PART 1 – APPLICANT DETAILS
Application FormGenetic testing for the diagnosis of cardiomyopathiesThis application form is to be completed for new and amended requests for public funding (including but not limited to the Medicare Benefits Schedule (MBS)). It describes the detailed information that the Australian Government Department of Health requires in order to determine whether a proposed medical service is suitable.Please use this template, along with the associated Application Form Guidelines to prepare your application. Please complete all questions that are applicable to the proposed service, providing relevant information only. Applications not completed in full will not be accepted.Should you require any further assistance, departmental staff are available through the Health Technology Assessment Team (HTA Team) on the contact numbers and email below to discuss the application form, or any other component of the Medical Services Advisory Committee process.Phone: +61 2 6289 7550Fax: +61 2 6289 5540Email: hta@.auWebsite: .au PART 1 – APPLICANT DETAILSApplicant details (primary and alternative contacts)Corporation / partnership details (where relevant): Corporation name: The Royal College of Pathologists of AustralasiaABN: REDACTEDBusiness trading name: REDACTEDPrimary contact name: REDACTEDPrimary contact numbersBusiness: REDACTEDMobile:REDACTED Email: REDACTEDAlternative contact name: REDACTEDAlternative contact numbersBusiness: REDACTEDMobile: REDACTED Email: REDACTEDAlternative contact name: REDACTEDAlternative contact numbersBusiness: Mobile: REDACTEDEmail: REDACTED(a) Are you a lobbyist acting on behalf of an Applicant? FORMCHECKBOX Yes FORMCHECKBOX No If yes, are you listed on the Register of Lobbyists? FORMCHECKBOX Yes FORMCHECKBOX No PART 2 – INFORMATION ABOUT THE PROPOSED MEDICAL SERVICEApplication title Genetic testing for the diagnosis of cardiomyopathiesProvide a succinct description of the medical condition relevant to the proposed service (no more than 150 words – further information will be requested at Part F of the Application Form)Cardiomyopathies comprise a small group of related but clinically distinct primary diseases of the heart muscle and are one of the major causes of sudden cardiac death (SCD) and/or progressive heart failure (HF) ADDIN EN.CITE <EndNote><Cite><Author>Szabadosova</Author><Year>2018</Year><RecNum>4</RecNum><IDText>28594148</IDText><DisplayText>(Szabadosova et al 2018)</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1519173417">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Szabadosova, V.</author><author>Boronova, I.</author><author>Ferenc, P.</author><author>Tothova, I.</author><author>Bernasovska, J.</author><author>Zigova, M.</author><author>Kmec, J.</author><author>Bernasovsky, I.</author></authors></contributors><auth-address>Department of Biology, Faculty of Humanities and Natural Sciences, University of Presov, Presov, Slovakia.
Cardiocentre, Faculty Hospital of J.A. Reiman, Presov, Slovakia.
Center of Languages and Cultures of National Minorities, University of Presov, Presov, Slovakia.</auth-address><titles><title>Analysis of selected genes associated with cardiomyopathy by next-generation sequencing</title><secondary-title>J Clin Lab Anal</secondary-title></titles><periodical><full-title>J Clin Lab Anal</full-title></periodical><volume>32</volume><number>2</number><edition>2017/06/09</edition><keywords><keyword>bioinformatic analysis</keyword><keyword>cardiomyopathies</keyword><keyword>next-generation sequencing</keyword><keyword>panel of genes</keyword><keyword>pathogenic variants</keyword></keywords><dates><year>2018</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1098-2825 (Electronic)
0887-8013 (Linking)</isbn><accession-num>28594148</accession-num><urls><related-urls><url>;(Szabadosova et al 2018). The most common cardiomyopathies are usually inherited as autosomal-dominant PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkbXVsbGVyPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkbXVsbGVyPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE.DATA (Waldmuller et al 2015) and include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC. The phenotypic spectrum of many inherited cardiomyopathies can be varied and in some cases sub-classification by genotype is increasingly a more clinically useful approach, i.e. LMNA-cardiomyopathy. In many cases clinical management will not change for patients with a positive genetic diagnosis; however, identification of variant negative family members will represent significant savings to the health system by reducing the number of patients who require ongoing clinical monitoring.Provide a succinct description of the proposed medical service (no more than 150 words – further information will be requested at Part 6 of the Application Form)Diagnostic genetic testing of affected individuals: characterisation of germline gene variants for inherited cardiomyopathies in patients where clinical criteria or a family history indicate that genetic testing is warranted. HCM: MYBPC3, MYH7, TNNI3, TNNT2, TPM1, ACTC1, MYL2, MYL3 plus “mimic” genes PRKAG2, LAMP2, GLADCM: LMNA, SCN5A, TTN, RBM20, PLN, DSP, MYH7ARVC: DSC2, DSG2, DSP, JUP, PKP2, and TMEM43Predictive genetic testing of family members: detection of a clinically actionable pathogenic variant previously identified in a first-degree relative. Variant-specific genetic testing is recommended for family members and appropriate relatives following the identification of causative variant in an index case after clinical evaluation by a cardiologist PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011).(a) Is this a request for MBS funding? FORMCHECKBOX Yes FORMCHECKBOX No If yes, is the medical service(s) proposed to be covered under an existing MBS item number(s) or is a new MBS item(s) being sought altogether? FORMCHECKBOX Amendment to existing MBS item(s) FORMCHECKBOX New MBS item(s)If an amendment to an existing item(s) is being sought, please list the relevant MBS item number(s) that are to be amended to include the proposed medical service: If an amendment to an existing item(s) is being sought, what is the nature of the amendment(s)? FORMCHECKBOX An amendment to the way the service is clinically delivered under the existing item(s) FORMCHECKBOX An amendment to the patient population under the existing item(s) FORMCHECKBOX An amendment to the schedule fee of the existing item(s) FORMCHECKBOX An amendment to the time and complexity of an existing item(s) FORMCHECKBOX Access to an existing item(s) by a different health practitioner group FORMCHECKBOX Minor amendments to the item descriptor that does not affect how the service is delivered FORMCHECKBOX An amendment to an existing specific single consultation item FORMCHECKBOX An amendment to an existing global consultation item(s) FORMCHECKBOX Other (please describe below):If a new item(s) is being requested, what is the nature of the change to the MBS being sought? FORMCHECKBOX A new item which also seeks to allow access to the MBS for a specific health practitioner group FORMCHECKBOX A new item that is proposing a way of clinically delivering a service that is new to the MBS (in terms of new technology and / or population) FORMCHECKBOX A new item for a specific single consultation item FORMCHECKBOX A new item for a global consultation item(s)Is the proposed service seeking public funding other than the MBS? FORMCHECKBOX Yes FORMCHECKBOX NoIf yes, please advise:N/AWhat is the type of service: FORMCHECKBOX Therapeutic medical service FORMCHECKBOX Investigative medical service FORMCHECKBOX Single consultation medical service FORMCHECKBOX Global consultation medical service FORMCHECKBOX Allied health service FORMCHECKBOX Co-dependent technology FORMCHECKBOX Hybrid health technologyFor investigative services, advise the specific purpose of performing the service (which could be one or more of the following): FORMCHECKBOX To be used as a screening tool in asymptomatic populations FORMCHECKBOX Assists in establishing a diagnosis in symptomatic patients FORMCHECKBOX Provides information about prognosis FORMCHECKBOX Identifies a patient as suitable for therapy by predicting a variation in the effect of the therapy FORMCHECKBOX Monitors a patient over time to assess treatment response and guide subsequent treatment decisions FORMCHECKBOX A service that tests for heritable mutations in clinically affected individuals to make a genetic diagnosis and thus estimate their variation in (predisposition for) future risk of further disease and, when also appropriate, cascade testing of family members of those individuals who test positive for one or more relevant mutations, to make a genetic diagnosis and thus estimate each family member’s variation in (predisposition for) future risk of developing the clinical disease.Does your service rely on another medical product to achieve or to enhance its intended effect? FORMCHECKBOX Pharmaceutical / Biological FORMCHECKBOX Prosthesis or device FORMCHECKBOX No(a) If the proposed service has a pharmaceutical component to it, is it already covered under an existing Pharmaceutical Benefits Scheme (PBS) listing? FORMCHECKBOX Yes FORMCHECKBOX No If yes, please list the relevant PBS item code(s):N/AIf no, is an application (submission) in the process of being considered by the Pharmaceutical Benefits Advisory Committee (PBAC)? FORMCHECKBOX Yes (please provide PBAC submission item number below) FORMCHECKBOX NoN/AIf you are seeking both MBS and PBS listing, what is the trade name and generic name of the pharmaceutical?Trade name: Generic name: (a) If the proposed service is dependent on the use of a prosthesis, is it already included on the Prostheses List? FORMCHECKBOX Yes FORMCHECKBOX No If yes, please provide the following information (where relevant): Billing code(s): Trade name of prostheses: Clinical name of prostheses: Other device components delivered as part of the service: If no, is an application in the process of being considered by a Clinical Advisory Group or the Prostheses List Advisory Committee (PLAC)? FORMCHECKBOX Yes FORMCHECKBOX No Are there any other sponsor(s) and / or manufacturer(s) that have a similar prosthesis or device component in the Australian market place which this application is relevant to? FORMCHECKBOX Yes FORMCHECKBOX No If yes, please provide the name(s) of the sponsor(s) and / or manufacturer(s):N/APlease identify any single and / or multi-use consumables delivered as part of the service?Single use consumables: Laboratory consumables used for standard sequencing Multi-use consumables: PART 3 – INFORMATION ABOUT REGULATORY REQUIREMENTSThe National Association of Testing Authorities (NATA) and the Royal College of Pathologists Australasia (RCPA) oversee the regulation of genetic sequencing for clinical purposes. Laboratories require accreditation by a joint NATA/RCPA process to ISO 15189, and specifically accredited to provide genetic testing via massively parallel sequencing with full whole exome analysis studies. This accreditation process covers the technical aspects of the laboratory sequencing, analysis pipelines, curation (or interpretation) of results and production of the report to a clinical standard. This allows any accredited laboratory to provide equivalent genetic variant analysis services to a minimum standard. There are no requirements for use of specific manufacturers, reagents, equipment or analysis pipelines.(a) If the proposed medical service involves the use of a medical device, in-vitro diagnostic test, pharmaceutical product, radioactive tracer or any other type of therapeutic good, please provide the following details:Type of therapeutic good: In-vitro diagnostic testManufacturer’s name: N/ASponsor’s name: Not applicableIs the medical device classified by the TGA as either a Class III or Active Implantable Medical Device (AIMD) against the TGA regulatory scheme for devices? FORMCHECKBOX Class III FORMCHECKBOX AIMD FORMCHECKBOX N/A(a) Is the therapeutic good to be used in the service exempt from the regulatory requirements of the Therapeutic Goods Act 1989? FORMCHECKBOX Yes (If yes, please provide supporting documentation as an attachment to this application form) FORMCHECKBOX NoIf no, has it been listed or registered or included in the Australian Register of Therapeutic Goods (ARTG) by the Therapeutic Goods Administration (TGA)? FORMCHECKBOX Yes (if yes, please provide details below) FORMCHECKBOX NoARTG listing, registration or inclusion number: TGA approved indication(s), if applicable: TGA approved purpose(s), if applicable: If the therapeutic good has not been listed, registered or included in the ARTG, is the therapeutic good in the process of being considered for inclusion by the TGA? FORMCHECKBOX Yes (please provide details below) FORMCHECKBOX NoDate of submission to TGA: Estimated date by which TGA approval can be expected: TGA Application ID: TGA approved indication(s), if applicable: TGA approved purpose(s), if applicable: If the therapeutic good is not in the process of being considered for listing, registration or inclusion by the TGA, is an application to the TGA being prepared? FORMCHECKBOX Yes (please provide details below) FORMCHECKBOX NoEstimated date of submission to TGA: Proposed indication(s), if applicable: Proposed purpose(s), if applicable: PART 4 – SUMMARY OF EVIDENCEProvide an overview of all key journal articles or research published in the public domain related to the proposed service that is for your application (limiting these to the English language only). Please do not attach full text articles, this is just intended to be a summary.Type of study design*Title of journal article or research project (including any trial identifier or study lead if relevant)Short description of research (max 50 words)**Website link to journal article or research (if available)Date of publication***1.Clinical practice guidelinesWorld-wide2019 HRS Expert Consensus Statement on Evaluation, Risk Stratification, and Management of Arrhythmogenic Cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Towbin et al 2019)This expert consensus statement provides the clinician with guidance on evaluation and management of arrhythmogenic cardiomyopathy and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilised to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. practice guidelinesEuropeHRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011)This international consensus statement provides the state of genetic testing for the channelopathies and cardiomyopathies. It summarises the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of genetic testing for these potentially heritable cardiac conditions. practice guidelinesUSA2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HZXJzaDwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HZXJzaDwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE.DATA (Gersh et al 2011a)Although the Task Force was aware of the lack of high levels of evidence regarding HCM provided by clinical trials, it was believed that a guideline document based on expert consensus that outlines the most important diagnostic and management strategies would be helpful. practice guidelinesUSAGenetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IZXJzaGJlcmdlcjwvQXV0aG9yPjxZZWFyPjIwMTg8L1ll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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IZXJzaGJlcmdlcjwvQXV0aG9yPjxZZWFyPjIwMTg8L1ll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ADDIN EN.CITE.DATA (Hershberger et al 2018)Genetic testing is indicated for cardiomyopathy to assist in patient care and management of at-risk family members. A genetic evaluation of cardiomyopathy is indicated with a cardiomyopathy diagnosis, which includes genetic testing. Guidance is also provided for clinical approaches to secondary findings from cardiomyopathy genes. This is relevant as cardiomyopathy is the phenotype associated with 27% of the genes on the ACMG list for return of secondary findings. Recommendations herein are considered expert opinion per current ACMG policy as no systematic approach to literature review was conducted. analysisAustraliaA cost-effectiveness model of genetic testing and periodical clinical screening for the evaluation of families with dilated cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRjaHBvb2w8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFy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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRjaHBvb2w8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFy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ADDIN EN.CITE.DATA (Catchpool et al 2019)The incremental cost per additional QALY of cascade genetic testing prior to periodical clinical surveillance of first-degree relatives compared with periodical clinical surveillance alone was approximately $6,100. At established thresholds of cost-effectiveness, there is a 90% probability that cascade genetic testing is cost-effective. Sensitivity analyses, including the addition of second-degree relatives, did not alter this conclusion. As the DCM pathogenic variant detection rate rises and new evidence for personalized treatment of at-risk individuals becomes available, the cost-effectiveness of cascade testing will further increase. yieldThe NetherlandsToward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IZXJrZXJ0PC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48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 EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IZXJrZXJ0PC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48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 EN.CITE.DATA (Herkert et al 2018)Diagnostic yield in paediatric DCM of combining exome sequencing (ES)-based targeted analysis and genome-wide copy-number variation (CNV) analysis. We reached a genetic diagnosis in 15/31 (48.4%) families. ES yielded a diagnosis in 13 probands (13/15; 86.7%), with most variants being found in genes encoding structural cardiomyocyte components. Two large deletions were identified using SNP array. This diagnostic approach yields the highest increase at each subsequent step and reduces analytic effort, cost, the number of variants of unknown clinical significance, and the chance of incidental findings. value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYWRlbW9udC1Tb2xlcjwvQXV0aG9yPjxZZWFyPjIwMTc8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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYWRlbW9udC1Tb2xlcjwvQXV0aG9yPjxZZWFyPjIwMTc8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ADDIN EN.CITE.DATA (Mademont-Soler et al 2017)Unrelated patients (n=223) clinically diagnosed with HCM screened for MYBPC3, MYH7, TNNI3, TNNT2 and TPM1. First 84 patients underwent Sanger sequencing with remaining 303 using NGS panels. Each CNV identified by NGS was validated by MLPA or –qPCR. Family members of carriers of rare nonsynonymous variants, indels and/or CNVs were invited to undergo genetic analysis. 180 relatives were referred for genetic testing by Sanger sequencing or MLPA. seriesUSAResults of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity ADDIN EN.CITE <EndNote><Cite><Author>Alfares</Author><Year>2015</Year><RecNum>78</RecNum><DisplayText>(Alfares & Kelly 2015)</DisplayText><record><rec-number>78</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1544497616">78</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Alfares, A. A.</author><author>Kelly, M. A.</author></authors></contributors><auth-address>Laboratory for Molecular Medicine, Partners Healthcare Personalized Medicine, Boston, Massachusetts, USA.
Department of Pediatrics, Qassim University, Buraydah, Saudi Arabia.</auth-address><titles><title>Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity</title></titles><pages>880-8</pages><volume>17</volume><number>11</number><dates><year>2015</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1098-3600</isbn><accession-num>25611685</accession-num><urls><related-urls><url>;(Alfares & Kelly 2015)We r`eport genetic testing results for HCM in 2,912 unrelated individuals with nonsyndromic presentations from a broad referral population over 10 years. Genetic testing was performed by Sanger sequencing for 10 genes from 2004 to 2007, by HCM CardioChip for 11 genes from 2007 to 2011 and by NGS for 18, 46, or 51 genes from 2011 onward. The detection rate is ~32% among unselected probands, with inconclusive results in an additional 15%. An expanded gene panel encompassing more than 50 genes identified only a very small number of additional pathogenic variants beyond those identifiable in our original panels, which examined 11 genes. Familial genetic testing in at-risk family members eliminated the need for longitudinal cardiac evaluations in 691 individuals. Data indicate that genetic testing resulted in a minimum cost savings of about $0.7 million., clinical effectivenessThe NetherlandsOutcomes of Contemporary Family Screening in Hypertrophic Cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj52YW4gVmVsemVuPC9BdXRob3I+PFllYXI+MjAxODwvWWVh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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj52YW4gVmVsemVuPC9BdXRob3I+PFllYXI+MjAxODwvWWVh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ADDIN EN.CITE.DATA (van Velzen et al 2018)777 relatives of 209 probands underwent HCM screening. Genotype-positive relatives and relatives without genetic testing underwent repeated clinical evaluations. A pathogenic mutation was identified in 72% of probands. Genetic testing was performed in 620 (80%) relatives: 264 (43%) were genotype-positive and 356 (57%) were genotype-negative. At first screening, HCM was diagnosed in 98 (37%) genotype-positive relatives and 28 (17%) relatives without gene testing (p<0.001). During 9 years follow-up of relatives diagnosed with HCM, 8 (6%) underwent septal reduction therapy, 16 (16%) received primary prevention ICDs, and cardiac mortality was 0.3%/year. During 7 years follow-up of relatives without HCM, 29 (16%) developed HCM. Survival at 5/10 years was 99%/95% in genotype-positive relatives, 97%/94% in genotype-negative relatives (p=0.8), and 100%/100% in relatives without gene testing. HCM was identified in 30% of relatives at first screening, and 16% developed HCM during 7 years of repeated evaluation. GT led to a discharge from clinical follow-up in 46% of the study population. UKGenetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb3BlczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb3BlczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl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ADDIN EN.CITE.DATA (Lopes et al 2013)Unrelated patients (n=223) clinically diagnosed with HCM underwent MPS for 20 genes associated with HCM and DCM, 17 genes implicated in other inherited cardiomyopathies and arrhythmia syndromes, and a further four candidate genes. Sequencing results were compared to 1,287 control samples. All 50 variants were successfully validated by Sanger sequencing. Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SdWJhdHR1PC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SdWJhdHR1PC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48
UmVjTnVtPjc8L1JlY051bT48SURUZXh0PjI3NDgzMjYwPC9JRFRleHQ+PERpc3BsYXlUZXh0PihS
dWJhdHR1IGV0IGFsIDIwMTYpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjc8L3Jl
Yy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJmYWRzeDUyNXd2NWR0
NWVwcnd3eDBzcHN6dHd2czkyMHAwdzkiIHRpbWVzdGFtcD0iMTUxOTE3MzQxNyI+Nzwva2V5Pjwv
Zm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlw
ZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+UnViYXR0dSwgUy48L2F1dGhvcj48YXV0
aG9yPkJvenphbywgQy48L2F1dGhvcj48YXV0aG9yPlBlbm5hY2NoaW5pLCBFLjwvYXV0aG9yPjxh
dXRob3I+UGFnYW5ub25lLCBFLjwvYXV0aG9yPjxhdXRob3I+TXVzdW1lY2ksIEIuIE0uPC9hdXRo
b3I+PGF1dGhvcj5QaWFuZSwgTS48L2F1dGhvcj48YXV0aG9yPkdlcm1hbmksIEEuPC9hdXRob3I+
PGF1dGhvcj5TYXZpbywgQy48L2F1dGhvcj48YXV0aG9yPkZyYW5jaWEsIFAuPC9hdXRob3I+PGF1
dGhvcj5Wb2xwZSwgTS48L2F1dGhvcj48YXV0aG9yPkF1dG9yZSwgQy48L2F1dGhvcj48YXV0aG9y
PkNoZXNzYSwgTC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz
cz5EZXBhcnRtZW50IG9mIENsaW5pY2FsIGFuZCBNb2xlY3VsYXIgTWVkaWNpbmUsIFNjaG9vbCBv
ZiBNZWRpY2luZSBhbmQgUHN5Y2hvbG9neSwgVW5pdmVyc2l0eSBTYXBpZW56YSBvZiBSb21lLCAw
MDE4NSBSb21lLCBJdGFseS4gcnViYXR0dS5zcGVyYW56YUBuZXVyb21lZC5pdC4mI3hEO0RlcGFy
dG1lbnQgb2YgQW5naW9jYXJkaW9uZXVyb2xvZ3ksIElSQ0NTIE5ldXJvbWVkLCA4NjA3NyBQb3p6
aWxsaSwgSXRhbHkuIHJ1YmF0dHUuc3BlcmFuemFAbmV1cm9tZWQuaXQuJiN4RDtEZXBhcnRtZW50
IG9mIENsaW5pY2FsIGFuZCBNb2xlY3VsYXIgTWVkaWNpbmUsIFNjaG9vbCBvZiBNZWRpY2luZSBh
bmQgUHN5Y2hvbG9neSwgVW5pdmVyc2l0eSBTYXBpZW56YSBvZiBSb21lLCAwMDE4NSBSb21lLCBJ
dGFseS4gY3Jpc3RpbmEuYm96emFvQGxpYmVyby5pdC4mI3hEO0RlcGFydG1lbnQgb2YgQ2xpbmlj
YWwgYW5kIE1vbGVjdWxhciBNZWRpY2luZSwgU2Nob29sIG9mIE1lZGljaW5lIGFuZCBQc3ljaG9s
b2d5LCBVbml2ZXJzaXR5IFNhcGllbnphIG9mIFJvbWUsIDAwMTg1IFJvbWUsIEl0YWx5LiBhcmlh
bm5hZXJtZWxpbmRhQGhvdG1haWwuaXQuJiN4RDtEZXBhcnRtZW50IG9mIENsaW5pY2FsIGFuZCBN
b2xlY3VsYXIgTWVkaWNpbmUsIFNjaG9vbCBvZiBNZWRpY2luZSBhbmQgUHN5Y2hvbG9neSwgVW5p
dmVyc2l0eSBTYXBpZW56YSBvZiBSb21lLCAwMDE4NSBSb21lLCBJdGFseS4gZXBhZ2Fubm9uZUBn
bWFpbC5jb20uJiN4RDtEZXBhcnRtZW50IG9mIENsaW5pY2FsIGFuZCBNb2xlY3VsYXIgTWVkaWNp
bmUsIFNjaG9vbCBvZiBNZWRpY2luZSBhbmQgUHN5Y2hvbG9neSwgVW5pdmVyc2l0eSBTYXBpZW56
YSBvZiBSb21lLCAwMDE4NSBSb21lLCBJdGFseS4gYmVhdHJpY2UubXVzdW1lY2lAdW5pcm9tYTEu
aXQuJiN4RDtEZXBhcnRtZW50IG9mIENsaW5pY2FsIGFuZCBNb2xlY3VsYXIgTWVkaWNpbmUsIFNj
aG9vbCBvZiBNZWRpY2luZSBhbmQgUHN5Y2hvbG9neSwgVW5pdmVyc2l0eSBTYXBpZW56YSBvZiBS
b21lLCAwMDE4NSBSb21lLCBJdGFseS4gbWFyaWEucGlhbmVAdW5pcm9tYTEuaXQuJiN4RDtEZXBh
cnRtZW50IG9mIENsaW5pY2FsIGFuZCBNb2xlY3VsYXIgTWVkaWNpbmUsIFNjaG9vbCBvZiBNZWRp
Y2luZSBhbmQgUHN5Y2hvbG9neSwgVW5pdmVyc2l0eSBTYXBpZW56YSBvZiBSb21lLCAwMDE4NSBS
b21lLCBJdGFseS4gYWxkby5nZXJtYW5pQHVuaXJvbWExLml0LiYjeEQ7RGVwYXJ0bWVudCBvZiBD
bGluaWNhbCBhbmQgTW9sZWN1bGFyIE1lZGljaW5lLCBTY2hvb2wgb2YgTWVkaWNpbmUgYW5kIFBz
eWNob2xvZ3ksIFVuaXZlcnNpdHkgU2FwaWVuemEgb2YgUm9tZSwgMDAxODUgUm9tZSwgSXRhbHku
IGNhbWlsbGEuc2F2aW9Ab3NwZWRhbGVzYW50YW5kcmVhLml0LiYjeEQ7RGVwYXJ0bWVudCBvZiBD
bGluaWNhbCBhbmQgTW9sZWN1bGFyIE1lZGljaW5lLCBTY2hvb2wgb2YgTWVkaWNpbmUgYW5kIFBz
eWNob2xvZ3ksIFVuaXZlcnNpdHkgU2FwaWVuemEgb2YgUm9tZSwgMDAxODUgUm9tZSwgSXRhbHku
IHBpZXRyby5mcmFuY2lhQHVuaXJvbWExLml0LiYjeEQ7RGVwYXJ0bWVudCBvZiBDbGluaWNhbCBh
bmQgTW9sZWN1bGFyIE1lZGljaW5lLCBTY2hvb2wgb2YgTWVkaWNpbmUgYW5kIFBzeWNob2xvZ3ks
IFVuaXZlcnNpdHkgU2FwaWVuemEgb2YgUm9tZSwgMDAxODUgUm9tZSwgSXRhbHkuIG1hc3NpbW8u
dm9scGVAdW5pcm9tYTEuaXQuJiN4RDtEZXBhcnRtZW50IG9mIEFuZ2lvY2FyZGlvbmV1cm9sb2d5
LCBJUkNDUyBOZXVyb21lZCwgODYwNzcgUG96emlsbGksIEl0YWx5LiBtYXNzaW1vLnZvbHBlQHVu
aXJvbWExLml0LiYjeEQ7RGVwYXJ0bWVudCBvZiBDbGluaWNhbCBhbmQgTW9sZWN1bGFyIE1lZGlj
aW5lLCBTY2hvb2wgb2YgTWVkaWNpbmUgYW5kIFBzeWNob2xvZ3ksIFVuaXZlcnNpdHkgU2FwaWVu
emEgb2YgUm9tZSwgMDAxODUgUm9tZSwgSXRhbHkuIGNhbWlsbG8uYXV0b3JlQHVuaXJvbWExLml0
LiYjeEQ7RGVwYXJ0bWVudCBvZiBDbGluaWNhbCBhbmQgTW9sZWN1bGFyIE1lZGljaW5lLCBTY2hv
b2wgb2YgTWVkaWNpbmUgYW5kIFBzeWNob2xvZ3ksIFVuaXZlcnNpdHkgU2FwaWVuemEgb2YgUm9t
ZSwgMDAxODUgUm9tZSwgSXRhbHkuIGx1Y2lhbmEuY2hlc3NhQHVuaXJvbWExLml0LjwvYXV0aC1h
ZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkEgTmV4dC1HZW5lcmF0aW9uIFNlcXVlbmNpbmcgQXBwcm9h
Y2ggdG8gSWRlbnRpZnkgR2VuZSBNdXRhdGlvbnMgaW4gRWFybHktIGFuZCBMYXRlLU9uc2V0IEh5
cGVydHJvcGhpYyBDYXJkaW9teW9wYXRoeSBQYXRpZW50cyBvZiBhbiBJdGFsaWFuIENvaG9ydDwv
dGl0bGU+PHNlY29uZGFyeS10aXRsZT5JbnQgSiBNb2wgU2NpPC9zZWNvbmRhcnktdGl0bGU+PC90
aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SW50IEogTW9sIFNjaTwvZnVsbC10aXRsZT48
L3BlcmlvZGljYWw+PHZvbHVtZT4xNzwvdm9sdW1lPjxudW1iZXI+ODwvbnVtYmVyPjxlZGl0aW9u
PjIwMTYvMDgvMDM8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkdWx0PC9rZXl3b3JkPjxr
ZXl3b3JkPkFnZSBvZiBPbnNldDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3
b3JkPkJpb21hcmtlcnMvIGFuYWx5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGh5
LCBIeXBlcnRyb3BoaWMvIGRpYWdub3Npcy9lcGlkZW1pb2xvZ3kvIGdlbmV0aWNzPC9rZXl3b3Jk
PjxrZXl3b3JkPkNvaG9ydCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPkZlbWFsZTwva2V5d29y
ZD48a2V5d29yZD5HZW5ldGljIFRlc3Rpbmc8L2tleXdvcmQ+PGtleXdvcmQ+SGlnaC1UaHJvdWdo
cHV0IE51Y2xlb3RpZGUgU2VxdWVuY2luZy8gbWV0aG9kczwva2V5d29yZD48a2V5d29yZD5IdW1h
bnM8L2tleXdvcmQ+PGtleXdvcmQ+SXRhbHkvZXBpZGVtaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3Jk
Pk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+TXV0
YXRpb24vIGdlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPmdlbmUgdmFyaWFudHM8L2tleXdvcmQ+
PGtleXdvcmQ+Z2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+aHlwZXJ0cm9waGljIGNhcmRpb215
b3BhdGh5PC9rZXl3b3JkPjxrZXl3b3JkPm5leHQtZ2VuZXJhdGlvbiBzZXF1ZW5jaW5nPC9rZXl3
b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTY8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5K
dWwgMzA8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xNDIyLTAwNjcgKEVsZWN0cm9u
aWMpJiN4RDsxNDIyLTAwNjcgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjI3NDgzMjYw
PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm1kcGku
Y29tLzE0MjItMDA2Ny8xNy84LzEyMzkvcGRmPC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxj
dXN0b20yPlBNQzUwMDA2Mzc8L2N1c3RvbTI+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjMz
OTAvaWptczE3MDgxMjM5PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNl
LXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xh
bmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+
ADDIN EN.CITE.DATA (Rubattu et al 2016)Patients with a clinical diagnosis of HCM:Group 1 = early-onset mean age at diagnosis of 18.6 ± 8.5 years (n=35)Group 2 = late-onset mean age at diagnosis of 70.4 ± 4.8 years (n=35)17 HCM phenotype causative genes sequenced on Personal Genome Machine (PGM) IonTorrent sequencer. The identified variants were validated by Sanger sequencing. 46-gene and clinical exome sequencing for mutations causing cardiomyopathies PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkbXVsbGVyPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkbXVsbGVyPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE.DATA (Waldmuller et al 2015)Consecutive patients clinically diagnosed with HCM (n =4), DCM (n = 7) or LVNC (n = 2) underwent NGS with either Illumina’s TruSight Cardiomyopathy Enrichment Panel (tsCM, 46 genes) in conjunction with the MiSeq or Illumina’s TruSight ONE Enrichment Panel (tsONE, 4813 genes). Relevant DNA sequence variants were confirmed by Sanger sequencing. sequencing as a first-line genetic test in familial dilated cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaW5vY2hlPC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaW5vY2hlPC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48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ADDIN EN.CITE.DATA (Minoche et al 2018)42 patients with familial DCM underwent multigene panel sequencing and genome sequencing, and detection rates of rare single-nucleotide variants and small insertions/deletions in panel genes were compared. Loss-of function variants in 406 cardiac-enriched genes were evaluated, and an assessment of structural variation was performed. studyItalyTargeted next-generation sequencing detects novel gene ± phenotype associations and expands the mutational spectrum in cardiomyopathies PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3JsZW88L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3JsZW88L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Forleo et al 2017)Unrelated patients (n=38) with a clinical diagnosis of DCM (n=16), HCM (n=14) and ARVC (n=8) underwent targeted NGS screening of 115 genes using the Illumina MiSeq platform analysisAustraliaA cost-effectiveness model of genetic testing for the evaluation of families with hypertrophic cardiomyopathy ADDIN EN.CITE <EndNote><Cite><Author>Ingles</Author><Year>2012</Year><RecNum>54</RecNum><DisplayText>(Ingles et al 2012)</DisplayText><record><rec-number>54</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529988228">54</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ingles, J.</author><author>McGaughran, J.</author><author>Scuffham, P. A.</author><author>Atherton, J.</author><author>Semsarian, C.</author></authors></contributors><auth-address>Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia.</auth-address><titles><title>A cost-effectiveness model of genetic testing for the evaluation of families with hypertrophic cardiomyopathy</title><secondary-title>Heart</secondary-title></titles><periodical><full-title>Heart</full-title></periodical><pages>625-30</pages><volume>98</volume><number>8</number><edition>2011/12/01</edition><keywords><keyword>Adolescent</keyword><keyword>Australia/epidemiology</keyword><keyword>Cardiomyopathy, Hypertrophic, Familial/ diagnosis/economics/genetics/mortality</keyword><keyword>Cost-Benefit Analysis</keyword><keyword>Genetic Carrier Screening/methods</keyword><keyword>Genetic Testing/ economics/methods</keyword><keyword>Health Care Costs/statistics & numerical data</keyword><keyword>Humans</keyword><keyword>Markov Chains</keyword><keyword>Models, Econometric</keyword><keyword>Mutation</keyword><keyword>Quality-Adjusted Life Years</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2012</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1468-201X (Electronic)
1355-6037 (Linking)</isbn><accession-num>22128210</accession-num><urls><related-urls><url>;(Ingles et al 2012)The addition of genetic testing to the management of HCM families is cost-effective in comparison with conventional clinical screening. The ICER was $A785 per QALY, and $A12,720 per additional life-year gained. As the cost of proband genetic testing decreased, the ICER decreased and was cost saving when the cost fell below $A248. The mutation identification rate was also important in reducing the overall ICER. yieldAustraliaWhole Genome Sequencing Improves Outcomes of Genetic Testing in Patients With Hypertrophic Cardiomyopathy ADDIN EN.CITE <EndNote><Cite><Author>Bagnall</Author><Year>2018</Year><RecNum>64</RecNum><IDText>30025578</IDText><DisplayText>(Bagnall et al 2018)</DisplayText><record><rec-number>64</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1536113971">64</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bagnall, R. D.</author><author>Ingles, J.</author><author>Dinger, M. E.</author><author>Cowley, M. J.</author><author>Ross, S. B.</author><author>Minoche, A. E.</author><author>Lal, S.</author><author>Turner, C.</author><author>Colley, A.</author><author>Rajagopalan, S.</author><author>Berman, Y.</author><author>Ronan, A.</author><author>Fatkin, D.</author><author>Semsarian, C.</author></authors></contributors><auth-address>
</auth-address><titles><title>Whole Genome Sequencing Improves Outcomes of Genetic Testing in Patients With Hypertrophic Cardiomyopathy</title><secondary-title>J Am Coll Cardiol</secondary-title><alt-title>Journal of the American College of Cardiology</alt-title></titles><periodical><full-title>J Am Coll Cardiol</full-title></periodical><pages>419-429</pages><volume>72</volume><number>4</number><edition>2018/07/22</edition><keywords><keyword>deep intronic variant</keyword><keyword>hypertrophic cardiomyopathy</keyword><keyword>whole genome sequencing</keyword></keywords><dates><year>2018</year><pub-dates><date>Jul 24</date></pub-dates></dates><isbn>0735-1097</isbn><accession-num>30025578</accession-num><urls></urls><electronic-resource-num>10.1016/j.jacc.2018.04.078</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Bagnall et al 2018)WGS performed on 58 unrelated patients with HCM, 14 affected family members, and 2 unaffected parents of a severely affected proband. A pathogenic or likely pathogenic variant was identified in 9 of 46 families (20%) for which prior genetic testing was inconclusive. Three families had variants in genes not included in prior genetic testing. One family had a pathogenic variant that was filtered out with prior exome sequencing. Five families had pathogenic variants in noncoding regions, including 4 with deep intronic variants that activate novel splicing, and 1 mitochondrial genome variant. As a first-line genetic test, WGS identified a pathogenic variant in 5 of 12 families (42%) that had never received prior genetic testing. case-control studyUSA, AustraliaA gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy ADDIN EN.CITE <EndNote><Cite><Author>Horvat</Author><Year>2019</Year><RecNum>95</RecNum><DisplayText>(Horvat et al 2019)</DisplayText><record><rec-number>95</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1549333809">95</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Horvat, Claire</author><author>Johnson, Renee</author><author>Lam, Lien</author><author>Munro, Jacob</author><author>Mazzarotto, Francesco</author><author>Roberts, Angharad M.</author><author>Herman, Daniel S.</author><author>Parfenov, Michael</author><author>Haghighi, Alireza</author><author>McDonough, Barbara</author><author>DePalma, Steven R.</author><author>Keogh, Anne M.</author><author>Macdonald, Peter S.</author><author>Hayward, Christopher S.</author><author>Roberts, Amy</author><author>Barton, Paul J. R.</author><author>Felkin, Leanne E.</author><author>Giannoulatou, Eleni</author><author>Cook, Stuart A.</author><author>Seidman, J. G.</author><author>Seidman, Christine E.</author><author>Fatkin, Diane</author></authors></contributors><titles><title>A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy</title><secondary-title>Genetics in Medicine</secondary-title></titles><periodical><full-title>Genetics in Medicine</full-title></periodical><pages>133-143</pages><volume>21</volume><number>1</number><dates><year>2019</year><pub-dates><date>2019/01/01</date></pub-dates></dates><isbn>1530-0366</isbn><urls><related-urls><url>;(Horvat et al 2019)Cardiomyopathy gene panel testing was performed in 532 DCM patients and 527 healthy control subjects. Rare variants in 41 genes were stratified using variant-level and gene-level characteristics. Variants that met these criteria were found in 407 (77%) DCM cases and in 348 (66%) control subjects (P?=?0.0002), with the number of rare variants per person ranging from 0 to 13 (mean 1.63) in DCM cases and from 0 to 8 (mean 1.24) in controls (P?<?0.0001). yieldPortugalMolecular characterization of Portuguese patients with dilated cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Tb3VzYTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl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==
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Tb3VzYTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl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==
ADDIN EN.CITE.DATA (Sousa et al 2019)A multicentre study of 107 unrelated patients. Variants in 15 genes were screened using PCR with direct sequencing (NGS with at least 30-fold coverage combined with Sanger sequencing). 31 rare variants in 8 genes (mainly in MYBPC3, TNNT2 and LMNA) were identified, in 28 patients (26%). Only 4 variants had been previously described in association with DCM, 11 with HCM, and 9 variants were novel. yieldSpainClinical and Genetic Diagnosis of Non-ischemic Sudden Cardiac Death PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KaW1lbmV6LUphaW1lejwvQXV0aG9yPjxZZWFyPjIwMTc8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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KaW1lbmV6LUphaW1lejwvQXV0aG9yPjxZZWFyPjIwMTc8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ADDIN EN.CITE.DATA (Jimenez-Jaimez et al 2017)56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with ECG, cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the post-mortem findings, familial evaluation, and molecular autopsy with NGS.A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and non-survivors (P=.53). Cardiac channelopathies were more prevalent among survivors than non-survivors (66.6% vs 40%, P=.03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and non-survivors (P=.21). yieldDenmarkDiagnostic Yield, Interpretation, and Clinical Utility of Mutation Screening of Sarcomere Encoding Genes in Danish Hypertrophic Cardiomyopathy Patients and Relatives PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbmRlcnNlbjwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbmRlcnNlbjwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+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ADDIN EN.CITE.DATA (Andersen et al 2009)Family screening combining clinical evaluation and screening for sarcomere gene mutations in a cohort of 90 Danish HCM patients and their close relatives (n= 451). Index patients were screened for mutations in all coding regions of 10 sarcomere genes and five exons of TTN. Relatives were screened for minor or major diagnostic criteria for HCM. The genetic diagnostic yield was almost 2x in familial HCM (53%) vs. HCM of sporadic or unclear inheritance (19%). The yield was highest in families with an additional history of HCM-related clinical events. In relatives, 29.9% of mutation carriers did not fulfil any clinical diagnostic criterion, and in 37.5% of relatives without a mutation, one or more criteria was fulfilled. A total of 60% of family members had no mutation and follow-up ceased. next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DZWNjb25pPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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==
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DZWNjb25pPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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==
ADDIN EN.CITE.DATA (Cecconi et al 2016)Unrelated patients (n=92) with a clinical diagnosis of HCM underwent sequencing using NGS: Ion AmpliSeq? Custom Panel for the mutational screening of 19 genes, compared to Sanger sequencing. in English, body in Portuguese Clinical and genetic diagnosis of familial hypertrophic cardiomyopathy: Results in pediatric cardiology PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXJkb3NvPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXJkb3NvPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48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ADDIN EN.CITE.DATA (Cardoso et al 2017)Outcome of clinical screening and genetic testing of child probands and relatives (<18 years of age) from families with HCM and assessed the age-related penetrance of HCM during the follow-up. 20 patients from 10 families consisting of three probands and 17 first-degree relatives. 14 child relatives were mutation carriers (70%), 7 (50%) of the 14 mutation carriers were diagnosed with HCM at initial assessment. At-risk child relatives were defined as those with a positive mutation but negative phenotype at enrolment. At 3.5±0.8 years follow-up, 2 of the phenotype-negative mutation carriers developed HCM at 10 and 15 years of age (28% penetrance rate), underlining the need for long-term monitoring of mutation carriers. case-control studyRussiaTargeted next-generation sequencing (NGS) of nine candidate genes with custom AmpliSeq in patients and a cardiomyopathy risk group PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HbG90b3Y8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HbG90b3Y8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
ZWNOdW0+MTA1PC9SZWNOdW0+PElEVGV4dD4yNTg5MjY3MzwvSURUZXh0PjxEaXNwbGF5VGV4dD4o
R2xvdG92IGV0IGFsIDIwMTUpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwNTwv
cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImZhZHN4NTI1d3Y1
ZHQ1ZXByd3d4MHNwc3p0d3ZzOTIwcDB3OSIgdGltZXN0YW1wPSIxNTYyMTI1MTUxIj4xMDU8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkdsb3RvdiwgQS4gUy48L2F1dGhv
cj48YXV0aG9yPkthemFrb3YsIFMuIFYuPC9hdXRob3I+PGF1dGhvcj5aaHVrb3ZhLCBFLiBBLjwv
YXV0aG9yPjxhdXRob3I+QWxleGFuZHJvdiwgQS4gVi48L2F1dGhvcj48YXV0aG9yPkdsb3Rvdiwg
Ty4gUy48L2F1dGhvcj48YXV0aG9yPlBha2luLCBWLiBTLjwvYXV0aG9yPjxhdXRob3I+RGFuaWxv
dmEsIE0uIE0uPC9hdXRob3I+PGF1dGhvcj5Qb2xpYWtvdmEsIEkuIFYuPC9hdXRob3I+PGF1dGhv
cj5OaXlhem92YSwgUy4gUy48L2F1dGhvcj48YXV0aG9yPkNoYWtvdmEsIE4uIE4uPC9hdXRob3I+
PGF1dGhvcj5Lb21pc3Nhcm92YSwgUy4gTS48L2F1dGhvcj48YXV0aG9yPkt1cm5pa292YSwgRS4g
QS48L2F1dGhvcj48YXV0aG9yPlNhcmFuYSwgQS4gTS48L2F1dGhvcj48YXV0aG9yPlNoZXJiYWss
IFMuIEcuPC9hdXRob3I+PGF1dGhvcj5TZXJndXNoaWNoZXYsIEEuIEEuPC9hdXRob3I+PGF1dGhv
cj5TaGFseXRvLCBBLiBBLjwvYXV0aG9yPjxhdXRob3I+QmFyYW5vdiwgVi4gUy48L2F1dGhvcj48
L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9mIEdlbmV0
aWNzIGFuZCBCaW90ZWNobm9sb2d5LCBTYWludCBQZXRlcnNidXJnIFN0YXRlIFVuaXZlcnNpdHks
IFVuaXZlcnNpdGV0c2theWEgbmFiLiwgNy05LCBTdC4gUGV0ZXJzYnVyZyAxOTkwMzQsIFJ1c3Np
YTsgTGFib3JhdG9yeSBvZiBQcmVuYXRhbCBEaWFnbm9zdGljcyBvZiBIZXJlZGl0YXJ5IERpc2Vh
c2VzLCBGZWRlcmFsIFN0YXRlIEJ1ZGdldCBTY2llbnRpZmljIEluc3RpdHV0aW9uICZxdW90O1Ro
ZSBSZXNlYXJjaCBJbnN0aXR1dGUgb2YgT2JzdGV0cmljcywgR3luZWNvbG9neSBhbmQgUmVwcm9k
dWN0b2xvZ3kgbmFtZWQgYWZ0ZXIgRC5PLk90dCZxdW90OywgTWVuZGVsZXlldnNrYXlhIGxpbi4s
IDMsIFN0LiBQZXRlcnNidXJnIDE5OTAzNCwgUnVzc2lhLiBFbGVjdHJvbmljIGFkZHJlc3M6IGFu
Z2xvdG92QG1haWwucnUuJiN4RDtDb21wdXRlciBUZWNobm9sb2dpZXMgTGFib3JhdG9yeSwgSVRN
TyBVbml2ZXJzaXR5LCBLcm9udmVya3NreSBwci4sIDQ5LCBTdC4gUGV0ZXJzYnVyZyAxOTcxMDEs
IFJ1c3NpYS4mI3hEO0xhYm9yYXRvcnkgb2YgUHJlbmF0YWwgRGlhZ25vc3RpY3Mgb2YgSGVyZWRp
dGFyeSBEaXNlYXNlcywgRmVkZXJhbCBTdGF0ZSBCdWRnZXQgU2NpZW50aWZpYyBJbnN0aXR1dGlv
biAmcXVvdDtUaGUgUmVzZWFyY2ggSW5zdGl0dXRlIG9mIE9ic3RldHJpY3MsIEd5bmVjb2xvZ3kg
YW5kIFJlcHJvZHVjdG9sb2d5IG5hbWVkIGFmdGVyIEQuTy5PdHQmcXVvdDssIE1lbmRlbGV5ZXZz
a2F5YSBsaW4uLCAzLCBTdC4gUGV0ZXJzYnVyZyAxOTkwMzQsIFJ1c3NpYS4mI3hEO0RlcGFydG1l
bnQgb2YgR2VuZXRpY3MgYW5kIEJpb3RlY2hub2xvZ3ksIFNhaW50IFBldGVyc2J1cmcgU3RhdGUg
VW5pdmVyc2l0eSwgVW5pdmVyc2l0ZXRza2F5YSBuYWIuLCA3LTksIFN0LiBQZXRlcnNidXJnIDE5
OTAzNCwgUnVzc2lhOyBMYWJvcmF0b3J5IG9mIFByZW5hdGFsIERpYWdub3N0aWNzIG9mIEhlcmVk
aXRhcnkgRGlzZWFzZXMsIEZlZGVyYWwgU3RhdGUgQnVkZ2V0IFNjaWVudGlmaWMgSW5zdGl0dXRp
b24gJnF1b3Q7VGhlIFJlc2VhcmNoIEluc3RpdHV0ZSBvZiBPYnN0ZXRyaWNzLCBHeW5lY29sb2d5
IGFuZCBSZXByb2R1Y3RvbG9neSBuYW1lZCBhZnRlciBELk8uT3R0JnF1b3Q7LCBNZW5kZWxleWV2
c2theWEgbGluLiwgMywgU3QuIFBldGVyc2J1cmcgMTk5MDM0LCBSdXNzaWEuJiN4RDtMYWJvcmF0
b3J5IG9mIE1vZGVsbGluZyBvZiBHZW5ldGljIFByb2Nlc3NlcywgSW5zdGl0dXRlIG9mIEdlbmV0
aWNzIGFuZCBDeXRvbG9neSwgTmF0aW9uYWwgQWNhZGVteSBvZiBTY2llbmNlcywgQWthZGVtaWNo
ZXNrYXlhIHN0ci4sIDI3LCBNaW5zayAyMjAwNzIsIEJlbGFydXMuJiN4RDtTY2llbnRpZmljIGFu
ZCBQcmFjdGljYWwgY2VudGVyIG9mIENhcmRpb2xvZ3ksIFJvenkgTHV4ZW1idXJnIHN0ci4sIDEx
MCwgTWluc2sgMjIwMDM2LCBCZWxhcnVzLiYjeEQ7RGVwYXJ0bWVudCBvZiBGYWN1bHR5IFRoZXJh
cHkgb24gQmVoYWxmIG9mIFByb2YuIFZBIFdhbGRtYW4sIFNhaW50IFBldGVyc2J1cmcgU3RhdGUg
UGVkaWF0cmljIE1lZGljYWwgVW5pdmVyc2l0eSwgTGl0aHVhbmlhbiBzdHIuLCAyLCBTdC4gUGV0
ZXJzYnVyZyAxOTQxMDAsIFJ1c3NpYS4mI3hEO0NpdHkgSG9zcGl0YWwgTm8uIDQwLCBCb3Jpc292
IHN0ci4sIDksIFNlc3Ryb3JldHNrLCBTdC4gUGV0ZXJzYnVyZyAxOTc3MDYsIFJ1c3NpYS48L2F1
dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5UYXJnZXRlZCBuZXh0LWdlbmVyYXRpb24gc2VxdWVu
Y2luZyAoTkdTKSBvZiBuaW5lIGNhbmRpZGF0ZSBnZW5lcyB3aXRoIGN1c3RvbSBBbXBsaVNlcSBp
biBwYXRpZW50cyBhbmQgYSBjYXJkaW9teW9wYXRoeSByaXNrIGdyb3VwPC90aXRsZT48c2Vjb25k
YXJ5LXRpdGxlPkNsaW4gQ2hpbSBBY3RhPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlv
ZGljYWw+PGZ1bGwtdGl0bGU+Q2xpbiBDaGltIEFjdGE8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2Fs
PjxwYWdlcz4xMzItNDA8L3BhZ2VzPjx2b2x1bWU+NDQ2PC92b2x1bWU+PGVkaXRpb24+MjAxNS8w
NC8yMjwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QWRvbGVzY2VudDwva2V5d29yZD48a2V5
d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkNhbHNl
cXVlc3RyaW4vYmxvb2QvIGdlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpYWMgTXlvc2lu
cy9ibG9vZC8gZ2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlvbXlvcGF0aHksIEh5cGVy
dHJvcGhpYy9ibG9vZC8gZGlhZ25vc2lzL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNhcnJp
ZXIgUHJvdGVpbnMvYmxvb2QvIGdlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNoZXN0IFBhaW4v
Ymxvb2QvIGRpYWdub3Npcy9nZW5ldGljczwva2V5d29yZD48a2V5d29yZD5Db2hvcnQgU3R1ZGll
czwva2V5d29yZD48a2V5d29yZD5FYXJseSBEaWFnbm9zaXM8L2tleXdvcmQ+PGtleXdvcmQ+RmVt
YWxlPC9rZXl3b3JkPjxrZXl3b3JkPkdlbmUgRXhwcmVzc2lvbjwva2V5d29yZD48a2V5d29yZD5H
ZW5ldGljIE1hcmtlcnM8L2tleXdvcmQ+PGtleXdvcmQ+SGlnaC1UaHJvdWdocHV0IE51Y2xlb3Rp
ZGUgU2VxdWVuY2luZzwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+
TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29yZD48a2V5d29yZD5Nb2Rl
bHMsIEdlbmV0aWM8L2tleXdvcmQ+PGtleXdvcmQ+TXlvc2luIEhlYXZ5IENoYWlucy9ibG9vZC8g
Z2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+T3BlbiBSZWFkaW5nIEZyYW1lczwva2V5d29yZD48
a2V5d29yZD5SaXNrPC9rZXl3b3JkPjxrZXl3b3JkPlNvZnR3YXJlPC9rZXl3b3JkPjxrZXl3b3Jk
PlRyb3BvbmluIFQvYmxvb2QvIGdlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3Bh
dGh5PC9rZXl3b3JkPjxrZXl3b3JkPkdyb3VwIHJpc2s8L2tleXdvcmQ+PGtleXdvcmQ+TXV0YXRp
b25zPC9rZXl3b3JkPjxrZXl3b3JkPk5nczwva2V5d29yZD48a2V5d29yZD5TbnA8L2tleXdvcmQ+
PGtleXdvcmQ+U3R1ZGVudHM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxNTwv
eWVhcj48cHViLWRhdGVzPjxkYXRlPkp1biAxNTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxp
c2JuPjE4NzMtMzQ5MiAoRWxlY3Ryb25pYykmI3hEOzAwMDktODk4MSAoTGlua2luZyk8L2lzYm4+
PGFjY2Vzc2lvbi1udW0+MjU4OTI2NzM8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVj
dHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouY2NhLjIwMTUuMDQuMDE0PC9lbGVjdHJvbmlj
LXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFi
YXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0Vu
ZE5vdGU+
ADDIN EN.CITE.DATA (Glotov et al 2015)A genetic analysis of student cohorts (with and without cardiomyopathy risk in their medical histories) and patients with cardiomyopathies was performed using a custom AmpliSeq panel for NGS sequencing of the coding sequences of ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNI3, TNNT2, TPM1, and CASQ2. of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZW5zZW48L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS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 EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZW5zZW48L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS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 EN.CITE.DATA (Jensen et al 2013)90 probands and 361 relatives were included in a family screening program for HCM. 12 child relatives were carriers, and 26 had unknown genetic status. 28 non-carriers served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2-18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Forty-two percent of the child relatives were non-carriers, and repeat clinical follow-up could be safely limited to the remaining children = Multiplex ligation dependent probe amplification, qPCR = quantitative polymerase chain reaction (PCR), HCM = hypertrophic cardiomyopathy, DCM = dilated cardiomyopathy, ARVC = arrhythmogenic right ventricular cardiomyopathy, NGS = next generation sequencing, WGS = whole genome sequencing, CNV = copy number variant, WGS = Whole genome sequencing* Categorise study design, for example meta-analysis, randomised trials, non-randomised trial or observational study, study of diagnostic accuracy, etc. **Provide high level information including population numbers and whether patients are being recruited or in post-recruitment, including providing the trial registration number to allow for tracking purposes.*** If the publication is a follow-up to an initial publication, please advise.Identify yet to be published research that may have results available in the near future that could be relevant in the consideration of your application by MSAC (limiting these to the English language only). Please do not attach full text articles, this is just intended to be a summary.Type of study design*Title of research (including any trial identifier if relevant)Short description of research (max 50 words)**Website link to research (if available)Date***1.* Categorise study design, for example meta-analysis, randomised trials, non-randomised trial or observational study, study of diagnostic accuracy, etc. **Provide high level information including population numbers and whether patients are being recruited or in post-recruitment.***Date of when results will be made available (to the best of your knowledge).PART 5 – CLINICAL ENDORSEMENT AND CONSUMER INFORMATIONList all appropriate professional bodies / organisations representing the group(s) of health professionals who provide the service (please attach a statement of clinical relevance from each group nominated):Royal College of Pathologists of AustralasiaList any professional bodies / organisations that may be impacted by this medical service (i.e. those who provide the comparator service):Other medical professionals may request the medical service and would perform evaluation of patients prior, and subsequent to the test. Some patients may require, or become exempt from, longitudinal evaluation after the test. Organisations impacted by this medical service would include Fellows of Royal Australasian College of Physicians, the Royal Australasian College of General Practitioners and the Cardiac Society of Australia & New Zealand.List the relevant consumer organisations relevant to the proposed medical service (please attach a letter of support for each consumer organisation nominated):Cardiomyopathy Association of Australia LtdList the relevant sponsor(s) and / or manufacturer(s) who produce similar products relevant to the proposed medical service:N/ANominate two experts who could be approached about the proposed medical service and the current clinical management of the service(s):Name of expert 1: REDACTEDTelephone number(s): REDACTEDEmail address: REDACTEDJustification of expertise: REDACTEDName of expert 2: REDACTEDTelephone number(s): REDACTEDEmail address: REDACTEDJustification of expertise: REDACTED.Please note that the Department may also consult with other referrers, proceduralists and disease specialists to obtain their insight.PART 6 – POPULATION (AND PRIOR TESTS), INTERVENTION, COMPARATOR, OUTCOME (PICO)PART 6a – INFORMATION ABOUT THE PROPOSED POPULATIONDefine the medical condition, including providing information on the natural history of the condition and a high-level summary of associated burden of disease in terms of both morbidity and mortality:Cardiomyopathies comprise a small group of related but clinically distinct primary diseases of the heart muscle and are one of the major causes of sudden cardiac death (SCD) and/or progressive heart failure (HF) ADDIN EN.CITE <EndNote><Cite><Author>Szabadosova</Author><Year>2018</Year><RecNum>4</RecNum><IDText>28594148</IDText><DisplayText>(Szabadosova et al 2018)</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1519173417">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Szabadosova, V.</author><author>Boronova, I.</author><author>Ferenc, P.</author><author>Tothova, I.</author><author>Bernasovska, J.</author><author>Zigova, M.</author><author>Kmec, J.</author><author>Bernasovsky, I.</author></authors></contributors><auth-address>Department of Biology, Faculty of Humanities and Natural Sciences, University of Presov, Presov, Slovakia.
Cardiocentre, Faculty Hospital of J.A. Reiman, Presov, Slovakia.
Center of Languages and Cultures of National Minorities, University of Presov, Presov, Slovakia.</auth-address><titles><title>Analysis of selected genes associated with cardiomyopathy by next-generation sequencing</title><secondary-title>J Clin Lab Anal</secondary-title></titles><periodical><full-title>J Clin Lab Anal</full-title></periodical><volume>32</volume><number>2</number><edition>2017/06/09</edition><keywords><keyword>bioinformatic analysis</keyword><keyword>cardiomyopathies</keyword><keyword>next-generation sequencing</keyword><keyword>panel of genes</keyword><keyword>pathogenic variants</keyword></keywords><dates><year>2018</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1098-2825 (Electronic)
0887-8013 (Linking)</isbn><accession-num>28594148</accession-num><urls><related-urls><url>;(Szabadosova et al 2018). Cardiomyopathies are usually inherited as autosomal-dominant PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkbXVsbGVyPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkbXVsbGVyPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE.DATA (Waldmuller et al 2015) and include:Hypertrophic cardiomyopathy (HCM), is a common cardiac genetic disease, with an estimated prevalence of 1 in 200 to 1 in 500 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXJuczwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXJuczwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJl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ADDIN EN.CITE.DATA (Burns et al 2017). HCM is characterised by the presence of unexplained left ventricular hypertrophy (LVH). The LVH associated with HCM usually develops during adolescence or young adulthood. HCM was initially thought to be associated with high mortality, however, the majority of individuals with HCM will experience a normal life expectancy and manageable symptoms. Individuals with HCM are at an increased risk for atrial fibrillation (AF), which is associated with significant morbidity due to increased risk of thromboembolism and symptomatic deterioration. Approximately 5%-10% of individuals with HCM progress to end-stage disease with impaired systolic function and, in some cases, left ventricular dilatation and regression of LVH. The annual mortality rate in individuals with end-stage disease is estimated at 11% and cardiac transplantation may be required. A small number of individuals with HCM are at increased risk for SCD related to ventricular tachycardia / ventricular fibrillation. SCD may be the first manifestation of disease, usually occurring in adolescents or young adults ADDIN EN.CITE <EndNote><Cite><Author>Cirino</Author><Year>2014</Year><RecNum>26</RecNum><DisplayText>(Cirino & Ho 2014)</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529385275">26</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Cirino, A.L.</author><author>Ho, C.</author></authors><secondary-authors><author>Adam, M.P.</author><author>Ardinger, H.H.</author><author>Pagon, R.A.</author></secondary-authors></contributors><titles><title>Hypertrophic Cardiomyopathy Overview</title><secondary-title>GeneReviews?</secondary-title></titles><volume>2018</volume><number>19 June</number><dates><year>2014</year></dates><pub-location>Seattle</pub-location><publisher>University of Washington</publisher><urls><related-urls><url>;(Cirino & Ho 2014). Patients can be risk stratified clinically for SCD via holter, echo, and family history; however, specific variants may add additional clinical information and assist risk stratification.Dilated cardiomyopathy (DCM) is characterised by LV enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. Onset may occur at any time in life but is more common in adults aged 40-60 years. Few estimates of the prevalence of DCM exist; however, it has been estimated to be twice that of HCM (1:250) ADDIN EN.CITE <EndNote><Cite><Author>Hershberger</Author><Year>2015</Year><RecNum>27</RecNum><DisplayText>(Hershberger & Morales 2015)</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529385474">27</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Hershberger, R. E.</author><author>Morales, A.</author></authors><secondary-authors><author>Adam, M.P.</author><author>Ardinger, H.H.</author><author>Pagon, R.A.</author></secondary-authors></contributors><titles><title>Dilated Cardiomyopathy Overview</title><secondary-title>GeneReviews?</secondary-title></titles><volume>2018</volume><number>19 June</number><dates><year>2015</year></dates><pub-location>Seattle</pub-location><publisher>University of Washington</publisher><urls><related-urls><url>;(Hershberger & Morales 2015).Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterised by progressive fibro-fatty replacement of the myocardium, predisposing young individuals and athletes to ventricular tachycardia and SCD affecting the right and/or left ventricle. The mean age at diagnosis is 31 ± 13 years (range 4-64 years). The prevalence of ARVC is estimated at 1:1,000 to 1:1,250 in the general population ADDIN EN.CITE <EndNote><Cite><Author>McNally</Author><Year>2017</Year><RecNum>28</RecNum><DisplayText>(McNally et al 2017)</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529385880">28</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>McNally, E.</author><author>MacLeod, H.</author><author>Dellefave-Castillo, L.</author></authors><secondary-authors><author>Adam, M.P.</author><author>Ardinger, H.H.</author><author>Pagon, R.A.</author></secondary-authors></contributors><titles><title>Arrhythmogenic Right Ventricular Cardiomyopathy</title><secondary-title>GeneReviews?</secondary-title></titles><volume>2018</volume><number>19 June</number><dates><year>2017</year></dates><pub-location>Seattle</pub-location><publisher>University of Washington</publisher><urls><related-urls><url>;(McNally et al 2017).Specify any characteristics of patients with the medical condition, or suspected of, who are proposed to be eligible for the proposed medical service, including any details of how a patient would be investigated, managed and referred within the Australian health care system in the lead up to being considered eligible for the service:Diagnostic genetic testing of affected individuals: characterisation of germline gene variants for inherited cardiomyopathies in patients where clinical criteria or a family history indicate that genetic testing is warranted. The 2019 HRS guidelines recommends (Class I) genetic testing of established arrhythmogenic cardiomyopathy (ACM) susceptibility genes for individuals and decedents with either a clinical or necropsy diagnosis of ACM. In addition, it is recommended (Class I) that for genetic testing of the established ACM-susceptibility genes, a comprehensive analysis of all established genes with full coverage should be conducted PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Towbin et al 2019).HCM: Class I (is recommended): Comprehensive or targeted (MYBPC3, MYH7, TNNI3, TNNT2, TPM1) HCM genetic testing is recommended for any patient in whom a cardiologist has established a clinical diagnosis of HCM based on examination of the patient’s clinical history, family history, and electrocardiographic/echocardiographic phenotype PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011).DCM: Class I (is recommended): Comprehensive or targeted (LMNA and SCN5A) DCM genetic testing is recommended for patients with DCM and significant cardiac conduction disease and/or a family history of premature unexpected sudden death PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011).ARVC: Class I (is recommended): Comprehensive or targeted (DSC2, DSG2, DSP, JUP, PKP2, and TMEM43) ACM/ARVC genetic testing is recommended for patients satisfying task force diagnostic criteria for ACM/ARVC. PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Towbin et al 2019)Predictive genetic testing of family members: detection of a clinically actionable pathogenic variant previously identified in a first-degree relative.HCM: Variant-specific genetic testing is recommended for family members and appropriate relatives following the identification of the HCM-causative variant in an index case PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+
PFJlY051bT4yOTwvUmVjTnVtPjxJRFRleHQ+MjE3ODc5OTk8L0lEVGV4dD48RGlzcGxheVRleHQ+
KEFja2VybWFuIGV0IGFsIDIwMTEpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjI5
PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZmFkc3g1MjV3
djVkdDVlcHJ3d3gwc3BzenR3dnM5MjBwMHc5IiB0aW1lc3RhbXA9IjE1MjkzODg2NTciPjI5PC9r
ZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3Jl
Zi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1
dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1dGhvcj48YXV0aG9yPldpbGxlbXMsIFMuPC9h
dXRob3I+PGF1dGhvcj5CZXJ1bCwgQy48L2F1dGhvcj48YXV0aG9yPkJydWdhZGEsIFIuPC9hdXRo
b3I+PGF1dGhvcj5DYWxraW5zLCBILjwvYXV0aG9yPjxhdXRob3I+Q2FtbSwgQS4gSi48L2F1dGhv
cj48YXV0aG9yPkVsbGlub3IsIFAuIFQuPC9hdXRob3I+PGF1dGhvcj5Hb2xsb2IsIE0uPC9hdXRo
b3I+PGF1dGhvcj5IYW1pbHRvbiwgUi48L2F1dGhvcj48YXV0aG9yPkhlcnNoYmVyZ2VyLCBSLiBF
LjwvYXV0aG9yPjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5MZSBNYXJlYywg
SC48L2F1dGhvcj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5TY2h1bHpl
LUJhaHIsIEUuPC9hdXRob3I+PGF1dGhvcj5TZW1zYXJpYW4sIEMuPC9hdXRob3I+PGF1dGhvcj5U
b3diaW4sIEouIEEuPC9hdXRob3I+PGF1dGhvcj5XYXRraW5zLCBILjwvYXV0aG9yPjxhdXRob3I+
V2lsZGUsIEEuPC9hdXRob3I+PGF1dGhvcj5Xb2xwZXJ0LCBDLjwvYXV0aG9yPjxhdXRob3I+Wmlw
ZXMsIEQuIFAuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+
TWF5byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLCBVU0EuPC9hdXRoLWFkZHJlc3M+PHRp
dGxlcz48dGl0bGU+SFJTL0VIUkEgZXhwZXJ0IGNvbnNlbnN1cyBzdGF0ZW1lbnQgb24gdGhlIHN0
YXRlIG9mIGdlbmV0aWMgdGVzdGluZyBmb3IgdGhlIGNoYW5uZWxvcGF0aGllcyBhbmQgY2FyZGlv
bXlvcGF0aGllcyB0aGlzIGRvY3VtZW50IHdhcyBkZXZlbG9wZWQgYXMgYSBwYXJ0bmVyc2hpcCBi
ZXR3ZWVuIHRoZSBIZWFydCBSaHl0aG0gU29jaWV0eSAoSFJTKSBhbmQgdGhlIEV1cm9wZWFuIEhl
YXJ0IFJoeXRobSBBc3NvY2lhdGlvbiAoRUhSQSk8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+SGVh
cnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0
bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48cGFnZXM+MTMwOC0zOTwv
cGFnZXM+PHZvbHVtZT44PC92b2x1bWU+PG51bWJlcj44PC9udW1iZXI+PGVkaXRpb24+MjAxMS8w
Ny8yNzwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QnJ1Z2FkYSBTeW5kcm9tZS9nZW5ldGlj
czwva2V5d29yZD48a2V5d29yZD5DYXJkaW9teW9wYXRoaWVzLyBkaWFnbm9zaXMvIGdlbmV0aWNz
PC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGh5LCBIeXBlcnRyb3BoaWMvZGlhZ25vc2lz
L2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGh5LCBSZXN0cmljdGl2ZS9j
b21wbGljYXRpb25zL2RpYWdub3Npczwva2V5d29yZD48a2V5d29yZD5DaGFubmVsb3BhdGhpZXMv
IGRpYWdub3Npcy8gZ2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+RGlzZWFzZSBQcm9ncmVzc2lv
bjwva2V5d29yZD48a2V5d29yZD5HZW5ldGljIENvdW5zZWxpbmc8L2tleXdvcmQ+PGtleXdvcmQ+
R2VuZXRpYyBUZXN0aW5nL3N0YW5kYXJkczwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv
cmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkF1
ZzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykm
I3hEOzE1NDctNTI3MSAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjE3ODc5OTk8L2Fj
Y2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHBzOi8vd3d3LnNjaWVuY2Vk
aXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkvUzE1NDc1MjcxMTEwMDYwNzI/dmlhJTNEaWh1
YjwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAu
MTAxNi9qLmhydGhtLjIwMTEuMDUuMDIwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3Rl
LWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFn
ZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==
ADDIN EN.CITE.DATA (Ackerman et al 2011).DCM: Variant-specific genetic testing is recommended for family members and appropriate relatives following the identification of a DCM-causative variant in the index case PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011).ARVC: Class I (is recommended): Variant-specific genetic testing is recommended for family members and appropriate relatives following the identification of the ACM/ARVC causative variant in an index case PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011).Define and summarise the current clinical management pathway before patients would be eligible for the proposed medical service (supplement this summary with an easy to follow flowchart [as an attachment to the Application Form] depicting the current clinical management pathway up to this point):Patients would normally undergo diagnosis on the basis of clinical criteria.The diagnosis of HCM is most often established with non-invasive cardiac imaging, including echocardiography and/or cardiac magnetic resonance imaging (cardiac MRI). HCM can also be diagnosed by pathognomonic histopathologic findings in cardiac tissue, including myocyte disarray and fibrosis. Clinical cardiovascular screening by ECG and echocardiography in relatives at risk for HCM should be performed in accordance with published recommendations ADDIN EN.CITE <EndNote><Cite><Author>Cirino</Author><Year>2014</Year><RecNum>26</RecNum><DisplayText>(Cirino & Ho 2014)</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529385275">26</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Cirino, A.L.</author><author>Ho, C.</author></authors><secondary-authors><author>Adam, M.P.</author><author>Ardinger, H.H.</author><author>Pagon, R.A.</author></secondary-authors></contributors><titles><title>Hypertrophic Cardiomyopathy Overview</title><secondary-title>GeneReviews?</secondary-title></titles><volume>2018</volume><number>19 June</number><dates><year>2014</year></dates><pub-location>Seattle</pub-location><publisher>University of Washington</publisher><urls><related-urls><url>;(Cirino & Ho 2014).The position statement of the Cardiac Society of Australia and New Zealand states that “The diagnosis of DCM is made using echocardiography or other imaging modalities such as magnetic resonance imaging. Approximately 25% patients with “idiopathic” DCM are likely to have a genetic basis for disease and a detailed three-generation family history needs to be taken in all newly-diagnosed cases. First-degree family members of individuals with known or suspected familial DCM should undergo clinical screening with physical examination, 12-lead ECG and transthoracic echocardiography. A detailed medical history needs to be taken to identify any co-morbidities or acquired factors that might contribute to DCM development or exacerbate disease severity. In female family members, DCM may present during pregnancy or in the postpartum period. It has been recommended that all first-degree family members of individuals with “idiopathic” DCM, and of individuals with suspected familial DCM on the basis of a positive family history, should undergo clinical screening with physical examination, 12-lead ECG and transthoracic echocardiography to identify familial disease and to determine the number of affected individuals within families” ADDIN EN.CITE <EndNote><Cite><Author>CSANZ</Author><Year>2016</Year><RecNum>69</RecNum><DisplayText>(CSANZ 2016)</DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1536131839">69</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>CSANZ</author></authors></contributors><titles><title>Diagnosis and Management of Familial Dilated Cardiomyopathy – Position Statement</title></titles><volume>2018</volume><number>5th September</number><dates><year>2016</year></dates><pub-location>Sydney</pub-location><publisher>Cardiac Society of Australia and New Zealand</publisher><urls><related-urls><url>;(CSANZ 2016).The diagnosis of DCM is established by the presence of both of the following:Left ventricular enlargement, most commonly assessed in adults by 2D echocardiographySystolic dysfunction, a reduction in the myocardial force of contractionAn ejection fraction of less than 50% is considered systolic dysfunction. LVEF is the most commonly used clinical measure of systolic dysfunction, and is usually estimated from a 2D-echocardiogram, from other non-invasive studies (e.g., cardiac nuclear or MRI studies), or from a left ventricular angiogram.Fractional shortening is another clinical measure of systolic function. A fractional shortening of less than 25% is considered systolic dysfunction ADDIN EN.CITE <EndNote><Cite><Author>Hershberger</Author><Year>2015</Year><RecNum>27</RecNum><DisplayText>(Hershberger & Morales 2015)</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529385474">27</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Hershberger, R. E.</author><author>Morales, A.</author></authors><secondary-authors><author>Adam, M.P.</author><author>Ardinger, H.H.</author><author>Pagon, R.A.</author></secondary-authors></contributors><titles><title>Dilated Cardiomyopathy Overview</title><secondary-title>GeneReviews?</secondary-title></titles><volume>2018</volume><number>19 June</number><dates><year>2015</year></dates><pub-location>Seattle</pub-location><publisher>University of Washington</publisher><urls><related-urls><url>;(Hershberger & Morales 2015).ARVC is a primary cardiomyopathy that is most commonly diagnosed after an individual presents with arrhythmia findings. Diagnostic criteria rely on a combination of ECG and signal averaged ECGs, imaging studies that include 2D echocardiography, cardiac MRI or RV angiography, and arrhythmia presence documented by telemetric monitoring, genetic testing, and family history. ARVC should be suspected in individuals with any of the following: syncope, palpitations, SCD, abnormal ECG, or abnormal right ventricle observed by cardiac imaging ADDIN EN.CITE <EndNote><Cite><Author>McNally</Author><Year>2017</Year><RecNum>28</RecNum><DisplayText>(McNally et al 2017)</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529385880">28</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>McNally, E.</author><author>MacLeod, H.</author><author>Dellefave-Castillo, L.</author></authors><secondary-authors><author>Adam, M.P.</author><author>Ardinger, H.H.</author><author>Pagon, R.A.</author></secondary-authors></contributors><titles><title>Arrhythmogenic Right Ventricular Cardiomyopathy</title><secondary-title>GeneReviews?</secondary-title></titles><volume>2018</volume><number>19 June</number><dates><year>2017</year></dates><pub-location>Seattle</pub-location><publisher>University of Washington</publisher><urls><related-urls><url>;(McNally et al 2017).PART 6b – INFORMATION ABOUT THE INTERVENTIONDescribe the key components and clinical steps involved in delivering the proposed medical service: REF _Ref9414555 \h Figure 1 outlines the pathway for the genetic and clinical screening of probands and relatives.123825107315Obtain family historyIdentify individual who meets diagnostic criteria and test using a multi-gene panelPathogenic variant identifiedLikely pathogenic variant identifiedNo pathogenic variant identifiedVariant of unknown significance identifiedTest at-risk family members for family-specific variant Segregation study of selected family membersAbsentPresentDismiss from routine clinical cardiac evaluation Perform clinical cardiac evaluations at recommended intervals Pathogenicity supportedPathogenicity refuted or uncertainPerform clinical cardiac evaluations at recommended intervals on at-risk family membersObtain family historyIdentify individual who meets diagnostic criteria and test using a multi-gene panelPathogenic variant identifiedLikely pathogenic variant identifiedNo pathogenic variant identifiedVariant of unknown significance identifiedTest at-risk family members for family-specific variant Segregation study of selected family membersAbsentPresentDismiss from routine clinical cardiac evaluation Perform clinical cardiac evaluations at recommended intervals Pathogenicity supportedPathogenicity refuted or uncertainPerform clinical cardiac evaluations at recommended intervals on at-risk family membersFigure SEQ Figure \* ARABIC 1Flow chart for the genetic and clinical screening of probands and relativesOnce a clinical diagnosis has been made, a confirmatory genetic diagnosis is recommended and requested from a specialist cardiologist. The HRS guidelines recommend (Class I) that a detailed ≥ 3-generation family history from the proband be obtained by a genetic counsellor or an appropriately experienced clinician, which would be used to determine the existence of familial disease and identify relatives who should be informed of the need for cardiac evaluation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
ZWNOdW0+MTAwPC9SZWNOdW0+PElEVGV4dD4zMTA3ODY1MjwvSURUZXh0PjxEaXNwbGF5VGV4dD4o
VG93YmluIGV0IGFsIDIwMTkpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwMDwv
cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImZhZHN4NTI1d3Y1
ZHQ1ZXByd3d4MHNwc3p0d3ZzOTIwcDB3OSIgdGltZXN0YW1wPSIxNTU4MzMxMzE0Ij4xMDA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRvd2JpbiwgSi4gQS48L2F1dGhv
cj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5BYnJhbXMsIEQuIEouPC9h
dXRob3I+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1dGhvcj48YXV0aG9yPkNhbGtpbnMsIEgu
PC9hdXRob3I+PGF1dGhvcj5EYXJyaWV1eCwgRi4gQy4gQy48L2F1dGhvcj48YXV0aG9yPkRhdWJl
cnQsIEouIFAuPC9hdXRob3I+PGF1dGhvcj5kZSBDaGlsbG91LCBDLjwvYXV0aG9yPjxhdXRob3I+
RGVQYXNxdWFsZSwgRS4gQy48L2F1dGhvcj48YXV0aG9yPkRlc2FpLCBNLiBZLjwvYXV0aG9yPjxh
dXRob3I+RXN0ZXMsIE4uIEEuIE0uLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkh1YSwgVy48L2F1dGhv
cj48YXV0aG9yPkluZGlrLCBKLiBILjwvYXV0aG9yPjxhdXRob3I+SW5nbGVzLCBKLjwvYXV0aG9y
PjxhdXRob3I+SmFtZXMsIEMuIEEuPC9hdXRob3I+PGF1dGhvcj5Kb2huLCBSLiBNLjwvYXV0aG9y
PjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5LZWVnYW4sIFIuPC9hdXRob3I+
PGF1dGhvcj5LcmFobiwgQS4gRC48L2F1dGhvcj48YXV0aG9yPkxpbmssIE0uIFMuPC9hdXRob3I+
PGF1dGhvcj5NYXJjdXMsIEYuIEkuPC9hdXRob3I+PGF1dGhvcj5NY0xlb2QsIEMuIEouPC9hdXRo
b3I+PGF1dGhvcj5NZXN0cm9uaSwgTC48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1
dGhvcj48YXV0aG9yPlNhZmZpdHosIEouIEUuPC9hdXRob3I+PGF1dGhvcj5TYW5hdGFuaSwgUy48
L2F1dGhvcj48YXV0aG9yPlNoaW1penUsIFcuPC9hdXRob3I+PGF1dGhvcj5QZXRlciB2YW4gVGlu
dGVsZW4sIEouPC9hdXRob3I+PGF1dGhvcj5XaWxkZSwgQS4gQS4gTS48L2F1dGhvcj48YXV0aG9y
PlphcmViYSwgVy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz
cz5MZSBCb25oZXVyIENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgTWVtcGhpcywgVGVubmVzc2Vl
OyBVbml2ZXJzaXR5IG9mIFRlbm5lc3NlZSBIZWFsdGggU2NpZW5jZSBDZW50ZXIsIE1lbXBoaXMs
IFRlbm5lc3NlZS4mI3hEO1VuaXZlcnNpdHkgQ29sbGVnZSBMb25kb24sIEluc3RpdHV0ZSBvZiBD
YXJkaW92YXNjdWxhciBTY2llbmNlLCBMb25kb24sIFVuaXRlZCBLaW5nZG9tLiYjeEQ7Qm9zdG9u
IENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgQm9zdG9uLCBNYXNzYWNodXNldHRzLiYjeEQ7TWF5
byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLiYjeEQ7Sm9obnMgSG9wa2lucyBVbml2ZXJz
aXR5LCBCYWx0aW1vcmUsIE1hcnlsYW5kLiYjeEQ7VW5pdmVyc2lkYWRlIGRlIFNhbyBQYXVsbywg
SW5zdGl0dXRvIGRvIENvcmFjYW8gSENGTVVTUCwgU2FvIFBhdWxvLCBCcmF6aWwuJiN4RDtEdWtl
IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIER1cmhhbSwgTm9ydGggQ2Fyb2xpbmEuJiN4RDtO
YW5jeSBVbml2ZXJzaXR5IEhvc3BpdGFsLCBWYW5kb2V1dnJlLWxlcy1OYW5jeSwgRnJhbmNlLiYj
eEQ7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBMb3MgQW5nZWxlcywgTG9zIEFuZ2VsZXMsIENh
bGlmb3JuaWEuJiN4RDtDbGV2ZWxhbmQgQ2xpbmljLCBDbGV2ZWxhbmQsIE9oaW8uJiN4RDtVbml2
ZXJzaXR5IG9mIFBpdHRzYnVyZ2ggTWVkaWNhbCBDZW50ZXIsIFBpdHRzYnVyZ2gsIFBlbm5zeWx2
YW5pYS4mI3hEO0Z1IFdhaSBIb3NwaXRhbCwgQmVpamluZywgQ2hpbmEuJiN4RDtVbml2ZXJzaXR5
IG9mIEFyaXpvbmEsIFNhcnZlciBIZWFydCBDZW50ZXIsIFR1Y3NvbiwgQXJpem9uYS4mI3hEO0Fn
bmVzIEdpbmdlcyBDZW50cmUgZm9yIE1vbGVjdWxhciBDYXJkaW9sb2d5IGF0IENlbnRlbmFyeSBJ
bnN0aXR1dGUsIFRoZSBVbml2ZXJzaXR5IG9mIFN5ZG5leSwgU3lkbmV5LCBBdXN0cmFsaWEuJiN4
RDtWYW5kZXJiaWx0IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIE5hc2h2aWxsZSwgVGVubmVz
c2VlLiYjeEQ7TWVkaWNhbCBVbml2ZXJzaXR5IG9mIFNvdXRoIENhcm9saW5hLCBDaGFybGVzdG9u
LCBTb3V0aCBDYXJvbGluYS4mI3hEO0hvc3BpdGFsIFByaXZhZG8gRGVsIFN1ciwgQnVlbm9zIEFp
cmVzLCBBcmdlbnRpbmE7IEhvc3BpdGFsIEVzcGFub2wsIEJhaGlhIEJsYW5jYSwgQXJnZW50aW5h
LiYjeEQ7VGhlIFVuaXZlcnNpdHkgb2YgQnJpdGlzaCBDb2x1bWJpYSwgVmFuY291dmVyLCBDYW5h
ZGEuJiN4RDtVVCBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywgVGV4YXMuJiN4
RDtVbml2ZXJzaXR5IG9mIENvbG9yYWRvIEFuc2NodXR6IE1lZGljYWwgQ2FtcHVzLCBBdXJvcmEs
IENvbG9yYWRvLiYjeEQ7VW5pdmVyc2l0eSBvZiBQYXZpYSwgUGF2aWEsIEl0YWx5OyBFdXJvcGVh
biBSZWZlcmVuY2UgTmV0d29yayBmb3IgUmFyZSBhbmQgTG93IFByZXZhbGVuY2UgQ29tcGxleCBE
aXNlYXNlcyBvZiB0aGUgSGVhcnQgKEVSTiBHVUFSRC1IZWFydCk7IElDUyBNYXVnZXJpLCBJUkND
UywgUGF2aWEsIEl0YWx5LiYjeEQ7QmV0aCBJc3JhZWwgRGVhY29uZXNzIE1lZGljYWwgQ2VudGVy
LCBCb3N0b24sIE1hc3NhY2h1c2V0dHMuJiN4RDtDaGlsZHJlbiZhcG9zO3MgSGVhcnQgQ2VudGVy
LCBWYW5jb3V2ZXIsIENhbmFkYS4mI3hEO0RlcGFydG1lbnQgb2YgQ2FyZGlvdmFzY3VsYXIgTWVk
aWNpbmUsIE5pcHBvbiBNZWRpY2FsIFNjaG9vbCwgVG9reW8sIEphcGFuLiYjeEQ7VW5pdmVyc2l0
eSBvZiBBbXN0ZXJkYW0sIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBO
ZXRoZXJsYW5kczsgVXRyZWNodCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyIFV0cmVjaHQsIFVu
aXZlcnNpdHkgb2YgVXRyZWNodCwgRGVwYXJ0bWVudCBvZiBHZW5ldGljcywgVXRyZWNodCwgdGhl
IE5ldGhlcmxhbmRzLiYjeEQ7RXVyb3BlYW4gUmVmZXJlbmNlIE5ldHdvcmsgZm9yIFJhcmUgYW5k
IExvdyBQcmV2YWxlbmNlIENvbXBsZXggRGlzZWFzZXMgb2YgdGhlIEhlYXJ0IChFUk4gR1VBUkQt
SGVhcnQpOyBVbml2ZXJzaXR5IG9mIEFtc3RlcmRhbSwgQWNhZGVtaWMgTWVkaWNhbCBDZW50ZXIs
IEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzOyBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBDb2x1
bWJpYSBVbml2ZXJzaXR5IElydmluZyBNZWRpY2FsIENlbnRlciwgTmV3IFlvcmssIE5ldyBZb3Jr
LiYjeEQ7VW5pdmVyc2l0eSBvZiBSb2NoZXN0ZXIgTWVkaWNhbCBDZW50ZXIsIFJvY2hlc3Rlciwg
TmV3IFlvcmsuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+MjAxOSBIUlMgRXhwZXJ0IENv
bnNlbnN1cyBTdGF0ZW1lbnQgb24gRXZhbHVhdGlvbiwgUmlzayBTdHJhdGlmaWNhdGlvbiwgYW5k
IE1hbmFnZW1lbnQgb2YgQXJyaHl0aG1vZ2VuaWMgQ2FyZGlvbXlvcGF0aHk8L3RpdGxlPjxzZWNv
bmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlv
ZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48
ZWRpdGlvbj4yMDE5LzA1LzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BcnJoeXRobW9n
ZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5JQ0QgZGVjaXNpb25zPC9rZXl3
b3JkPjxrZXl3b3JkPmFycmh5dGhtb2dlbmljIHJpZ2h0IHZlbnRyaWN1bGFyIGNhcmRpb215b3Bh
dGh5IGFycmh5dGhtb2dlbmljIGxlZnQgdmVudHJpY3VsYXI8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fy
ZGlvbXlvcGF0aHk8L2tleXdvcmQ+PGtleXdvcmQ+Y2FzY2FkZSBmYW1pbHkgc2NyZWVuaW5nPC9r
ZXl3b3JkPjxrZXl3b3JkPmNhdGhldGVyIGFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPmRpYWdu
b3NpcyBvZiBhcnJoeXRobW9nZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5k
aXNlYXNlIG1lY2hhbmlzbXM8L2tleXdvcmQ+PGtleXdvcmQ+ZWxlY3Ryb3BoeXNpb2xvZ3k8L2tl
eXdvcmQ+PGtleXdvcmQ+ZXhlcmNpc2UgcmVzdHJpY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+Z2Vu
ZXRpYyB0ZXN0aW5nPC9rZXl3b3JkPjxrZXl3b3JkPmdlbmV0aWMgdmFyaWFudHM8L2tleXdvcmQ+
PGtleXdvcmQ+bGVmdCB2ZW50cmljdWxhciBub25jb21wYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk
PnJpc2sgc3RyYXRpZmljYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+dHJlYXRtZW50IG9mIGFycmh5
dGhtb2dlbmljIGNhcmRpb215b3BhdGh5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFy
PjIwMTk8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgOTwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh
dGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykmI3hEOzE1NDctNTI3MSAoTGlua2luZyk8
L2lzYm4+PGFjY2Vzc2lvbi1udW0+MzEwNzg2NTI8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0
ZWQtdXJscz48dXJsPjxzdHlsZSBmYWNlPSJ1bmRlcmxpbmUiIGZvbnQ9ImRlZmF1bHQiIHNpemU9
IjEwMCUiPmh0dHBzOi8vd3d3LnNjaWVuY2VkaXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkv
UzE1NDc1MjcxMTkzMDQzODI/dmlhJTNEaWh1Yjwvc3R5bGU+PC91cmw+PC9yZWxhdGVkLXVybHM+
PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouaHJ0aG0uMjAxOS4wNS4w
MDc8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN
PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv
cmQ+PC9DaXRlPjwvRW5kTm90ZT5=
ADDIN EN.CITE.DATA (Towbin et al 2019). For the genetic test, the patient would be required to provide a blood sample, from which DNA is extracted for analysis by a gene panel. The samples analysed are most commonly blood samples from affected individuals except in the case of cascade testing where duplicate and independent blood samples from affected and/or unaffected family members are submitted for specific analysis. Interpretation of variants should only be performed where there is high-level of disease-specific expertise. Targeted panel testing of genes as stipulated should be undertaken, and if negative for a variant, then review by a multidisciplinary, specialised cardiac genetic team should be undertaken. The 2019 HRS guidelines recommends (Class IIa) that the interpretation of a cardiac genetic test by a team of providers with expertise in genetics and cardiology can be useful. This expert team should therefore consist, at minimum, of cardiologists, clinical and molecular geneticists, genetic counsellors, and pathologists, or individuals with expertise that encompass these subspecialties.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Towbin et al 2019)Does the proposed medical service include a registered trademark component with characteristics that distinguishes it from other similar health components?NoIf the proposed medical service has a prosthesis or device component to it, does it involve a new approach towards managing a particular sub-group of the population with the specific medical condition?NoIf applicable, are there any limitations on the provision of the proposed medical service delivered to the patient (i.e. accessibility, dosage, quantity, duration or frequency):Once off diagnostic testIf applicable, identify any healthcare resources or other medical services that would need to be delivered at the same time as the proposed medical service:Consultation with clinical geneticists / genetic counsellor with expertise in genetic counselling. The delivery of results to the patients and / or family would require a formal consultation with the referring cardiologist with expertise in the condition, and clinical geneticist / genetic counsellor.If applicable, advise which health professionals will primarily deliver the proposed service:This test is usually requested by a cardiologist with experience in the genetic management of cardiac disease or a clinical geneticist.A pathologist would perform the service and provide the clinical report, including interpretation of the results.If applicable, advise whether the proposed medical service could be delegated or referred to another professional for delivery:NoIf applicable, specify any proposed limitations on who might deliver the proposed medical service, or who might provide a referral for it:Consideration should be given to restricting this service to a specialised setting. If applicable, advise what type of training or qualifications would be required to perform the proposed service as well as any accreditation requirements to support service delivery:Testing would be delivered only by Approved Practising Pathologists in NATA Accredited Pathology Laboratories (as defined in MBS Pathology table) by referral only by registered Medical Practitioners (non-pathologists) in line with other tests in the MBS Pathology Table.(a) Indicate the proposed setting(s) in which the proposed medical service will be delivered (select all relevant settings): FORMCHECKBOX Inpatient private hospital FORMCHECKBOX Inpatient public hospital FORMCHECKBOX Outpatient clinic FORMCHECKBOX Emergency Department FORMCHECKBOX Consulting rooms FORMCHECKBOX Day surgery centre FORMCHECKBOX Residential aged care facility FORMCHECKBOX Patient’s home FORMCHECKBOX Laboratory FORMCHECKBOX Other – please specify below FORMTEXT Specify further details hereWhere the proposed medical service is provided in more than one setting, please describe the rationale related to each:N/AIs the proposed medical service intended to be entirely rendered in Australia? FORMCHECKBOX Yes FORMCHECKBOX No – please specify below PART 6c – INFORMATION ABOUT THE COMPARATOR(S)Nominate the appropriate comparator(s) for the proposed medical service, i.e. how is the proposed population currently managed in the absence of the proposed medical service being available in the Australian health care system (including identifying health care resources that are needed to be delivered at the same time as the comparator service):No genetic testing – clinical diagnosis alone. Usual standard of care, without genetic testing.The 2019 HRS guidelines recommends (Class I) that cardiovascular evaluation should include 12-lead ECG, ambulatory ECG, and cardiac imaging (echocardiogram, cardiac MRI, or CT depending on availability and institutional expertise). In addition, exercise stress testing may be useful when evaluating family members (Class IIb recommendation) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
ZWNOdW0+MTAwPC9SZWNOdW0+PElEVGV4dD4zMTA3ODY1MjwvSURUZXh0PjxEaXNwbGF5VGV4dD4o
VG93YmluIGV0IGFsIDIwMTkpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwMDwv
cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImZhZHN4NTI1d3Y1
ZHQ1ZXByd3d4MHNwc3p0d3ZzOTIwcDB3OSIgdGltZXN0YW1wPSIxNTU4MzMxMzE0Ij4xMDA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRvd2JpbiwgSi4gQS48L2F1dGhv
cj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5BYnJhbXMsIEQuIEouPC9h
dXRob3I+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1dGhvcj48YXV0aG9yPkNhbGtpbnMsIEgu
PC9hdXRob3I+PGF1dGhvcj5EYXJyaWV1eCwgRi4gQy4gQy48L2F1dGhvcj48YXV0aG9yPkRhdWJl
cnQsIEouIFAuPC9hdXRob3I+PGF1dGhvcj5kZSBDaGlsbG91LCBDLjwvYXV0aG9yPjxhdXRob3I+
RGVQYXNxdWFsZSwgRS4gQy48L2F1dGhvcj48YXV0aG9yPkRlc2FpLCBNLiBZLjwvYXV0aG9yPjxh
dXRob3I+RXN0ZXMsIE4uIEEuIE0uLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkh1YSwgVy48L2F1dGhv
cj48YXV0aG9yPkluZGlrLCBKLiBILjwvYXV0aG9yPjxhdXRob3I+SW5nbGVzLCBKLjwvYXV0aG9y
PjxhdXRob3I+SmFtZXMsIEMuIEEuPC9hdXRob3I+PGF1dGhvcj5Kb2huLCBSLiBNLjwvYXV0aG9y
PjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5LZWVnYW4sIFIuPC9hdXRob3I+
PGF1dGhvcj5LcmFobiwgQS4gRC48L2F1dGhvcj48YXV0aG9yPkxpbmssIE0uIFMuPC9hdXRob3I+
PGF1dGhvcj5NYXJjdXMsIEYuIEkuPC9hdXRob3I+PGF1dGhvcj5NY0xlb2QsIEMuIEouPC9hdXRo
b3I+PGF1dGhvcj5NZXN0cm9uaSwgTC48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1
dGhvcj48YXV0aG9yPlNhZmZpdHosIEouIEUuPC9hdXRob3I+PGF1dGhvcj5TYW5hdGFuaSwgUy48
L2F1dGhvcj48YXV0aG9yPlNoaW1penUsIFcuPC9hdXRob3I+PGF1dGhvcj5QZXRlciB2YW4gVGlu
dGVsZW4sIEouPC9hdXRob3I+PGF1dGhvcj5XaWxkZSwgQS4gQS4gTS48L2F1dGhvcj48YXV0aG9y
PlphcmViYSwgVy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz
cz5MZSBCb25oZXVyIENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgTWVtcGhpcywgVGVubmVzc2Vl
OyBVbml2ZXJzaXR5IG9mIFRlbm5lc3NlZSBIZWFsdGggU2NpZW5jZSBDZW50ZXIsIE1lbXBoaXMs
IFRlbm5lc3NlZS4mI3hEO1VuaXZlcnNpdHkgQ29sbGVnZSBMb25kb24sIEluc3RpdHV0ZSBvZiBD
YXJkaW92YXNjdWxhciBTY2llbmNlLCBMb25kb24sIFVuaXRlZCBLaW5nZG9tLiYjeEQ7Qm9zdG9u
IENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgQm9zdG9uLCBNYXNzYWNodXNldHRzLiYjeEQ7TWF5
byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLiYjeEQ7Sm9obnMgSG9wa2lucyBVbml2ZXJz
aXR5LCBCYWx0aW1vcmUsIE1hcnlsYW5kLiYjeEQ7VW5pdmVyc2lkYWRlIGRlIFNhbyBQYXVsbywg
SW5zdGl0dXRvIGRvIENvcmFjYW8gSENGTVVTUCwgU2FvIFBhdWxvLCBCcmF6aWwuJiN4RDtEdWtl
IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIER1cmhhbSwgTm9ydGggQ2Fyb2xpbmEuJiN4RDtO
YW5jeSBVbml2ZXJzaXR5IEhvc3BpdGFsLCBWYW5kb2V1dnJlLWxlcy1OYW5jeSwgRnJhbmNlLiYj
eEQ7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBMb3MgQW5nZWxlcywgTG9zIEFuZ2VsZXMsIENh
bGlmb3JuaWEuJiN4RDtDbGV2ZWxhbmQgQ2xpbmljLCBDbGV2ZWxhbmQsIE9oaW8uJiN4RDtVbml2
ZXJzaXR5IG9mIFBpdHRzYnVyZ2ggTWVkaWNhbCBDZW50ZXIsIFBpdHRzYnVyZ2gsIFBlbm5zeWx2
YW5pYS4mI3hEO0Z1IFdhaSBIb3NwaXRhbCwgQmVpamluZywgQ2hpbmEuJiN4RDtVbml2ZXJzaXR5
IG9mIEFyaXpvbmEsIFNhcnZlciBIZWFydCBDZW50ZXIsIFR1Y3NvbiwgQXJpem9uYS4mI3hEO0Fn
bmVzIEdpbmdlcyBDZW50cmUgZm9yIE1vbGVjdWxhciBDYXJkaW9sb2d5IGF0IENlbnRlbmFyeSBJ
bnN0aXR1dGUsIFRoZSBVbml2ZXJzaXR5IG9mIFN5ZG5leSwgU3lkbmV5LCBBdXN0cmFsaWEuJiN4
RDtWYW5kZXJiaWx0IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIE5hc2h2aWxsZSwgVGVubmVz
c2VlLiYjeEQ7TWVkaWNhbCBVbml2ZXJzaXR5IG9mIFNvdXRoIENhcm9saW5hLCBDaGFybGVzdG9u
LCBTb3V0aCBDYXJvbGluYS4mI3hEO0hvc3BpdGFsIFByaXZhZG8gRGVsIFN1ciwgQnVlbm9zIEFp
cmVzLCBBcmdlbnRpbmE7IEhvc3BpdGFsIEVzcGFub2wsIEJhaGlhIEJsYW5jYSwgQXJnZW50aW5h
LiYjeEQ7VGhlIFVuaXZlcnNpdHkgb2YgQnJpdGlzaCBDb2x1bWJpYSwgVmFuY291dmVyLCBDYW5h
ZGEuJiN4RDtVVCBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywgVGV4YXMuJiN4
RDtVbml2ZXJzaXR5IG9mIENvbG9yYWRvIEFuc2NodXR6IE1lZGljYWwgQ2FtcHVzLCBBdXJvcmEs
IENvbG9yYWRvLiYjeEQ7VW5pdmVyc2l0eSBvZiBQYXZpYSwgUGF2aWEsIEl0YWx5OyBFdXJvcGVh
biBSZWZlcmVuY2UgTmV0d29yayBmb3IgUmFyZSBhbmQgTG93IFByZXZhbGVuY2UgQ29tcGxleCBE
aXNlYXNlcyBvZiB0aGUgSGVhcnQgKEVSTiBHVUFSRC1IZWFydCk7IElDUyBNYXVnZXJpLCBJUkND
UywgUGF2aWEsIEl0YWx5LiYjeEQ7QmV0aCBJc3JhZWwgRGVhY29uZXNzIE1lZGljYWwgQ2VudGVy
LCBCb3N0b24sIE1hc3NhY2h1c2V0dHMuJiN4RDtDaGlsZHJlbiZhcG9zO3MgSGVhcnQgQ2VudGVy
LCBWYW5jb3V2ZXIsIENhbmFkYS4mI3hEO0RlcGFydG1lbnQgb2YgQ2FyZGlvdmFzY3VsYXIgTWVk
aWNpbmUsIE5pcHBvbiBNZWRpY2FsIFNjaG9vbCwgVG9reW8sIEphcGFuLiYjeEQ7VW5pdmVyc2l0
eSBvZiBBbXN0ZXJkYW0sIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBO
ZXRoZXJsYW5kczsgVXRyZWNodCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyIFV0cmVjaHQsIFVu
aXZlcnNpdHkgb2YgVXRyZWNodCwgRGVwYXJ0bWVudCBvZiBHZW5ldGljcywgVXRyZWNodCwgdGhl
IE5ldGhlcmxhbmRzLiYjeEQ7RXVyb3BlYW4gUmVmZXJlbmNlIE5ldHdvcmsgZm9yIFJhcmUgYW5k
IExvdyBQcmV2YWxlbmNlIENvbXBsZXggRGlzZWFzZXMgb2YgdGhlIEhlYXJ0IChFUk4gR1VBUkQt
SGVhcnQpOyBVbml2ZXJzaXR5IG9mIEFtc3RlcmRhbSwgQWNhZGVtaWMgTWVkaWNhbCBDZW50ZXIs
IEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzOyBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBDb2x1
bWJpYSBVbml2ZXJzaXR5IElydmluZyBNZWRpY2FsIENlbnRlciwgTmV3IFlvcmssIE5ldyBZb3Jr
LiYjeEQ7VW5pdmVyc2l0eSBvZiBSb2NoZXN0ZXIgTWVkaWNhbCBDZW50ZXIsIFJvY2hlc3Rlciwg
TmV3IFlvcmsuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+MjAxOSBIUlMgRXhwZXJ0IENv
bnNlbnN1cyBTdGF0ZW1lbnQgb24gRXZhbHVhdGlvbiwgUmlzayBTdHJhdGlmaWNhdGlvbiwgYW5k
IE1hbmFnZW1lbnQgb2YgQXJyaHl0aG1vZ2VuaWMgQ2FyZGlvbXlvcGF0aHk8L3RpdGxlPjxzZWNv
bmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlv
ZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48
ZWRpdGlvbj4yMDE5LzA1LzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BcnJoeXRobW9n
ZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5JQ0QgZGVjaXNpb25zPC9rZXl3
b3JkPjxrZXl3b3JkPmFycmh5dGhtb2dlbmljIHJpZ2h0IHZlbnRyaWN1bGFyIGNhcmRpb215b3Bh
dGh5IGFycmh5dGhtb2dlbmljIGxlZnQgdmVudHJpY3VsYXI8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fy
ZGlvbXlvcGF0aHk8L2tleXdvcmQ+PGtleXdvcmQ+Y2FzY2FkZSBmYW1pbHkgc2NyZWVuaW5nPC9r
ZXl3b3JkPjxrZXl3b3JkPmNhdGhldGVyIGFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPmRpYWdu
b3NpcyBvZiBhcnJoeXRobW9nZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5k
aXNlYXNlIG1lY2hhbmlzbXM8L2tleXdvcmQ+PGtleXdvcmQ+ZWxlY3Ryb3BoeXNpb2xvZ3k8L2tl
eXdvcmQ+PGtleXdvcmQ+ZXhlcmNpc2UgcmVzdHJpY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+Z2Vu
ZXRpYyB0ZXN0aW5nPC9rZXl3b3JkPjxrZXl3b3JkPmdlbmV0aWMgdmFyaWFudHM8L2tleXdvcmQ+
PGtleXdvcmQ+bGVmdCB2ZW50cmljdWxhciBub25jb21wYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk
PnJpc2sgc3RyYXRpZmljYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+dHJlYXRtZW50IG9mIGFycmh5
dGhtb2dlbmljIGNhcmRpb215b3BhdGh5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFy
PjIwMTk8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgOTwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh
dGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykmI3hEOzE1NDctNTI3MSAoTGlua2luZyk8
L2lzYm4+PGFjY2Vzc2lvbi1udW0+MzEwNzg2NTI8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0
ZWQtdXJscz48dXJsPjxzdHlsZSBmYWNlPSJ1bmRlcmxpbmUiIGZvbnQ9ImRlZmF1bHQiIHNpemU9
IjEwMCUiPmh0dHBzOi8vd3d3LnNjaWVuY2VkaXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkv
UzE1NDc1MjcxMTkzMDQzODI/dmlhJTNEaWh1Yjwvc3R5bGU+PC91cmw+PC9yZWxhdGVkLXVybHM+
PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouaHJ0aG0uMjAxOS4wNS4w
MDc8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN
PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv
cmQ+PC9DaXRlPjwvRW5kTm90ZT5=
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
ZWNOdW0+MTAwPC9SZWNOdW0+PElEVGV4dD4zMTA3ODY1MjwvSURUZXh0PjxEaXNwbGF5VGV4dD4o
VG93YmluIGV0IGFsIDIwMTkpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwMDwv
cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImZhZHN4NTI1d3Y1
ZHQ1ZXByd3d4MHNwc3p0d3ZzOTIwcDB3OSIgdGltZXN0YW1wPSIxNTU4MzMxMzE0Ij4xMDA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRvd2JpbiwgSi4gQS48L2F1dGhv
cj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5BYnJhbXMsIEQuIEouPC9h
dXRob3I+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1dGhvcj48YXV0aG9yPkNhbGtpbnMsIEgu
PC9hdXRob3I+PGF1dGhvcj5EYXJyaWV1eCwgRi4gQy4gQy48L2F1dGhvcj48YXV0aG9yPkRhdWJl
cnQsIEouIFAuPC9hdXRob3I+PGF1dGhvcj5kZSBDaGlsbG91LCBDLjwvYXV0aG9yPjxhdXRob3I+
RGVQYXNxdWFsZSwgRS4gQy48L2F1dGhvcj48YXV0aG9yPkRlc2FpLCBNLiBZLjwvYXV0aG9yPjxh
dXRob3I+RXN0ZXMsIE4uIEEuIE0uLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkh1YSwgVy48L2F1dGhv
cj48YXV0aG9yPkluZGlrLCBKLiBILjwvYXV0aG9yPjxhdXRob3I+SW5nbGVzLCBKLjwvYXV0aG9y
PjxhdXRob3I+SmFtZXMsIEMuIEEuPC9hdXRob3I+PGF1dGhvcj5Kb2huLCBSLiBNLjwvYXV0aG9y
PjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5LZWVnYW4sIFIuPC9hdXRob3I+
PGF1dGhvcj5LcmFobiwgQS4gRC48L2F1dGhvcj48YXV0aG9yPkxpbmssIE0uIFMuPC9hdXRob3I+
PGF1dGhvcj5NYXJjdXMsIEYuIEkuPC9hdXRob3I+PGF1dGhvcj5NY0xlb2QsIEMuIEouPC9hdXRo
b3I+PGF1dGhvcj5NZXN0cm9uaSwgTC48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1
dGhvcj48YXV0aG9yPlNhZmZpdHosIEouIEUuPC9hdXRob3I+PGF1dGhvcj5TYW5hdGFuaSwgUy48
L2F1dGhvcj48YXV0aG9yPlNoaW1penUsIFcuPC9hdXRob3I+PGF1dGhvcj5QZXRlciB2YW4gVGlu
dGVsZW4sIEouPC9hdXRob3I+PGF1dGhvcj5XaWxkZSwgQS4gQS4gTS48L2F1dGhvcj48YXV0aG9y
PlphcmViYSwgVy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz
cz5MZSBCb25oZXVyIENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgTWVtcGhpcywgVGVubmVzc2Vl
OyBVbml2ZXJzaXR5IG9mIFRlbm5lc3NlZSBIZWFsdGggU2NpZW5jZSBDZW50ZXIsIE1lbXBoaXMs
IFRlbm5lc3NlZS4mI3hEO1VuaXZlcnNpdHkgQ29sbGVnZSBMb25kb24sIEluc3RpdHV0ZSBvZiBD
YXJkaW92YXNjdWxhciBTY2llbmNlLCBMb25kb24sIFVuaXRlZCBLaW5nZG9tLiYjeEQ7Qm9zdG9u
IENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgQm9zdG9uLCBNYXNzYWNodXNldHRzLiYjeEQ7TWF5
byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLiYjeEQ7Sm9obnMgSG9wa2lucyBVbml2ZXJz
aXR5LCBCYWx0aW1vcmUsIE1hcnlsYW5kLiYjeEQ7VW5pdmVyc2lkYWRlIGRlIFNhbyBQYXVsbywg
SW5zdGl0dXRvIGRvIENvcmFjYW8gSENGTVVTUCwgU2FvIFBhdWxvLCBCcmF6aWwuJiN4RDtEdWtl
IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIER1cmhhbSwgTm9ydGggQ2Fyb2xpbmEuJiN4RDtO
YW5jeSBVbml2ZXJzaXR5IEhvc3BpdGFsLCBWYW5kb2V1dnJlLWxlcy1OYW5jeSwgRnJhbmNlLiYj
eEQ7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBMb3MgQW5nZWxlcywgTG9zIEFuZ2VsZXMsIENh
bGlmb3JuaWEuJiN4RDtDbGV2ZWxhbmQgQ2xpbmljLCBDbGV2ZWxhbmQsIE9oaW8uJiN4RDtVbml2
ZXJzaXR5IG9mIFBpdHRzYnVyZ2ggTWVkaWNhbCBDZW50ZXIsIFBpdHRzYnVyZ2gsIFBlbm5zeWx2
YW5pYS4mI3hEO0Z1IFdhaSBIb3NwaXRhbCwgQmVpamluZywgQ2hpbmEuJiN4RDtVbml2ZXJzaXR5
IG9mIEFyaXpvbmEsIFNhcnZlciBIZWFydCBDZW50ZXIsIFR1Y3NvbiwgQXJpem9uYS4mI3hEO0Fn
bmVzIEdpbmdlcyBDZW50cmUgZm9yIE1vbGVjdWxhciBDYXJkaW9sb2d5IGF0IENlbnRlbmFyeSBJ
bnN0aXR1dGUsIFRoZSBVbml2ZXJzaXR5IG9mIFN5ZG5leSwgU3lkbmV5LCBBdXN0cmFsaWEuJiN4
RDtWYW5kZXJiaWx0IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIE5hc2h2aWxsZSwgVGVubmVz
c2VlLiYjeEQ7TWVkaWNhbCBVbml2ZXJzaXR5IG9mIFNvdXRoIENhcm9saW5hLCBDaGFybGVzdG9u
LCBTb3V0aCBDYXJvbGluYS4mI3hEO0hvc3BpdGFsIFByaXZhZG8gRGVsIFN1ciwgQnVlbm9zIEFp
cmVzLCBBcmdlbnRpbmE7IEhvc3BpdGFsIEVzcGFub2wsIEJhaGlhIEJsYW5jYSwgQXJnZW50aW5h
LiYjeEQ7VGhlIFVuaXZlcnNpdHkgb2YgQnJpdGlzaCBDb2x1bWJpYSwgVmFuY291dmVyLCBDYW5h
ZGEuJiN4RDtVVCBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywgVGV4YXMuJiN4
RDtVbml2ZXJzaXR5IG9mIENvbG9yYWRvIEFuc2NodXR6IE1lZGljYWwgQ2FtcHVzLCBBdXJvcmEs
IENvbG9yYWRvLiYjeEQ7VW5pdmVyc2l0eSBvZiBQYXZpYSwgUGF2aWEsIEl0YWx5OyBFdXJvcGVh
biBSZWZlcmVuY2UgTmV0d29yayBmb3IgUmFyZSBhbmQgTG93IFByZXZhbGVuY2UgQ29tcGxleCBE
aXNlYXNlcyBvZiB0aGUgSGVhcnQgKEVSTiBHVUFSRC1IZWFydCk7IElDUyBNYXVnZXJpLCBJUkND
UywgUGF2aWEsIEl0YWx5LiYjeEQ7QmV0aCBJc3JhZWwgRGVhY29uZXNzIE1lZGljYWwgQ2VudGVy
LCBCb3N0b24sIE1hc3NhY2h1c2V0dHMuJiN4RDtDaGlsZHJlbiZhcG9zO3MgSGVhcnQgQ2VudGVy
LCBWYW5jb3V2ZXIsIENhbmFkYS4mI3hEO0RlcGFydG1lbnQgb2YgQ2FyZGlvdmFzY3VsYXIgTWVk
aWNpbmUsIE5pcHBvbiBNZWRpY2FsIFNjaG9vbCwgVG9reW8sIEphcGFuLiYjeEQ7VW5pdmVyc2l0
eSBvZiBBbXN0ZXJkYW0sIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBO
ZXRoZXJsYW5kczsgVXRyZWNodCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyIFV0cmVjaHQsIFVu
aXZlcnNpdHkgb2YgVXRyZWNodCwgRGVwYXJ0bWVudCBvZiBHZW5ldGljcywgVXRyZWNodCwgdGhl
IE5ldGhlcmxhbmRzLiYjeEQ7RXVyb3BlYW4gUmVmZXJlbmNlIE5ldHdvcmsgZm9yIFJhcmUgYW5k
IExvdyBQcmV2YWxlbmNlIENvbXBsZXggRGlzZWFzZXMgb2YgdGhlIEhlYXJ0IChFUk4gR1VBUkQt
SGVhcnQpOyBVbml2ZXJzaXR5IG9mIEFtc3RlcmRhbSwgQWNhZGVtaWMgTWVkaWNhbCBDZW50ZXIs
IEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzOyBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBDb2x1
bWJpYSBVbml2ZXJzaXR5IElydmluZyBNZWRpY2FsIENlbnRlciwgTmV3IFlvcmssIE5ldyBZb3Jr
LiYjeEQ7VW5pdmVyc2l0eSBvZiBSb2NoZXN0ZXIgTWVkaWNhbCBDZW50ZXIsIFJvY2hlc3Rlciwg
TmV3IFlvcmsuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+MjAxOSBIUlMgRXhwZXJ0IENv
bnNlbnN1cyBTdGF0ZW1lbnQgb24gRXZhbHVhdGlvbiwgUmlzayBTdHJhdGlmaWNhdGlvbiwgYW5k
IE1hbmFnZW1lbnQgb2YgQXJyaHl0aG1vZ2VuaWMgQ2FyZGlvbXlvcGF0aHk8L3RpdGxlPjxzZWNv
bmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlv
ZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48
ZWRpdGlvbj4yMDE5LzA1LzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BcnJoeXRobW9n
ZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5JQ0QgZGVjaXNpb25zPC9rZXl3
b3JkPjxrZXl3b3JkPmFycmh5dGhtb2dlbmljIHJpZ2h0IHZlbnRyaWN1bGFyIGNhcmRpb215b3Bh
dGh5IGFycmh5dGhtb2dlbmljIGxlZnQgdmVudHJpY3VsYXI8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fy
ZGlvbXlvcGF0aHk8L2tleXdvcmQ+PGtleXdvcmQ+Y2FzY2FkZSBmYW1pbHkgc2NyZWVuaW5nPC9r
ZXl3b3JkPjxrZXl3b3JkPmNhdGhldGVyIGFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPmRpYWdu
b3NpcyBvZiBhcnJoeXRobW9nZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5k
aXNlYXNlIG1lY2hhbmlzbXM8L2tleXdvcmQ+PGtleXdvcmQ+ZWxlY3Ryb3BoeXNpb2xvZ3k8L2tl
eXdvcmQ+PGtleXdvcmQ+ZXhlcmNpc2UgcmVzdHJpY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+Z2Vu
ZXRpYyB0ZXN0aW5nPC9rZXl3b3JkPjxrZXl3b3JkPmdlbmV0aWMgdmFyaWFudHM8L2tleXdvcmQ+
PGtleXdvcmQ+bGVmdCB2ZW50cmljdWxhciBub25jb21wYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk
PnJpc2sgc3RyYXRpZmljYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+dHJlYXRtZW50IG9mIGFycmh5
dGhtb2dlbmljIGNhcmRpb215b3BhdGh5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFy
PjIwMTk8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgOTwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh
dGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykmI3hEOzE1NDctNTI3MSAoTGlua2luZyk8
L2lzYm4+PGFjY2Vzc2lvbi1udW0+MzEwNzg2NTI8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0
ZWQtdXJscz48dXJsPjxzdHlsZSBmYWNlPSJ1bmRlcmxpbmUiIGZvbnQ9ImRlZmF1bHQiIHNpemU9
IjEwMCUiPmh0dHBzOi8vd3d3LnNjaWVuY2VkaXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkv
UzE1NDc1MjcxMTkzMDQzODI/dmlhJTNEaWh1Yjwvc3R5bGU+PC91cmw+PC9yZWxhdGVkLXVybHM+
PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouaHJ0aG0uMjAxOS4wNS4w
MDc8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN
PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv
cmQ+PC9DaXRlPjwvRW5kTm90ZT5=
ADDIN EN.CITE.DATA (Towbin et al 2019).In the absence of a genetic diagnosis, the frequency of clinical screening for asymptomatic HCM family members ranges from 1 to 5 times per year ( REF _Ref517775744 \h Table 1) ADDIN EN.CITE <EndNote><Cite><Author>CSANZ</Author><Year>2016</Year><RecNum>69</RecNum><DisplayText>(CSANZ 2016)</DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1536131839">69</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>CSANZ</author></authors></contributors><titles><title>Diagnosis and Management of Familial Dilated Cardiomyopathy – Position Statement</title></titles><volume>2018</volume><number>5th September</number><dates><year>2016</year></dates><pub-location>Sydney</pub-location><publisher>Cardiac Society of Australia and New Zealand</publisher><urls><related-urls><url>;(CSANZ 2016). It is strongly recommended that all first-degree relatives of an affected individual be clinically screened for HCM. Screening of at-risk, asymptomatic family members is important due to incomplete penetrance or age-related and varied expression. At-risk relatives who undergo clinical evaluation may be clinically affected, have borderline disease (incomplete penetrance), or be clinically unaffected. Serial evaluation can define ongoing disease expression and risk stratification PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Towbin et al 2019). Clinical evaluation involves a physical examination by a cardiologist, an ECG and an echocardiogram. The suggested time intervals for clinical screening of unaffected family members should follow the format shown in Table 1 but should be individually tailored to each person. The HRS guidelines recommends that first-degree relatives undergo clinical evaluation every 1-3 years starting at 10-12 years of age (Class I, level of evidence B-NR) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
ZWNOdW0+MTAwPC9SZWNOdW0+PElEVGV4dD4zMTA3ODY1MjwvSURUZXh0PjxEaXNwbGF5VGV4dD4o
VG93YmluIGV0IGFsIDIwMTkpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwMDwv
cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImZhZHN4NTI1d3Y1
ZHQ1ZXByd3d4MHNwc3p0d3ZzOTIwcDB3OSIgdGltZXN0YW1wPSIxNTU4MzMxMzE0Ij4xMDA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRvd2JpbiwgSi4gQS48L2F1dGhv
cj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5BYnJhbXMsIEQuIEouPC9h
dXRob3I+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1dGhvcj48YXV0aG9yPkNhbGtpbnMsIEgu
PC9hdXRob3I+PGF1dGhvcj5EYXJyaWV1eCwgRi4gQy4gQy48L2F1dGhvcj48YXV0aG9yPkRhdWJl
cnQsIEouIFAuPC9hdXRob3I+PGF1dGhvcj5kZSBDaGlsbG91LCBDLjwvYXV0aG9yPjxhdXRob3I+
RGVQYXNxdWFsZSwgRS4gQy48L2F1dGhvcj48YXV0aG9yPkRlc2FpLCBNLiBZLjwvYXV0aG9yPjxh
dXRob3I+RXN0ZXMsIE4uIEEuIE0uLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkh1YSwgVy48L2F1dGhv
cj48YXV0aG9yPkluZGlrLCBKLiBILjwvYXV0aG9yPjxhdXRob3I+SW5nbGVzLCBKLjwvYXV0aG9y
PjxhdXRob3I+SmFtZXMsIEMuIEEuPC9hdXRob3I+PGF1dGhvcj5Kb2huLCBSLiBNLjwvYXV0aG9y
PjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5LZWVnYW4sIFIuPC9hdXRob3I+
PGF1dGhvcj5LcmFobiwgQS4gRC48L2F1dGhvcj48YXV0aG9yPkxpbmssIE0uIFMuPC9hdXRob3I+
PGF1dGhvcj5NYXJjdXMsIEYuIEkuPC9hdXRob3I+PGF1dGhvcj5NY0xlb2QsIEMuIEouPC9hdXRo
b3I+PGF1dGhvcj5NZXN0cm9uaSwgTC48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1
dGhvcj48YXV0aG9yPlNhZmZpdHosIEouIEUuPC9hdXRob3I+PGF1dGhvcj5TYW5hdGFuaSwgUy48
L2F1dGhvcj48YXV0aG9yPlNoaW1penUsIFcuPC9hdXRob3I+PGF1dGhvcj5QZXRlciB2YW4gVGlu
dGVsZW4sIEouPC9hdXRob3I+PGF1dGhvcj5XaWxkZSwgQS4gQS4gTS48L2F1dGhvcj48YXV0aG9y
PlphcmViYSwgVy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz
cz5MZSBCb25oZXVyIENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgTWVtcGhpcywgVGVubmVzc2Vl
OyBVbml2ZXJzaXR5IG9mIFRlbm5lc3NlZSBIZWFsdGggU2NpZW5jZSBDZW50ZXIsIE1lbXBoaXMs
IFRlbm5lc3NlZS4mI3hEO1VuaXZlcnNpdHkgQ29sbGVnZSBMb25kb24sIEluc3RpdHV0ZSBvZiBD
YXJkaW92YXNjdWxhciBTY2llbmNlLCBMb25kb24sIFVuaXRlZCBLaW5nZG9tLiYjeEQ7Qm9zdG9u
IENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgQm9zdG9uLCBNYXNzYWNodXNldHRzLiYjeEQ7TWF5
byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLiYjeEQ7Sm9obnMgSG9wa2lucyBVbml2ZXJz
aXR5LCBCYWx0aW1vcmUsIE1hcnlsYW5kLiYjeEQ7VW5pdmVyc2lkYWRlIGRlIFNhbyBQYXVsbywg
SW5zdGl0dXRvIGRvIENvcmFjYW8gSENGTVVTUCwgU2FvIFBhdWxvLCBCcmF6aWwuJiN4RDtEdWtl
IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIER1cmhhbSwgTm9ydGggQ2Fyb2xpbmEuJiN4RDtO
YW5jeSBVbml2ZXJzaXR5IEhvc3BpdGFsLCBWYW5kb2V1dnJlLWxlcy1OYW5jeSwgRnJhbmNlLiYj
eEQ7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBMb3MgQW5nZWxlcywgTG9zIEFuZ2VsZXMsIENh
bGlmb3JuaWEuJiN4RDtDbGV2ZWxhbmQgQ2xpbmljLCBDbGV2ZWxhbmQsIE9oaW8uJiN4RDtVbml2
ZXJzaXR5IG9mIFBpdHRzYnVyZ2ggTWVkaWNhbCBDZW50ZXIsIFBpdHRzYnVyZ2gsIFBlbm5zeWx2
YW5pYS4mI3hEO0Z1IFdhaSBIb3NwaXRhbCwgQmVpamluZywgQ2hpbmEuJiN4RDtVbml2ZXJzaXR5
IG9mIEFyaXpvbmEsIFNhcnZlciBIZWFydCBDZW50ZXIsIFR1Y3NvbiwgQXJpem9uYS4mI3hEO0Fn
bmVzIEdpbmdlcyBDZW50cmUgZm9yIE1vbGVjdWxhciBDYXJkaW9sb2d5IGF0IENlbnRlbmFyeSBJ
bnN0aXR1dGUsIFRoZSBVbml2ZXJzaXR5IG9mIFN5ZG5leSwgU3lkbmV5LCBBdXN0cmFsaWEuJiN4
RDtWYW5kZXJiaWx0IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIE5hc2h2aWxsZSwgVGVubmVz
c2VlLiYjeEQ7TWVkaWNhbCBVbml2ZXJzaXR5IG9mIFNvdXRoIENhcm9saW5hLCBDaGFybGVzdG9u
LCBTb3V0aCBDYXJvbGluYS4mI3hEO0hvc3BpdGFsIFByaXZhZG8gRGVsIFN1ciwgQnVlbm9zIEFp
cmVzLCBBcmdlbnRpbmE7IEhvc3BpdGFsIEVzcGFub2wsIEJhaGlhIEJsYW5jYSwgQXJnZW50aW5h
LiYjeEQ7VGhlIFVuaXZlcnNpdHkgb2YgQnJpdGlzaCBDb2x1bWJpYSwgVmFuY291dmVyLCBDYW5h
ZGEuJiN4RDtVVCBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywgVGV4YXMuJiN4
RDtVbml2ZXJzaXR5IG9mIENvbG9yYWRvIEFuc2NodXR6IE1lZGljYWwgQ2FtcHVzLCBBdXJvcmEs
IENvbG9yYWRvLiYjeEQ7VW5pdmVyc2l0eSBvZiBQYXZpYSwgUGF2aWEsIEl0YWx5OyBFdXJvcGVh
biBSZWZlcmVuY2UgTmV0d29yayBmb3IgUmFyZSBhbmQgTG93IFByZXZhbGVuY2UgQ29tcGxleCBE
aXNlYXNlcyBvZiB0aGUgSGVhcnQgKEVSTiBHVUFSRC1IZWFydCk7IElDUyBNYXVnZXJpLCBJUkND
UywgUGF2aWEsIEl0YWx5LiYjeEQ7QmV0aCBJc3JhZWwgRGVhY29uZXNzIE1lZGljYWwgQ2VudGVy
LCBCb3N0b24sIE1hc3NhY2h1c2V0dHMuJiN4RDtDaGlsZHJlbiZhcG9zO3MgSGVhcnQgQ2VudGVy
LCBWYW5jb3V2ZXIsIENhbmFkYS4mI3hEO0RlcGFydG1lbnQgb2YgQ2FyZGlvdmFzY3VsYXIgTWVk
aWNpbmUsIE5pcHBvbiBNZWRpY2FsIFNjaG9vbCwgVG9reW8sIEphcGFuLiYjeEQ7VW5pdmVyc2l0
eSBvZiBBbXN0ZXJkYW0sIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBO
ZXRoZXJsYW5kczsgVXRyZWNodCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyIFV0cmVjaHQsIFVu
aXZlcnNpdHkgb2YgVXRyZWNodCwgRGVwYXJ0bWVudCBvZiBHZW5ldGljcywgVXRyZWNodCwgdGhl
IE5ldGhlcmxhbmRzLiYjeEQ7RXVyb3BlYW4gUmVmZXJlbmNlIE5ldHdvcmsgZm9yIFJhcmUgYW5k
IExvdyBQcmV2YWxlbmNlIENvbXBsZXggRGlzZWFzZXMgb2YgdGhlIEhlYXJ0IChFUk4gR1VBUkQt
SGVhcnQpOyBVbml2ZXJzaXR5IG9mIEFtc3RlcmRhbSwgQWNhZGVtaWMgTWVkaWNhbCBDZW50ZXIs
IEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzOyBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBDb2x1
bWJpYSBVbml2ZXJzaXR5IElydmluZyBNZWRpY2FsIENlbnRlciwgTmV3IFlvcmssIE5ldyBZb3Jr
LiYjeEQ7VW5pdmVyc2l0eSBvZiBSb2NoZXN0ZXIgTWVkaWNhbCBDZW50ZXIsIFJvY2hlc3Rlciwg
TmV3IFlvcmsuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+MjAxOSBIUlMgRXhwZXJ0IENv
bnNlbnN1cyBTdGF0ZW1lbnQgb24gRXZhbHVhdGlvbiwgUmlzayBTdHJhdGlmaWNhdGlvbiwgYW5k
IE1hbmFnZW1lbnQgb2YgQXJyaHl0aG1vZ2VuaWMgQ2FyZGlvbXlvcGF0aHk8L3RpdGxlPjxzZWNv
bmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlv
ZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48
ZWRpdGlvbj4yMDE5LzA1LzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BcnJoeXRobW9n
ZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5JQ0QgZGVjaXNpb25zPC9rZXl3
b3JkPjxrZXl3b3JkPmFycmh5dGhtb2dlbmljIHJpZ2h0IHZlbnRyaWN1bGFyIGNhcmRpb215b3Bh
dGh5IGFycmh5dGhtb2dlbmljIGxlZnQgdmVudHJpY3VsYXI8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fy
ZGlvbXlvcGF0aHk8L2tleXdvcmQ+PGtleXdvcmQ+Y2FzY2FkZSBmYW1pbHkgc2NyZWVuaW5nPC9r
ZXl3b3JkPjxrZXl3b3JkPmNhdGhldGVyIGFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPmRpYWdu
b3NpcyBvZiBhcnJoeXRobW9nZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5k
aXNlYXNlIG1lY2hhbmlzbXM8L2tleXdvcmQ+PGtleXdvcmQ+ZWxlY3Ryb3BoeXNpb2xvZ3k8L2tl
eXdvcmQ+PGtleXdvcmQ+ZXhlcmNpc2UgcmVzdHJpY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+Z2Vu
ZXRpYyB0ZXN0aW5nPC9rZXl3b3JkPjxrZXl3b3JkPmdlbmV0aWMgdmFyaWFudHM8L2tleXdvcmQ+
PGtleXdvcmQ+bGVmdCB2ZW50cmljdWxhciBub25jb21wYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk
PnJpc2sgc3RyYXRpZmljYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+dHJlYXRtZW50IG9mIGFycmh5
dGhtb2dlbmljIGNhcmRpb215b3BhdGh5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFy
PjIwMTk8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgOTwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh
dGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykmI3hEOzE1NDctNTI3MSAoTGlua2luZyk8
L2lzYm4+PGFjY2Vzc2lvbi1udW0+MzEwNzg2NTI8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0
ZWQtdXJscz48dXJsPjxzdHlsZSBmYWNlPSJ1bmRlcmxpbmUiIGZvbnQ9ImRlZmF1bHQiIHNpemU9
IjEwMCUiPmh0dHBzOi8vd3d3LnNjaWVuY2VkaXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkv
UzE1NDc1MjcxMTkzMDQzODI/dmlhJTNEaWh1Yjwvc3R5bGU+PC91cmw+PC9yZWxhdGVkLXVybHM+
PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouaHJ0aG0uMjAxOS4wNS4w
MDc8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN
PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv
cmQ+PC9DaXRlPjwvRW5kTm90ZT5=
ADDIN EN.CITE.DATA (Towbin et al 2019).Table SEQ Table \* ARABIC 1Recommended frequency of clinical screening of asymptomatic HCM family members ADDIN EN.CITE <EndNote><Cite><Author>CSANZ</Author><Year>2016</Year><RecNum>69</RecNum><DisplayText>(CSANZ 2016)</DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1536131839">69</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>CSANZ</author></authors></contributors><titles><title>Diagnosis and Management of Familial Dilated Cardiomyopathy – Position Statement</title></titles><volume>2018</volume><number>5th September</number><dates><year>2016</year></dates><pub-location>Sydney</pub-location><publisher>Cardiac Society of Australia and New Zealand</publisher><urls><related-urls><url>;(CSANZ 2016)Age (years)Frequency of screening (years)0-10Optional: unless clinical suspicion, symptoms, malignant family history of HCM111-201 – 1.521 -302 -331+3 - 5Does the medical service that has been nominated as the comparator have an existing MBS item number(s)? FORMCHECKBOX Yes (please provide all relevant MBS item numbers below) FORMCHECKBOX No Item number 57360: COMPUTED TOMOGRAPHY OF THE CORONARY ARTERIES performed on a minimum of a 64 slice (or equivalent) scanner, where the request is made by a specialist or consultant physician, and:a) the patient has stable symptoms consistent with coronary ischaemia, is at low to intermediate risk of coronary artery disease and would have been considered for coronary angiography; orb) the patient requires exclusion of coronary artery anomaly or fistula; orc) the patient will be undergoing non-coronary cardiac surgery (R) (K)Fee: $700.00 Benefit: 75% = $525.00 85% = $618.30Item number 55116: EXERCISE STRESS ECHOCARDIOGRAPHY performed in conjunction with item 11712, with two-dimensional recordings before exercise (baseline) from at least three acoustic windows and matching recordings from the same windows at, or immediately after, peak exercise, not being a service associated with a service to which an item in Subgroups 1 (with the exception of item 55054) or 3, or another item in this Subgroup applies (with the exception of items 55118 and 55130). Recordings must be made on digital media with equipment permitting display of baseline and matching peak images on the same screen (R)Fee: $261.65 Benefit: 75% = $196.25 85% = $222.45Item number 55122: EXERCISE STRESS ECHOCARDIOGRAPHY performed in conjunction with item 11712, with two-dimensional recordings before exercise (baseline) from at least three acoustic windows and matching recordings from the same windows at, or immediately after, peak exercise, not being a service associated with a service to which an item in Subgroups 1 (with the exception of items 55026 and 55054) or 3, or another item in this Subgroup applies (with the exception of items 55118, 55125, 55130 and 55131). Recordings must be made on digital media with equipment permitting display of baseline and matching peak images on the same screen (R) (NK)Fee: $130.85 Benefit: 75% = $98.15 85% = $111.25Item number 11700: TWELVE-LEAD ELECTROCARDIOGRAPHY, tracing and reportFee: $31.25 Benefit: 75% = $23.45 85% = $26.60Item number 11709: Continuous ECG recording (Holter) of ambulatory patient for 12 or more hours (including resting ECG and the recording of parameters), not in association with ambulatory blood pressure monitoring, utilising a system capable of superimposition and full disclosure printout of at least 12 hours of recorded ECG data, microprocessor based scanning analysis, with interpretation and report by a specialist physician or consultant physician.Fee: $167.45 Benefit: 75% = $125.60 85% = $142.35Item number 11712: MULTI CHANNEL ECG MONITORING AND RECORDING during exercise (motorised treadmill or cycle ergometer capable of quantifying external workload in watts) or pharmacological stress, involving the continuous attendance of a medical practitioner for not less than 20 minutes, with resting ECG, and with or without continuous blood pressure monitoring and the recording of other parameters, on premises equipped with mechanical respirator and defibrillator.Fee: $152.15 Benefit: 75% = $114.15 85% = $129.35Define and summarise the current clinical management pathways that patients may follow after they receive the medical service that has been nominated as the comparator (supplement this summary with an easy to follow flowchart [as an attachment to the Application Form] depicting the current clinical management pathway that patients may follow from the point of receiving the comparator onwards including health care resources):Many treatment options are currently available for HCM patients. This ranges from no treatment; lifestyle modifications, eg avoiding competitive sports in all patients with HCM; use of pharmacological agents eg beta-blockers, calcium channel blockers, and diuretics; to dual chamber pacing, septal myotomy-myectomy and trans-coronary alcohol septal ablation of the myocardium for individuals with significant left ventricular outflow tract obstruction with symptoms unresponsive to drug therapy. The most important advance in the clinical management of HCM has been the use of ICD therapy to prevent sudden death. Recent studies indicate that treatment of individuals at highest risk of sudden death with an ICD is the most definitive form of therapy in preventing sudden death, surpassing preventative strategies previously used such as amiodarone and beta blockers ADDIN EN.CITE <EndNote><Cite><Author>Semsarian</Author><Year>2011</Year><RecNum>41</RecNum><IDText>22000299</IDText><DisplayText>(Semsarian 2011)</DisplayText><record><rec-number>41</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529902763">41</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Semsarian, C.</author></authors></contributors><auth-address>Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Newtown, NSW 2042, Australia. c.semsarian@.au</auth-address><titles><title>Guidelines for the diagnosis and management of hypertrophic cardiomyopathy</title><secondary-title>Heart Lung Circ</secondary-title></titles><periodical><full-title>Heart Lung Circ</full-title><abbr-1>Heart, lung & circulation</abbr-1></periodical><pages>688-90</pages><volume>20</volume><number>11</number><edition>2011/10/18</edition><keywords><keyword>Adult</keyword><keyword>Cardiomyopathy, Hypertrophic, Familial/diagnosis/genetics/therapy</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Practice Guidelines as Topic</keyword></keywords><dates><year>2011</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1444-2892 (Electronic)
1443-9506 (Linking)</isbn><accession-num>22000299</accession-num><urls><related-urls><url>;(Semsarian 2011). See Figure 2.Figure SEQ Figure \* ARABIC 2Treatment algorithm for hypertrophic cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HZXJzaDwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HZXJzaDwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE.DATA (Gersh et al 2011b)According to the 2016 CSANZ guidelines, “clinically-affected family members with DCM should receive standard pharmacological, device, and surgical management (circulatory support and transplantation) as indicated by the severity of symptoms and signs of heart failure, the electrocardiographic findings and the degree of left ventricular dysfunction. In families with DCM and conduction-system disease, young family members who present with conduction-system disturbances (sinus bradycardia, atrioventricular conduction block, ± atrial fibrillation) should be followed for arrhythmias that might necessitate pacemaker implantation and for the onset of DCM in later life. Electrophysiological studies/review ± ICD implantation should be considered in individuals with syncopal episodes, and/or a strong family history of sudden death, particularly in those families with LMNA variants. In most families, however, treatment choices for affected individuals are not currently altered by the discovery of a causative gene variant. In selected cases, elucidation of the molecular mechanisms underpinning disease may permit specific gene-targeted intervention. The natural history of familial DCM varies widely. It is likely that family genotype will be a very important determinant of prognosis but genotype-phenotype correlations in large populations of family members have yet to be performed. Recent data suggest that patients with genetic causes of DCM have a worse long-term outcome if there are co-existent non-genetic environmental factors including viral infection, immune-mediated cardiac inflammation and toxic exposure.” ADDIN EN.CITE <EndNote><Cite><Author>CSANZ</Author><Year>2016</Year><RecNum>69</RecNum><DisplayText>(CSANZ 2016)</DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1536131839">69</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>CSANZ</author></authors></contributors><titles><title>Diagnosis and Management of Familial Dilated Cardiomyopathy – Position Statement</title></titles><volume>2018</volume><number>5th September</number><dates><year>2016</year></dates><pub-location>Sydney</pub-location><publisher>Cardiac Society of Australia and New Zealand</publisher><urls><related-urls><url>;(CSANZ 2016)In asymptomatic (DCM) family members, the CSANZ recommend “Periodic cardiac screening (ECG and transthoracic echocardiography) of family members of probands with familial DCM is recommended, to identify arrhythmias and asymptomatic abnormalities of left ventricular size and function. The frequency of follow-up assessments should be determined in each individual case by factors such as the typical age of onset of disease in symptomatic family members, and “suspicious” echocardiographic changes that may be indicative of early disease and may range from 6-12 months to 5 years. Familial DCM exhibits age-related penetrance, i.e. family members who are born with a gene defect may not develop manifestations of disease until later in life. Young family members with a normal ECG and echo, particularly offspring of an affected parent, should not be dismissed as “unaffected” and require ongoing medical surveillance. In the case of an affected child, all first-degree relatives, including parents, should be screened and siblings are offered ongoing screening into adult life.” ADDIN EN.CITE <EndNote><Cite><Author>CSANZ</Author><Year>2016</Year><RecNum>69</RecNum><DisplayText>(CSANZ 2016)</DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1536131839">69</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>CSANZ</author></authors></contributors><titles><title>Diagnosis and Management of Familial Dilated Cardiomyopathy – Position Statement</title></titles><volume>2018</volume><number>5th September</number><dates><year>2016</year></dates><pub-location>Sydney</pub-location><publisher>Cardiac Society of Australia and New Zealand</publisher><urls><related-urls><url>;(CSANZ 2016)As with HCM, a recent international task force consensus statement recommends that patients with a definitive diagnosis of ARVC avoid competitive and/or endurance sports and should have restricted participation in athletic activities, with the possible exception of recreational low-intensity sports. In addition, family members with a negative ARVC phenotype (Health gene carriers or those with unknown genotype) should consider restriction from competitive sports. Treatment with anti-arrhythmic drugs such as amiodarone alone or in conjunction with beta blockers is recommended for some ARVC patients, and are recommended as an adjunct to therapy with an ICD. Anti-arrhythmic drugs and beta blockers are not recommended for use in healthy gene carriers. For ARVC patients who develop right- and/or left-sided heart failure treatment with ACE inhibitors, angiotensin II receptor blockers, beta-blockers, and diuretics is recommended. In addition, catheter ablation is an option for ARVC patients who have ventricular tachycardia. ICD implantation (single chamber) should only be considered in high-risk ARVC patients, that is those patients who have experienced an aborted SCD event due to ventricular fibrillation, those with sustained ventricular tachycardia or those with severe left or right (or both) ventricular dysfunction PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db3JyYWRvPC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db3JyYWRvPC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48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ADDIN EN.CITE.DATA (Corrado et al 2015).(a) Will the proposed medical service be used in addition to, or instead of, the nominated comparator(s)? FORMCHECKBOX Yes In addition to FORMCHECKBOX No If yes, please outline the extent of which the current service/comparator is expected to be substituted:Genetic diagnosis will be used in conjunction with the usual clinical diagnosis.Define and summarise how current clinical management pathways (from the point of service delivery onwards) are expected to change as a consequence of introducing the proposed medical service including variation in health care resources (Refer to Question 39 as baseline):The key role of genetic testing for many ACM conditions is to identify asymptomatic carriers who can be targeted for closer surveillance or gene-negative relatives who are unlikely to develop disease and can be released from future screening PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
ZWNOdW0+MTAwPC9SZWNOdW0+PElEVGV4dD4zMTA3ODY1MjwvSURUZXh0PjxEaXNwbGF5VGV4dD4o
VG93YmluIGV0IGFsIDIwMTkpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwMDwv
cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImZhZHN4NTI1d3Y1
ZHQ1ZXByd3d4MHNwc3p0d3ZzOTIwcDB3OSIgdGltZXN0YW1wPSIxNTU4MzMxMzE0Ij4xMDA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRvd2JpbiwgSi4gQS48L2F1dGhv
cj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5BYnJhbXMsIEQuIEouPC9h
dXRob3I+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1dGhvcj48YXV0aG9yPkNhbGtpbnMsIEgu
PC9hdXRob3I+PGF1dGhvcj5EYXJyaWV1eCwgRi4gQy4gQy48L2F1dGhvcj48YXV0aG9yPkRhdWJl
cnQsIEouIFAuPC9hdXRob3I+PGF1dGhvcj5kZSBDaGlsbG91LCBDLjwvYXV0aG9yPjxhdXRob3I+
RGVQYXNxdWFsZSwgRS4gQy48L2F1dGhvcj48YXV0aG9yPkRlc2FpLCBNLiBZLjwvYXV0aG9yPjxh
dXRob3I+RXN0ZXMsIE4uIEEuIE0uLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkh1YSwgVy48L2F1dGhv
cj48YXV0aG9yPkluZGlrLCBKLiBILjwvYXV0aG9yPjxhdXRob3I+SW5nbGVzLCBKLjwvYXV0aG9y
PjxhdXRob3I+SmFtZXMsIEMuIEEuPC9hdXRob3I+PGF1dGhvcj5Kb2huLCBSLiBNLjwvYXV0aG9y
PjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5LZWVnYW4sIFIuPC9hdXRob3I+
PGF1dGhvcj5LcmFobiwgQS4gRC48L2F1dGhvcj48YXV0aG9yPkxpbmssIE0uIFMuPC9hdXRob3I+
PGF1dGhvcj5NYXJjdXMsIEYuIEkuPC9hdXRob3I+PGF1dGhvcj5NY0xlb2QsIEMuIEouPC9hdXRo
b3I+PGF1dGhvcj5NZXN0cm9uaSwgTC48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1
dGhvcj48YXV0aG9yPlNhZmZpdHosIEouIEUuPC9hdXRob3I+PGF1dGhvcj5TYW5hdGFuaSwgUy48
L2F1dGhvcj48YXV0aG9yPlNoaW1penUsIFcuPC9hdXRob3I+PGF1dGhvcj5QZXRlciB2YW4gVGlu
dGVsZW4sIEouPC9hdXRob3I+PGF1dGhvcj5XaWxkZSwgQS4gQS4gTS48L2F1dGhvcj48YXV0aG9y
PlphcmViYSwgVy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz
cz5MZSBCb25oZXVyIENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgTWVtcGhpcywgVGVubmVzc2Vl
OyBVbml2ZXJzaXR5IG9mIFRlbm5lc3NlZSBIZWFsdGggU2NpZW5jZSBDZW50ZXIsIE1lbXBoaXMs
IFRlbm5lc3NlZS4mI3hEO1VuaXZlcnNpdHkgQ29sbGVnZSBMb25kb24sIEluc3RpdHV0ZSBvZiBD
YXJkaW92YXNjdWxhciBTY2llbmNlLCBMb25kb24sIFVuaXRlZCBLaW5nZG9tLiYjeEQ7Qm9zdG9u
IENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgQm9zdG9uLCBNYXNzYWNodXNldHRzLiYjeEQ7TWF5
byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLiYjeEQ7Sm9obnMgSG9wa2lucyBVbml2ZXJz
aXR5LCBCYWx0aW1vcmUsIE1hcnlsYW5kLiYjeEQ7VW5pdmVyc2lkYWRlIGRlIFNhbyBQYXVsbywg
SW5zdGl0dXRvIGRvIENvcmFjYW8gSENGTVVTUCwgU2FvIFBhdWxvLCBCcmF6aWwuJiN4RDtEdWtl
IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIER1cmhhbSwgTm9ydGggQ2Fyb2xpbmEuJiN4RDtO
YW5jeSBVbml2ZXJzaXR5IEhvc3BpdGFsLCBWYW5kb2V1dnJlLWxlcy1OYW5jeSwgRnJhbmNlLiYj
eEQ7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBMb3MgQW5nZWxlcywgTG9zIEFuZ2VsZXMsIENh
bGlmb3JuaWEuJiN4RDtDbGV2ZWxhbmQgQ2xpbmljLCBDbGV2ZWxhbmQsIE9oaW8uJiN4RDtVbml2
ZXJzaXR5IG9mIFBpdHRzYnVyZ2ggTWVkaWNhbCBDZW50ZXIsIFBpdHRzYnVyZ2gsIFBlbm5zeWx2
YW5pYS4mI3hEO0Z1IFdhaSBIb3NwaXRhbCwgQmVpamluZywgQ2hpbmEuJiN4RDtVbml2ZXJzaXR5
IG9mIEFyaXpvbmEsIFNhcnZlciBIZWFydCBDZW50ZXIsIFR1Y3NvbiwgQXJpem9uYS4mI3hEO0Fn
bmVzIEdpbmdlcyBDZW50cmUgZm9yIE1vbGVjdWxhciBDYXJkaW9sb2d5IGF0IENlbnRlbmFyeSBJ
bnN0aXR1dGUsIFRoZSBVbml2ZXJzaXR5IG9mIFN5ZG5leSwgU3lkbmV5LCBBdXN0cmFsaWEuJiN4
RDtWYW5kZXJiaWx0IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIE5hc2h2aWxsZSwgVGVubmVz
c2VlLiYjeEQ7TWVkaWNhbCBVbml2ZXJzaXR5IG9mIFNvdXRoIENhcm9saW5hLCBDaGFybGVzdG9u
LCBTb3V0aCBDYXJvbGluYS4mI3hEO0hvc3BpdGFsIFByaXZhZG8gRGVsIFN1ciwgQnVlbm9zIEFp
cmVzLCBBcmdlbnRpbmE7IEhvc3BpdGFsIEVzcGFub2wsIEJhaGlhIEJsYW5jYSwgQXJnZW50aW5h
LiYjeEQ7VGhlIFVuaXZlcnNpdHkgb2YgQnJpdGlzaCBDb2x1bWJpYSwgVmFuY291dmVyLCBDYW5h
ZGEuJiN4RDtVVCBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywgVGV4YXMuJiN4
RDtVbml2ZXJzaXR5IG9mIENvbG9yYWRvIEFuc2NodXR6IE1lZGljYWwgQ2FtcHVzLCBBdXJvcmEs
IENvbG9yYWRvLiYjeEQ7VW5pdmVyc2l0eSBvZiBQYXZpYSwgUGF2aWEsIEl0YWx5OyBFdXJvcGVh
biBSZWZlcmVuY2UgTmV0d29yayBmb3IgUmFyZSBhbmQgTG93IFByZXZhbGVuY2UgQ29tcGxleCBE
aXNlYXNlcyBvZiB0aGUgSGVhcnQgKEVSTiBHVUFSRC1IZWFydCk7IElDUyBNYXVnZXJpLCBJUkND
UywgUGF2aWEsIEl0YWx5LiYjeEQ7QmV0aCBJc3JhZWwgRGVhY29uZXNzIE1lZGljYWwgQ2VudGVy
LCBCb3N0b24sIE1hc3NhY2h1c2V0dHMuJiN4RDtDaGlsZHJlbiZhcG9zO3MgSGVhcnQgQ2VudGVy
LCBWYW5jb3V2ZXIsIENhbmFkYS4mI3hEO0RlcGFydG1lbnQgb2YgQ2FyZGlvdmFzY3VsYXIgTWVk
aWNpbmUsIE5pcHBvbiBNZWRpY2FsIFNjaG9vbCwgVG9reW8sIEphcGFuLiYjeEQ7VW5pdmVyc2l0
eSBvZiBBbXN0ZXJkYW0sIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBO
ZXRoZXJsYW5kczsgVXRyZWNodCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyIFV0cmVjaHQsIFVu
aXZlcnNpdHkgb2YgVXRyZWNodCwgRGVwYXJ0bWVudCBvZiBHZW5ldGljcywgVXRyZWNodCwgdGhl
IE5ldGhlcmxhbmRzLiYjeEQ7RXVyb3BlYW4gUmVmZXJlbmNlIE5ldHdvcmsgZm9yIFJhcmUgYW5k
IExvdyBQcmV2YWxlbmNlIENvbXBsZXggRGlzZWFzZXMgb2YgdGhlIEhlYXJ0IChFUk4gR1VBUkQt
SGVhcnQpOyBVbml2ZXJzaXR5IG9mIEFtc3RlcmRhbSwgQWNhZGVtaWMgTWVkaWNhbCBDZW50ZXIs
IEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzOyBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBDb2x1
bWJpYSBVbml2ZXJzaXR5IElydmluZyBNZWRpY2FsIENlbnRlciwgTmV3IFlvcmssIE5ldyBZb3Jr
LiYjeEQ7VW5pdmVyc2l0eSBvZiBSb2NoZXN0ZXIgTWVkaWNhbCBDZW50ZXIsIFJvY2hlc3Rlciwg
TmV3IFlvcmsuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+MjAxOSBIUlMgRXhwZXJ0IENv
bnNlbnN1cyBTdGF0ZW1lbnQgb24gRXZhbHVhdGlvbiwgUmlzayBTdHJhdGlmaWNhdGlvbiwgYW5k
IE1hbmFnZW1lbnQgb2YgQXJyaHl0aG1vZ2VuaWMgQ2FyZGlvbXlvcGF0aHk8L3RpdGxlPjxzZWNv
bmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlv
ZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48
ZWRpdGlvbj4yMDE5LzA1LzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BcnJoeXRobW9n
ZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5JQ0QgZGVjaXNpb25zPC9rZXl3
b3JkPjxrZXl3b3JkPmFycmh5dGhtb2dlbmljIHJpZ2h0IHZlbnRyaWN1bGFyIGNhcmRpb215b3Bh
dGh5IGFycmh5dGhtb2dlbmljIGxlZnQgdmVudHJpY3VsYXI8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fy
ZGlvbXlvcGF0aHk8L2tleXdvcmQ+PGtleXdvcmQ+Y2FzY2FkZSBmYW1pbHkgc2NyZWVuaW5nPC9r
ZXl3b3JkPjxrZXl3b3JkPmNhdGhldGVyIGFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPmRpYWdu
b3NpcyBvZiBhcnJoeXRobW9nZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5k
aXNlYXNlIG1lY2hhbmlzbXM8L2tleXdvcmQ+PGtleXdvcmQ+ZWxlY3Ryb3BoeXNpb2xvZ3k8L2tl
eXdvcmQ+PGtleXdvcmQ+ZXhlcmNpc2UgcmVzdHJpY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+Z2Vu
ZXRpYyB0ZXN0aW5nPC9rZXl3b3JkPjxrZXl3b3JkPmdlbmV0aWMgdmFyaWFudHM8L2tleXdvcmQ+
PGtleXdvcmQ+bGVmdCB2ZW50cmljdWxhciBub25jb21wYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk
PnJpc2sgc3RyYXRpZmljYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+dHJlYXRtZW50IG9mIGFycmh5
dGhtb2dlbmljIGNhcmRpb215b3BhdGh5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFy
PjIwMTk8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgOTwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh
dGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykmI3hEOzE1NDctNTI3MSAoTGlua2luZyk8
L2lzYm4+PGFjY2Vzc2lvbi1udW0+MzEwNzg2NTI8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0
ZWQtdXJscz48dXJsPjxzdHlsZSBmYWNlPSJ1bmRlcmxpbmUiIGZvbnQ9ImRlZmF1bHQiIHNpemU9
IjEwMCUiPmh0dHBzOi8vd3d3LnNjaWVuY2VkaXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkv
UzE1NDc1MjcxMTkzMDQzODI/dmlhJTNEaWh1Yjwvc3R5bGU+PC91cmw+PC9yZWxhdGVkLXVybHM+
PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouaHJ0aG0uMjAxOS4wNS4w
MDc8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN
PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv
cmQ+PC9DaXRlPjwvRW5kTm90ZT5=
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
ZWNOdW0+MTAwPC9SZWNOdW0+PElEVGV4dD4zMTA3ODY1MjwvSURUZXh0PjxEaXNwbGF5VGV4dD4o
VG93YmluIGV0IGFsIDIwMTkpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwMDwv
cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImZhZHN4NTI1d3Y1
ZHQ1ZXByd3d4MHNwc3p0d3ZzOTIwcDB3OSIgdGltZXN0YW1wPSIxNTU4MzMxMzE0Ij4xMDA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRvd2JpbiwgSi4gQS48L2F1dGhv
cj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5BYnJhbXMsIEQuIEouPC9h
dXRob3I+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1dGhvcj48YXV0aG9yPkNhbGtpbnMsIEgu
PC9hdXRob3I+PGF1dGhvcj5EYXJyaWV1eCwgRi4gQy4gQy48L2F1dGhvcj48YXV0aG9yPkRhdWJl
cnQsIEouIFAuPC9hdXRob3I+PGF1dGhvcj5kZSBDaGlsbG91LCBDLjwvYXV0aG9yPjxhdXRob3I+
RGVQYXNxdWFsZSwgRS4gQy48L2F1dGhvcj48YXV0aG9yPkRlc2FpLCBNLiBZLjwvYXV0aG9yPjxh
dXRob3I+RXN0ZXMsIE4uIEEuIE0uLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkh1YSwgVy48L2F1dGhv
cj48YXV0aG9yPkluZGlrLCBKLiBILjwvYXV0aG9yPjxhdXRob3I+SW5nbGVzLCBKLjwvYXV0aG9y
PjxhdXRob3I+SmFtZXMsIEMuIEEuPC9hdXRob3I+PGF1dGhvcj5Kb2huLCBSLiBNLjwvYXV0aG9y
PjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5LZWVnYW4sIFIuPC9hdXRob3I+
PGF1dGhvcj5LcmFobiwgQS4gRC48L2F1dGhvcj48YXV0aG9yPkxpbmssIE0uIFMuPC9hdXRob3I+
PGF1dGhvcj5NYXJjdXMsIEYuIEkuPC9hdXRob3I+PGF1dGhvcj5NY0xlb2QsIEMuIEouPC9hdXRo
b3I+PGF1dGhvcj5NZXN0cm9uaSwgTC48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1
dGhvcj48YXV0aG9yPlNhZmZpdHosIEouIEUuPC9hdXRob3I+PGF1dGhvcj5TYW5hdGFuaSwgUy48
L2F1dGhvcj48YXV0aG9yPlNoaW1penUsIFcuPC9hdXRob3I+PGF1dGhvcj5QZXRlciB2YW4gVGlu
dGVsZW4sIEouPC9hdXRob3I+PGF1dGhvcj5XaWxkZSwgQS4gQS4gTS48L2F1dGhvcj48YXV0aG9y
PlphcmViYSwgVy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz
cz5MZSBCb25oZXVyIENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgTWVtcGhpcywgVGVubmVzc2Vl
OyBVbml2ZXJzaXR5IG9mIFRlbm5lc3NlZSBIZWFsdGggU2NpZW5jZSBDZW50ZXIsIE1lbXBoaXMs
IFRlbm5lc3NlZS4mI3hEO1VuaXZlcnNpdHkgQ29sbGVnZSBMb25kb24sIEluc3RpdHV0ZSBvZiBD
YXJkaW92YXNjdWxhciBTY2llbmNlLCBMb25kb24sIFVuaXRlZCBLaW5nZG9tLiYjeEQ7Qm9zdG9u
IENoaWxkcmVuJmFwb3M7cyBIb3NwaXRhbCwgQm9zdG9uLCBNYXNzYWNodXNldHRzLiYjeEQ7TWF5
byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLiYjeEQ7Sm9obnMgSG9wa2lucyBVbml2ZXJz
aXR5LCBCYWx0aW1vcmUsIE1hcnlsYW5kLiYjeEQ7VW5pdmVyc2lkYWRlIGRlIFNhbyBQYXVsbywg
SW5zdGl0dXRvIGRvIENvcmFjYW8gSENGTVVTUCwgU2FvIFBhdWxvLCBCcmF6aWwuJiN4RDtEdWtl
IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIER1cmhhbSwgTm9ydGggQ2Fyb2xpbmEuJiN4RDtO
YW5jeSBVbml2ZXJzaXR5IEhvc3BpdGFsLCBWYW5kb2V1dnJlLWxlcy1OYW5jeSwgRnJhbmNlLiYj
eEQ7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBMb3MgQW5nZWxlcywgTG9zIEFuZ2VsZXMsIENh
bGlmb3JuaWEuJiN4RDtDbGV2ZWxhbmQgQ2xpbmljLCBDbGV2ZWxhbmQsIE9oaW8uJiN4RDtVbml2
ZXJzaXR5IG9mIFBpdHRzYnVyZ2ggTWVkaWNhbCBDZW50ZXIsIFBpdHRzYnVyZ2gsIFBlbm5zeWx2
YW5pYS4mI3hEO0Z1IFdhaSBIb3NwaXRhbCwgQmVpamluZywgQ2hpbmEuJiN4RDtVbml2ZXJzaXR5
IG9mIEFyaXpvbmEsIFNhcnZlciBIZWFydCBDZW50ZXIsIFR1Y3NvbiwgQXJpem9uYS4mI3hEO0Fn
bmVzIEdpbmdlcyBDZW50cmUgZm9yIE1vbGVjdWxhciBDYXJkaW9sb2d5IGF0IENlbnRlbmFyeSBJ
bnN0aXR1dGUsIFRoZSBVbml2ZXJzaXR5IG9mIFN5ZG5leSwgU3lkbmV5LCBBdXN0cmFsaWEuJiN4
RDtWYW5kZXJiaWx0IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIE5hc2h2aWxsZSwgVGVubmVz
c2VlLiYjeEQ7TWVkaWNhbCBVbml2ZXJzaXR5IG9mIFNvdXRoIENhcm9saW5hLCBDaGFybGVzdG9u
LCBTb3V0aCBDYXJvbGluYS4mI3hEO0hvc3BpdGFsIFByaXZhZG8gRGVsIFN1ciwgQnVlbm9zIEFp
cmVzLCBBcmdlbnRpbmE7IEhvc3BpdGFsIEVzcGFub2wsIEJhaGlhIEJsYW5jYSwgQXJnZW50aW5h
LiYjeEQ7VGhlIFVuaXZlcnNpdHkgb2YgQnJpdGlzaCBDb2x1bWJpYSwgVmFuY291dmVyLCBDYW5h
ZGEuJiN4RDtVVCBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywgVGV4YXMuJiN4
RDtVbml2ZXJzaXR5IG9mIENvbG9yYWRvIEFuc2NodXR6IE1lZGljYWwgQ2FtcHVzLCBBdXJvcmEs
IENvbG9yYWRvLiYjeEQ7VW5pdmVyc2l0eSBvZiBQYXZpYSwgUGF2aWEsIEl0YWx5OyBFdXJvcGVh
biBSZWZlcmVuY2UgTmV0d29yayBmb3IgUmFyZSBhbmQgTG93IFByZXZhbGVuY2UgQ29tcGxleCBE
aXNlYXNlcyBvZiB0aGUgSGVhcnQgKEVSTiBHVUFSRC1IZWFydCk7IElDUyBNYXVnZXJpLCBJUkND
UywgUGF2aWEsIEl0YWx5LiYjeEQ7QmV0aCBJc3JhZWwgRGVhY29uZXNzIE1lZGljYWwgQ2VudGVy
LCBCb3N0b24sIE1hc3NhY2h1c2V0dHMuJiN4RDtDaGlsZHJlbiZhcG9zO3MgSGVhcnQgQ2VudGVy
LCBWYW5jb3V2ZXIsIENhbmFkYS4mI3hEO0RlcGFydG1lbnQgb2YgQ2FyZGlvdmFzY3VsYXIgTWVk
aWNpbmUsIE5pcHBvbiBNZWRpY2FsIFNjaG9vbCwgVG9reW8sIEphcGFuLiYjeEQ7VW5pdmVyc2l0
eSBvZiBBbXN0ZXJkYW0sIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBO
ZXRoZXJsYW5kczsgVXRyZWNodCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyIFV0cmVjaHQsIFVu
aXZlcnNpdHkgb2YgVXRyZWNodCwgRGVwYXJ0bWVudCBvZiBHZW5ldGljcywgVXRyZWNodCwgdGhl
IE5ldGhlcmxhbmRzLiYjeEQ7RXVyb3BlYW4gUmVmZXJlbmNlIE5ldHdvcmsgZm9yIFJhcmUgYW5k
IExvdyBQcmV2YWxlbmNlIENvbXBsZXggRGlzZWFzZXMgb2YgdGhlIEhlYXJ0IChFUk4gR1VBUkQt
SGVhcnQpOyBVbml2ZXJzaXR5IG9mIEFtc3RlcmRhbSwgQWNhZGVtaWMgTWVkaWNhbCBDZW50ZXIs
IEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzOyBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBDb2x1
bWJpYSBVbml2ZXJzaXR5IElydmluZyBNZWRpY2FsIENlbnRlciwgTmV3IFlvcmssIE5ldyBZb3Jr
LiYjeEQ7VW5pdmVyc2l0eSBvZiBSb2NoZXN0ZXIgTWVkaWNhbCBDZW50ZXIsIFJvY2hlc3Rlciwg
TmV3IFlvcmsuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+MjAxOSBIUlMgRXhwZXJ0IENv
bnNlbnN1cyBTdGF0ZW1lbnQgb24gRXZhbHVhdGlvbiwgUmlzayBTdHJhdGlmaWNhdGlvbiwgYW5k
IE1hbmFnZW1lbnQgb2YgQXJyaHl0aG1vZ2VuaWMgQ2FyZGlvbXlvcGF0aHk8L3RpdGxlPjxzZWNv
bmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlv
ZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48
ZWRpdGlvbj4yMDE5LzA1LzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BcnJoeXRobW9n
ZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5JQ0QgZGVjaXNpb25zPC9rZXl3
b3JkPjxrZXl3b3JkPmFycmh5dGhtb2dlbmljIHJpZ2h0IHZlbnRyaWN1bGFyIGNhcmRpb215b3Bh
dGh5IGFycmh5dGhtb2dlbmljIGxlZnQgdmVudHJpY3VsYXI8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fy
ZGlvbXlvcGF0aHk8L2tleXdvcmQ+PGtleXdvcmQ+Y2FzY2FkZSBmYW1pbHkgc2NyZWVuaW5nPC9r
ZXl3b3JkPjxrZXl3b3JkPmNhdGhldGVyIGFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPmRpYWdu
b3NpcyBvZiBhcnJoeXRobW9nZW5pYyBjYXJkaW9teW9wYXRoeTwva2V5d29yZD48a2V5d29yZD5k
aXNlYXNlIG1lY2hhbmlzbXM8L2tleXdvcmQ+PGtleXdvcmQ+ZWxlY3Ryb3BoeXNpb2xvZ3k8L2tl
eXdvcmQ+PGtleXdvcmQ+ZXhlcmNpc2UgcmVzdHJpY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+Z2Vu
ZXRpYyB0ZXN0aW5nPC9rZXl3b3JkPjxrZXl3b3JkPmdlbmV0aWMgdmFyaWFudHM8L2tleXdvcmQ+
PGtleXdvcmQ+bGVmdCB2ZW50cmljdWxhciBub25jb21wYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk
PnJpc2sgc3RyYXRpZmljYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+dHJlYXRtZW50IG9mIGFycmh5
dGhtb2dlbmljIGNhcmRpb215b3BhdGh5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFy
PjIwMTk8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgOTwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh
dGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykmI3hEOzE1NDctNTI3MSAoTGlua2luZyk8
L2lzYm4+PGFjY2Vzc2lvbi1udW0+MzEwNzg2NTI8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0
ZWQtdXJscz48dXJsPjxzdHlsZSBmYWNlPSJ1bmRlcmxpbmUiIGZvbnQ9ImRlZmF1bHQiIHNpemU9
IjEwMCUiPmh0dHBzOi8vd3d3LnNjaWVuY2VkaXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkv
UzE1NDc1MjcxMTkzMDQzODI/dmlhJTNEaWh1Yjwvc3R5bGU+PC91cmw+PC9yZWxhdGVkLXVybHM+
PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouaHJ0aG0uMjAxOS4wNS4w
MDc8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN
PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv
cmQ+PC9DaXRlPjwvRW5kTm90ZT5=
ADDIN EN.CITE.DATA (Towbin et al 2019).The CSANZ guidelines state that “In most families, treatment choices are not currently altered by the discovery of a causative gene variant and clinically-affected individuals should receive standard pharmacological and device management. Asymptomatic family members should have baseline cardiac assessment and ongoing periodic cardiac screening for early detection of pre-clinical disease. When a pathogenic genetic variant has been identified in an affected individual, appropriate family members should be offered predictive genetic testing and genetic counselling” ADDIN EN.CITE <EndNote><Cite><Author>CSANZ</Author><Year>2016</Year><RecNum>69</RecNum><DisplayText>(CSANZ 2016)</DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1536131839">69</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>CSANZ</author></authors></contributors><titles><title>Diagnosis and Management of Familial Dilated Cardiomyopathy – Position Statement</title></titles><volume>2018</volume><number>5th September</number><dates><year>2016</year></dates><pub-location>Sydney</pub-location><publisher>Cardiac Society of Australia and New Zealand</publisher><urls><related-urls><url>;(CSANZ 2016). The greatest benefit of genetic testing is the cascade testing of family members of the proband.A genetic diagnosis delivers increased certainty – gene negative relatives may avoid inappropriate treatments and can be released from future clinical surveillance if variant interpretation has been performed robustly, delivering savings to the health system. The 2019 HRS guidelines recommends (Class IIb) that in families with a variant classified as pathogenic, it is reasonable for asymptomatic members of a family who are negative for the familial variant and have a normal cardiovascular evaluation to be released from regular screening PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Towbin et al 2019).PART 6d – INFORMATION ABOUT THE CLINICAL OUTCOMESummarise the clinical claims for the proposed medical service against the appropriate comparator(s), in terms of consequences for health outcomes (comparative benefits and harms):Public funding of genetic testing for the diagnosis of cardiomyopathies would provide equity of access for all Australian patients. Identifying the disease-causing gene variant can be valuable for a family, as it allows the earlier identification, treatment and management of affected probands in addition to at-risk family members, avoiding unnecessary screening of non-carriers. Genetic testing may also help to discriminate between all causes of left ventricular hypertrophy, including hypertension and “athlete’s heart” ADDIN EN.CITE <EndNote><Cite><Author>Semsarian</Author><Year>2011</Year><RecNum>41</RecNum><IDText>22000299</IDText><DisplayText>(Semsarian 2011)</DisplayText><record><rec-number>41</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529902763">41</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Semsarian, C.</author></authors></contributors><auth-address>Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Newtown, NSW 2042, Australia. c.semsarian@.au</auth-address><titles><title>Guidelines for the diagnosis and management of hypertrophic cardiomyopathy</title><secondary-title>Heart Lung Circ</secondary-title></titles><periodical><full-title>Heart Lung Circ</full-title><abbr-1>Heart, lung & circulation</abbr-1></periodical><pages>688-90</pages><volume>20</volume><number>11</number><edition>2011/10/18</edition><keywords><keyword>Adult</keyword><keyword>Cardiomyopathy, Hypertrophic, Familial/diagnosis/genetics/therapy</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Practice Guidelines as Topic</keyword></keywords><dates><year>2011</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1444-2892 (Electronic)
1443-9506 (Linking)</isbn><accession-num>22000299</accession-num><urls><related-urls><url>;(Semsarian 2011). The diagnostic, prognostic and therapeutic impact of variant analysis for the genes involved in the various cardiomyopathies is summarised in REF _Ref517775611 \h Table 2. Although clinical management may not change in all patients who already have a clinical diagnosis that is then confirmed by genetic testing, the value in testing lies in confirming variant-negative family members, who may then avoid clinical monitoring, representing ongoing cost-savings to the health system. Clinical screening may involve a consultation with a cardiologist, an ECG and possibly an exercise stress test conducted on average every two years (item number: 55116 Fee: $261.65 or 55122 Fee: $130.85 in conjunction with 11712 Fee: $152.15, plus consultation 105 Fee $43.65)In addition, evidence is emerging that genotype knowledge may expedite treatments such as heart transplantation for some patients with high-risk genotypes with truncating variants PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3diaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS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ADDIN EN.CITE.DATA (Towbin et al 2019).HCMKnowledge of the underlying gene and variant may have a limited role in risk assessment and management of the individual patient, which instead is based largely on clinical diagnosis. However, validated clinical risk factors including a family history of SCD, suggest that a greater knowledge of genotype–phenotype correlations is useful in HCM. For example, patients with features of HCM but without pathogenic sarcomere variants have a lower likelihood of a positive family history and, on average, a milder phenotype; thus, a negative genetic test may be of prognostic significance. There are only a few specific variants that carry a prognostic implication, and ordinarily a genetic test result in isolation will not constitute an indication for an ICD for primary prevention. Many families have a previously unrecorded variant. Long-term efforts are needed to accumulate reliable evidence on genotype–phenotype correlations, especially those pertaining to specific variants. Within typical, sarcomeric HCM, no HCM variant-specific therapeutic implications exist, as therapy in HCM is not disease modifying and treatment response is not influenced by variant type PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011).ARVCLeft ventricular involvement is more marked in families with chain-termination variants and/or desmoplakin disease, while individuals harbouring PKP2 variants may have earlier onset of both symptoms and ventricular arrhythmia. Intra-familial phenotype diversity, however, is prominent. Variance component analysis suggests that both genetic and environmental modifiers contribute significantly to varying disease penetrance and phenotypic manifestations, including arrhythmic outcome, between family members who carry a gene variant in arrhythmogenic cardiomyopathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+
PFJlY051bT4yOTwvUmVjTnVtPjxJRFRleHQ+MjE3ODc5OTk8L0lEVGV4dD48RGlzcGxheVRleHQ+
KEFja2VybWFuIGV0IGFsIDIwMTEpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjI5
PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZmFkc3g1MjV3
djVkdDVlcHJ3d3gwc3BzenR3dnM5MjBwMHc5IiB0aW1lc3RhbXA9IjE1MjkzODg2NTciPjI5PC9r
ZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3Jl
Zi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5BY2tlcm1hbiwgTS4gSi48L2F1
dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1dGhvcj48YXV0aG9yPldpbGxlbXMsIFMuPC9h
dXRob3I+PGF1dGhvcj5CZXJ1bCwgQy48L2F1dGhvcj48YXV0aG9yPkJydWdhZGEsIFIuPC9hdXRo
b3I+PGF1dGhvcj5DYWxraW5zLCBILjwvYXV0aG9yPjxhdXRob3I+Q2FtbSwgQS4gSi48L2F1dGhv
cj48YXV0aG9yPkVsbGlub3IsIFAuIFQuPC9hdXRob3I+PGF1dGhvcj5Hb2xsb2IsIE0uPC9hdXRo
b3I+PGF1dGhvcj5IYW1pbHRvbiwgUi48L2F1dGhvcj48YXV0aG9yPkhlcnNoYmVyZ2VyLCBSLiBF
LjwvYXV0aG9yPjxhdXRob3I+SnVkZ2UsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5MZSBNYXJlYywg
SC48L2F1dGhvcj48YXV0aG9yPk1jS2VubmEsIFcuIEouPC9hdXRob3I+PGF1dGhvcj5TY2h1bHpl
LUJhaHIsIEUuPC9hdXRob3I+PGF1dGhvcj5TZW1zYXJpYW4sIEMuPC9hdXRob3I+PGF1dGhvcj5U
b3diaW4sIEouIEEuPC9hdXRob3I+PGF1dGhvcj5XYXRraW5zLCBILjwvYXV0aG9yPjxhdXRob3I+
V2lsZGUsIEEuPC9hdXRob3I+PGF1dGhvcj5Xb2xwZXJ0LCBDLjwvYXV0aG9yPjxhdXRob3I+Wmlw
ZXMsIEQuIFAuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+
TWF5byBDbGluaWMsIFJvY2hlc3RlciwgTWlubmVzb3RhLCBVU0EuPC9hdXRoLWFkZHJlc3M+PHRp
dGxlcz48dGl0bGU+SFJTL0VIUkEgZXhwZXJ0IGNvbnNlbnN1cyBzdGF0ZW1lbnQgb24gdGhlIHN0
YXRlIG9mIGdlbmV0aWMgdGVzdGluZyBmb3IgdGhlIGNoYW5uZWxvcGF0aGllcyBhbmQgY2FyZGlv
bXlvcGF0aGllcyB0aGlzIGRvY3VtZW50IHdhcyBkZXZlbG9wZWQgYXMgYSBwYXJ0bmVyc2hpcCBi
ZXR3ZWVuIHRoZSBIZWFydCBSaHl0aG0gU29jaWV0eSAoSFJTKSBhbmQgdGhlIEV1cm9wZWFuIEhl
YXJ0IFJoeXRobSBBc3NvY2lhdGlvbiAoRUhSQSk8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+SGVh
cnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0
bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48cGFnZXM+MTMwOC0zOTwv
cGFnZXM+PHZvbHVtZT44PC92b2x1bWU+PG51bWJlcj44PC9udW1iZXI+PGVkaXRpb24+MjAxMS8w
Ny8yNzwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QnJ1Z2FkYSBTeW5kcm9tZS9nZW5ldGlj
czwva2V5d29yZD48a2V5d29yZD5DYXJkaW9teW9wYXRoaWVzLyBkaWFnbm9zaXMvIGdlbmV0aWNz
PC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGh5LCBIeXBlcnRyb3BoaWMvZGlhZ25vc2lz
L2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGh5LCBSZXN0cmljdGl2ZS9j
b21wbGljYXRpb25zL2RpYWdub3Npczwva2V5d29yZD48a2V5d29yZD5DaGFubmVsb3BhdGhpZXMv
IGRpYWdub3Npcy8gZ2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+RGlzZWFzZSBQcm9ncmVzc2lv
bjwva2V5d29yZD48a2V5d29yZD5HZW5ldGljIENvdW5zZWxpbmc8L2tleXdvcmQ+PGtleXdvcmQ+
R2VuZXRpYyBUZXN0aW5nL3N0YW5kYXJkczwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv
cmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkF1
ZzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NTYtMzg3MSAoRWxlY3Ryb25pYykm
I3hEOzE1NDctNTI3MSAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjE3ODc5OTk8L2Fj
Y2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHBzOi8vd3d3LnNjaWVuY2Vk
aXJlY3QuY29tL3NjaWVuY2UvYXJ0aWNsZS9waWkvUzE1NDc1MjcxMTEwMDYwNzI/dmlhJTNEaWh1
YjwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAu
MTAxNi9qLmhydGhtLjIwMTEuMDUuMDIwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3Rl
LWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFn
ZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==
ADDIN EN.CITE.DATA (Ackerman et al 2011).DCMThere is no prognostic role of genetic testing for DCM except for the increased risk of sudden cardiac death in LMNA- and DES mediated disease. A therapeutic role for DCM genetic testing exists for patients with DCM and prominent cardiac conduction system disease that often stems from variants in LMNA. Because cardiac conduction disease (e.g., first-, second-, or third-degree heart block) and supra-ventricular arrhythmias commonly precede life-threatening ventricular arrhythmias, early or pre-emptive use of an implantable cardiac defibrillator (rather than a pacemaker) has been advocated prior to the occurrence of life-threatening syncope or SCD. It is unknown whether early pharmacological treatment of variant-positive, pre-clinical subjects can prevent or delay manifestation of the disease. Genetic testing also has a therapeutic role for syndromic disease (e.g., muscular dystrophy) with known arrhythmia and/or conduction system disease (e.g., LMNA, DES variants) in terms of possible consideration of a prophylactic pacemaker and/or ICD PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BY2tlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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ADDIN EN.CITE.DATA (Ackerman et al 2011).Table SEQ Table \* ARABIC 2Impact of genetic testing for the index case ADDIN EN.CITE <EndNote><Cite><Author>Semsarian</Author><Year>2011</Year><RecNum>41</RecNum><IDText>22000299</IDText><DisplayText>(Semsarian 2011)</DisplayText><record><rec-number>41</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529902763">41</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Semsarian, C.</author></authors></contributors><auth-address>Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Newtown, NSW 2042, Australia. c.semsarian@.au</auth-address><titles><title>Guidelines for the diagnosis and management of hypertrophic cardiomyopathy</title><secondary-title>Heart Lung Circ</secondary-title></titles><periodical><full-title>Heart Lung Circ</full-title><abbr-1>Heart, lung & circulation</abbr-1></periodical><pages>688-90</pages><volume>20</volume><number>11</number><edition>2011/10/18</edition><keywords><keyword>Adult</keyword><keyword>Cardiomyopathy, Hypertrophic, Familial/diagnosis/genetics/therapy</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Practice Guidelines as Topic</keyword></keywords><dates><year>2011</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1444-2892 (Electronic)
1443-9506 (Linking)</isbn><accession-num>22000299</accession-num><urls><related-urls><url>;(Semsarian 2011)DiseaseDiagnosticPrognosticTherapeuticHCM++++++ACM/ARVC++/--DCM---Relative strength: - = negligible to +++ = strongPlease advise if the overall clinical claim is for: FORMCHECKBOX Superiority FORMCHECKBOX Non-inferiorityBelow, list the key health outcomes (major and minor – prioritising major key health outcomes first) that will need to be specifically measured in assessing the clinical claim of the proposed medical service versus the comparator:Direct evidenceSafety Outcomes: Physical and/or psychological harms from testing or no testing, adverse events from testingClinical Effectiveness Outcomes: Quality of life, reduced morbidity, mortalityCost-effectivenessIndirect evidenceAnalytical validity: test failure rate, sensitivity, specificity, concordance, unsatisfactory or uninterpretable results, diagnostic yieldClinical validity: predictive or prognostic valueTherapeutic efficacy: change in patient management, change in detection and treatment of family membersTherapeutic effectiveness: effect of change in management (e.g. reduction in mortality, increased quality of life)PART 7 – INFORMATION ABOUT ESTIMATED UTILISATIONEstimate the prevalence and/or incidence of the proposed population:Australian prevalence and incidence data for the cardiomyopathies are not well defined. The National Australian Childhood Cardiomyopathy Study (NACCS) is a population-based cohort study comprising all Australian children under the age of 10 years who were diagnosed with cardiomyopathy over a 10-year period (January 1, 1987 to December 31, 1996). A total of 314 new cases of cardiomyopathy were reported during the 10-year study period: 184 cases of DCM (58.6%), 80 cases of HCM (25.5%), 42 cases of unclassified cardiomyopathy (13.4%), and 8 cases of restrictive cardiomyopathy (2.5%). Of 42 children with unclassified cardiomyopathy, 29 had LVNC (9.2% of all cases), 9 had cardiac hypertrophy with initially impaired systolic function, 2 had familial neonatal cardiomyopathy that caused death within hours after delivery, 1 had oncocytic cardiomyopathy, and 1 had left ventricular dysfunction associated with a congenital left ventricular diverticulum. The annual incidence of each type of cardiomyopathy is summarised in REF _Ref517775522 \h Table 3. The overall annual incidence for all cardiomyopathies combined was 1.24 per 100,000 children younger than 10 years of age ADDIN EN.CITE <EndNote><Cite><Author>Nugent</Author><Year>2003</Year><RecNum>51</RecNum><IDText>12711738</IDText><DisplayText>(Nugent et al 2003)</DisplayText><record><rec-number>51</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529910084">51</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nugent, A. W.</author><author>Daubeney, P. E.</author><author>Chondros, P.</author><author>Carlin, J. B.</author><author>Cheung, M.</author><author>Wilkinson, L. C.</author><author>Davis, A. M.</author><author>Kahler, S. G.</author><author>Chow, C. W.</author><author>Wilkinson, J. L.</author><author>Weintraub, R. G.</author></authors></contributors><auth-address>Departments of Cardiology, Royal Children's Hospital, Melbourne, Australia.</auth-address><titles><title>The epidemiology of childhood cardiomyopathy in Australia</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><pages>1639-46</pages><volume>348</volume><number>17</number><edition>2003/04/25</edition><keywords><keyword>Age Distribution</keyword><keyword>Australia/epidemiology</keyword><keyword>Cardiomyopathies/ epidemiology/ethnology/etiology</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Cohort Studies</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Infant</keyword><keyword>Lymphocytes</keyword><keyword>Male</keyword><keyword>Myocarditis/complications/immunology</keyword><keyword>Retrospective Studies</keyword><keyword>Sex Distribution</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr 24</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>12711738</accession-num><urls></urls><electronic-resource-num>10.1056/NEJMoa021737</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Nugent et al 2003). Based on ABS population data, the number of children aged 10 years and under in the year ending June 2017 was 3,474,771, which would result in an expectation of 43 new paediatric cases per year ADDIN EN.CITE <EndNote><Cite><Author>ABS</Author><Year>2018</Year><RecNum>52</RecNum><DisplayText>(ABS 2018)</DisplayText><record><rec-number>52</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529980231">52</key></foreign-keys><ref-type name="Online Database">45</ref-type><contributors><authors><author>ABS</author></authors></contributors><titles><title>3101.0 - Australian Demographic Statistics, Dec 2017: TABLE 59. Estimated Resident Population By Single Year Of Age, Australia </title></titles><dates><year>2018</year><pub-dates><date>26th June 2018</date></pub-dates></dates><pub-location>Canberra</pub-location><publisher>Australian Bureau of Statistics</publisher><urls></urls></record></Cite></EndNote>(ABS 2018). However, the issue of age-related penetrance, and variable penetrance makes cardiomyopathies more complex. Relying on the potential incidence in a paediatric population will be misleading as cardiomyopathies are generally later onset diseases, and although they may present in childhood, more often they will not.HCMThe estimated prevalence of HCM of 1 in 500 is based on data originally collected almost 20 years ago in the landmark CARDIA (Coronary Artery Risk Development in Young Adults) cohort study conducted in the US, which reported standard echocardiographic analyses in 4,111 unrelated people 23 to 35 years of age PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJvbjwvQXV0aG9yPjxZZWFyPjE5OTU8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJvbjwvQXV0aG9yPjxZZWFyPjE5OTU8L1llYXI+PFJl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ADDIN EN.CITE.DATA (Maron et al 1995; Semsarian 2011). Probable or definite echocardiographic evidence of HCM was present in 7 subjects (0.17%) on the basis of identification of a hypertrophied, non-dilated left ventricle and maximal wall thickness ≥15 mm that were not associated with systemic hypertension. Prevalence was higher in men compared to women (0.26% vs 0.09%) and in African-Americans compared to Caucasians (0.24% vs 0.10%) ADDIN EN.CITE <EndNote><Cite><Author>Maron</Author><Year>1995</Year><RecNum>45</RecNum><IDText>7641357</IDText><DisplayText>(Maron et al 1995)</DisplayText><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529908442">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Maron, B. J.</author><author>Gardin, J. M.</author><author>Flack, J. M.</author><author>Gidding, S. S.</author><author>Kurosaki, T. T.</author><author>Bild, D. E.</author></authors></contributors><auth-address>Cardiovascular Research Division, Minneapolis Heart Institute Foundation, MN 55407, USA.</auth-address><titles><title>Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></periodical><pages>785-9</pages><volume>92</volume><number>4</number><edition>1995/08/15</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Cardiomyopathy, Hypertrophic/ diagnostic imaging/ epidemiology</keyword><keyword>Cohort Studies</keyword><keyword>Coronary Disease/epidemiology</keyword><keyword>Echocardiography</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Hypertrophy, Left Ventricular/diagnostic imaging</keyword><keyword>Male</keyword><keyword>Prevalence</keyword><keyword>Risk Factors</keyword></keywords><dates><year>1995</year><pub-dates><date>Aug 15</date></pub-dates></dates><isbn>0009-7322 (Print)
0009-7322 (Linking)</isbn><accession-num>7641357</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Maron et al 1995). Semsarian et al (2015), however, re-examined data on the variant analysis of asymptomatic individuals in the general population and has estimated that the prevalence of HCM gene carriers could be more than 1 in 200 people or greater PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TZW1zYXJpYW48L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TZW1zYXJpYW48L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy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ADDIN EN.CITE.DATA (Semsarian et al 2015).Few estimates of the prevalence of DCM exist; however, it has been estimated to be twice that of HCM (1:250) (Hershberger & Morales 2015). The prevalence of ARVC is estimated at 1:1,000 to 1:1,250 in the general population (McNally et al 2017).Table SEQ Table \* ARABIC 3Annual incidence of each type of cardiomyopathy in a paediatric population, according to the age at presentation ADDIN EN.CITE <EndNote><Cite><Author>Nugent</Author><Year>2003</Year><RecNum>51</RecNum><IDText>12711738</IDText><DisplayText>(Nugent et al 2003)</DisplayText><record><rec-number>51</rec-number><foreign-keys><key app="EN" db-id="fadsx525wv5dt5eprwwx0spsztwvs920p0w9" timestamp="1529910084">51</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nugent, A. W.</author><author>Daubeney, P. E.</author><author>Chondros, P.</author><author>Carlin, J. B.</author><author>Cheung, M.</author><author>Wilkinson, L. C.</author><author>Davis, A. M.</author><author>Kahler, S. G.</author><author>Chow, C. W.</author><author>Wilkinson, J. L.</author><author>Weintraub, R. G.</author></authors></contributors><auth-address>Departments of Cardiology, Royal Children's Hospital, Melbourne, Australia.</auth-address><titles><title>The epidemiology of childhood cardiomyopathy in Australia</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><pages>1639-46</pages><volume>348</volume><number>17</number><edition>2003/04/25</edition><keywords><keyword>Age Distribution</keyword><keyword>Australia/epidemiology</keyword><keyword>Cardiomyopathies/ epidemiology/ethnology/etiology</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Cohort Studies</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Infant</keyword><keyword>Lymphocytes</keyword><keyword>Male</keyword><keyword>Myocarditis/complications/immunology</keyword><keyword>Retrospective Studies</keyword><keyword>Sex Distribution</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr 24</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>12711738</accession-num><urls></urls><electronic-resource-num>10.1056/NEJMoa021737</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Nugent et al 2003)Type of cardiomyopathyAge at presentation0 to <1 year1 to < 2 year2 < 5 year5 to <10 yearTotalDilated cardiomyopathyNumber of children121291816184Annual incidence/100,000 children4.761.140.240.130.7395 % CI3.95, 5.690.77, 1.640.14, 0.370.07, 0.210.63, 0.84Hypertrophic cardiomyopathyNumber of children489101380Annual incidence/100,000 children1.890.360.130.100.3295 % CI1.39, 2.510.16, 0.670.06, 0.240.06, 0.180.25, 0.39Restrictive cardiomyopathyNumber of children01438Annual incidence/100,000 children00.040.050.020.0395 % CI0, 0.150, 0.220.01, 0.130.01, 0.070.01, 0.06UnclassifiedNumber of children3054342Annual incidence/100,000 children1.180.200.050.020.1795 % CI0.80, 1.690.06, 0.460.01, 0.130.01, 0.070.12, 0.22TotalNumber of children199443635314Annual incidence/100,000 children7.841.730.470.281.2495 % CI6.79, 9.01.26, 2.330.33, 0.650.19, 0.391.11, 1.38Estimate the number of times the proposed medical service(s) would be delivered to a patient per year:The test would be conducted once per patient lifetime. Cascade testing would also be a one-off single gene investigation for first-degree relatives of the affected patient, where clinically indicated.How many years would the proposed medical service(s) be required for the patient?N/A - testing would be conducted once per lifetime. Testing may be repeated in variant-negative patients if, in the future, new genes are added to the panel.Estimate the projected number of patients who will utilise the proposed medical service(s) for the first full year:Initially there may be some “catch up”, with testing of the prevalent (those with a clinical diagnosis) rather than the true incident population. It would therefore be expected that testing numbers may be slightly higher in the first year, compared to following years. Incidence data has been difficult to obtain. The RCPA conducted a survey, on behalf of the Commonwealth Department of Health, of all Australian laboratories (n=87) known to offer genetic/ genomic tests that yielded results with medical utility during the 2016/17 financial year. This data remains confidential until such time that the Department publishes the report. Participation in the survey was 96.6% of all public and private sector laboratories. The private and public sector delivered 71% and 29% of all genomic tests for heritable conditions, respectively; however, the data is unclear which sector provided testing for cardiovascular indications. It should be noted that those tests conducted in the private sector would be on a user-pays basis, and would therefore represent an underestimation of the true number as many patients would be unable to meet the cost of testing. Similarly, the number of tests conducted in the public sector would also represent an underestimation of the true number due to long waiting lists and limited funding.During the one year sample period, cardiologists requested a total of 2,324 tests. It would also be expected that a proportion of 40,579 tests requested by clinical geneticists would be for cardiology indications. In addition, a total of 244 samples were referred to international laboratories for genetic testing for cardiac disorders.The number of tests conducted with targeted multi-gene panels (testing ≥3 genes) were:Panel – Cardiomyopathy (11-50 genes)86Panel – Cardiomyopathy (51+ genes)159.However, it is possible that some cardiomyopathy tests may have been conducted in the following:Panel – Cardiac (11-50 genes)403Panel – Cardiac (51+ genes)461.In addition, targeted analysis of single genes took place:Cardiomyopathy, dilated, RBM206Cardiomyopathy, dilated, TTN5These figures may be used to approximate a potential upper and lower utilisation estimation, both of which would be an underestimation of usage: Lower limit (# of cardiomyopathy tests only)256Upper limit 417It should also be noted that the Australian Genomics Cardiac Flagship is currently conducting an audit of flagship sites in Queensland, Victoria and New South Wales to ascertain the number of cardiac diagnostic genetic tests being conducted – this data will be available in the near future and would inform costing calculations for the assessment.Estimate the anticipated uptake of the proposed medical service over the next three years factoring in any constraints in the health system in meeting the needs of the proposed population (such as supply and demand factors) as well as provide commentary on risk of ‘leakage’ to populations not targeted by the service:Testing levels are likely to be slightly less in the second and third years of implementation due to the likely testing of some of the prevalent population in year 1 of funding.PART 8 – COST INFORMATIONIndicate the likely cost of providing the proposed medical service. Where possible, please provide overall cost and breakdown:The estimated cost of providing the test is $1,800, with cascade testing of a known variant in a relative costing $400.Specify how long the proposed medical service typically takes to perform:It would be expected that a test would be performed and reported on within a 4-8 week turnaround time.If public funding is sought through the MBS, please draft a proposed MBS item descriptor to define the population and medical service usage characteristics that would define eligibility for MBS funding.Item descriptor diagnostic genetic testing of affected individualsCategory 6 – PATHOLOGY SERVICES Proposed item descriptor: AAAACharacterisation of germline variants for inherited cardiomyopathies in a patient who fulfils diagnostic criteria for cardiomyopathy, as assessed by specialist or consultant physician such as a cardiologist with experience in the genetic management of cardiac disease.Fee: $1800Item descriptor predictive genetic testing of family membersCategory 6 – PATHOLOGY SERVICES Proposed item descriptor: BBBBRequest by a clinical geneticist, or a medical specialist providing professional genetic counselling services, for the detection of a clinically actionable pathogenic variant previously identified by Item AAAA in a first- or second-degree relative.Fee: $400References ADDIN EN.REFLIST ABS (2018). 3101.0 - Australian Demographic Statistics, Dec 2017: TABLE 59. Estimated Resident Population By Single Year Of Age, Australia [Internet]. Australian Bureau of Statistics. Available from: [Accessed 26th June 2018].Ackerman, M. J., Priori, S. G. et al (2011). 'HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA)', Heart Rhythm, 8 (8), 1308-1339.Alfares, A. A. & Kelly, M. A. (2015). 'Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity', 17 (11), 880-888.Andersen, P. S., Havndrup, O. et al (2009). 'Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives', Hum Mutat, 30 (3), 363-370.Bagnall, R. D., Ingles, J. et al (2018). 'Whole Genome Sequencing Improves Outcomes of Genetic Testing in Patients With Hypertrophic Cardiomyopathy', J Am Coll Cardiol, 72 (4), 419-429.Burns, C., Bagnall, R. D. et al (2017). 'Multiple Gene Variants in Hypertrophic Cardiomyopathy in the Era of Next-Generation Sequencing', Circ Cardiovasc Genet, 10 (4).Cardoso, B., Gomes, I. et al (2017). 'Clinical and genetic diagnosis of familial hypertrophic cardiomyopathy: Results in pediatric cardiology', Rev Port Cardiol, 36 (3), 155-165.Catchpool, M., Ramchand, J. et al (2019). 'A cost-effectiveness model of genetic testing and periodical clinical screening for the evaluation of families with dilated cardiomyopathy', Genet Med.Cecconi, M., Parodi, M. I. et al (2016). 'Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy', Int J Mol Med, 38 (4), 1111-1124.Cirino, A. L. & Ho, C. (2014). Hypertrophic Cardiomyopathy Overview [Internet]. University of Washington. Available from: [Accessed 19 June 2018].Corrado, D., Wichter, T. et al (2015). 'Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement', Eur Heart J, 36 (46), 3227-3237.CSANZ (2016). Diagnosis and Management of Familial Dilated Cardiomyopathy – Position Statement [Internet]. Cardiac Society of Australia and New Zealand. Available from: [Accessed 5th September 2018].Forleo, C., D'Erchia, A. M. et al (2017). 'Targeted next-generation sequencing detects novel gene-phenotype associations and expands the mutational spectrum in cardiomyopathies', PLoS One, 12 (7), e0181842.Gersh, B. J., Maron, B. J. et al (2011a). '2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines', Circulation, 124 (24), e783-831.Gersh, B. J., Maron, B. J. et al (2011b). '2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons', J Am Coll Cardiol, 58 (25), e212-260.Glotov, A. S., Kazakov, S. V. et al (2015). 'Targeted next-generation sequencing (NGS) of nine candidate genes with custom AmpliSeq in patients and a cardiomyopathy risk group', Clin Chim Acta, 446, 132-140.Herkert, J. C., Abbott, K. M. et al (2018). 'Toward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy', Genet Med, 20 (11), 1374-1386.Hershberger, R. E., Givertz, M. M. et al (2018). 'Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)', Genet Med.Hershberger, R. E. & Morales, A. (2015). Dilated Cardiomyopathy Overview [Internet]. University of Washington. Available from: [Accessed 19 June 2018].Horvat, C., Johnson, R. et al (2019). 'A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy', Genetics in Medicine, 21 (1), 133-143.Ingles, J., McGaughran, J. et al (2012). 'A cost-effectiveness model of genetic testing for the evaluation of families with hypertrophic cardiomyopathy', Heart, 98 (8), 625-630.Jensen, M. K., Havndrup, O. et al (2013). 'Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing', Circulation, 127 (1), 48-54.Jimenez-Jaimez, J., Alcalde Martinez, V. et al (2017). 'Clinical and Genetic Diagnosis of Nonischemic Sudden Cardiac Death', Rev Esp Cardiol (Engl Ed), 70 (10), 808-816.Lopes, L. R., Zekavati, A. et al (2013). 'Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing', J Med Genet, 50 (4), 228-239.Mademont-Soler, I., Mates, J. et al (2017). 'Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy', PLoS One, 12 (8), e0181465.Maron, B. J., Gardin, J. M. et al (1995). 'Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults', Circulation, 92 (4), 785-789.McNally, E., MacLeod, H. & Dellefave-Castillo, L. (2017). Arrhythmogenic Right Ventricular Cardiomyopathy [Internet]. University of Washington. Available from: [Accessed 19 June 2018].Minoche, A. E., Horvat, C. et al (2018). 'Genome sequencing as a first-line genetic test in familial dilated cardiomyopathy', Genet Med.Nugent, A. W., Daubeney, P. E. et al (2003). 'The epidemiology of childhood cardiomyopathy in Australia', N Engl J Med, 348 (17), 1639-1646.Rubattu, S., Bozzao, C. et al (2016). 'A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort', Int J Mol Sci, 17 (8).Semsarian, C. (2011). 'Guidelines for the diagnosis and management of hypertrophic cardiomyopathy', Heart Lung Circ, 20 (11), 688-690.Semsarian, C., Ingles, J. et al (2015). 'New perspectives on the prevalence of hypertrophic cardiomyopathy', J Am Coll Cardiol, 65 (12), 1249-1254.Sousa, A., Canedo, P. et al (2019). 'Molecular characterization of Portuguese patients with dilated cardiomyopathy', Rev Port Cardiol, 38 (2), 129-139.Szabadosova, V., Boronova, I. et al (2018). 'Analysis of selected genes associated with cardiomyopathy by next-generation sequencing', J Clin Lab Anal, 32 (2).Towbin, J. A., McKenna, W. J. et al (2019). '2019 HRS Expert Consensus Statement on Evaluation, Risk Stratification, and Management of Arrhythmogenic Cardiomyopathy', Heart Rhythm.van Velzen, H. G., Schinkel, A. F. L. et al (2018). 'Outcomes of Contemporary Family Screening in Hypertrophic Cardiomyopathy', Circ Genom Precis Med, 11 (4), e001896.Waldmuller, S., Schroeder, C. et al (2015). 'Targeted 46-gene and clinical exome sequencing for mutations causing cardiomyopathies', Mol Cell Probes, 29 (5), 308-314. ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related searches
- part 1 illuminating photosynthesis answers
- part 1 illuminating photosynthesis worksheet
- ielts writing part 1 tips
- ielts speaking part 1 questions and answers
- ielts speaking part 1 education
- ielts speaking part 1 sample
- ielts speaking part 1 questions
- ielts speaking part 1 vocabulary
- ielts speaking part 1 question
- ielts speaking part 1 history
- ielts speaking part 1 samples
- breaking dawn twilight part 1 full movie