Preventing Sudden Death in Young Athletes. Outline. Scope of the Problem. Causes of SCD in Young Athletes. Sudden death in the young athlete
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1 Preventing Sudden Death in Young Athletes Ronn E. Tanel, MD Director, Pediatric Arrhythmia Service UCSF Children s Hospital Associate Professor of Pediatrics UCSF School of Medicine Outline Sudden death in the young athlete Scope of the problem Etiology Diagnosis Advances Controversies Scope of the Problem Causes of SCD in Young Athletes Incidence estimates vary with methods, subject age, and population studied US Sudden Death in Young Athletes Registry: 115 cases/year = 1 in 3 days th Bethesda Conference: 1:33,000 to 1:50,000 Male predominance of 5:1 to 9:1 Papadakis, 2009 The combined prevalence of CV diseases that potentially predisposes athletes to SCD is 0.3% (3 in 1000)
2 Cardiac Causes of SCD in Young Athletes CORONARY ANOMALY Cardiac causes of SCD HYPERTROPHIC CARDIOMYOPAT Y MARFAN 5% AORTIC STENOS 4% MYOCARDITI 3% Myocardial disease Anatomic disease ARVD 3% OTHER 25% Electrical disease Reports vary according to study population, autopsy techniques, geographic location, genetic and ethnic diversity Combined disease Myocardial disease Anatomic disease Hypertrophic Cardiomyopathy (HCM) Aortic stenosis (AS) Myocarditis Anomalous coronary artery origin (ACA) Dilated Cardiomyopathy (DCM)
3 Electrical disease Combined disease Wolff-Parkinson-White syndrome (WPW) Long QT syndrome (LQTS) Brugada syndrome (BS) Arrhythmogenic right ventricular dysplasia/ cardiomyopathy (ARVD/C) Electrical Disease WPW LQTS CPVT BS ARVD/C HCM DCM AS ACA Anatomic Disease Catecholaminergic polymorphic ventricular tachycardia (CPVT) Myocardial Disease Myocarditis Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy 50% of all SCD in young athletes (< 30 y) is attributable to HCM Mechanism of SCD: Myofibrilar Disarray Myocardial Ischemia Hypertrophy Coronary anomalies LV outflow obstruction Maron, Circ 2010 Ventricular Arrhythmia
4 HCM Histology 12 yo boy with a history of palpitation and syncope Normal myocardium Myofibril disarray Increased fibrosis Cirino and Ho, Gene Reviews 2009 Coronary Artery Abnormalities Wolff-Parkinson-White syndrome 10-20% of sudden death in athletes 97% of SCD due to coronary artery abnormalities occurs < 22 yo 78% of SCD due coronary artery abnormalities occurs during or immediately after exercise
5 Mechanisms of AV reciprocating tachycardia 16 yo boy presents to the ED after experiencing palpitations during football practice Repeat ECG after termination of palpitations Long QT Syndrome A familial disorder in which affected individuals have QT interval prolongation, abnormal repolarization and a predisposition for syncope and sudden death.
6 A 12-year-old boy presents to the ED after exertional syncope A 4-year-old girl with a family history of SCD is being treated for a systemic fungal infection Advances Genetic basis for inherited arrhythmia syndromes and cardiomyopathy LQT1 (42-54%) LQT2 (35-45%) LQT3 (1.7-8%) LQT4 (<1%) LQT5 (<1%) LQT6 (<1%) Andersen Timothy LQT9 LQT10 LQT11 LQT12 LQTS Genetics Chromosome Gene Protein 11p15.5 KCNQ1 K + channel (KvLQT1) 7q35-q36 KCNH2 K + channel (HERG) 3p21 SCN5A Na + channel (Nav 1.5) 4q25-q27 ANK2 Ankyrin B (ANKB) 21q22.1-q22.2 KCNE1 K + channel subunit (MinK) 21q22.1-q22.2 KCNE2 K + channel subunit (MiRP) 17q23.1-q24.2 KCNJ2 K + channel (Kir2.1) 12p13.3 CACNA1c Ca ++ channel (CaV1.2) 3p25 CAV3 Caveolin-3 11q23 SCN4B Na + channel beta4 subunit 7q21-22 makap A-kinase anchor proteins 20q11.2 SNTA1 Syntrophin
7 HCM Genetics Genetics of LQTS CMH1 CMH2 CMH3 CMH4 CMH7 CMH8 CMH9 Chromosome 14q12 1q32 15q p p13.2 3p21.3-3p q Gene MYH7 TNNT2 TPM1 MYBPC3 TNNI3 MYL3 ACTC1 CSRP3 TTN MYH6 TCAP Protein -Myosin heavy chain Cardiac troponin T -Tropomyosin Myosin binding protein-c Cardiac troponin I Myosin light polypeptide 3 Cardiac -actin Cysteine and glycine-rich protein 3 Titin Myosin heavy chain Telothonin Genetic causes of LQTS established by mutations in proteins forming cardiac Na + and K + channels that delay repolarization (1995) 70% of affected patients have a mutation Only LQT1, LQT2, LQT3 have robust data to allow clinical use of genotyping Understanding the genetic basis of LQTS allows for genotype:phenotype correlations CMH10 12q23-12q24.3 MYL2 Myosin reg light chain 2 Genetics of LQTS Diagnosis of family members Advances Device therapy: ICD Diagnosis of borderline index cases Risk stratification (LQT subtype) Targeted therapy Family counseling Reproductive risk
8 Advances Device therapy: ICD Controversies Pre-participation ECG Screening Maron, NEJM 2003 ESC and IOC vs AHA Reasons for disagreement Cost Limitations of test sensitivity Limitations of test specificity Resource utilization Program implementation Annual athlete mortality per 100,00 personyears in Veneto region and Minnesota Controversies Beginning of Italian national preparticipation screening (1981) Genetic Testing for Inherited Arrhythmias: Expense Poor test sensitivity Genotype positive/phenotype negative individuals Genetic discrimination Maron, et al. AJC 2009
9 Controversies Hypertrophic Cardiomyopathy Controversies Hypertrophic Cardiomyopathy Physiologic athlete s heart vs pathologic CM Prevention of sudden death vs unnecessary restrictions Methods for differentiation: Response of cardiac mass to deconditioning Assessment of diastolic function Genetic testing (?) Maron, Heart 2005 Conclusions Sudden death in the young athlete is rare, but tragic when it occurs Cardiac causes, particularly HCM, are most common Many cardiac causes of sudden death may be detected by noninvasive testing Significant progress had been made in the detection and management of causes of SCD over recent years A number of unresolved issues remain with regard to the diagnosis and management of SCD
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