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Sudden Cardiac Death in Athletes and Preparticipation CV screening Antonio Pelliccia, MD Institute of Sport Medicine and Science. Rome. [email protected] Global Debate or Common Ground ? SCD is a catastrophic event Athletes are at increased risk Prevention is critical Screening for occult disease is efficient Sudden Cardiac Death in Athletes: incidence SCD Incidence Traditional Estimates in the U.S. 1 in 200,000 (i.e., 0.5 x 100,000) High School Athletes/yr 1,2 1 in 160,000 (i.e., 0.62 x 100,000) in young of 12-35 age 3 1. 2. 3. Van Camp; MSSE 1995 Maron; JACC 1998 Maron; Circulation 2009 Sudden Deaths in US Young Competitive Athletes: 1980-2006 Number of sudden deaths Number of cardiovascular sudden deaths (black bars) in 1,866 young US athletes Most recent incidence rate = 0.66 x 100,000 Actual incidence underestimated ? Maron et al. Circulation. 2009;119:1085-1092 Incidence of SCD in young athletes 0.6x100,000 Case identification were through : Lexis Nexis archival database, News media reports, Internet searches, Reports from the consumer Product Safety 3,55 x100,000 wasCommission, the incidence of sudden cardiac death in the residents of Olmsted Pathology from NHBLI, County, Minnesota, aged 40 years, in Reports submitted to 20 thetoauthor the period 1960 to 1989. 3.6x100,000 Cases were collected by a prospective registry of Juvenile SD, in a relatively limited geographical area, with causes identified by experienced pathologist Prospective population-based study on OHCA 11 US/Canadian sites; >260 EMS agencies All OHCA with EMS response; Dec 2005 – March 2007 Incidence of OHCA in adolescents (age 12-19) CV cause: 3.75/100,000 (1 in 27,000) (from Atkins et al. Circulation 2009) SCD Incidence: Challenges and Limitations Difficult to compare incidence studies with profoundly different methodology No mandatory reporting system in U.S. U.S. estimates reliant on media and other electronic sources What [Numerator] / What [Denominator]grossly estimated Sudden Cardiac Death in Athletes: pathologic findings Cardiovascular Causes of Sudden Death Combined prevalence of these cardiac diseases in the general athletic population is 0.3% (or 3 in 1,000) From the Minneapolis Heart Foundation Registry HCM ARVC Congenital coronary artery anomalies Marfan syndrome Myocarditis Brugada WPW WPW syndrome Long QT interval CPVT Short QT interval Sudden Cardiac Death in Athletes: The role of sport HCM athlete, judged to be at “low risk” for SCD Assessment of risk in HCM patients Risk Factors: High risk (1-3%) 100% 90% ≥ 1 risk factor 70% (45%) 80% 60% >3 2 Previous cardiac arrest Recurrent syncope Familial premature SD Sustained VT, or repetitive NSVT at Holter BP at exercise Massive LVH 50% 40% 1 30% 20% 10% 0 Atrial fibrillation, LVOT obstruction, myocardial ischemia Low risk (50-55%) 0% Competitive Sport RR = 2.5 CI = 1.8-3.4 p < 0.001 Sport activity may increase the risk for SCD in athletes with underlying structural CV disease from Corrado et al. JACC 2003 EXERCISE triggers SCD in athletes with cardiomyopathies TRIGGERS: Deydratation Electrolyte imbalance Adrenergic output Ischemia VF/Asystole Unstable Electrophysiological Substrate 10,611 6 In athletes with structural CV disease intensive training and48competition increases the incidence and severity of 2,165 9 arrhythmias at risk for SD. 0,5 On the contrary, detraning reduces the risk and may have life-saving impact. PEAK TRAINING AFTER DETRAINING Strategies to prevent SCDs in Athletes: The preparticipation screening ARVD 23% Anomalous c.a. origin 12% (Corrado et al. NEJM 1998) Atherosclerotic c.a. disease 18% Anomalous c.a. origin 17% More than 2/3 of all SCD causes of are CMPs detectable HCM 2% ARVD 4% Possible HCM 8% during life ! HCM 36% (Maron et al. Circulation 2009) Atherosclerotic c.a. disease 2% Prodromal Symptoms HCM: up to 21%1 CCAA: up to 37%2 ARVC: up to 68%3 AN-SUD: up to 14%4 CPVT: up to 95%5 1. 2. 3. 4. 5. Maron; JAMA 1996 Basso; JACC 2000 Corrado; PACE 2002 Tester; Mayo Clin Proc 2004 Leenhardt; Circulation 1995 Warning Symptoms & Family History in Children with SCA Retrospective survey of Parent Heart Watch families whose children had SCA 79 cases from 78 families analyzed 19 of 79 cases (24%) reported syncope and/or unexplained seizure activity that went undetected as CV disease Syncope 14 of 79 cases (18%) (average 2.3 events) Seizure 10 of 79 cases (13%) (average 2.9 events) The purpose of screening: Timely identification and selective withdrawal from competitive sport of athletes with underlying cardiac disease, to reduce the risk of sudden death (or disease progression) and start appropriate treatment, if necessary The efficacy of screening by history and P.E. Only history and PE 134 Total dead athletes 130 Additional CV testing 15 115 1 Correct Diagnosis 7 (Maron BJ, JAMA 1996) Protocol of preparticipation CV screening History, P.E., 12-lead ECG Normal Findings Start training Abnormal Findings No CV disease Additonal testing CV disease Management according to Guidelines The rationale for including the 12-lead ECG in the PPE 1. Symptoms are usually absent (or denied) in athletes with CMPs! 21% Syncope, dizziness, and/or chest pain in HCM (Maron BJ , JAMA 1996) 2. Physical examination is unremarkable in most CMPs patients 3. ECG abnormalites are present in up to 95% of HCM and 80% of ARVC patients ! The rationale for including the 12-lead ECG: ARVC HCM RV LV LA RA ECG abnormalities in up to 95%: ST-T wave changes Deep Q waves Left axis deviation Exceedingly high QRS voltages P wave changes (LAenlargement) ECG abnormalities in > 80%: Inverted T waves in anterior precordial leads (beyond V1) RV conduction delay Epsilon wave PVBs with LBBB morphology Diagnosis of HCM in young athletes Abnormal findings LV Hypertrophy Genotype anomalies Abnormal ECG Sudden death can occur at any time ! Adolescence Adulthood Long-term follow-up of athletes with abnormal ECG (Pelliccia et al. New Engl J Med 2008; 358: 152-63) Study group 81 9-year follow-up No symptoms, no CV disease 6 70 5 1, sudden death 1, cardiac arrest Other CV disease (hpt 3, Cardiomyopathies CAD 1, myoc 1, SVT 1) (HCM3; ARVC1; DCM1) MM, soccer player at age of 28 years PFW IVS LV RV RA LA MM, at the age of 33 years Probability to identify cardiac diseases at risk of SCD by ECG or by MH+PE: ECG Hypertrophic cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy Dilated cardiomyopathy Myocarditis Marfan’s syndrome Valvular Disease Long QT and Short QT syndrome Brugada syndrome Preexcitation syndrome (WPW) Congenital Coronary Artery Anomalies MH+PE up to 90% < 10% 60-80% 30-60% 30-60% < 10% < 10% > 80% > 90% > 90% < 10% < 10% < 10% < 10% > 90% > 90% zero zero zero < 10% “...The studies quoted indicate that the ECG is about 50–95% sensitive to detect underlying heart disease ...this represents a marked improvement over physical examination alone, where the sensitivity is only 3–6% ...” (Lawless et al. Med. Sci. Sports Exerc.; 2008; 5: 787–798) The 2009 IOC Consensus Statement Challenges for implementing the ESC proposal for preparticipation CV screening … …the central challenge is practicability, feasibility and implementation, with the primary obstacle being adequate resources and economic support … …the substantial burden placed on the system by false positive test results. (Maron BJ, Eur Heart J 2005) Costs of preparticipation CV screening • History + PE 150-350 $ • 12-lead ECG 50-150 • Echocardiogram 600-900 • Exercise testing 300 • History, PE, ECG 45 € • Echocardiogram 100-150 • Exercise testing 100-150 31,864 athletes evaluated in 19 National Medical Centers 3.756 (11.8%) 28.108 (88.2%) Normal ECGs Abnormal ECGs ECG abnormalities found at PPS LAFB WPW LVH (4%) (1%) Prolonged QT interval (0.03%) (7%) RBBB (9%) Inverted T waves (20%) Early repolarization; incomplete RBBB; mildly increased R/S wave voltages (59%) ECG Interpretation in athletes: Need for a new approach “Normal” Common and Physiologic Training-related ECG alteration “Abnormal” Uncommon and Pathologic Training-unrelated Need for further work-up 4,450 athletes judged free of CV diseases at CV preparticipation screening ECHOCARDIOGRAPHY 12 (<1%) Structural CV Abnormalities (i.e., false negatives) 4,438 (>99%) Witout CV diseases (i.e., true negatives) (Pelliccia et al. Eur Heart J. 2006) Athletes with Structural CV Abnormalities Marfan’s (n = 2) ARVC (n = 1) MVP (n = 3) Aortic valve disease (n = 2) Myocarditis (n = 4) No HCM was found ! (Pelliccia et al. Eur Heart J. 2006) Can we do better ? Screening for genetic anomalies in young athletes ? Genetic testing are commercially available … Detectable genetic anomalies HCM gene testing detection efficacy Génotype-Phenotype Relationship in HCM: There is no closeUnresolved relationship betwen the extent ethical, social andand locus or and pattern of LV hypertrophy economic mutation abnormality; implications of There is a large variability in the extent and genetic results! distribution of(see LV hypertrophy GINA act, for a given mutation between US and lawwithin 2010)families. Myofilament-positive HCM patients are more frequently characterized by progressive impairment of LV diastolic and systolic function, leading to clinical deterioration and occurrence of adverse events (Olivotto J et al. Mayo Cli Proc 2008; 83: 630) The efficacy of the PPS to reduce mortality in young athletes Reduction in SCDs in young athletes in the Veneto Region SD per 100,000 athlete-years Annual incidence of SCD in screened athletes vs. unscreened non-athletes 3.6 0.7 0.8 0.4 Corrado et al. JAMA 2006;296:1593-601 The Veneto region and the state of Minnesota (US) have similar population demographics and athlete populations in person-year suitable for comparison of SD estimates. (Maron et al. Am J Cardiol 2009) Comparison of Italian and US Sudden Deaths in Competitive Athletes Corrado et al. JAMA 2006; 296: 1593-601 Maron et al. Am J Cardiol 2009; in press CV Screening in 510 Bostonian College Athletes Cardiac morphology His. + PE ECG 1, Bicuspid aortic valve 2, Bicuspid aortic valve 3, MVP 4, MVP 5, MVP 6, Pulm. stenosis 7, LV hypertrophy 8, LV hypertrophy 9, LV dilation 10, LV dilation 11, RV dilation None None None None None None None None None None None Pul. St. QRS volt/LAE None QRS volt/T neg HCM LBBB None LBBB Myocarditis RBBB None Murmur Murmur/Click Murmur Murmur None Murmur None None None None None Diagnosis by A. Baggish et al. Ann Int Med 2010; 152: 269 H+P Correctly identified 5/11 subjects (45%) with valvular disease. Missed all athletes with structural myocardial disease, including HCM and myocarditis. Sensitivity: 45%; Specificity: 94%; NPV: 98% H + P + ECG: Correctly identified all 11 subjects with both valvular and myocardial abnormalities, including HCM and myocarditis, that required sport restriction. Sensitivity: 91%; Specificity: 83%; NPV: 99.8% Theoretical model to project the costs and survival rates for US highschool and college athletes undergoing screening. Screening with H + P resulted in 0.56 life-year saved per 1000 athletes compared to no screening. Cost-effectiveness ratio for H + P vs. no screening was $ 199,000 per life-year saved. The screening including also the ECG saved 2.1 life-years per 1000 athletes at an incremental cost of $88 per athletes. Cost-effectiveness ratio of adding ECG to history and physical examination was $42,000 per life-year saved H+PE +ECG 1,473 intercollegiate athletes from University of Virginia (50%males; mean age 19 years; 71% Caucasian) 5 palpitations: •3 AVNRT, •1 atrial tach. •1 atrial fib. 8 5 $ 68,745 cost for each CV abnormality 0 disqualified •1 BAV •4 WPW pattern •1 long QT • 2 arrhyth. CMPs? $ 68,893 2 (R. Malhotra et al. personal communication) Should be the electrocardiogram required in young athletes? Chaitman B Lancet 2008;371:1489-90 Electrocardiographic screening in athletes: the time is now for universal screening. Papadakis M, Sharma S. Controversies relating to pre-participation cardiovascular screening in young athletes: Time for a realistic solution? Papadakis M, Chandra N, Sharma S. TAKE HOME MESSAGE: Screening elite athletes to prevent SD is compelling on ethical, medical and legal ground; Scientific evidence suggest that screening with 12lead ECG is feasible and efficient to identify (or raise suspicion for) CV disease at risk of SD; Implementation of the CV screening in athletes is efficient to reduce mortality in young athletes Sudden Death in Athletes “The fragility of life” Dedicated to Marc-Vivien Foe Antonio Pelliccia, MD Institute of Sport Medicine and Science. Rome. [email protected]