concerning SD, lower left ventricular ejection fraction emerged as a predictor, while ICD was the only therapy with a protective role (HR 0.08, CI 95% 0.01-0.61). Treatment with digitalis emerged as a predictor of both DHF/HTx and SD. CONCLUSIONS: An effective management and evidence-based integrated therapeutic approach progressively and significantly improved the long-term prognosis of IDCM during the last three decades.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Heart Fail", "edition" : "2014/01/28", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "language" : "eng", "note" : "1879-0844\nMerlo, Marco\nPivetta, Alberto\nPinamonti, Bruno\nStolfo, Davide\nZecchin, Massimo\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nEngland\nEur J Heart Fail. 2014 Mar;16(3):317-24. doi: 10.1002/ejhf.16. Epub 2013 Dec 14.", "page" : "317-324", "title" : "Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jacc.2016.03.590", "ISSN" : "1558-3597 (Electronic)", "PMID" : "27339497", "abstract" : "Dilated cardiomyopathy (DCM) is best understood as the final common response of myocardium to diverse genetic and environmental insults. A rigorous work-up can exclude alternative causes of left ventricular (LV) dilation and dysfunction, identify etiologies that may respond to specific treatments, and guide family screening. A significant proportion of DCM cases have an underlying genetic or inflammatory basis. Measurement of LV size and ejection fraction remain central to diagnosis, risk stratification, and treatment, but other aspects of cardiac remodeling inform prognosis and carry therapeutic implications. Assessment of myocardial fibrosis predicts both risk of sudden cardiac death and likelihood of LV functional recovery, and has significant potential to guide patient selection for cardioverter-defibrillator implantation. Detailed mitral valve assessment is likely to assume increasing importance with the emergence of percutaneous interventions for functional mitral regurgitation. Detection of pre-clinical DCM could substantially reduce morbidity and mortality by allowing early instigation of cardioprotective therapy.", "author" : [ { "dropping-particle" : "", "family" : "Japp", "given" : "Alan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gulati", "given" : "Ankur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Stuart A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowie", "given" : "Martin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-2", "issue" : "25", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "language" : "eng", "page" : "2996-3010", "publisher-place" : "United States", "title" : "The Diagnosis and Evaluation of Dilated Cardiomyopathy.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(5, 33)", "plainTextFormattedCitation" : "(5, 33)", "previouslyFormattedCitation" : "(5, 33)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(5, 33). Consequently, affected patients followed for beyond 10-15 years are often encountered in clinical practice. Patients should be continuously re-assessed, particularly in the presence of cardiovascular risk factors. Indeed, abrupt worsening of LV function or an increased ventricular arrhythmic burden can be caused not only by the DCM progression but also by the development of new co-pathologies. Therefore, the possible presence of coronary artery disease, hypertensive heart disease, structured valve disease or an acute myocarditis should be systematically ruled out during the follow-up. (Table 1).3.2 - Pediatric DCMAlthough rare, DCM is the predominant cause of cardiomyopathy in children. The prevalence is approximately 1:170,000 in the United States ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa021715", "ISSN" : "1533-4406 (Electronic)", "PMID" : "12711739", "abstract" : "BACKGROUND: Population-based data on the incidence of pediatric cardiomyopathy are rare because of the lack of large, prospective studies. METHODS: Since 1996 the Pediatric Cardiomyopathy Registry sponsored by the National Heart, Lung, and Blood Institute has collected data on all children with newly diagnosed cardiomyopathy in New England and the Central Southwest region (Texas, Oklahoma, and Arkansas) of the United States. We report on all children in these regions who received this diagnosis between 1996 and 1999. RESULTS: We identified 467 cases of cardiomyopathy, for an overall annual incidence of 1.13 per 100,000 children (95 percent confidence interval, 1.03 to 1.23). The incidence was significantly higher among infants younger than 1 year old than among children and adolescents who were 1 to 18 years old (8.34 vs. 0.70 per 100,000, P<0.001). The annual incidence of cardiomyopathy was lower among white children (upper-bound estimate, 1.06 cases per 100,000) than among black children (lower-bound estimate, 1.47 per 100,000; P=0.02) and higher among boys than among girls (1.32 vs. 0.92 per 100,000, P<0.001). The incidence also varied significantly by region: 1.44 cases per 100,000 in New England and 0.98 per 100,000 in the Central Southwest region (P<0.001). When categorized according to type, dilated cardiomyopathy made up 51 percent of the cases, hypertrophic cardiomyopathy 42 percent, and restrictive or other types 3 percent; 4 percent were unspecified. There was no significant difference in the incidence rates according to the year. CONCLUSIONS: The estimated incidence of pediatric cardiomyopathy in two large regions of the United States is 1.13 cases per 100,000 children. Most cases are identified at an early age, and the incidence varies according to sex, region, and racial or ethnic origin.", "author" : [ { "dropping-particle" : "", "family" : "Lipshultz", "given" : "Steven E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sleeper", "given" : "Lynn A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Towbin", "given" : "Jeffrey A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowe", "given" : "April M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orav", "given" : "E John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Gerald F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lurie", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCoy", "given" : "Kristina L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McDonald", "given" : "Melissa A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Messere", "given" : "Jane E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colan", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England journal of medicine", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2003", "4" ] ] }, "language" : "ENG", "page" : "1647-1655", "publisher-place" : "United States", "title" : "The incidence of pediatric cardiomyopathy in two regions of the United States.", "type" : "article-journal", "volume" : "348" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(34)", "plainTextFormattedCitation" : "(34)", "previouslyFormattedCitation" : "(34)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(34) and the outcomes for children with DCM are poor, even in the presence of baseline characteristics of an early stage, as compared to adults. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/JAHA.116.003450", "ISSN" : "2047-9980 (Electronic)", "PMID" : "27364989", "abstract" : "BACKGROUND: The long-term progression of idiopathic dilated cardiomyopathy (DCM) in pediatric patients compared with adult patients has not been previously characterized. In this study, we compared outcome and long-term progression of pediatric and adult DCM populations. METHODS AND RESULTS: Between 1988 and 2014, 927 DCM patients were consecutively enrolled. The pediatric population (aged <18 years at enrollment) included 47 participants (5.1%). At presentation, the pediatric population compared with adult patients had a significantly increased occurrence of familial forms (P=0.03), shorter duration of heart failure (P=0.04), lower systolic blood pressure (P=0.01), decreased presence of left bundle-branch block (P=0.001), and increased left ventricular ejection fraction (P=0.03). Despite these baseline differences, long-term longitudinal trends of New York Heart Association class III to IV, left ventricular dimensions, left ventricular ejection fraction, and restrictive filling pattern were similar between the 2 populations. Regarding survival analysis, because of the size difference between the 2 populations, we compared the pediatric population with a sample of adult patients randomly matched using the above-mentioned baseline differences in a 3:1 ratio (141 adult versus 47 pediatric patients). During a median follow-up of 110 months, survival free from heart transplantation was significantly lower among pediatric patients compared with adults (P<0.001). Furthermore, pediatric age (ie, <18 years) was found to be associated with an increasing risk of both death from pump failure and life-threatening arrhythmias. CONCLUSIONS: Despite the pediatric DCM population having higher baseline left ventricular ejection fraction and similar long-term echocardiographic progression compared with the adult DCM population, the pediatric DCM patients had worse cardiovascular prognosis.", "author" : [ { "dropping-particle" : "", "family" : "Puggia", "given" : "Ilaria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rowland", "given" : "Teisha J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Heart Association", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "language" : "ENG", "publisher-place" : "England", "title" : "Natural History of Dilated Cardiomyopathy in Children.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(35)", "plainTextFormattedCitation" : "(35)", "previouslyFormattedCitation" : "(35)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(35). The causes of this particular severe phenotype of the disease in paediatric age remain poorly characterised. The generally poorer prognosis in paediatric DCM means that more aggressive therapeutic interventions including implantable cardiac defibrillator (ICD) implantation and heart transplant list are more frequent in the young ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/JAHA.116.003450", "ISSN" : "2047-9980 (Electronic)", "PMID" : "27364989", "abstract" : "BACKGROUND: The long-term progression of idiopathic dilated cardiomyopathy (DCM) in pediatric patients compared with adult patients has not been previously characterized. In this study, we compared outcome and long-term progression of pediatric and adult DCM populations. METHODS AND RESULTS: Between 1988 and 2014, 927 DCM patients were consecutively enrolled. The pediatric population (aged <18 years at enrollment) included 47 participants (5.1%). At presentation, the pediatric population compared with adult patients had a significantly increased occurrence of familial forms (P=0.03), shorter duration of heart failure (P=0.04), lower systolic blood pressure (P=0.01), decreased presence of left bundle-branch block (P=0.001), and increased left ventricular ejection fraction (P=0.03). Despite these baseline differences, long-term longitudinal trends of New York Heart Association class III to IV, left ventricular dimensions, left ventricular ejection fraction, and restrictive filling pattern were similar between the 2 populations. Regarding survival analysis, because of the size difference between the 2 populations, we compared the pediatric population with a sample of adult patients randomly matched using the above-mentioned baseline differences in a 3:1 ratio (141 adult versus 47 pediatric patients). During a median follow-up of 110 months, survival free from heart transplantation was significantly lower among pediatric patients compared with adults (P<0.001). Furthermore, pediatric age (ie, <18 years) was found to be associated with an increasing risk of both death from pump failure and life-threatening arrhythmias. CONCLUSIONS: Despite the pediatric DCM population having higher baseline left ventricular ejection fraction and similar long-term echocardiographic progression compared with the adult DCM population, the pediatric DCM patients had worse cardiovascular prognosis.", "author" : [ { "dropping-particle" : "", "family" : "Puggia", "given" : "Ilaria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rowland", "given" : "Teisha J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Heart Association", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "language" : "ENG", "publisher-place" : "England", "title" : "Natural History of Dilated Cardiomyopathy in Children.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(35)", "plainTextFormattedCitation" : "(35)", "previouslyFormattedCitation" : "(35)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(35).3.3 - The role of CMR CMR is emerging as a fundamental tool for diagnosis purposes and for prognostic stratification in patients presenting with LV dysfunction of uncertain origin. CMR represents the gold-standard for the assessment of biventricular dimensions and function. Tissue characterization and the distribution of scar aid the identification of secondary causes of DCM such as coronary occlusion ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2009.02.007", "ISSN" : "1558-3597 (Electronic)", "PMID" : "19389557", "abstract" : "Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., \"Lake Louise Criteria\").", "author" : [ { "dropping-particle" : "", "family" : "Friedrich", "given" : "Matthias G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sechtem", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schulz-Menger", "given" : "Jeanette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmvang", "given" : "Godtfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alakija", "given" : "Pauline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Leslie T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "James A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdel-Aty", "given" : "Hassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutberlet", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Sanjay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aletras", "given" : "Anthony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laissy", "given" : "Jean-Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paterson", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filipchuk", "given" : "Neil G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pauschinger", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American College of Cardiology", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "language" : "ENG", "page" : "1475-1487", "publisher-place" : "United States", "title" : "Cardiovascular magnetic resonance in myocarditis: A JACC White Paper.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(36)", "plainTextFormattedCitation" : "(36)", "previouslyFormattedCitation" : "(36)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(36) and approximately one-third of DCM cases have a distinctive mid-wall distribution, more frequently within the septal wall ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2013.1363", "ISSN" : "1538-3598 (Electronic)", "PMID" : "23462786", "abstract" : "IMPORTANCE: Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. OBJECTIVE: To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. DESIGN, SETTING, AND PATIENTS: Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. MAIN OUTCOME MEASURES: Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. RESULTS: Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .0\u2026", "author" : [ { "dropping-particle" : "", "family" : "Gulati", "given" : "Ankur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jabbour", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ismail", "given" : "Tevfik F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guha", "given" : "Kaushik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khwaja", "given" : "Jahanzaib", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raza", "given" : "Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morarji", "given" : "Kishen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Tristan D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ismail", "given" : "Nizar A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dweck", "given" : "Marc R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietro", "given" : "Elisa", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roughton", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wage", "given" : "Ricardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daryani", "given" : "Yousef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hanlon", "given" : "Rory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheppard", "given" : "Mary N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alpendurada", "given" : "Francisco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyon", "given" : "Alexander R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Stuart A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowie", "given" : "Martin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Assomull", "given" : "Ravi G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennell", "given" : "Dudley J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "language" : "eng", "page" : "896-908", "publisher-place" : "United States", "title" : "Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy.", "type" : "article-journal", "volume" : "309" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(37)", "plainTextFormattedCitation" : "(37)", "previouslyFormattedCitation" : "(37)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(37). LGE presence, patterns and quantification may also help to assess the risk for malignant ventricular arrhythmias and the probability of LVRR ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2013.1363", "ISSN" : "1538-3598 (Electronic)", "PMID" : "23462786", "abstract" : "IMPORTANCE: Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. OBJECTIVE: To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. DESIGN, SETTING, AND PATIENTS: Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. MAIN OUTCOME MEASURES: Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. RESULTS: Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .0\u2026", "author" : [ { "dropping-particle" : "", "family" : "Gulati", "given" : "Ankur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jabbour", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ismail", "given" : "Tevfik F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guha", "given" : "Kaushik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khwaja", "given" : "Jahanzaib", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raza", "given" : "Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morarji", "given" : "Kishen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Tristan D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ismail", "given" : "Nizar A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dweck", "given" : "Marc R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietro", "given" : "Elisa", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roughton", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wage", "given" : "Ricardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daryani", "given" : "Yousef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hanlon", "given" : "Rory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheppard", "given" : "Mary N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alpendurada", "given" : "Francisco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyon", "given" : "Alexander R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Stuart A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowie", "given" : "Martin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Assomull", "given" : "Ravi G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennell", "given" : "Dudley J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "language" : "eng", "page" : "896-908", "publisher-place" : "United States", "title" : "Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy.", "type" : "article-journal", "volume" : "309" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1161/CIRCIMAGING.113.000438", "ISSN" : "1942-0080 (Electronic)", "PMID" : "23934992", "abstract" : "BACKGROUND: In idiopathic dilated cardiomyopathy, there are scarce data on the influence of late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance on left ventricular (LV) remodeling. METHODS AND RESULTS: Fifty-eight consecutive patients with idiopathic dilated cardiomyopathy underwent baseline clinical, biohumoral, and instrumental workup. Medical therapy was optimized after study enrollment. Cardiovascular magnetic resonance was used to assess ventricular volumes, function, and LGE extent at baseline and 24-month follow-up. LV reverse remodeling (RR) was defined as an increase in LV ejection fraction >/=10 U, combined with a decrease in LV end-diastolic volume >/=10% at follow-up. DeltaLGE extent was the difference in LGE extent between follow-up and baseline. LV-RR was observed in 22 patients (38%). Multivariate regression analysis showed that the absence of LGE at baseline cardiovascular magnetic resonance was a strong predictor of LV-RR (odds ratio, 10.857 [95% confidence interval, 1.844-63.911]; P=0.008) after correction for age, heart rate, New York Heart Association class, LV volumes, and LV and right ventricular ejection fractions. All patients with baseline LGE (n=26; 45%) demonstrated LGE at follow-up, and no patient without baseline LGE developed LGE at follow-up. In LGE-positive patients, there was an increase in LGE extent over time (P=0.034), which was inversely related to LV ejection fraction variation (Spearman rho, -0.440; P=0.041). Five patients showed an increase in LGE extent >75th percentile of DeltaLGE extent, and among these none experienced LV-RR and 4 had a decrease in LV ejection fraction >/=10 U at follow-up. CONCLUSIONS: In patients with idiopathic dilated cardiomyopathy, the absence of LGE at baseline is a strong independent predictor of LV-RR at 2-year follow-up, irrespective of the initial clinical status and the severity of ventricular dilatation and dysfunction. The increase in LGE extent during follow-up was associated with progressive LV dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Masci", "given" : "Pier Giorgio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schuurman", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrea", "given" : "Barison", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripoli", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coceani", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiappino", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todiere", "given" : "Giancarlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srebot", "given" : "Vera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Passino", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aquaro", "given" : "Giovanni Donato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emdin", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lombardi", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation. Cardiovascular imaging", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "language" : "eng", "page" : "790-799", "publisher-place" : "United States", "title" : "Myocardial fibrosis as a key determinant of left ventricular remodeling in idiopathic dilated cardiomyopathy: a contrast-enhanced cardiovascular magnetic study.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "abstract" : "Objectives The aim of this study was to evaluate the association between late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging and ventricular arrhythmias or sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM).Background Risk stratification for SCD in DCM needs to be improved.Methods A systematic review and meta-analysis were conducted. A systematic search of PubMed and Ovid was performed, and observational studies that analyzed the arrhythmic endpoint (sustained ventricular arrhythmia, appropriate implantable cardioverter-defibrillator [ICD] therapy, or SCD) in patients with DCM, stratified by the presence or absence of LGE, were included.Results Twenty-nine studies were included, accounting for 2,948 patients. The studies covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 20% and 43%. LGE was significantly associated with the arrhythmic endpoint both in the overall population (odds ratio: 4.3; p &amp;lt; 0.001) and when including only those studies that performed multivariate analysis (hazard ratio: 6.7; p &amp;lt; 0.001). The association between LGE and the arrhythmic endpoint remained significant among studies with mean left ventricular ejection fractions &amp;gt;35% (odds ratio: 5.2; p &amp;lt; 0.001) and was maximal in studies that included only patients with primary prevention ICDs (odds ratio: 7.8; p = 0.008).Conclusions Across a wide spectrum of patients with DCM, LGE is strongly and independently associated with ventricular arrhythmia or SCD. LGE could be a powerful tool to improve risk stratification for SCD in patients with DCM. These results raise 2 major questions to be addressed in future studies: whether patients with LGE could benefit from primary prevention ICDs irrespective of their left ventricular ejection fractions, while patients without LGE might not need preventive ICDs despite having severe left ventricular dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Marco", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anguera", "given" : "Ignasi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmitt", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klem", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neilan", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "James A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sramko", "given" : "Marek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masci", "given" : "Pier Giorgio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barison", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mckenna", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mordi", "given" : "Ify", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haugaa", "given" : "Kristina H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leyva", "given" : "Francisco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez Capit\u00e1n", "given" : "Jorge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satoh", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nabeta", "given" : "Takeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dallaglio", "given" : "Paolo Domenico", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Niall G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sabat\u00e9", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cequier", "given" : "\u00c1ngel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JACC: Heart Failure", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2017", "12", "26" ] ] }, "page" : "28 LP - 38", "title" : "Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(37\u201339)", "plainTextFormattedCitation" : "(37\u201339)", "previouslyFormattedCitation" : "(37\u201339)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(37–39). Future multicenter and prospective studies are required to confirm the role of CMR in the prognostic stratification of DCM, especially when defining the arrhythmic risk of those patients. Currently no guidelines mention CMR as a tool for arrhythmic prognostication in DCM patients.3.4 - Endomyocardial biopsy The role of endomyocardial biopsy in diagnosis of heart muscle disorders is controversial due to the invasiveness of the procedure and poor sensitivity in certain scenarios. Contemporary cardiovascular imaging is also promoted as an alternative to tissue biopsy in some circumstances. 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In a patient with a newly diagnosed DCM endomyocardial biopsy is reasonable when there is a high probability of a specific diagnosis which can be confirmed only in myocardial samples and is amenable to therapy that has the potential to change the course of the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ponikowski", "given" : "Piotr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voors", "given" : "Adriaan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anker", "given" : "Stefan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bueno", "given" : "H\u00e9ctor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cleland", "given" : "John G F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coats", "given" : "Andrew J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Volkmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Juanatey", "given" : "Jos\u00e9 Ram\u00f3n", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harjola", "given" : "Veli-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jankowska", "given" : "Ewa A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jessup", "given" : "Mariell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linde", "given" : "Cecilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nihoyannopoulos", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parissis", "given" : "John T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pieske", "given" : "Burkert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Jillian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosano", "given" : "Giuseppe M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruilope", "given" : "Luis M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruschitzka", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rutten", "given" : "Frans H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meer", "given" : "Peter", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Heart Journal", "id" : "ITEM-1", "issue" : "27", "issued" : { "date-parts" : [ [ "2016", "6", "8" ] ] }, "page" : "2129-2200", "title" : "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/ejhf.579", "ISSN" : "1879-0844 (Electronic)", "PMID" : "27292200", "abstract" : "AIMS: Inflammatory heart disease represents an important cause of chronic dilated cardiomyopathy (DCM). Predicting the clinical course of patients with inflammatory cardiomyopathy (iCMP) is difficult, and the prognostic value of current biological markers remains controversial. We tested whether expression of selected microRNAs in endomyocardial biopsies (EMBs) is related to LV functional recovery and clinical events in iCMP patients. METHODS AND RESULTS: EMBs were obtained from patients with iCMP (n = 76) and non-inflammatory DCM (n = 22). A set of six microRNAs implicated in inflammation (miR-155 and miR-146b), heart failure (miR-21 and miR-133a), and endothelial cell (miR-126) and skeletal muscle function (miR-206) was pre-defined. Endomyocardial expression of miR-155 and miR-133a, as quantified by reverse transcription-PCR (RT-PCR), was up-regulated in patients with iCMP as compared with patients with DCM. Levels of miR-133a (R = 0.73, P < 0.01) and miR-155 (R = 0.63, P < 0.01) correlated with inflammatory cell count on EMBs from patients with iCMP. Patients with iCMP and preserved LV function at study entry demonstrated higher expression of miR-133a than patients with reduced LV function. Also, increased expression of miR-133a was associated with less fibrosis and myocyte necrosis on EMB, and LV functional recovery during a mean follow-up of 3.1 years. Importantly, patients with iCMP and miR-133a levels in the upper tertile showed longer survival free of death, malignant arrhythmias, and hospitalizations for heart failure. CONCLUSION: The present study demonstrates that miR-133a levels correlate with macrophage infiltration, cardiac injury, improved LV function, and clinical outcome in patients with iCMP. miR-133a may serve as a potential novel biomarker and therapeutic target in human iCMP.", "author" : [ { "dropping-particle" : "", "family" : "Besler", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Urban", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watzka", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lang", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rommel", "given" : "Karl-Philipp", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kandolf", "given" : "Reinhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klingel", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thiele", "given" : "Holger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linke", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schuler", "given" : "Gerhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lurz", "given" : "Philipp", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of heart failure", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2016", "12" ] ] }, "language" : "eng", "page" : "1442-1451", "publisher-place" : "England", "title" : "Endomyocardial miR-133a levels correlate with myocardial inflammation, improved left ventricular function, and clinical outcome in patients with inflammatory cardiomyopathy.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/ejhf.796", "ISSN" : "1879-0844 (Electronic)", "PMID" : "28370906", "abstract" : "AIMS: We sought to determine whether myocardial expression of Toll-like receptor 4 (TLR4) may predict the response to immunosuppression. METHODS AND RESULTS: Endomyocardial biopsies from 237 patients with virus-negative inflammatory cardiomyopathy treated with immunosuppression were retrospectively examined for the expression of TLR4, differentiating those patients responding to immunosuppression (n = 193) from non-responder patients (n = 44). A semiquantitative evaluation of the immunoreactivity (grading from 0 to 4) for TLR4 and human leucocyte antigen (HLA)-DR was performed together with real-time PCR and western blot for TLR4. Cardiomyocyte apoptosis and necrosis was evaluated by in situ ligation with hairpin probes. A focal intense positive cytoplasmic immunostaining for TLR4 was observed in cardiomyocytes of all responders (P < 0.001 vs. non-responders). A grading 2 or above (2+) at baseline showed a sensitivity of 100% and 90.9% specificity with a positive predictive value of 98% as a predictor of an immunosuppression-positive response. Real-time PCR and western blot analysis for TLR4 were 4.3-fold and 4.6-fold higher, respectively, in responders vs. non-responders. Correlation between TLR4 grading and TLR4 mRNA molecular and protein expression was highly significant. HLA-DR did not discriminate between the two groups. Cardiomyocyte death by apoptosis was 3.7-fold higher in responders vs. non-responders and significantly correlated with TLR4 expression, while necrosis was comparable. Intensity of baseline TLR4 expression correlated with the variation in ejection fraction after 6 months of immunosuppression. CONCLUSION: TLR4 is highly expressed in human myocarditis responding to immunosuppression. 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Examples of such scenarios include active myocarditis (see figure 2), the contemporary presence of hypertrophic and dilated LV (for example in end-stage hypertrophic cardiomyopathy), cardiac amyloidosis, sarcoidosis or hemochromatosis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anzini", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira L", "given" : "Naveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bussani", "given" : "Rossana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finocchiaro", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartunek", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mayo Clinic Proc", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Myocarditis in clinical practice. 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The rationale is to confirm the diagnosis, to identify individuals who are at high risk of arrhythmia and to facilitate cascade screening within familiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/ehq271", "ISSN" : "1522-9645 (Electronic)", "PMID" : "20823110", "abstract" : "Advances in molecular genetics present new opportunities and challenges for cardiologists who manage patients and families with cardiomyopathies. The aims of this position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases are to review the general issues related to genetic counselling, family screening and genetic testing in families with a cardiomyopathy, and to provide key messages and suggestions for clinicians involved in their management.", "author" : [ { "dropping-particle" : "", "family" : "Charron", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arad", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arbustini", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basso", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bilinska", "given" : "Zofia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Perry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helio", "given" : "Tiina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keren", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKenna", "given" : "William J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monserrat", "given" : "Lorenzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankuweit", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perrot", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rapezzi", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ristic", "given" : "Arsen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seggewiss", "given" : "Hubert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langen", "given" : "Irene", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavazzi", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European heart journal", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "language" : "eng", "page" : "2715-2726", "publisher-place" : "England", "title" : "Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(43)", "plainTextFormattedCitation" : "(43)", "previouslyFormattedCitation" : "(43)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(43). However, restriction of genetic testing to familial cases has been recently questioned following studies showing that the yield of genetic testing is similar between familial and non-familial cases ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cjca.2015.06.034", "ISSN" : "0828-282X", "author" : [ { "dropping-particle" : "", "family" : "Morales", "given" : "Ana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hershberger", "given" : "Ray E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian Journal of Cardiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015", "9", "2" ] ] }, "note" : "doi: 10.1016/j.cjca.2015.06.034", "page" : "1309-1312", "publisher" : "Elsevier", "title" : "The Rationale and Timing of Molecular Genetic Testing for Dilated Cardiomyopathy", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(44)", "plainTextFormattedCitation" : "(44)", "previouslyFormattedCitation" : "(44)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(44) and the presence of titin truncating mutations in 10-15% of sporadic DCMADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/gim.2013.204", "ISSN" : "1530-0366 (Electronic)", "PMID" : "24503780", "abstract" : "PURPOSE: Dilated cardiomyopathy is characterized by substantial locus, allelic, and clinical heterogeneity that necessitates testing of many genes across clinically overlapping diseases. Few studies have sequenced sufficient individuals; thus, the contributions of individual genes and the pathogenic variant spectrum are still poorly defined. We analyzed 766 dilated cardiomyopathy patients tested over 5 years in our molecular diagnostics laboratory. METHODS: Patients were tested using gene panels of increasing size from 5 to 46 genes, including 121 cases tested with a multiple-cardiomyopathy next-generation panel covering 46 genes. All variants were reassessed using our current clinical-grade scoring system to eliminate false-positive disease associations that afflict many older analyses. RESULTS: Up to 37% of dilated cardiomyopathy cases carry a clinically relevant variant in one of 20 genes, titin (TTN) being the largest contributor (up to 14%). Desmoplakin (DSP), an arrhythmogenic right ventricular cardiomyopathy gene, contributed 2.4%, illustrating the utility of multidisease testing. The clinical sensitivity increased from 10 to 37% as gene panel sizes increased. However, the number of inconclusive cases also increased from 4.6 to 51%. CONCLUSION: Our data illustrate the utility of broad gene panels for genetically and clinically heterogeneous diseases but also highlight challenges as molecular diagnostics moves toward genome-wide testing.", "author" : [ { "dropping-particle" : "", "family" : "Pugh", "given" : "Trevor J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "Melissa A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gowrisankar", "given" : "Sivakumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hynes", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seidman", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baxter", "given" : "Samantha M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowser", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Bryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aaron", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahanta", "given" : "Lisa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakdawala", "given" : "Neal K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McDermott", "given" : "Gregory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Emily T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehm", "given" : "Heidi L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lebo", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funke", "given" : "Birgit H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics in medicine : official journal of the American College of Medical Genetics", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "8" ] ] }, "language" : "eng", "page" : "601-608", "publisher-place" : "United States", "title" : "The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(45)", "plainTextFormattedCitation" : "(45)", "previouslyFormattedCitation" : "(45)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(45). Genotype-phenotype interactions are still an unmet issue of translational research and the effects of mutations on the mechanisms of disease expression remain largely unknown. Extreme genetic heterogeneity and variable penetrance prohibited robust genotype-phenotype correlation studies and actually genotype information do not strongly impact on clinical management of DCM. Nevertheless, despite the complex genetic architecture of DCM, an increasing number of actionable prognostic genotype-phenotype associations are emerging. For carriers of LMNA mutations the presence of non-sustained ventricular tachycardia, left ventricular impairment, male gender, and non-missense mutations (nonsense, frameshift insertion-deletions or splicing) are reported to be independent risk factors for malignant ventricular arrhythmias. Consequently, primary preventive ICD implantation is recommended in patients with high risk features. An increased risk of SCD is also reported in individuals with DCM caused by mutations in DES, RBM20, PLN and filamin C truncating mutations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jacc.2016.09.927", "ISSN" : "1558-3597 (Electronic)", "PMID" : "27908349", "abstract" : "BACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.", "author" : [ { "dropping-particle" : "", "family" : "Ortiz-Genga", "given" : "Martin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuenca", "given" : "Sofia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dal Ferro", "given" : "Matteo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zorio", "given" : "Esther", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salgado-Aranda", "given" : "Ricardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Climent", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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Multicenter studies are needed to fill the gap in knowledge of the multiple and heterogeneous genotype-phenotype correlations promoting the onset of DCM in carriers of disease-related gene mutations. Moreover it appears pivotal to clarify the influence of environmental factors (i.e. strenuous exercise) on still unknown predisposing gene variants, including the role of non-coding DNA regions and RNAs, in order to establish a complete expression of disease.3.6 – Arrhythmic risk stratification Primary prevention of SCD with ICD implantation significantly ameliorated overall mortality in patients with ischaemic heart failure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ponikowski", "given" : "Piotr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voors", "given" : "Adriaan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anker", "given" : "Stefan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bueno", "given" : "H\u00e9ctor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cleland", "given" : "John G F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coats", "given" : "Andrew J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Volkmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Juanatey", "given" : "Jos\u00e9 Ram\u00f3n", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harjola", "given" : "Veli-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jankowska", "given" : "Ewa A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jessup", "given" : "Mariell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linde", "given" : "Cecilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nihoyannopoulos", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parissis", "given" : "John T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pieske", "given" : "Burkert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Jillian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosano", "given" : "Giuseppe M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruilope", "given" : "Luis M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruschitzka", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rutten", "given" : "Frans H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meer", "given" : "Peter", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Heart Journal", "id" : "ITEM-1", "issue" : "27", "issued" : { "date-parts" : [ [ "2016", "6", "8" ] ] }, "page" : "2129-2200", "title" : "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(24)", "plainTextFormattedCitation" : "(24)", "previouslyFormattedCitation" : "(24)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(24) but in non-ischaemic DCM, randomized clinical trials such as SCD-HeFT, DEFINITE and the more recent DANISH trial have failed to demonstrate a clear survival benefit ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa033088", "ISSN" : "1533-4406 (Electronic)", "PMID" : "15152060", "abstract" : "BACKGROUND: Patients with nonischemic dilated cardiomyopathy are at substantial risk for sudden death from cardiac causes. However, the value of prophylactic implantation of an implantable cardioverter-defibrillator (ICD) to prevent sudden death in such patients is unknown. METHODS: We enrolled 458 patients with nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less than 36 percent, and premature ventricular complexes or nonsustained ventricular tachycardia. A total of 229 patients were randomly assigned to receive standard medical therapy, and 229 to receive standard medical therapy plus a single-chamber ICD. RESULTS: Patients were followed for a mean (+/-SD) of 29.0+/-14.4 months. The mean left ventricular ejection fraction was 21 percent. The vast majority of patients were treated with angiotensin-converting-enzyme (ACE) inhibitors (86 percent) and beta-blockers (85 percent). There were 68 deaths: 28 in the ICD group, as compared with 40 in the standard-therapy group (hazard ratio, 0.65; 95 percent confidence interval, 0.40 to 1.06; P=0.08). The mortality rate at two years was 14.1 percent in the standard-therapy group (annual mortality rate, 7 percent) and 7.9 percent in the ICD group. There were 17 sudden deaths from arrhythmia: 3 in the ICD group, as compared with 14 in the standard-therapy group (hazard ratio, 0.20; 95 percent confidence interval, 0.06 to 0.71; P=0.006). CONCLUSIONS: In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause.", "author" : [ { "dropping-particle" : "", "family" : "Kadish", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dyer", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daubert", "given" : "James P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quigg", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estes", "given" : "N A Mark", "non-dropping-particle" : "", 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"article-journal", "volume" : "375" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1056/NEJMoa043399", "ISSN" : "1533-4406 (Electronic)", "PMID" : "15659722", "abstract" : "BACKGROUND: Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients. METHODS: We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. RESULTS: The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. CONCLUSIONS: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.", "author" : [ { "dropping-particle" : "", "family" : "Bardy", "given" : "Gust H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Kerry L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mark", "given" : "Daniel B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poole", "given" : "Jeanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Packer", "given" : "Douglas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boineau", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Domanski", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Troutman", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Jill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNulty", "given" : "Steven E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clapp-Channing", "given" : "Nancy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davidson-Ray", "given" : "Linda D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraulo", "given" : "Elizabeth S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fishbein", "given" : "Daniel P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luceri", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ip", "given" : "John H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England journal of medicine", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "language" : "eng", "page" : "225-237", "publisher-place" : "United States", "title" : "Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.", "type" : "article-journal", "volume" : "352" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(46\u201348)", "plainTextFormattedCitation" : "(46\u201348)", "previouslyFormattedCitation" : "(46\u201348)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(46–48). Current indications for primary prevention with an ICD are based on a simplicistic assessment of LV function and HF symptoms (25, 46). However it is clear that the risk of ventricular arrhythmia varies according the etiology. For example, it has been reported that patients with dilated cardiomyopathy secondary to systemic hypertension (usually older and with more comorbidities) have lower arrhythmic event-rate during follow-up ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.amjcard.2016.10.014", "ISSN" : "1879-1913 (Electronic)", "PMID" : "27988039", "abstract" : "Hypertensive hypokinetic cardiomyopathy (HHC) is defined by left ventricular (LV) systolic dysfunction with a history of systemic hypertension as the only possible cause. Although commonly encountered in clinical practice, its characterization and differences with true idiopathic dilated cardiomyopathy (IDC) are lacking. The aim of this study was to characterize the clinical instrumental features and the natural history of HHC. We analyzed the data of 4,191 patients referred to our center for newly diagnosed LV systolic dysfunction from 2005 to 2010. Of them, 310 presented idiopathic LV systolic dysfunction (LV ejection fraction <50%): 136 (44%) had a history of systemic hypertension and were defined HHC. The remaining 174 patients were considered IDC. Compared with patients with IDC, those with HHC were older (63 +/- 11 vs 47 +/- 14 years, p <0.001), with worse comorbidity profile, higher blood pressure, and increased LV mass. During follow-up, patients with HHC showed earlier and higher proportion of LV reverse remodeling (46% vs 21% at 6 months' follow-up). Moreover, they had a better long-term survival free from cardiovascular death/ventricular assist device/heart transplant/malignant ventricular arrhythmias (5.1 vs 12.6 in HHC and IDC, p = 0.03). Indeed, their mortality was mainly driven by noncardiovascular causes (at 10 years 9.6% vs 1.7% in HHC and IDC, p <0.001). In conclusion, HHC has a high prevalence among patients with \"idiopathic\" LV dysfunction. The natural history of patients with HHC is characterized by a rapid response to optimal therapy for heart failure, a favorable cardiovascular outcome, and a relevant incidence of noncardiovascular events.", "author" : [ { "dropping-particle" : "", "family" : "Bobbo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iorio", "given" : "Annamaria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carriere", "given" : "Cosimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Massa", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poli", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scapol", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "Andrea", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of cardiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2017", "2" ] ] }, "language" : "eng", "page" : "483-489", "publisher-place" : "United States", "title" : "Comparison of Patient Characteristics and Course of Hypertensive Hypokinetic Cardiomyopathy Versus Idiopathic Dilated Cardiomyopathy.", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(49)", "plainTextFormattedCitation" : "(49)", "previouslyFormattedCitation" : "(49)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(49). Conversely younger patients with some of the more malignant genetic forms of DCM may have a greater survival benefit from ICD implantation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ejhf.16", "ISBN" : "1388-9842", "PMID" : "24464640", "abstract" : "AIMS: ACE-inhibitors, beta-blockers, implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) improved prognosis of heart failure. We sought to analyse the long-term prognostic impact of evidence-based integrated therapeutic strategies in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: From 1978 to 2007, 853 IDCM patients (45 +/- 15 years, 72% males) were enrolled and classified as follows: Group 1, 110 patients (12.8%) enrolled during 1978-1987; Group 2, 376 patients (44.1%) enrolled during 1988-1997; Group 3, 367 patients (43.1%) enrolled during 1998-2007. ACE-inhibitors/angiotensin receptor blockers were administered in 34%, 93%, and 93% (P <0.001), and beta-blockers in 11%, 82%, and 86% (P <0.001) in Groups 1, 2, and 3, respectively; ICDs were implanted in 2%, 14%, and 13% (P = 0.005); mean time to device implantation was lower in Group 3. At 8 years, heart transplant (HTx)-free survival rates were 55%, 71%, and 87% in Groups 1, 2, and 3, respectively (P <0.001). Similar progressive improvement was found for pump-failure death (DHF)/HTx, while survival free from sudden death (SD) was significantly improved only in Group 3. Multivariable models considering competing risk indicated early diagnosis (i.e. a baseline less advanced disease stage) and tailored medical therapy (HR 0.44, CI 95% 0.19-0.98) as independent protectors against DHF/HTx. Concerning SD, lower left ventricular ejection fraction emerged as a predictor, while ICD was the only therapy with a protective role (HR 0.08, CI 95% 0.01-0.61). Treatment with digitalis emerged as a predictor of both DHF/HTx and SD. CONCLUSIONS: An effective management and evidence-based integrated therapeutic approach progressively and significantly improved the long-term prognosis of IDCM during the last three decades.", "author" : [ { "dropping-particle" : "", "family" : "Merlo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pivetta", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenarda", "given" : "A", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Heart Fail", "edition" : "2014/01/28", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "language" : "eng", "note" : "1879-0844\nMerlo, Marco\nPivetta, Alberto\nPinamonti, Bruno\nStolfo, Davide\nZecchin, Massimo\nBarbati, Giulia\nDi Lenarda, Andrea\nSinagra, Gianfranco\nJournal Article\nEngland\nEur J Heart Fail. 2014 Mar;16(3):317-24. doi: 10.1002/ejhf.16. Epub 2013 Dec 14.", "page" : "317-324", "title" : "Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1056/NEJMoa1608029", "ISSN" : "0028-4793", "author" : [ { "dropping-particle" : "", "family" : "K\u00f8ber", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thune", "given" : "Jens J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Jens C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haarbo", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Videb\u00e6k", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korup", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jensen", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hildebrandt", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steffensen", "given" : "Flemming H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruun", "given" : "Niels E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiskj\u00e6r", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandes", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Th\u00f8gersen", "given" : "Anna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gustafsson", "given" : "Finn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egstrup", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Videb\u00e6k", "given" : "Regitze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassager", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Svendsen", "given" : "Jesper H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00f8fsten", "given" : "Dan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torp-Pedersen", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pehrson", "given" : "Steen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-2", "issue" : "13", "issued" : { "date-parts" : [ [ "2016", "8", "27" ] ] }, "note" : "doi: 10.1056/NEJMoa1608029", "page" : "1221-1230", "publisher" : "Massachusetts Medical Society", "title" : "Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure", "type" : "article-journal", "volume" : "375" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1056/NEJMoa043399", "ISSN" : "1533-4406 (Electronic)", "PMID" : "15659722", "abstract" : "BACKGROUND: Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients. METHODS: We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. RESULTS: The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. CONCLUSIONS: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.", "author" : [ { "dropping-particle" : "", "family" : "Bardy", "given" : "Gust H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Kerry L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mark", "given" : "Daniel B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poole", "given" : "Jeanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Packer", "given" : "Douglas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boineau", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Domanski", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Troutman", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Jill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNulty", "given" : "Steven E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clapp-Channing", "given" : "Nancy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davidson-Ray", "given" : "Linda D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraulo", "given" : "Elizabeth S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fishbein", "given" : "Daniel P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luceri", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ip", "given" : "John H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England journal of medicine", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "language" : "eng", "page" : "225-237", "publisher-place" : "United States", "title" : "Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.", "type" : "article-journal", "volume" : "352" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(5, 47, 48)", "plainTextFormattedCitation" : "(5, 47, 48)", "previouslyFormattedCitation" : "(5, 47, 48)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(5, 47, 48). In addition, only one third of DCM cases admitted with current criteria for ICD still fulfill indications for implantation 6 months after initiation of optimal medical treatment ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.amjcard.2011.10.033", "ISSN" : "1879-1913 (Electronic)", "PMID" : "22176998", "abstract" : "To assess the proportion and long-term outcomes of patients with idiopathic dilated cardiomyopathy and potential indications for implantable cardioverter-defibrillator before and after optimization of medical treatment, 503 consecutive patients with idiopathic dilated cardiomyopathy were evaluated from 1988 to 2006. A total of 245 patients (49%) satisfied the \"Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) criteria,\" defined as a left ventricular ejection fraction of </=0.35 and New York Heart Association (NYHA) class II-III on registration. Among these, 162 (group A) were re-evaluated 5.4 +/- 2 months later with concurrent beta-blockers and angiotensin-converting enzyme inhibitor use. Of the 162 patients, 50 (31%) still had \"SCD-HeFT criteria\" (group A1), 109 (67%) had an improved left ventricular ejection fraction and/or New York Heart Association class (group A2), and 3 (2%) were in NYHA class IV. Of the 227 patients without baseline \"SCD-HeFT criteria\" (left ventricular ejection fraction >0.35 or NYHA class I), 125 were evaluated after 5.5 +/- 2 months. Of these 227 patients, 13 (10%) developed \"SCD-HeFT criteria\" (group B1), 111 (89%) remained without \"SCD-HeFT criteria\" (group B2), and 1 (1%) had worsened to NYHA class IV. The 10-year mortality/heart transplantation and sudden death/sustained ventricular arrhythmia rate was 57% and 37% in group A1, 23% and 20% in group A2 (p <0.001 for mortality/heart transplantation and p = 0.014 for sudden death/sustained ventricular arrhythmia vs group A1), 45% and 41% in group B1 (p = NS vs group A1), 16% and 14% in group B2 (p = NS vs group A2), respectively. In conclusion, two thirds of patients with idiopathic dilated cardiomyopathy and \"SCD-HeFT criteria\" at presentation did not maintain implantable cardioverter-defibrillator indications 3 to 9 months later with optimal medical therapy. 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However, in a large series of recently onset DCM, approximately 2% of patients died suddenly in the first 6 months after diagnosis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Losurdo", "given" : "Pasquale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gobbo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finocchiaro", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JACC Clinical Electrophisiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "535-543", "title" : "Early arrhythmic events in idiopathic dilated cardiomyopathy.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(50)", "plainTextFormattedCitation" : "(50)", "previouslyFormattedCitation" : "(50)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(50). Patients presenting with severe LV dilatation, longer QRS and long duration of symptoms were at higher risk, while LV ejection fraction alone did not show any association with early events ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Losurdo", "given" : "Pasquale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stolfo", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merlo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbati", "given" : "Giulia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gobbo", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigli", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramani", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinamonti", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecchin", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finocchiaro", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mestroni", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinagra", "given" : "Gianfranco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JACC Clinical Electrophisiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "535-543", "title" : "Early arrhythmic events in idiopathic dilated cardiomyopathy.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(50)", "plainTextFormattedCitation" : "(50)", "previouslyFormattedCitation" : "(50)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(50). It is clear that alternative and more reliable multiparametric models that incorporate aetiology, CMR biomarkers such as natriuretic peptides are required. 5 - Conclusions and future perspectivesIn recent decades, long-term survival of DCM patients has markedly increased. Several strategies have contributed to this improvement, including early diagnosis through systematic familial screening, more refined phenotyping at the onset of disease, implementation of evidence-based medical and device treatments and a rigorous long-term individualized follow-up. However, DCM remains the most common cause of heart transplant and one of the leading causes of death in the Western world. Further progress in reducing morbidity and mortality requires systematic use of diagnostic tools including genetic testing, improved risk modelling and a deeper investigation of the basic mechanisms underlying the disease. References ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. 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Long-term reverse remodeling with cardiac resynchronization therapy: results of extended echocardiographic follow-up. J. Am. Coll. Cardiol. 2010;55:1788–1795.26. Zecchin M, Proclemer A, Magnani S, et al. Long-term outcome of “super-responder” patients to cardiac resynchronization therapy. Europace 2014;16:363–371.27. Gulati A, Ismail TF, Jabbour A, et al. The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy. Circulation 2013;128:1623–1633.28. Merlo M, Gobbo M, Stolfo D, et al. The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM. JACC. Cardiovasc. Imaging 2016;9:1034–1042.29. Stolfo D, Merlo M, Pinamonti B, et al. Early Improvement of Functional Mitral Regurgitation in Patients With Idiopathic Dilated Cardiomyopathy. Am. J. Cardiol. 2015;115:1137–1143.30. Stolfo D, Tonet E, Barbati G, et al. Acute Hemodynamic Response to Cardiac Resynchronization in Dilated Cardiomyopathy: Effect on Late Mitral Regurgitation. Pacing Clin. Electrophysiol. 2015;38:1287–1296.31. Aleksova A, Carriere C, Zecchin M, et al. New-onset left bundle branch block independently predicts long-term mortality in patients with idiopathic dilated cardiomyopathy: data from the Trieste Heart Muscle Disease Registry. Europace 2014;16:1450–1459.32. Aleksova A, Merlo M, Zecchin M, et al. Impact of atrial fibrillation on outcome of patients with idiopathic dilated cardiomyopathy: data from the Heart Muscle Disease Registry of Trieste. Clin. Med. Res. 2010;8:142–149.33. Japp AG, Gulati A, Cook SA, Cowie MR, Prasad SK. The Diagnosis and Evaluation of Dilated Cardiomyopathy. J. Am. Coll. Cardiol. 2016;67:2996–3010.34. Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N. Engl. J. Med. 2003;348:1647–1655.35. Puggia I, Merlo M, Barbati G, et al. Natural History of Dilated Cardiomyopathy in Children. J. Am. Heart Assoc. 2016;5.36. Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J. Am. Coll. Cardiol. 2009;53:1475–1487.37. Gulati A, Jabbour A, Ismail TF, et al. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 2013;309:896–908.38. Masci PG, Schuurman R, Andrea B, et al. Myocardial fibrosis as a key determinant of left ventricular remodeling in idiopathic dilated cardiomyopathy: a contrast-enhanced cardiovascular magnetic study. Circ. Cardiovasc. Imaging 2013;6:790–799.39. Di Marco A, Anguera I, Schmitt M, et al. Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy. JACC Hear. Fail. 2017;5:28 LP-38.40. Caforio ALP, Pankuweit S, Arbustini E, et al. 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Cardiol. 2017;119:483–489.50. Losurdo P, Stolfo D, Merlo M, et al. Early arrhythmic events in idiopathic dilated cardiomyopathy. JACC Clin. Electrophisiology 2016;5:535–543.Figure Legend. Figure 1. Etiologic characterization of DCM. Legend: DCM: dilated cardiomyopathy; iDCM: idiopathic dilated cardiomyopathyFigure 2. Characterization of DCM vs. active myocarditis at diagnosis. The role of ECG (panels A vs. B: note the left bundle branch block vs. low QRS voltages), echocardiography (panels C vs. D: note the huge vs. mild left ventricular/atrial dilation), cardiac magnetic resonance (panels D vs. E: note the midwall distribution pattern of late gadolinium enhancement vs. myocardial edema at T2-weighted imaging), endomyocardial biopsy (panels F vs G: note the cardiomyocyte damage and the myocardial fibrosis [in blue] vs. active lymphocytic inflammation).Figure 3. Genotype-Phenotype correlations in DCM, the red-flags approach and overlap syndromes. Note on the left the main genes involved in DCM pathogenesis and, on the right their corresponding frequent phenotypic expression (red-flags approach and overlapping shown on the right). * Desmosomal Genes (PKP2,DSC2,DSG2 DSP,JUP)** Sarcomeric Genes (MYH6, MYH7, MYBPC3, TNNT2)Figure 4. Scheme of current usual natural history of DCM and corresponding clinical management over time. Often occurs within 2 years, followed by a period of stability and then by the long-term progression of disease. Note cornerstones of clinical management right after diagnosis (in red) and during the follow-up (in orange). Finally, note remaining open issues (in grey) and the suggestion to continue therapy also in persistently apparently healed patients (in green).Figure 5. The importance of a global evaluation of DCM different phenotypes (i.e. left ventricular dilation degree, right ventricular involvement, mitral regurgitation, diastolic dysfunction, syndromic phenotypes, arrhythmic expression, late gadolinium enhancement presence/pattern/quantification) and possible correlations with genotype.Table 1. Diagnostic tools recommended at baseline and during follow-upBaselineFollow-upNotesClinical HistoryIndicatedAetiological definition (identification of possible cause of DCM)Improvement of prognostic stratification (i.e presence of syncope; duration of symptoms)IndicatedImprovement of prognostic stratification (i.e presence of syncope);Useful in re-classification of the disease during the long-termAt every follow-up evaluationFamilial screeningIndicatedEarly diagnosis in family membersIndication to genetic testing if presence of familial formImprovement of prognostic stratification in presence of family history for SCDIndicated Indication to genetic testing if presence of familial formImprovement of prognostic stratification in presence of family history for SCDUpdates at every follow-up evaluationClinical evaluationIndicated Aetiological definition (muscle disease)Improvement of prognostic stratification (severity of heart failure)IndicatedImprovement of prognostic stratification (severity of heart failure)At every follow-up evaluationE.C.G.IndicatedAetiological definition (clues of genotype-phenotype correlation )Possible indication to genetic testingImprovement of prognostic stratification (atrial fibrillation; duration of disease; clues of amount of myocardial fibrosis/edema : left bundle branch clock, low QRS voltages)IndicatedImprovement of prognostic stratification (atrial fibrillation; duration of disease; clues of amount of myocardial fibrosis/edema : left bundle branch clock, low QRS voltages)At every follow-up evaluationEchoIndicated Aetiological definition (differential diagnosis between acute myocarditis and DCM; clues of genotype-phenotype correlation)Possible indication to genetic testingImprovement of prognostic stratification (left/right ventricular involvement; left atrial enlargement; mitral regurgitation, diastolic dysfunction assessment)IndicatedImprovement of prognostic stratification (left/right ventricular reverse remodeling; mitral regurgitation improvement: left ventricular restrictive filling pattern improvement)At every follow-up evaluationLABsIndicatedAetiological definition (CPK; TSH)Improvement of prognostic stratification (BNP/NTproBNP; Anemia; Chronic renal failure)IndicatedImprovement of prognostic stratification (BNP/NTproBNP; Anemia; Chronic renal failure)Need of future research for the implementation of BNP/NTproBNP during follow-up.STRESS TESTNo data supporting No data supportingCPETIndicated after stabilizationPrognostic stratificationIndicated in stable patientsPrognostic stratificationNeed of future research for the implementation of CPET during follow-up.Not indicated at every follow-up evaluationUseful in selection of heart transplanantion screeningHOLTER ECG 24 HOURSIndicated Aetiological definition (tachy-induced cardiomyopathies)Possible indication to genetic testingImprovement of prognostic stratification (arrhytmogenic DCM)IndicatedImprovement of prognostic stratification (arrhytmogenic DCM)Not always indicated in presence of CRTD/ICD implantationSAECGNo data supportingNo data supportingCMRIndicatedAetiological definition (differential diagnosis: infiltrative cardiomyopathies; active myocarditis)Possible indication to genetic testingImprovement of prognostic stratification in particular for arrhythmic events (left/right ventricular morphology/involvement; late gadolinium enhancement )No data supportingNeed of future research for the implementation of CMR during follow-up.Useful in re-classification of the disease in the long-termCoronary angiography/CTIndicatedAetiological definition (exclusion of ischemic heart disease)No data supportingUseful in re-classification of the disease in the long-termRight catheterizationNo data supportingNo data supportingUseful in selection of heart transplanantion screeeningEndomyocardial biopsyIndicated in suspect of active myocarditis No data supportingUseful in re-classification of the disease in the long-termLegend: BNP: brain natriuretic peptide; CMR: cardiac magnetic resonance; CPET: cardiopulmonary exercise test; CPK: creatin-phospho-kinase; CRT-D: cardiac resynchronisation therapy-defibrillator; CT: computed tomography; DCM: dilated cardiomyopathy; ICD: implanted cardioverter defibrillator; SAECG: signal average electrocardiogram; SCD: sudden cardiac deathTable 2. Main red flags in the diagnosis of DCMRed FlagFindingSuggested causeClinical History and Physical ExaminationMental ritardationDystrophinopathiesMitochondrial diseaseNeurosensory disordersMitochondrial diseaseSkeletal muscle involvementDystrophinopathiesDesminopathiesLaminopathiesCarpal tunnel and macroglossiaInfiltrative DCMSkin pigmentationHemocromatosisHistory of severe hypertensionDCM secondary to hypertensionPregnancyPeripartum DCMBiohumoral findingsCreatin kinaseDystrophinopathieDesminopathiesMyofibrillar miopathyLaminopathiesProteinuriaInfiltrative DCMHyperferritinaemiaHemochromatosisECGP wave alterationsEmerinopathiesLaminopathiesAV blocksLaminopathiesDesminopathiesPost-inflammatory DCMSarcoidosisLow voltagesInfiltrative DCMActive myocarditisPosterolateral pseudonecrosisDystrophinopathiesIntraventricular conduction delaysLaminopathiesEchocardiographyCardiac hypertrophyDCM secondary to hypertensionInfiltrative DCMPosterolateral akinesiaDystrophinopathiesCMRSubendocardial/transmural LGEIschemic DCMSubepicardial LGEPost-inflammatory DCMSeptal LGEPost-inflammatory DCM SarcoidosisMidwall LGEArrhythmogenic phenotypeLV aneurysm SarcoidosisLegend: AV: atrioventricular; CMR: cardiac magnetic resonance; DCM: dilated cardiomyopathy; LGE: late gadolinium enhancement; LV: left ventricle.Table 3. Important time points in the natural history of DCMTimeEvaluationBaselineComplete evaluation (non-invasive and invasive, if necessary) in order to assess an etiological characterization, to decide timing of individualized follow-up and timing and type of therapeutic strategiesAdministration of optimal medical treatment3 to 9 months“Hemodynamic” reverse remodeling (improvement of mitral regurgitation; normalization of right ventricular systolic function; improvement of diastolic dysfunction)Consider ICD/CRT-D implantationAttention to the onset of negative prognostic factors*24 monthsLeft ventricular reverse remodeling completedAttention to the onset of negative prognostic factors*72-84 monthsPossible progression of the disease after stability induced by medical therapyRe-classification of the disease in presence of progression of the disease (attention to possible onset of possible causes of left ventricular dysfunction: hypertension; diabetes; ischemic heart disease; structural valve disease)Attention to the onset of negative prognostic factors*After 120 monthsNeed of continuing follow-up and therapy life-long in order to early detect signs of progression of the disease in the long-termAttention to the onset of negative prognostic factors** negative prognostic factors: atrial fibrillation; right ventricular dysfunction; left ventricular bundle branch block; functional mitral regurgitationLegend: CRT-D: cardiac resynchronisation therapy-defibrillator; ICD: implanted cardioverter defibrillatorFigure 1 Figure 2 1714526162000Figure 3 Figure 4 Figure 5. ................
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