SUDDEN CARDIAC DEATH IN ATHLETES

SUDDEN CARDIAC DEATH IN ATHLETES Alix Dufresne, MD, FACP, FACC, FESC Cardiology Division Chief, Interfaith Medical Center Director Cardiology Clinic, Kingsbrook Jewish Center

PURPOSE AND OBJECTIVES PURPOSE The goal of the presentation is to review the most common pathologies seen in the USA that can lead to sudden death and consider the necessary steps to prevent such a bleak outcome OBJECTIVES Identify normal EKG variants in young athletes Be able to stratify patients at high risk of sudden death Be familiar with the latest available tools to present sudden cardiac death FINANCIAL DISCLOSURE None

EPIDEMIOLOGY College and Professional Athletes 500,000 participants each year Competitive Athletics: Several million high school students participate in competitive athletics each year in the United States Organized Sports Participation 25 million children and young adults

SUDDEN DEATH IN ATHLETES In the United States, the incidence of SCD averages 0.5 per 100, 000 athletes a year Similar to the current incidence in Italy This incidence has been relatively stable over time in the United States but has decreased in Italy. The incidence of SCD increases as people age due to the expanding prevalence of CAD.

Number of cardiovascular (CV), trauma-related, and other sudden death events in 1866 young competitive athletes, tabulated by year Maron, B. J. et al. Circulation 2009;119:1085-1092 Copyright 2009 American Heart Association

Basketball Football Track Soccer Baseball Swimming SCD BY SPORTS 50 40 30 20 10 No of athletes 0 Maron BJ et al, JAMA 1996 ; 276 : 199-203

INCIDENCE OF NCAA SCD BY SPORT Harmon, K. G. et al. Circulation 2011;123:1594-1600

CAUSES OF SCD IN ATHLETES In athletes with SCD, most patients have underlying structural heart disease The most common cause in the US is hypertrophic cardiomyopathy (HCM). Commotio cordis is the second most common etiology in the United States. accounts for nearly 20% of SCD in athletes LQTS, coronary artery anomalies, myocarditis, Marfan syndrome, arrhythmogenic right ventricular cardiomyopathy (ARVC), valvular disease, and dilated cardiomyopathies account for most of the remaining underlying heart disease.

Table 1. Cardiovascular causes of exercise-related SCD in young athletes. Van Camp et al.[8] (n = 100), % Maron et al.[9] (n = 134), % Corrado et al. (25) (n = 55), % Hypertrophic cardiomyopathy 51 36 1 Probable hypertrophic cardiomyopathy 5 10 Coronary anomalies 18 23 9 Valvular and subvalvular aortic stenosis 8 4 Possible myocarditis 7 3 5 Dilated and nonspecific cardiomyopathy 7 3 1 Atherosclerotic CAD 3 2 10 Aortic dissection/rupture 2 5 1 Arrhythmogenic right ventricular cardiomyopathy 1 3 11 Myocardial scarring 3 Mitral valve prolapse 1 2 6 Other congenital abnormalities 1.5 Long-QT syndrome 0.5 1 Wolff-Parkinson-White syndrome 1 1 Cardiac conduction disease 3 Cardiac sarcoidosis 0.5 Coronary artery aneurysm 1 Normal heart at necropsy 7 2 1 Pulmonary thromboembolism 1

Table 1. Causes of Sudden Cardiac Death in the Young

Table 2. Genetic Causes of Sudden Cardiac Death in the Young

RELATIVE INCIDENCE OF UNDERLYING DISEASES IN SUDDEN CARDIAC DEATH OF ATHLETES In Italian series of SCD in athletes, ARVC is the most common underlying heart disease. HCM accounts for a much lower percentage perhaps related to the screening process, a lower underlying genetic penetration, or less-lethal forms of the gene or disease.

RELATIVE INCIDENCE OF UNDERLYING DISEASES IN SUDDEN CARDIAC DEATH OF ATHLETES In non-athletic populations such as the military and general public, the causes of SCD in the young are less commonly cardiomyopathies and more commonly myocarditis, anomalous coronary arteries, and CAD.

Gray Area of Overlap between Athlete's Heart and Cardiomyopathies, Including Myocarditis, Hypertrophic Cardiomyopathy, and Arrhythmogenic Right Ventricular Cardiomyopathy. Maron BJ. N Engl J Med 2003;349:1064-1075.

HCM VS. ATHLETE S HEART Circulation 1995;91.

ABNORMALITIES POINTING TO POSSIBLY INCREASED SUDDEN-DEATH RISK IN THE SEATTLE CRITERIA INCLUDE: T-wave inversion (defined as >1 mm in depth in two or more of leads V2-V6, II and avf, or I and avl). Long QT interval (corrected QT [QTc] >470 ms in men, >480 ms in women ). Short QT interval (QTc <320 ms). ST-segment depression (>0.5 mm in two or more leads). Pathologic Q waves (>3 mm in depth or >40 ms in duration in two or more leads, excluding III and avr). Left atrial enlargement (P-wave duration >120 ms in leads I or II with negative portion of the P wave >1 mm in depth and >40 ms in duration in lead V1). Right ventricular hypertrophy (R-V1 + S-V5 >10.5 mm plus right axis deviation >120 )..

Compete left bundle branch block (LBBB) or any QRS >140ms Mobitz type II 2 AV block or complete heart block. Ventricular preexcitation (PR interval <120 ms with a delta wave and QRS >120 ms). Profound sinus bradycardia defined as <30 beats per minute or sinus pauses >3 s. Atrial tachyarrhythmias (supraventricular tachycardia or atrial fibrillation or flutter). Premature ventricular contractions (>2 per 10 second tracing), ventricular arrhythmias (couplets, nonsustained VT). Type 1 Brugada pattern.

ELECTROCARDIOGRAM IN ATHLETES Abnormalities in ECGs of athletes are common. In the Corrado screening series published in 1998, nearly 10% of their subjects who wished to begin an athletic program or who were involved in an athletic program had abnormal ECGs. Sinus bradycardia, first-degree heart block, and second-degree heart block are common, as are early repolarization and isolated voltage criteria for left ventricular hypertrophy.

ELECTROCARDIOGRAM IN ATHLETES Abnormal vs normal variant Distinguishing the atypical ECG of a young athlete from truly abnormal ECG results is very important Complete evaluation of the heart (echocardiography, MRI, CT, stress test,etc) in every one of these athletes could not be justified on the basis of cost

ELECTROCARDIOGRAM IN ATHLETES Atrioventricular block First-degree AV block and Mobitz Type I (Wenkebach) second degree AV block are common in trained athletes, being present 35 and 10% of athlete s ECGs, respectively. AV conduction slowing and block are mediated by increased parasympathetic tone and/or decreased resting sympathetic tone. Second-degree Mobitz Type II and third-degree heart block are rare in the athlete and caution should be used in accepting these findings as normal adaptive changes to training.

ELECTROCARDIOGRAM IN ATHLETES Isolated increase of QRS voltages Physiological LV hypertrophy in trained athletes usually manifests as an isolated increase of QRS amplitude, with normal QRS axis, normal atrial and ventricular activation patterns, and normal ST-segment T-wave repolarization. A high prevalence of ECGs that fulfill Sokolow Lyon voltage criteria for LV hypertrophy has been consistently reported in trained athletes. Non-voltage ECG criteria for LV hypertrophy such as atrial enlargement, left-axis deviation, a strain pattern of repolarization, and delayed intrinsicoid deflection are not usually seen in athletes.

ELECTROCARDIOGRAM IN ATHLETES The prevalence of incomplete RBBB has been estimated to range from 35 to 50% in athletes compared with less than 10% in young, healthy controls. The ECG pattern is more often noted in athletes engaged in endurance sports, with a male preponderance. Right ventricular conduction delay is most likely not within the conduction system, but as a result of increased conduction time across the RV due to the physiologically enlarged RV cavity size/increased cardiac muscle mass The RBBB morphology has been shown to be reversible with deconditioning

ELECTROCARDIOGRAM IN ATHLETES Incomplete RBBB should be differentiated from ARVC and Brugada ECG ARVC should be suspected when the pattern of incomplete RBBB is associated with T-wave inversion extending beyond V2 to include leads V3 and V4 or in the presence of premature ventricular beats with a left bundle branch block (LBBB) morphology. Brugada-ECG is characterized by a slow, positive deflection at the R-ST junction ( J-wave ), which is most evident in leads V1 and V2, with minimal or no reciprocal changes in other leads Unlike the R -wave seen in RBBB, the J-wave seen in Brugada syndrome does not indicate delayed RV activation, but reflects early repolarization with J-point elevation and a high take-off ST-segment. The down-sloping ST-segment is followed by a negative ( coved type) or a positive ( saddle-back type) T-wave.

BRUGADA ECG PATTERN

EPSILON WAVE

EARLY REPOLARIZATION Traditionally been regarded as an idiopathic and benign ECG phenomenon, with an estimated prevalence in healthy young individuals of 1 2%, and a clear male preponderance. The early repolarization ECG pattern is observed in 50 80% of resting ECGs among highly trained athletes The early repolarization ECG shows elevation of J-point of at least 0.1 mv from baseline, associated with notching or slurring of the terminal QRS complex which may vary in location, morphology, and degree

EARLY REPOLARIZATION Recently, isolated changes of early repolarization in inferior and/ or lateral leads with terminal QRS slurring has been reported in patients with idiopathic ventricular fibrillation. The study was a retrospective analysis of a selected cohort with episodes of short coupled rapid/polymorphic ventricular tachycardia or ventricular fibrillation leading to syncope or cardiac arrest. Haıssaguerre et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358:2016 2023.

EARLY REPOLARIZATION PATTERN Early repolarization pattern in a healthy black athlete characterized by right precordial T- wave inversion (arrowhead) preceded by STsegment elevation (arrow)

ARVC Right precordial T-wave inversion in a patient with ARVC Note that unlike early repolarization, in the ARVC the right precordial leads do not demonstrate any elevation of the ST-segment.

ECHOCARDIOGRAPHIC CHANGES IN ATHLETES Competitive athletes have myocardial remodeling, including left ventricular dilation and hypertrophy Left ventricular wall dimensions have been shown to increase to up to 14 mm in Italian and British athletes American football players have been demonstrated to have even more marked myocardial hypertrophy of up to 16 mm In a cohort of 156 asymptomatic National Football League players, 23% had evidence of left ventricular hypertrophy, including 6% with wall thicknesses greater than 14 mm.

INCIDENCE OF PROFESSIONAL ATHLETES IN ITALY, BRITAIN, AND UNITED STATES WITH ECHOCARDIOGRAPHIC DEFINED LV WALL THICKNESS 12 MM

ECHOCARDIOGRAPHIC CHANGES IN ATHLETES Differentiation of physiologic hypertrophy from HCM can be difficult. In general, physiologic hypertrophy is marked by left ventricular dilatation and excellent exercise tolerance, whereas patients with HCM more commonly demonstrate marked abnormal ECGs, bizarre patterns of hypertrophy, and left atrial enlargement. The changes in athletes are ADAPTIVE and REVERSIBLE.

Electrocardiograms of a Swimmer With LVH and Inferolateral T-Wave Inversions Before and After Detraining for 12 Weeks Basavarajaiah, S. et al. J Am Coll Cardiol 2008;51:1033-1039 Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

CAUSES OF SCD IN ATHLETES

COMMOTIO CORDIS Commotio Cordis sudden death with relatively innocent chest wall impact first described in the 19th century The second leading cause of sudden death in young athletes in the United States The median age of commotio cordis victims is 14 years Nearly two thirds of the deaths are in competitive sports, and the others are during recreational sports and routine daily activities. Impacts occur directly over the cardiac silhouette and are thought to be of routine velocity for the age and sex of the person struck by the ball.

DISTRIBUTION OF COMMOTIO CORDIS EVENTS ACCORDING TO AGE AND ACTIVITY Maron BJ, Estes N III. N Engl J Med 2010;362:917-927.

SPORTS DURING WHICH A COMMOTIO CORDIS EVENT OCCURRED

Pathophysiology of Commotio Cordis Maron BJ, Estes N III. N Engl J Med 2010;362:917-927.

T WO-LEAD ECG AND RIGHT ATRIAL AND LEFT VENTRICULAR PRESSURE TRACINGS OF A 16 -KG SWINE UNDERGOING CHEST WALL IMPACT WITH A 40-MPH LACROSSE BALL

COMMOTIO CORDIS Commotio cordis has occurred despite the use of safety baseballs and chest wall protection. In nearly one third of the players who underwent a commotio cordis event during competitive sports, a chest protector was worn. There are cases during lacrosse and baseball where the ball struck the chest protector, which was directly over the heart, and commotio cordis still resulted.

HYPERTROPHIC CARDIOMYOPATHY

HYPERTROPHIC CARDIOMYOPATHY Occurs in 1 of 500 in general population Men and African-Americans affected by almost 2:1 ratio over women and Caucasians Most common cause of sudden death in young athletes Mutation in genes encoding sarcomeric proteins Histological examination reveals myocyte disarray and myocyte loss with fibrosis Variable clinical symptomology Watkins H et al. N Engl J Med 2011;364:1643-1656.

The principal pathways of disease progression in hypertrophic cardiomyopathy (HCM) Maron, B. J. et al. J Am Coll Cardiol 2003;42:1687-1713 Copyright 2003 American College of Cardiology Foundation. Restrictions may apply.

INTEGRATED PATHOPHYSIOLOGY Braunwald. Atlas of Heart Diseases: Cardiomyopathies, Myocarditis, and Pericardial Disease. 1998.

Incidence of SCD of 1% per year Selected patients treated with an ICD receive appropriate shocks in up to 10% per year SCD occurs more often in younger patients, but does take place in the elderly. The treatment of choice for patients at higher risk for SCD is the ICD. About half of the SCD cases occur during strenuous exercise and competitive sports should therefore be avoided. No evidence that medical Rx (β-blockers, amiodarone) reduces the risk of SCD and prevention should therefore not rely on medical treatment alone. SCD IN HCM

Intracardiac Electrogram Showing the Mechanism of Sudden Death in Hypertrophic Cardiomyopathy. Maron BJ. N Engl J Med 2003;349:1064-1075.

Septal hypertrophy (arrow) demonstrated on four chamber MRI (A) and on four chamber two dimensional (2D) echocardiography (B). ten Berg J et al. Heart 2010;96:1764-1772 2010 by BMJ Publishing Group Ltd and British Cardiovascular Society

Systolic anterior movement (SAM; arrow) of the anterior mitral valve leaflet in a patient with hypertrophic obstructive cardiomyopathy demonstrated with 2D echocardiography in parasternal long axis view. ten Berg J et al. Heart 2010;96:1764-1772 2010 by BMJ Publishing Group Ltd and British Cardiovascular Society

Apical hypertrophy (arrow) demonstrated with four chamber MRI (A) and with four chamber 2D echocardiography (B and C). ten Berg J et al. Heart 2010;96:1764-1772 2010 by BMJ Publishing Group Ltd and British Cardiovascular Society

Angiogram of the left ventricle in the right oblique view. 1, small end-systolic left ventricular cavity; 2, septal bulge impinging on left ventricular cavity; 3, severe eccentric mitral regurgitation. ten Berg J et al. Heart 2010;96:1764-1772 2010 by BMJ Publishing Group Ltd and British Cardiovascular Society

Electrocardiograms and Parasternal Short-Axis Views of the LV at the Level of Papillary Muscle of the 3 Athletes With LVH and a Nondilated LV Cavity Basavarajaiah, S. et al. J Am Coll Cardiol 2008;51:1033-1039 Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

RIGHT VENTRICULAR CARDIOMYOPATHY The term "ARVC" was first proposed by Fontaine et al. in a 1977 report describing six patients with sustained ventricular tachycardia Prevalence estimated at 1:5000 Incidence: 6/10,000 up to 44/10,000 Inherited as an autosomal dominant trait with variable penetrance and incomplete expression

PATHOGENESIS OF ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY The main feature of ARVC is fibrofatty replacement of the myocardium, mainly in the right ventricle but also in the left ventricle This change results in the predominant clinical feature of susceptibility to ventricular arrhythmias The disease is familial, and typically autosomal dominant, in about half the cases. Watkins H et al. N Engl J Med 2011;364:1643-1656.

ARVC Mallat Z et al. N Engl J Med 1996;335:1190-1197

ARVD Epsilon wave a late positive deflection in the terminal QRS complex Triangle of dysplasia. Anderson EL. Arrhythmogenic Right Ventricular Dysplasia Am Fam Physician. 2006;73:1391-8

EPSILON WAVE

Figure 2. Conventional angiogram of the right ventricle in a patient with ARVD shows heavy trabeculation and aneurysmal bulges of the right ventricular outflow tract. Kayser H W M et al. Radiographics 2002;22:639-648 2002 by Radiological Society of North America

SCD IN ARVC In the US ARVC accounts for approximately 5% of SCD in individuals under the age of 65 Responsible for at least 3% to 4% of deaths associated with physical activity in young athletes In the Veneto region of Italy, ARVC is the most common cause of sudden arrhythmic deaths in individuals under the age of 35 years and the overwhelming cause of sudden death associated with exertion in young athletes in The annual mortality rate of ARVC has been estimated at 3% without treatment and at 1% with pharmacologic medical treatment not including ICD

SCD IN ARVC The mechanism of sudden death in ARVC is, in most cases, acceleration of VT with degeneration into ventricular fibrillation. VT in ARVC is due to sympathetic stimulation. accounting for the high prevalence of this condition in individuals who die during exertion. Ambulatory ECG recordings of patients developing sustained VT demonstrate a progressive increase in the sinus rate before the onset of the arrhythmia, suggesting progressive sympathetic stimulation

SCREENING Screening programs are not widely adopted in the United States. High false positive rates High cost-to-benefit ratio Low rate of sports-related sudden death

SCREENING In Italy and most other countries of Europe, in addition to the history and examination, a resting ECG is mandated by law. a decline in sports-related sudden death after ECG screening was instituted in 1982 (Corrado et al). In 1982 the incidence of SCD in Italy was 4.2/100,000 athletes In 2004 the incidence of SCD decreased markedly to 0.9/100,000 In Israel, both a resting ECG and a symptom-limited stress test are mandated

NUMBERS AND MONEY HCM 1:500 incidence $500/ECHO $250,000 to detect 1 case 1 death 1000 at risk of sudden cardiac death 200,000 Athletes

AHA CONSENSUS PANEL

HCM

ARVC

Table 3. Triggers and Drug Responses in Familial LQTS Types 1 3

Figure 2. Different patterns of precordial early repolarization in two healthy athletes. (A) ST-segment elevation with upward concavity (arrows), followed by a positive T-wave (arrowheads). (B) ST-segment elevation with upward convexity (arrows), followed by a negative T-wave (arrowheads).

Figure 3. (A) Early repolarization pattern in a healthy black athlete characterized by right precordial T-wave inversion (arrowhead) preceded by ST-segment elevation (arrow). (B) Right precordial T-wave inversion in a patient with ARVC. Note that unlike early repolarization, in the ARVC the right precordial leads do not demonstrate any elevation of the ST-segment.

SUDDEN DEATH IN ATHLETES WITH SICKLE CELL TRAIT

The majority of individuals who have sickle cell trait have no personal medical problems related to their carrier status, and there are no significant differences in performance between athletes who have SCT versus those who do not have SCT.

Since 2013, NCAA, incorporated SCT screening for all athletes from Division I to Division III One in 12 African Americans has SCT Epidemiologic studies suggest a greater relative risks of sudden cardiac death during basic training in army recruits Recent study shows that out 247 cases of sudden death, only 5 (2%) were associated with SCT All cases occur in football players, none during the games but most of them during pre-season conditioning practice Rhabdomyolysis _ as an inciting event due to muscle Hypoxia and sickling_ has been studied

PROPOSED UNIVERSAL PRECAUTIONS Managing heat exposure, including the implementation of, and adherence to, established acclimatization protocols. Heat, dehydration, altitude and asthma can increase the risk for and worsen complications associated with SCT, even when exercise is not intense. Supporting adequate nutrition and hydration, especially in hot and humid climates. Studentathletes should refrain from consuming high-caffeine energy drinks and supplements, or other stimulants, as they may contribute to dehydration.

Understanding the impact of exercise intensity, especially in the untrained or undertrained student-athlete, and implementation of progressively intense exercise in the first few weeks of the season. Providing adequate time for rest and recovery both during an exercise session and after intense and/or extended periods of physical activity. Development, implementation and adherence to site -specific emergency action plans with appropriate medical equipment and staff to intervene during an emergency situation. Education and counseling are essential for helping student - athletes with SCT understand the potential risks associated with SCT and intense physical activity.

CONTACT Alix Dufresne, MD, FACP, FACC, FESC Cardiology Division Chief, Interfaith Medical Center Director Cardiology Clinic, Kingsbrook Jewish Center Fellow American College of Physicians, American College of Cardiology, European Society of Cardiology Email: alixdufresne@yahoo.com