Introduction .uk



MINOCA presenting with STEMI – incidence, aetiology and outcome in a contemporaneous cohortYing X. Gue MB BS, MRCP 1,2 *, Natasha Corballis MB BS, MRCP 3*, Alisdair Ryding MB BCh, MRCP, PhD 3,4, Juan Carlos Kaski DSc, MD, DM (Hons), FRCP 5?, Diana A. Gorog MB BS, MD, PhD 1,2,6?1. University of Hertfordshire, Hertfordshire, United Kingdom2. East and North Hertfordshire NHS Trust, Hertfordshire, United Kingdom3. Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom4. University of East Anglia, Norwich, United Kingdom5. Molecular and Clinical Sciences Research Institute, St. George’s, University of London, United Kingdom6. National Heart and Lung Institute, Imperial College, London, United Kingdom*these authors contributed equally to the manuscript (both residents/in early training)? joint senior authorsWord count: 1514Correspondence to:Dr. Ying X Gue MB BS, MRCPCardiology DepartmentLister HospitalEast and North Hertfordshire NHS TrustCorey’s Mill LaneStevenageHertfordshire SG1 4ABUnited KingdomEmail: y.gue@ABSTRACTBackgroundHistorical data indicate that approximately 10% of acute coronary syndrome patients have no obstructive coronary artery disease (CAD) but contemporary incidence of non-obstructed coronary arteries in ST-segment elevation myocardial infarction (STEMI) is not clear. We aimed both to identify the contemporary incidence of MI without obstructive CAD (MINOCA) -using the ESC definition- and assess clinical outcomes. MethodsWe assessed consecutive unselected STEMI patients presenting to the cardiac catheterisation laboratory with a view to undergoing primary percutaneous coronary intervention (PPCI). MINOCA was defined according to ESC criteria. Electronic patient records, blood results, angiographic and echocardiographic data were interrogated to determine final diagnosis, as well as 30-day and 1-year mortality rate.ResultsOf 2521 patients with full electronic dataset, 2158 (85.6%) underwent PPCI for obstructive CAD (angiographic stenosis >70%). A further 167 (6.6%) with obstructive CAD were treated medically or surgically. The remaining 196 (7.8%) patients had absence of obstructive CAD at angiography, of whom 167 had no stenosis (<30%) and 29 had mild coronary atheroma (stenosis >30% but <50%). A total of 110 (4.4%) patients met diagnostic criteria for MINOCA. All-cause mortality at 30-days and 1-year were 3.6% and 4.5%, respectively.ConclusionIn our cohort, 1 in 20 patients presenting with STEMI had MINOCA. This is the first description of the relatively high incidence of MINOCA in a STEMI cohort using current ESC definition and diagnostic criteria and could help power future trials in this area. Mortality rate was relatively high in our study and similar to that in large meta-analyses.Word count: 251Key wordsMyocardial infarction MINOCASTEMIMortalityIntroductionApproximately 90% of patients with myocardial infarction have angiographic evidence of obstructive coronary artery disease (CAD) based on registry studies published more than 30 years ago.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1056/NEJM198010163031601","ISSN":"0028-4793","PMID":"7412821","abstract":"To define the prevalence of total coronary occlusion in the hours after transmural myocardial infarction, we used coronary arteriography to study the degree of coronary obstruction in 322 patients admitted within 24 hours of infarction. Total coronary occlusion was observed in 110 of 126 patients (87 per cent) who were evaluated within four hours of the onset of symptoms; this proportion decreased significantly, to 37 of 57 (65 per cent), when patients were studied 12 to 24 hours after the onset of symptoms. Among 59 patients with angiographic features of coronary thrombosis, the thrombus was retrieved by Fogarty catheter in 52 (88 per cent) but was absent in seven (12 per cent false positive). Among an additional 20 patients without angiographic features of thrombosis, a thrombus was discovered in five (25 per cent false negative). Thus, total coronary occlusion is frequent during the early hours of transmural infarction and decreases in frequency during the initial 24 hours, suggesting that coronary spasm or thrombus formation with subsequent recanalization or both may be important in the evolution of infarction.","author":[{"dropping-particle":"","family":"DeWood","given":"Marcus A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Spores","given":"Julie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Notske","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mouser","given":"Lowell T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burroughs","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Golden","given":"Michael S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lang","given":"Henry T.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"New England Journal of Medicine","id":"ITEM-1","issue":"16","issued":{"date-parts":[["1980","10","16"]]},"page":"897-902","title":"Prevalence of Total Coronary Occlusion during the Early Hours of Transmural Myocardial Infarction","type":"article-journal","volume":"303"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1056/NEJM198608143150703","ISSN":"0028-4793","PMID":"3736619","abstract":"Complete occlusion of the infarct-related coronary artery is a frequent finding soon after Q-wave (transmural) myocardial infarction. We performed coronary arteriography to study the frequency of total coronary occlusion and of angiographically visible collateral vessels in 341 patients within one week of non-Q-wave myocardial infarction. In this cross-sectional study, 192, 94, and 55 patients underwent coronary arteriography within 24 hours of peak symptoms, between 24 and 72 hours after peak symptoms, and between 72 hours and seven days after peak symptoms, respectively. In the three groups, total occlusion of the infarct-related vessel was found in 26 percent (49 of 192), 37 percent (35 of 94), and 42 percent (23 of 55) of the patients, respectively (P less than 0.05). The presence of visible collateral vessels increased in parallel: 27 percent (52 of 192), 34 percent (32 of 94), and 42 percent (23 of 55), respectively (P less than 0.05). The frequency of subtotal occlusion (i.e., greater than or equal to 90 percent stenosis) decreased inversely: 34 percent (65 of 192), 25.5 percent (24 of 94), and 18 percent (10 of 55), respectively (P less than 0.05). Thus, in contrast to Q-wave infarction, total coronary occlusion of the infarct-related vessel is infrequently observed in the early hours of non-Q-wave infarction, but it increases moderately in frequency over the next several days. These cross-sectional data suggest that non-Q-wave infarction may be related to a preserved but marginal blood supply, which sufficiently disrupts the relation between the supply of and the demand for myocardial oxygen to cause tissue necrosis.","author":[{"dropping-particle":"","family":"DeWood","given":"Marcus A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stifter","given":"William F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Simpson","given":"Carroll S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Spores","given":"Julie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eugster","given":"George S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Judge","given":"Terrance P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hinnen","given":"Michael L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"New England Journal of Medicine","id":"ITEM-2","issue":"7","issued":{"date-parts":[["1986","8","14"]]},"page":"417-423","title":"Coronary Arteriographic Findings Soon after Non-Q-Wave Myocardial Infarction","type":"article-journal","volume":"315"},"uris":[""]}],"mendeley":{"formattedCitation":"^1,2","plainTextFormattedCitation":"1,2","previouslyFormattedCitation":"^1,2"},"properties":{"noteIndex":0},"schema":""}1,2 The realisation that obstructive CAD was causative in the majority of patients with ST-segment elevation myocardial infarction (STEMI), led to the development of current management strategies including primary percutaneous coronary intervention (PPCI). 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the management of acute myocardial infarction in patients presenting with ST-segment elevation","type":"article-journal","volume":"39"},"uris":[""]}],"mendeley":{"formattedCitation":"³","plainTextFormattedCitation":"3","previouslyFormattedCitation":"³"},"properties":{"noteIndex":0},"schema":""}3 Until recently, myocardial infarction with non-obstructive coronary arteries (MINOCA) was a “Cinderella” condition: little known, little understood and under-appreciated. In 2015, Pasupathy and co-workers published a comprehensive systematic review of patients with suspected myocardial infarction without obstructive CADADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/CIRCULATIONAHA.114.011201","ISBN":"1524-4539 (Electronic)\\r0009-7322 (Linking)","ISSN":"15244539","PMID":"25587100","abstract":"BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder.\\n\\nMETHODS AND RESULTS: Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence interval, 51-59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval, 2.6%-6.9%) compared with myocardial infarction associated with obstructive coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative assessment of 46 publications evaluating the underlying pathophysiology responsible for MINOCA revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in 14%.\\n\\nCONCLUSIONS: MINOCA should be considered as a working diagnosis with multiple potential causes that require evaluation so that directed therapies may improve its guarded prognosis.","author":[{"dropping-particle":"","family":"Pasupathy","given":"Sivabaskari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Air","given":"Tracy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dreyer","given":"Rachel P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tavella","given":"Rosanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Circulation","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2015"]]},"page":"861-870","title":"Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries","type":"article-journal","volume":"131"},"uris":[""]}],"mendeley":{"formattedCitation":"⁴","plainTextFormattedCitation":"4","previouslyFormattedCitation":"⁴"},"properties":{"noteIndex":0},"schema":""}4 and in 2017, the European Society of Cardiology (ESC) Working Group on Cardiovascular Pharmacotherapy published a position paper which was, arguably, the first authoritative statement on definition, clinical features and recommended investigations in patients with MINOCA.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/eurheartj/ehw149","ISSN":"0195-668X","author":[{"dropping-particle":"","family":"Agewall","given":"Stefan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reynolds","given":"Harmony R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Niessner","given":"Alexander","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosano","given":"Giuseppe","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":"Caterina","given":"Raffaele","non-dropping-particle":"De","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zimarino","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roffi","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kjeldsen","given":"Keld","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Atar","given":"Dan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaski","given":"Juan C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sechtem","given":"Udo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tornvall","given":"Per","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Heart Journal","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2016","4","28"]]},"publisher":"Oxford University Press","title":"ESC working group position paper on myocardial infarction with non-obstructive coronary arteries","type":"article-journal","volume":"38"},"uris":[""]}],"mendeley":{"formattedCitation":"⁵","plainTextFormattedCitation":"5","previouslyFormattedCitation":"⁵"},"properties":{"noteIndex":0},"schema":""}5 Although a large registry of patients with non-ST-elevation myocardial infarction published 10 years ago showed the incidence of non-obstructive CAD to be 10%,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.ahj.2009.08.004","ISSN":"00028703","PMID":"19781432","abstract":"BACKGROUND Women with non-ST-segment elevation myocardial infarction (NSTEMI) who undergo coronary angiography have no obstructive coronary lesions more often than men. Sex-specific characteristics and outcomes of patients without obstructive coronary artery disease (CAD) have not been described previously. METHODS Using data from NSTEMI patients enrolled in CRUSADE from 2001 to 2005, we evaluated differences in clinical features and in-hospital outcomes between men and women with no obstructive CAD. RESULTS After excluding patients with missing catheterization and sex data (n = 1,494), previous coronary artery bypass grafting or percutaneous coronary intervention (47,907), catheterization contraindications (n = 6,588), and missing obstructive CAD status (n = 1,565), there were 55,514 patients (68.4%) with NSTE acute coronary syndromes (ACS) who underwent angiography (among women, 62.1% [21,294/34,290], and among men, 73% [34,220/46,875]; P < .001). Among these, a total of 5,538 patients (10.0%) had nonnonobstructive CAD-15.1% (3,221/21,294) of women and 6.8% (2,317/34,220) of men (P < .0001). In patients without obstructive CAD, women were as likely as men to have MI (troponin elevation in 89% vs 87%, P = .37). Women and men were equally likely to have larger troponin elevations (58.9% vs 58.6% with troponin >5x upper limit of normal, P = .69, respectively). In NSTEMI patients without obstructive CAD, in-hospital death (0.6% women vs 0.7% men) and cardiogenic shock (1.0% women vs 0.7% men) were infrequent. CONCLUSIONS Among NSTE ACS patients undergoing coronary angiography, absence of obstructive CAD is more common in women than men. Although nonobstructive CAD was twice as common among women with NSTEMI, sex differences in characteristics and outcomes were similar to those found with obstructive CAD. Unadjusted in-hospital outcomes of NSTEMI patients with nonobstructive CAD are favorable in both sexes. Whether the underlying pathophysiology of NSTE ACS without documentation of obstructive CAD is different between women and men requires further study.","author":[{"dropping-particle":"","family":"Gehrie","given":"Erika R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reynolds","given":"Harmony R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Anita Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Neelon","given":"Brian H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roe","given":"Matthew T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibler","given":"W. Brian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ohman","given":"E. Magnus","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Newby","given":"L. Kristin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Peterson","given":"Eric D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hochman","given":"Judith S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Heart Journal","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2009","10"]]},"page":"688-694","title":"Characterization and outcomes of women and men with non–ST-segment elevation myocardial infarction and nonobstructive coronary artery disease: Results from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early ","type":"article-journal","volume":"158"},"uris":[""]}],"mendeley":{"formattedCitation":"⁶","plainTextFormattedCitation":"6","previouslyFormattedCitation":"⁶"},"properties":{"noteIndex":0},"schema":""}6 another registry around the same time showed the incidence of angiographically normal coronaries in acute coronary syndrome to be only 2.8%.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.amjcard.2004.09.014","ISSN":"0002-9149","PMID":"15642564","abstract":"This study on patients undergoing coronary angiography for acute myocardial infarction demonstrated that 2.8% of patients had angiographically normal coronary arteries and that these patients have a better prognosis than patients with angiographically verified coronary artery disease. The trend toward a higher prevalence of malignancy in this unique patient group raises the possibility of malignancy-induced hypercoagulability or inflammation as an underlying etiologic factor.","author":[{"dropping-particle":"","family":"Larsen","given":"Alf Inge","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Galbraith","given":"P Diane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ghali","given":"William A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Norris","given":"Colleen M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Graham","given":"Michelle M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knudtson","given":"Merril L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"APPROACH Investigators","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American journal of cardiology","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2005","1","15"]]},"page":"261-3","publisher":"Elsevier","title":"Characteristics and outcomes of patients with acute myocardial infarction and angiographically normal coronary arteries.","type":"article-journal","volume":"95"},"uris":[""]}],"mendeley":{"formattedCitation":"⁷","plainTextFormattedCitation":"7","previouslyFormattedCitation":"⁷"},"properties":{"noteIndex":0},"schema":""}7 These studies did not define the incidence of MINOCA in STEMI, and MINOCA definition was not based on contemporary criteria. MINOCA is not a benign condition; a meta-analysis indicated that 1-year all-cause mortality was 4.7%.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/CIRCULATIONAHA.114.011201","ISBN":"1524-4539 (Electronic)\\r0009-7322 (Linking)","ISSN":"15244539","PMID":"25587100","abstract":"BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder.\\n\\nMETHODS AND RESULTS: Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence interval, 51-59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval, 2.6%-6.9%) compared with myocardial infarction associated with obstructive coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative assessment of 46 publications evaluating the underlying pathophysiology responsible for MINOCA revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in 14%.\\n\\nCONCLUSIONS: MINOCA should be considered as a working diagnosis with multiple potential causes that require evaluation so that directed therapies may improve its guarded prognosis.","author":[{"dropping-particle":"","family":"Pasupathy","given":"Sivabaskari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Air","given":"Tracy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dreyer","given":"Rachel P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tavella","given":"Rosanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Circulation","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2015"]]},"page":"861-870","title":"Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries","type":"article-journal","volume":"131"},"uris":[""]}],"mendeley":{"formattedCitation":"⁴","plainTextFormattedCitation":"4","previouslyFormattedCitation":"⁴"},"properties":{"noteIndex":0},"schema":""}4 More recently, data from the 2003-2013 SWEDEHEART registry revealed that over a 4-year follow-up, 23.9% patients with MINOCA experienced a major cardiac event.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/CIRCULATIONAHA.116.026336","ISSN":"0009-7322","PMID":"28179398","abstract":"BACKGROUND Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 5% to 10% of all patients with myocardial infarction. Clinical trials of secondary prevention treatment in MINOCA patients are lacking. Therefore, the aim of this study was to examine the associations between treatment with statins, renin-angiotensin system blockers, β-blockers, dual antiplatelet therapy, and long-term cardiovascular events. METHODS This is an observational study of MINOCA patients recorded in the SWEDEHEART registry (the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy) between July 2003 and June 2013 and followed until December 2013 for outcome events in the Swedish Cause of Death Register and National Patient Register. Of 199?162 myocardial infarction admissions, 9466 consecutive unique patients with MINOCA were identified. Among those, the 9136 patients surviving the first 30 days after discharge constituted the study population. Mean age was 65.3 years, and 61% were women. No patient was lost to follow-up. A stratified propensity score analysis was performed to match treated and untreated groups. The association between treatment and outcome was estimated by comparing between treated and untreated groups by using Cox proportional hazards models. The exposures were treatment at discharge with statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy. The primary end point was major adverse cardiac events defined as all-cause mortality, hospitalization for myocardial infarction, ischemic stroke, and heart failure. RESULTS At discharge, 84.5%, 64.1%, 83.4%, and 66.4% of the patients were on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy, respectively. During the follow-up of a mean of 4.1 years, 2183 (23.9%) patients experienced a major adverse cardiac event. The hazard ratios (95% confidence intervals) for major adverse cardiac events were 0.77 (0.68-0.87), 0.82 (0.73-0.93), and 0.86 (0.74-1.01) in patients on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and β-blockers, respectively. For patients on dual antiplatelet therapy followed for 1 year, the hazard ratio was 0.90 (0.74-1.08). CONCLUSIONS The results indicate long-term beneficial effects of treatment with statins and angiotensin-co…","author":[{"dropping-particle":"","family":"Lindahl","given":"Bertil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baron","given":"Tomasz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Erlinge","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hadziosmanovic","given":"Nermin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nordenskj?ld","given":"Anna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gard","given":"Anton","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jernberg","given":"Tomas","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Circulation","id":"ITEM-1","issue":"16","issued":{"date-parts":[["2017","4","18"]]},"page":"1481-1489","title":"Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery DiseaseClinical Perspective","type":"article-journal","volume":"135"},"uris":[""]}],"mendeley":{"formattedCitation":"⁸","plainTextFormattedCitation":"8","previouslyFormattedCitation":"⁸"},"properties":{"noteIndex":0},"schema":""}8 Establishing the true incidence of MINOCA among patients presenting with STEMI is important as these patients may require specific emergency investigation and ad hoc treatments that may differ from those currently recommended in conventional CAD STEMI. Future trials of new treatments for MINOCA STEMI patients will need to be adequately powered based on contemporary incidence, aetiology and outcomes. It was our aim to identify the contemporary incidence of MINOCA amongst patients with ST-segment elevation, delineate the underlying diagnoses using the ESC definitionADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/eurheartj/ehw149","ISSN":"0195-668X","author":[{"dropping-particle":"","family":"Agewall","given":"Stefan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reynolds","given":"Harmony R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Niessner","given":"Alexander","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosano","given":"Giuseppe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Caforio","given":"Alida L. 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MethodsWe assessed all consecutive patients with ST-elevation admitted with a view to PPCI, to East and North Hertfordshire NHS Trust and Norfolk and Norwich University Hospital, United Kingdom. These Heart Attack Centres (HAC) serve a population of 1.5 million, supported by East of England Ambulance Service?NHS Trust. According to standard protocol, all patients who meet the criteria for STEMI are brought directly to the HAC for emergency PPCI. Criteria for PPCI protocol activation are symptoms compatible with an acute myocardial infarction within 12 hours with any of the following electrocardiographic (ECG) criteria: ST-segment elevation 1mm in contiguous limb leads, >2mm in contiguous chest leads, bundle branch block believed to be new in the context of acute cardiac-sounding chest pain, or patients resuscitated from cardiac arrest with ECG criteria as above. All patients who met these criteria were included.Patients with MINOCA according to the ESC position paper and InterTAK Diagnostic CriteriaADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/eurheartj/ehw149","ISSN":"0195-668X","author":[{"dropping-particle":"","family":"Agewall","given":"Stefan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reynolds","given":"Harmony R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Niessner","given":"Alexander","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosano","given":"Giuseppe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Caforio","given":"Alida L. 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Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. 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Of these, 85.6% underwent PPCI for obstructive CAD. A further 6.6% patients with obstructive CAD were treated medically or with surgical revascularisation. Angiographically-significant CAD was absent in 7.8% patients. A total of 110 patients (4.4% of all STEMIs) met diagnostic criteria for MINOCA, 54% were male, with mean age 63.5±13.9 years. The aetiology of MINOCA was determined to be a coronary cause in 28%, non-coronary cardiac cause in 61% and non-coronary extra-cardiac cause in 11% of patients. Coronary causes included plaque disruption (39%), coronary spasm (10%), spontaneous coronary artery dissection (19%), coronary embolism (23%) and aortic dissection (10%). Non-coronary cardiac causes included myocarditis (36%), Takotsubo syndrome (30%) and type 2 myocardial infarction (34%) – the latter comprising patients with cardiomyopathy, anaemia, valvular disease and arrhythmia. Non-coronary (extra-cardiac) causes included pulmonary embolism (50%), cerebrovascular event (8%), and other causes included sepsis, gallstone pancreatitis and extracardiac tumour compressing the heart. In the remaining 86 patients with absence of angiographically-significant CAD, the final diagnoses were predominantly pericarditis, myocarditis and normal-variant ECG. In MINOCA patients, 30-day all-cause mortality was 3.6% and 1-year mortality was 4.5%. 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Knowing the incidence is important for planning future studies of treatment for this cohort, particularly in the acute phase, as treatments may differ markedly between STEMI patients with CAD and MINOCA patients. In the most recent publication on the incidence of this condition in STEMI, derived from the HORIZONS-AMI trial conducted >10 years ago, the reported incidence of “apical ballooning syndrome” based on the Mayo Clinic diagnostic criteria was 0.5% in 2648 STEMI patients.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1002/ccd.23441","ISSN":"15221946","author":[{"dropping-particle":"","family":"Prasad","given":"Abhiram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dangas","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Srinivasan","given":"Manivannan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"Jennifer","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gersh","given":"Bernard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mehran","given":"Roxana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stone","given":"Gregg W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Catheterization and Cardiovascular Interventions","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2014","2","15"]]},"page":"343-348","publisher":"Wiley-Blackwell","title":"Incidence and angiographic characteristics of patients With apical ballooning syndrome (takotsubo/stress cardiomyopathy) in the HORIZONS-AMI trial","type":"article-journal","volume":"83"},"uris":[""]}],"mendeley":{"formattedCitation":"¹²","plainTextFormattedCitation":"12","previouslyFormattedCitation":"¹²"},"properties":{"noteIndex":0},"schema":""}12 In the largest systematic review by Pasupathy and co-workers, the incidence of MINOCA was reported to be 6% amongst patients with acute coronary syndromes,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/CIRCULATIONAHA.114.011201","ISBN":"1524-4539 (Electronic)\\r0009-7322 (Linking)","ISSN":"15244539","PMID":"25587100","abstract":"BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder.\\n\\nMETHODS AND RESULTS: Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence interval, 51-59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval, 2.6%-6.9%) compared with myocardial infarction associated with obstructive coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative assessment of 46 publications evaluating the underlying pathophysiology responsible for MINOCA revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in 14%.\\n\\nCONCLUSIONS: MINOCA should be considered as a working diagnosis with multiple potential causes that require evaluation so that directed therapies may improve its guarded prognosis.","author":[{"dropping-particle":"","family":"Pasupathy","given":"Sivabaskari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Air","given":"Tracy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dreyer","given":"Rachel P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tavella","given":"Rosanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Circulation","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2015"]]},"page":"861-870","title":"Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries","type":"article-journal","volume":"131"},"uris":[""]}],"mendeley":{"formattedCitation":"⁴","plainTextFormattedCitation":"4","previouslyFormattedCitation":"⁴"},"properties":{"noteIndex":0},"schema":""}4 but the incidence specifically in patients presenting with STEMI was not defined. This is very much lower than that reported in a retrospective analysis of the PRAGUE studies from pre-2002, in which the incidence of angiographically normal coronary arteries in 1004 emergency angiograms performed for STEMI, was reported as 26%.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"0828-282X","PMID":"17102833","abstract":"BACKGROUND Acute ST-elevation myocardial infarction in patients with normal coronary arteries has previously been described, but coronary angiography in these patients was performed after the acute phase of the infarction. It is possible that these patients did not have normal angiograms during the acute phase (transient coronary thrombosis or spasm were usually suspected to be the cause). Information on the prevalence of truly normal coronary angiograms during the acute phase of a suspected ST-elevation myocardial infarction is lacking. PATIENTS AND METHODS The Primary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis-1 (PRAGUE-1) and PRAGUE-2 studies enrolled 1150 patients with ST-elevation acute myocardial infarction, in whom 625 coronary angiograms were performed within 2 h of the initial electrocardiogram. A simultaneous registry included an additional 379 coronary angiograms performed during the ST-elevation phase of a suspected myocardial infarction. Thus, a total of 1004 angiograms were retrospectively analyzed. A normal coronary angiogram was defined as one with the absence of any visible angiographic signs of atherosclerosis, thrombosis or spontaneous spasm. RESULTS Normal coronary angiograms were obtained for 26 patients (2.6%). Among these, the diagnosis at discharge was a small myocardial infarction in seven patients (0.7%), acute (peri)myocarditis in five patients, dilated cardiomyopathy in four patients, hypertension with left ventricular hypertrophy in three patients, pulmonary embolism in two patients and misinterpretation of the electrocardiogram (ie, no cardiac disease) in five patients. Seven patients with small infarctions underwent angiography within 30 min to 90 min of complete relief of the signs of acute ischemia, and thus, angiograms during pain were not taken. None of the 898 patients catheterized during ongoing symptoms of ischemia had a normal coronary angiogram. Spontaneous coronary spasm as the only cause (without underlying coronary atherosclerosis) for the evolving infarction was not seen among these 898 patients. Thus, the causes of the seven small infarcts in patients with normal angiograms remain uncertain. CONCLUSIONS The observed prevalence of normal coronary angiography in patients presenting with acute chest pain and ST elevations was 2.6%. Most of these cases were misdiagnoses, not infarctions. A normal angiogram during a biochemi…","author":[{"dropping-particle":"","family":"Widimsky","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stellova","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Groch","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aschermann","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Branny","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zelizko","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stasek","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Formanek","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"PRAGUE Study Group Investigators","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The Canadian journal of cardiology","id":"ITEM-1","issue":"13","issued":{"date-parts":[["2006","11"]]},"page":"1147-52","publisher":"Pulsus Group","title":"Prevalence of normal coronary angiography in the acute phase of suspected ST-elevation myocardial infarction: experience from the PRAGUE studies.","type":"article-journal","volume":"22"},"uris":[""]}],"mendeley":{"formattedCitation":"¹³","plainTextFormattedCitation":"13","previouslyFormattedCitation":"¹³"},"properties":{"noteIndex":0},"schema":""}13 Although in the systematic review, some 30% of patients with MINOCA were reported to present with ST-segment elevation,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/CIRCULATIONAHA.114.011201","ISBN":"1524-4539 (Electronic)\\r0009-7322 (Linking)","ISSN":"15244539","PMID":"25587100","abstract":"BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder.\\n\\nMETHODS AND RESULTS: Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence interval, 51-59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval, 2.6%-6.9%) compared with myocardial infarction associated with obstructive coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative assessment of 46 publications evaluating the underlying pathophysiology responsible for MINOCA revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in 14%.\\n\\nCONCLUSIONS: MINOCA should be considered as a working diagnosis with multiple potential causes that require evaluation so that directed therapies may improve its guarded prognosis.","author":[{"dropping-particle":"","family":"Pasupathy","given":"Sivabaskari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Air","given":"Tracy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dreyer","given":"Rachel P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tavella","given":"Rosanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Circulation","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2015"]]},"page":"861-870","title":"Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries","type":"article-journal","volume":"131"},"uris":[""]}],"mendeley":{"formattedCitation":"⁴","plainTextFormattedCitation":"4","previouslyFormattedCitation":"⁴"},"properties":{"noteIndex":0},"schema":""}4 in the SWEDEHEART registry of MINOCA patients from 2003-2013, only 17% had ST-elevation.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/CIRCULATIONAHA.116.026336","ISSN":"0009-7322","PMID":"28179398","abstract":"BACKGROUND Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 5% to 10% of all patients with myocardial infarction. Clinical trials of secondary prevention treatment in MINOCA patients are lacking. Therefore, the aim of this study was to examine the associations between treatment with statins, renin-angiotensin system blockers, β-blockers, dual antiplatelet therapy, and long-term cardiovascular events. METHODS This is an observational study of MINOCA patients recorded in the SWEDEHEART registry (the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy) between July 2003 and June 2013 and followed until December 2013 for outcome events in the Swedish Cause of Death Register and National Patient Register. Of 199?162 myocardial infarction admissions, 9466 consecutive unique patients with MINOCA were identified. Among those, the 9136 patients surviving the first 30 days after discharge constituted the study population. Mean age was 65.3 years, and 61% were women. No patient was lost to follow-up. A stratified propensity score analysis was performed to match treated and untreated groups. The association between treatment and outcome was estimated by comparing between treated and untreated groups by using Cox proportional hazards models. The exposures were treatment at discharge with statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy. The primary end point was major adverse cardiac events defined as all-cause mortality, hospitalization for myocardial infarction, ischemic stroke, and heart failure. RESULTS At discharge, 84.5%, 64.1%, 83.4%, and 66.4% of the patients were on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy, respectively. During the follow-up of a mean of 4.1 years, 2183 (23.9%) patients experienced a major adverse cardiac event. The hazard ratios (95% confidence intervals) for major adverse cardiac events were 0.77 (0.68-0.87), 0.82 (0.73-0.93), and 0.86 (0.74-1.01) in patients on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and β-blockers, respectively. For patients on dual antiplatelet therapy followed for 1 year, the hazard ratio was 0.90 (0.74-1.08). CONCLUSIONS The results indicate long-term beneficial effects of treatment with statins and angiotensin-co…","author":[{"dropping-particle":"","family":"Lindahl","given":"Bertil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baron","given":"Tomasz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Erlinge","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hadziosmanovic","given":"Nermin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nordenskj?ld","given":"Anna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gard","given":"Anton","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jernberg","given":"Tomas","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Circulation","id":"ITEM-1","issue":"16","issued":{"date-parts":[["2017","4","18"]]},"page":"1481-1489","title":"Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery DiseaseClinical Perspective","type":"article-journal","volume":"135"},"uris":[""]}],"mendeley":{"formattedCitation":"⁸","plainTextFormattedCitation":"8","previouslyFormattedCitation":"⁸"},"properties":{"noteIndex":0},"schema":""}8 Neither of these registries applied the diagnostic criteria recently proposed by the ESC MINOCA position paper.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/eurheartj/ehw149","ISSN":"0195-668X","author":[{"dropping-particle":"","family":"Agewall","given":"Stefan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beltrame","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reynolds","given":"Harmony R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Niessner","given":"Alexander","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosano","given":"Giuseppe","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":"Caterina","given":"Raffaele","non-dropping-particle":"De","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zimarino","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roffi","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kjeldsen","given":"Keld","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Atar","given":"Dan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaski","given":"Juan C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sechtem","given":"Udo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tornvall","given":"Per","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Heart Journal","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2016","4","28"]]},"publisher":"Oxford University Press","title":"ESC working group position paper on myocardial infarction with non-obstructive coronary arteries","type":"article-journal","volume":"38"},"uris":[""]}],"mendeley":{"formattedCitation":"⁵","plainTextFormattedCitation":"5","previouslyFormattedCitation":"⁵"},"properties":{"noteIndex":0},"schema":""}5 The 1-year mortality rate of 4.5% in our cohort is similar to the mortality rate observed in the International Takotsubo Registry, where rate of mortality rate was 5.6% per patient-yearADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1056/NEJMoa1406761","ISSN":"0028-4793","PMID":"26332547","abstract":"BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; number, NCT01947621.).","author":[{"dropping-particle":"","family":"Templin","given":"Christian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ghadri","given":"Jelena R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Diekmann","given":"Johanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Napp","given":"L. 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Additionally, the effect of the triggering factors remains elusive. OBJECTIVES This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers. METHODS Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions. RESULTS Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients. CONCLUSIONS Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress?factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short-?and?long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621).","author":[{"dropping-particle":"","family":"Ghadri","given":"Jelena R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kato","given":"Ken","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cammann","given":"Victoria L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gili","given":"Sebastiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jurisic","given":"Stjepan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vece","given":"Davide","non-dropping-particle":"Di","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Candreva","given":"Alessandro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ding","given":"Katharina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Micek","given":"Jozef","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Szawan","given":"Konrad A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bacchi","given":"Beatrice","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bianchi","given":"Rahel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Levinson","given":"Rena A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wischnewsky","given":"Manfred","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seifert","given":"Burkhardt","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schlossbauer","given":"Susanne A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Citro","given":"Rodolfo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bossone","given":"Eduardo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Münzel","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knorr","given":"Maike","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heiner","given":"Susanne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"D’Ascenzo","given":"Fabrizio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Franke","given":"Jennifer","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sarcon","given":"Annahita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Napp","given":"L. 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On the other hand, it contrasts with the absence of major adverse cardiac or cardiovascular events seen over a 2-year follow-up in the HORIZONS-AMI trial in STEMI patients with apical ballooningADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1002/ccd.23441","ISSN":"15221946","author":[{"dropping-particle":"","family":"Prasad","given":"Abhiram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dangas","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Srinivasan","given":"Manivannan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"Jennifer","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gersh","given":"Bernard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mehran","given":"Roxana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stone","given":"Gregg W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Catheterization and Cardiovascular Interventions","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2014","2","15"]]},"page":"343-348","publisher":"Wiley-Blackwell","title":"Incidence and angiographic characteristics of patients With apical ballooning syndrome (takotsubo/stress cardiomyopathy) in the HORIZONS-AMI trial","type":"article-journal","volume":"83"},"uris":[""]}],"mendeley":{"formattedCitation":"¹²","plainTextFormattedCitation":"12","previouslyFormattedCitation":"¹²"},"properties":{"noteIndex":0},"schema":""}12 and the 0.05% mortality rate reported in the Swedish?Angiography?and?Angioplasty?Register (SCAAR),18 although the latter was not confined to STEMI.The heterogenous aetiology of MINOCA is further highlighted in our cohort, with coronary causes accounting for only 28% of cases. Approximately 10% of our cohort had a final diagnosis of plaque disruption, which is lower than the 40% incidence in MINOCA patients reported by Reynolds et al.19 using intravascular ultrasound or high resolution optical coherence tomography.20 Within our cohort, 2 of 6 patients required the use of intracoronary imaging to establish the diagnosis of spontaneous coronary artery dissection. Only 3% of our cohort had angiographically-apparent coronary spasm, although spasm provocation testing was not undertaken. This is much lower than the incidence in previous reports employing provocative spasm testing where coronary spasm was identified as a cause of MINOCA in ~50% of patients.21 The Coronary Vasomotion Disorders International Study Group (COVADIS)22 has recommended three criteria to diagnose coronary artery vasospastic disorders, that include a clinical history suggestive of vasospasm, documented transient ischaemic ECG changes and presence of coronary artery spasm either spontaneously or in response to provocative stimulation. The gold standard involves the use of provocative stimulus (typically intracoronary acetylcholine) to produce symptoms and signs of spasm. Provocative spasm testing is indicated in MINOCA,22 and has both diagnostic and prognostic importance, as recently shown by Montone et al.23,24 The Montone paper showed that provocative spasm testing is safe, even in the acute phases of MINOCA. Non-coronary cardiac-related causes accounted for 61% of cases, the most frequent diagnoses being myocarditis (22%) and Takotsubo syndrome (18%). The main limitations of our data are the relatively small, single-centre patient sample size and the retrospective nature of the analysis. Furthermore, coronary spasm provocation testing and intravascular imaging were not routinely performed, and therefore the underlying aetiology may have been inaccurately characterised in some patients. The major strength of our paper is the inclusion of all consecutive, unselected patients, who all met the stringent criteria for STEMI.ConclusionApproximately 4% of patients presenting with STEMI for PPCI have MINOCA. This is the first description of the relatively high incidence of MINOCA in a STEMI cohort using current ESC diagnostic criteria. The heterogenous aetiology highlights the need to actively seek the underlying diagnosis using diagnostic algorithms recommended by the ESC and the COVADIS group.FundingThis article is not funded by external sources.DisclosuresThe authors declare that there are no conflicts of interest to disclose.ReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. DeWood MA, Spores J, Notske R, et al. Prevalence of Total Coronary Occlusion during the Early Hours of Transmural Myocardial Infarction. N Engl J Med 1980; 303: 897–902.2. DeWood MA, Stifter WF, Simpson CS, et al. Coronary Arteriographic Findings Soon after Non-Q-Wave Myocardial Infarction. N Engl J Med 1986; 315: 417–423.3. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2017; 39: 119–177.4. Pasupathy S, Air T, Dreyer RP, et al. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation 2015; 131: 861–870.5. Agewall S, Beltrame JF, Reynolds HR, et al. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J; 38. Epub ahead of print 28 April 2016. DOI: 10.1093/eurheartj/ehw149.6. Gehrie ER, Reynolds HR, Chen AY, et al. Characterization and outcomes of women and men with non–ST-segment elevation myocardial infarction and nonobstructive coronary artery disease: Results from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early . Am Heart J 2009; 158: 688–694.7. Larsen AI, Galbraith PD, Ghali WA, et al. Characteristics and outcomes of patients with acute myocardial infarction and angiographically normal coronary arteries. Am J Cardiol 2005; 95: 261–3.8. Lindahl B, Baron T, Erlinge D, et al. Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery DiseaseClinical Perspective. Circulation 2017; 135: 1481–1489.9. Ghadri J-R, Wittstein IS, Prasad A, et al. International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology. Eur Heart J 2018; 39: 2032–2046.10. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J. Epub ahead of print 25 August 2018. DOI: 10.1093/eurheartj/ehy462.11. Ghadri J-R, Wittstein IS, Prasad A, et al. International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management. Eur Heart J 2018; 39: 2047–2062.12. Prasad A, Dangas G, Srinivasan M, et al. Incidence and angiographic characteristics of patients With apical ballooning syndrome (takotsubo/stress cardiomyopathy) in the HORIZONS-AMI trial. Catheter Cardiovasc Interv 2014; 83: 343–348.13. Widimsky P, Stellova B, Groch L, et al. Prevalence of normal coronary angiography in the acute phase of suspected ST-elevation myocardial infarction: experience from the PRAGUE studies. Can J Cardiol 2006; 22: 1147–52.14. Templin C, Ghadri JR, Diekmann J, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med 2015; 373: 929–938.15. Ghadri JR, Kato K, Cammann VL, et al. Long-Term Prognosis of Patients With Takotsubo Syndrome. J Am Coll Cardiol 2018; 72: 874–882.16. Hjort?M, Lindahl B, Baron T, Jernberg T, Tornvall P, Eggers KM. Prognosis?in relation to high-sensitivity cardiac troponin T levels in patients with myocardial infarction and non-obstructive coronary arteries. Am Heart J 2018; 200: 60-66. 17. Bainey?KR, Welsh RC, Alemayehu W, Westerhout CM, Traboulsi D, Anderson T, Brass N, Armstrong PW,?Kaul?P. Population-level incidence and outcomes of myocardial infarction with non-obstructive coronary arteries (MINOCA): Insights from the Alberta contemporary acute coronary syndrome patients invasive treatment strategies (COAPT) study. Int J Cardiol 2018; 264: 12-17. 18. Tornvall P, Collste O, Ehrenborg E, et al. A Case-Control Study of Risk Markers and?Mortality in Takotsubo Stress Cardiomyopathy. J Am Coll Cardiol 2016; 67: 1931–1936.19. Reynolds HR, Srichai MB, Iqbal SN, et al. Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease. Circulation 2011; 124: 1414–25.20. Niccoli G, Scalone G, Crea F. Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management. Eur Heart J 2015; 36: 475–481.21. Ong P, Athanasiadis A, Hill S, et al. Coronary Artery Spasm as a Frequent Cause of Acute Coronary Syndrome. J Am Coll Cardiol 2008; 52: 523–527.22. Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J 2015; 38: ehv351.23. Montone RA, Niccoli G, Fracassi F, et al. Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J 2017; 39: 91–98.24. Kaski JC. Provocative tests for coronary artery spasm in MINOCA: necessary and safe? Eur Heart J 2018; 39: 99–101.Figure LegendsFigure 1Flowchart for identification of patientsFor the purposes of this registry, the criteria for definition of myocardial infarction included a positive cardiac biomarker defined as a rise and/or fall in serial levels with at least 1 value above the 99th percentile upper reference limit and clinical evidence of myocardial infarction as evidenced by ischaemic symptoms and/or ischaemic changes manifesting in new ST-segment changes or left bundle branch block. Patients with fixed ST-segment changes without elevation of cardiac enzymes and subsequently labelled as having “normal variant” ECGs, were excluded from analysis.Figure 2Prevalence of coronary disease and management of patients presenting with STEMI.CAD= coronary artery disease. Numbers in brackets are (%) of total cohort.Figure 1-57277023558500Figure 2-11874520129500 ................
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