Yield and clinical significance of genetic screening in elite and amateur athletes.

AIMS The purpose of this study was to assess the value of genetic testing in addition to a comprehensive clinical evaluation, as part of the diagnostic work-up of elite and/or amateur Italian athletes referred for suspicion of inherited cardiac disease, following a pre-participation screening programme. METHODS Between January 2009-December 2018, of 5892 consecutive participants, 61 athletes were investigated: 30 elite and 31 amateur athletes. Elite and amateur athletes were selected, on the basis of clinical suspicion for inherited cardiac disease, from two experienced centres for a comprehensive cardiovascular evaluation. Furthermore, the elite and amateur athletes were investigated for variants at DNA level up to 138 genes suspected to bear predisposition for possible cardiac arrest or even sudden cardiac death. RESULTS Of these 61 selected subjects, six (10%) had diagnosis made possible by a deeper clinical evaluation, while genetic testing allowed a definite diagnosis in eight (13%). The presence of >3 clinical markers (i.e. family history, electrocardiogram and/or echocardiographic abnormalities, exercise-induced ventricular arrhythmias) was associated with a higher probability of positive genetic diagnosis (75%), compared with the presence of two or one clinical markers (14.2%, 8.1%, respectively, p-value = 0.004). CONCLUSION A combined clinical and genetic evaluation, based on the subtle evidence of clinical markers for inherited disease, was able to identify an inherited cardiac disease in about one-quarter of the examined athletes.

[1]  G. Limongelli,et al.  Genetic analysis resolves differential diagnosis of a familial syndromic dilated cardiomyopathy: A new case of Alström syndrome , 2020, Molecular genetics & genomic medicine.

[2]  A. Pressler,et al.  Brief recommendations for participation in leisure time or competitive sports in athletes–patients with coronary artery disease: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC) , 2020, European journal of preventive cardiology.

[3]  P. Elliott,et al.  Prevalence and clinical significance of red flags in patients with hypertrophic cardiomyopathy. , 2020, International journal of cardiology.

[4]  D. Corrado,et al.  The Italian preparticipation evaluation programme: diagnostic yield, rate of disqualification and cost analysis , 2019, British Journal of Sports Medicine.

[5]  M. Lafreniere-Roula,et al.  Family screening for hypertrophic cardiomyopathy: Is it time to change practice guidelines? , 2019, European heart journal.

[6]  A. Pressler,et al.  Brief recommendations for participation in competitive sports of athletes with arterial hypertension: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC) , 2019, European journal of preventive cardiology.

[7]  F. Pigozzi,et al.  Electrocardiographic and echocardiographic evaluation of a large cohort of peri-pubertal soccer players during pre-participation screening , 2019, European journal of preventive cardiology.

[8]  E. Behr,et al.  Diagnostic Yield of Genetic Testing in Young Athletes With T-Wave Inversion , 2018, Circulation.

[9]  H. Kwon,et al.  DIFFERENT CONTRIBUTION OF SARCOMERE AND MITOCHONDRIA RELATED GENE MUTATIONS TO HYPERTROPHIC CARDIOMYOPATHY , 2018 .

[10]  G. Lip,et al.  Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death: Position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE , 2017, European journal of preventive cardiology.

[11]  C. Yancy,et al.  Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association. , 2016, Circulation.

[12]  Andrea Mazzanti,et al.  2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. , 2016, Revista espanola de cardiologia.

[13]  B. Maron,et al.  Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. , 2015, Journal of the American College of Cardiology.

[14]  Bale,et al.  Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology , 2015, Genetics in Medicine.

[15]  F. Rutten,et al.  2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). , 2014, European heart journal.

[16]  C. Tracy,et al.  HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. , 2013, Heart rhythm.

[17]  K. Siminovitch,et al.  Sarcomere Protein Gene Mutations in Patients With Apical Hypertrophic Cardiomyopathy , 2011, Circulation. Cardiovascular genetics.

[18]  F. Salvatore,et al.  Efficacy of pharmacological treatment and genetic characterization in early diagnosed patients affected by long QT syndrome with impaired AV conduction. , 2011, International journal of cardiology.

[19]  Wojciech Zareba,et al.  Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: Proposed Modification of the Task Force Criteria , 2010, European heart journal.

[20]  Barry J Maron,et al.  Recommendations for interpretation of 12-lead electrocardiogram in the athlete. , 2009, European heart journal.

[21]  G. Limongelli,et al.  A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy , 2009, Clinical genetics.

[22]  D. Prior,et al.  Athlete's heart: the potential for multimodality imaging to address the critical remaining questions. , 2009, JACC. Cardiovascular imaging.

[23]  Maurizio Schiavon,et al.  Pre-participation screening of young competitive athletes for prevention of sudden cardiac death. , 2008, Journal of the American College of Cardiology.

[24]  B. Maron,et al.  Outcomes in athletes with marked ECG repolarization abnormalities. , 2008, The New England journal of medicine.

[25]  Domenico de Rasmo,et al.  A larger spectrum of intragenic short tandem repeats improves linkage analysis and localization of intragenic recombination detection in the dystrophin gene: an analysis of 93 families from southern Italy. , 2007, The Journal of molecular diagnostics : JMD.

[26]  Barry J Maron,et al.  The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death. , 2006, Circulation.

[27]  Maurizio Schiavon,et al.  Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. , 2006, JAMA.

[28]  Maurizio Schiavon,et al.  Does sports activity enhance the risk of sudden death in adolescents and young adults? , 2003, Journal of the American College of Cardiology.

[29]  K. P. Carney,et al.  Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. , 2003, Journal of the American College of Cardiology.

[30]  P. Kaufmann,et al.  Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy , 2001, Heart.

[31]  B. Maron,et al.  Prevalence of sudden cardiac death during competitive sports activities in Minnesota high school athletes. , 1998, Journal of the American College of Cardiology.

[32]  D. Corrado,et al.  Screening for hypertrophic cardiomyopathy in young athletes. , 1998, The New England journal of medicine.

[33]  D. Atkins,et al.  Cardiovascular preparticipation screening of competitive athletes. A statement for health professionals from the Sudden Death Committee (clinical cardiology) and Congenital Cardiac Defects Committee (cardiovascular disease in the young), American Heart Association. , 1996, Circulation.

[34]  F O Mueller,et al.  Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. , 1996, JAMA.

[35]  J E Smialek,et al.  Sports-related and non-sports-related sudden cardiac death in young adults. , 1991, American heart journal.

[36]  W. Roberts,et al.  Sudden Death in Young Athletes , 1980, Circulation.

[37]  G. Limongelli,et al.  Genetic analysis in a family affected by sick sinus syndrome may reduce the sudden death risk in a young aspiring competitive athlete. , 2014, International journal of cardiology.

[38]  G. Limongelli,et al.  DNA sequence capture and next-generation sequencing for the molecular diagnosis of genetic cardiomyopathies. , 2014, The Journal of molecular diagnostics : JMD.