Sudden Death in Athletes

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Sudden Death in Athletes Domenico Corrado, Anna Baritussio, Mariachiara Siciliano, Antonio Pelliccia, Maurizio Schiavon, Cristina Basso, Barry J. Maron, and Gaetano Thiene

Abstract

Competitive sports activity is associated with an increase in the risk of sudden cardiovascular death (SCD) in susceptible adolescents and young adults with clinically silent cardiovascular disorders. Screening including 12-lead electrocardiogram (ECG) has been demonstrated to allow identification of athletes affected by malignant heart muscle diseases at a pre-symptomatic stage and lead to substantial reduction of the risk of SCD during sports. The use of modern criteria for interpretation of the ECG in the athlete significantly improves the screening accuracy by reducing the false positive rate (increased specificity), with the important requisite of maintaining the ability for detection of life-threatening heart diseases (preserved sensitivity). Screening including ECG has a more favorable cost-benefit ratio than that based on history and physical examination alone, with cost estimates per year of life saved below the threshold to consider a health intervention as cost-effective. Screening with exercise testing middle aged/senior athletes engaged in leisure sports activity is likely to be cost-effective in older patients with coronary risk factors, while it is not justified in low-risk subgroups. Keywords

Athletes • Automated external defibrillator • Cardiomyopathy • Electrocardiogram Pre-participation screening • Sports cardiology • Sudden cardiac death • Ventricular arrhythmias

D. Corrado, MD, PhD (*) Division of Cardiology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Giustiniani, 2, 35121 Padova, Italy e-mail: [email protected] A. Baritussio, MD • M. Siciliano, MD Division of Cardiology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy e-mail: [email protected]; [email protected] A. Pelliccia, MD Department of Medicine, Institute of Sport Medicine and Science, Rome, Italy e-mail: [email protected]

M. Schiavon, MD Department of Social Health, Center for Sports Medicine and Physical Activity, Azienda ULSS 16 of Padova, Padua, Italy e-mail: [email protected] C. Basso, MD, PhD • G. Thiene, MD, FRCP Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padova, Italy B.J. Maron, MD Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN, USA [email protected]

I. Gussak, C. Antzelevitch (eds.), Electrical Diseases of the Heart, DOI 10.1007/978-1-4471-4978-1_23, © Springer-Verlag London 2013

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Introduction Regular physical exercise is recommended by the medical community because it is associated with a decrease in all cause-mortality, particularly from cardiovascular causes [1]. Several epidemiological and clinical studies have provided solid scientific evidence that habitual aerobic physical activity reduces the risk of acute myocardial infarction and sudden cardiac death (SCD) [2]. On the other hand, vigorous exertion may acutely and transiently increase the risk of acute coronary events and sudden cardiac arrest in susceptible individuals [3–5]. The riskbenefit ratio of sports activities varies according to athlete’s age and intensity of physical exercise. According to Maron et al. [6] athletes can be divided into two major categories. Competitive athletes are young (usually £35 years) subjects who participate in an organized team or individual sport that requires systematic training and regular competition against others and places a high premium on athletic excellence and achievement. Conversely, leisure athletes are individuals, most frequently middle-aged/ senior (usually >35 years), participating in a variety of informal recreational sports, within a range of exercise levels from modest to vigorous, on either a regular or inconsistent basis, which do not require systematic training or the pursuit of excellence. This report examines the prevalence, causes, and mechanisms of SCD in both categories of athletes, and reviews the currently available prevention programmes such as systematic preparticipation screening and early defibrillation by using AEDs.

Epidemiology of SCD in Athletes Although sudden cardiac death (SCD) during sports is a rare event, it always has a tragic impact on the community because it occurs in apparently healthy individuals and assumes great visibility through the news media, due to the high public profile of competitive athletes [7–10]. For centuries it was a mystery why cardiac arrest should occur in vigorous athletes, who had previously achieved extraordinary

D. Corrado et al. TABLE 23–1. Cardiovascular causes of sudden death associated with sports Age ³ 35 years Coronary artery disease Age < 35 years Hypertrophic cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy/dysplasia Congenital anomalies of coronary arteries Myocarditis Aortic rupture Valvular disease Preexcitation syndromes and conduction diseases Ion channel diseases Congenital heart disease

exercise performance without complaining of any symptoms. The cause was generally ascribed to myocardial infarction, even though evidence of ischemic myocardial necrosis was rarely reported; it is now clear that the most common mechanism of SCD during sports activity is an abrupt ventricular tachyarrhythmia as a consequence of a wide spectrum of cardiovascular diseases, either acquired or congenital. The culprit diseases are often clinically silent and unlikely to be suspected or diagnosed on the basis of spontaneous symptoms. Systematic pre-participation screening of all subjects embarking in sports activity has the potential to identify those athletes at risk and to reduce mortality.

Causes of SCD in the Athlete As reported in Table 23.1, the causes of SCD reflect the age of the participants. Although atherosclerotic coronary artery disease accounts for the majority of fatalities in adults (aged >35 years) (Fig. 23.1) [4, 11, 12], in younger athletes a broad spectrum of cardiovascular substrates (including Congenital and inherited heart disorders) has been reported (Fig. 23.2) [7–10, 14–23]. Cardiomyopathies have been consistently implicated as the leading cause of sports-related cardiac arrest in the young, with hypertrophic cardiomyopathy accounting for more than one-third of fatal cases in the United States and arrhythmogenic right ventricular cardiomyopathy/dysplasia for approximately one-fourth in the Veneto Region of Italy [7, 8]. Two to five percent

23. Sudden Death in Athletes

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b

c

FIGURE 23–1. Sudden death of a middle-aged athlete. Obstructive atherosclerotic coronary artery disease of both left (anterior descending branch) and right coronary arteries (a, b) Heidenhain trichrome. (c)

Histology of the myocardium shows replacement type fibrosis due to previous myocardial infarction (Adapted from Corrado et al. [13]. With permission from Oxford University Press)

of young people and athletes who die suddenly have no evidence of structural heart disease and the cause of their cardiac arrest in all likelihood is related to a primary electrical heart disease such as inherited cardiac ion channel defects (channelopathies), including long and short QT syndromes, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia [24]. Sudden death may also be caused by a

non-arrhythmic mechanism—e.g., spontaneous aortic rupture complicating Marfan’s syndrome or bicuspid aortic valve as well as by diseases not related to the heart—e.g., bronchial asthma or rupture of a cerebral aneurysm [2]. Blunt, nonpenetrating, and often innocently appearing blows to the precordium may trigger ventricular fibrillation without structural injury to ribs, sternum, or heart itself (commotio cordis) [9].

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d

FIGURE 23–2. Leading causes of sudden cardiovascular death in young competitive athletes. (a) Hypertrophic cardiomyopathy: short axis cut of the heart specimen showing asymmetric septal hypertrophy with multiple septal scars (top); histology of the interventricular septum revealing typical myocardial disarray with interstitial fibrosis (bottom) (Heidenhain trichrome); (b) Arrhythmogenic right ventricular cardiomyopathy/ dysplasia: section of the heart specimen along the right ventricular infundibulum (left); panoramic histological view of the right infundibular free wall showing wall thinning with fibro-fatty replacement (right)

Incidence of SCD Death usually occurs either during (80 %) or immediately after (20 %) athletic activity, suggesting that participation in competitive sports increases the likelihood of cardiac arrest. Fortunately, the frequency with which SCD occurs

(Heidenhain trichrome); (c) Atherosclerotic coronary artery disease: histology of the proximal tract of the left anterior descending coronary artery showing a non obstructive fibrous plaque complicated by luminal thrombosis due to endothelial erosion (Heidenhain trichrome). (d) Congenital coronary anomaly: gross view of the aortic root showing both coronary ostia located in the right coronary sinus, pointing to an anomalous left coronary artery arising from the right aortic sinus of Valsalva and running between the aorta and the pulmonary trunk (From Corrado et al. [13]. With permission from Oxford University Press)

during sports activity is low and varies in the different athlete age-groups because of the different nature of cardiovascular substrates [2, 3, 25]. It generally increases with age and is greater in men [9, 25, 26]. In middle-age/senior athletes engaged in leisure time sports such as jogging or marathon

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racing, the estimated rate of sports-related fatalities ranges from 1:15,000 to 1:50,000 [5]. Several epidemiological studies have assessed the relationship between physical exercise and the risk of acute myocardial infarction/SCD in leisure athletes, in which physical exercise can be regarded as a ‘two-edged sword’ [1–3, 5, 25] while epidemiological studies support the concept that habitual sports activity offers protection against cardiovascular events over the long-term [1–3, 25], vigorous exercise may acutely increase the incidence of both cardiac arrest and acute myocardial infarction, mostly in those who do not exercise regularly. In younger competitive athletes (£35 yoa), the reported incidence of sudden death from all causes in Veneto region was 2.3 per 100,000 athletes per year and of 2.1 per 100,000 athletes per year by cardiovascular diseases [26]. On the other hand, the prevalence of fatalities among US high-school and college athletes has been estimated to be less than 1 in 100,000 participants per year [9, 27]. Compared with US high school and college participants, the Italian athletic population included older athletes (age range 12–35 vs. 12–24 years) and a significantly higher proportion of men (85 vs. 65 %). This partly explains why the mortality rates found in the Italian investigations were significantly higher than those reported in the USA. In addition, while the Italian data were systematically gathered from a well-defined geographic area (the Veneto region of Italy) according to a prospective study design, the US SCD rates were mostly based on retrospective analysis of

SD per 100,000 person-years

4 3.5 3

data from public media reports and insurance claims, which unavoidably led to an incorrectly low number of events and underestimation of mortality. The accuracy of the determination of incidence rates of SCD among US athletes is further questionable, because denominator data did not reflect the real number of active athletes in each year, but the total participation figures divided by an estimate of the average number of sports, in which each high school and college athlete participated [9, 27, 28]. Other studies with more rigorous data collection and denominator estimates reported an incidence of either SCD or sudden cardiac arrest of young athletes in the USA quite similar to the incidences found in the Veneto region of Italy in the pre-screening period (Table 23.1) [28]. In this regard, Harmon et al. [29] recently reported that during a 5-year period, SCD incidence among national collegiate athletic association (NCAA) student-athletes was 2.3/100.000 participants per year. The Italian prospective study also demonstrated that adolescent and young adults involved in competitive sports activity have an estimated risk of SCD approximately three times greater (2.8) than that of their non-athletic counterpart (Fig. 23.3) [26, 28]. However, sport was not itself the cause of the enhanced mortality, since it triggered cardiac arrest in those athletes who were affected by cardiovascular conditions predisposing to life-threatening ventricular arrhythmias during physical exercise (Fig. 23.3). This reinforces the need for systematic evaluation of adolescent and young individuals embarking in

Athletes RR = 2.5 CI = 1.8–3.4 p < 0.001

RR = 2.8 CI = 1.9–3.7 p < 0.001

Non-athletes

2.5 2 1.5

RR = 1.7 CI = 0.32–5.7 p = 0.39 (NS)

1 0.5 0

Total

Cardiovascular

Noncardiovascular

FIGURE 23–3. Incidence and relative risk (RR) of sudden death among young athletes and non-athletes from total, cardiovascular and noncardiovascular causes (From Corrado et al. [30]. With permission from Sage Publications)

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sports activity in order to identify those with potentially lethal cardiovascular diseases and protect them against the increased risk of SCD.

Pre-participation Screening The primary purpose of pre-participation screening is to identify the cohort of athletes affected by unsuspected cardiovascular diseases and to prevent SCD during sports by appropriate interventions [29]. Sudden cardiac death during sports is often the first clinical manifestation of cardiovascular disease, because the culprit conditions are usually clinically silent and unlikely to be suspected during life on the basis of spontaneous alarming prodroma. The importance of early identification of clinically silent cardiovascular diseases at a pre-symptomatic stage relies on the concrete possibility of SCD prevention by lifestyle modification, including restriction of competitive sports activity (if necessary), but also by prophylactic treatment with drugs and implantable defibrillator [31]. The vast majority of ‘at riskathletes’ show neither a positive family history nor preexistent cardiovascular symptoms. This explains why a screening protocol based solely on the athlete’s history and a physical examination, as used in the United States, is of limited value (