Abstract Background Sudden deaths in young competitive athletes are tragic events, with high public visibility. The importance of race and gender with respect to sport and the diagnosis and causes of ...sudden death in athletes has generated substantial interest. Methods The US National Registry of Sudden Death in Athletes, 1980-2011, was accessed to define the epidemiology and causes of sudden deaths in competitive athletes. A total of 2406 deaths were identified in young athletes aged 19 ± 6 years engaged in 29 diverse sports. Results Among the 842 athletes with autopsy-confirmed cardiovascular diagnoses, the incidence in males exceeded that in females by 6.5-fold (1:121; 691 vs 1:787,392 athlete-years; P ≤.001). Hypertrophic cardiomyopathy was the single most common cause of sudden death, occurring in 302 of 842 athletes (36%) and accounting for 39% of male sudden deaths, almost 4-fold more common than among females (11%; P ≤.001). More frequent among females were congenital coronary artery anomalies (33% vs 17% of males; P ≤.001), arrhythmogenic right ventricular cardiomyopathy (13% vs 4%; P = .002), and clinically diagnosed long QT syndrome (7% vs 1.5%; P ≤.002). The cardiovascular death rate among African Americans/other minorities exceeded whites by almost 5-fold (1:12,778 vs 1:60; 746 athlete-years; P <.001), and hypertrophic cardiomyopathy was more common among African Americans/other minorities (42%) than in whites (31%; P ≤.001). Male and female basketball players were 3-fold more likely to be African American/other minorities than white. Conclusions Within this large forensic registry of competitive athletes, cardiovascular sudden deaths due to genetic and/or congenital heart diseases were uncommon in females and more common in African Americans/other minorities than in whites. Hypertrophic cardiomyopathy is an under-appreciated cause of sudden death in male minority athletes.
Objectives The goal of this study was to r eliably define the incidence and causes of sudden death in college student-athletes. Background The frequency with which cardiovascular-related sudden death ...occurs in competitive athletes importantly influences considerations for pre-participation screening strategies. Methods We assessed databases (including autopsy reports) from both the U.S. National Registry of Sudden Death in Athletes and the National Collegiate Athletic Association (2002 to 2011). Results Over the 10-year study period, 182 sudden deaths occurred (age 20 ± 1.7 years; 85% male; 64% white), 52 resulting from suicide (n = 31) or drug abuse (n = 21) and 64 probably or likely attributable to cardiovascular causes (6/year). Of these 64 athletes, 47 had a confirmed post-mortem diagnosis; the most common were hypertrophic cardiomyopathy in 21 and congenital coronary anomalies in 8. The 4,052,369 athlete participations (in 30 sports over 10 years) incurred mortality risks as follows: suicide and drugs combined, 1.3/100,000 athlete participation-years (5 deaths/year); and documented cardiovascular disease, 1.2/100,000 athlete participation-years (4 deaths/year). Notably, cardiovascular deaths were 5-fold more common in African-American athletes than in white athletes (3.8 vs. 0.7/100,000 athlete participation-years; p < 0.01) but did not differ from the general population of the same age and race (p = 0.6). Conclusions In college student-athletes, risk of sudden death due to cardiovascular disease is relatively low, with mortality rates similar to suicide and drug abuse, but less than expected in the general population, although highest in African-American athletes. A substantial minority of confirmed cardiovascular deaths would not likely have been reliably detected by pre-participation screening with 12-lead electrocardiograms.
Objectives This study was designed to define more completely the clinical spectrum and consequences of stress cardiomyopathy (SC) beyond the acute event. Background Stress cardiomyopathy is a ...recently recognized condition characterized by transient cardiac dysfunction with ventricular ballooning. Methods Clinical profile and outcome were prospectively assessed in 136 consecutive SC patients. Results Patients were predominantly women (n = 130; 96%), but 6 were men (4%). Ages were 32 to 94 years (mean age 68 ± 13 years); 13 (10%) were ≤50 years of age. In 121 patients (89%), SC was precipitated by intensely stressful emotional (n = 64) or physical (n = 57) events, including 22 associated with sympathomimetic drugs or medical/surgical procedures; 15 other patients (11%) had no evident stress trigger. Twenty-five patients (18%) were taking beta-blockers at the time of SC events. Three diverse ventricular contraction patterns were defined by cardiovascular magnetic resonance (CMR) imaging, usually with rapid return to normal systolic function, although delayed >2 months in 5%. Right and/or left ventricular thrombi were identified in 5 patients (predominantly by CMR imaging), including 2 with embolic events. Three patients (2%) died in-hospital and 116 (85%) have survived, including 5% with nonfatal recurrent SC events. All-cause mortality during follow-up exceeded a matched general population (p = 0.016) with most deaths occurring in the first year. Conclusions In this large SC cohort, the clinical spectrum was heterogeneous with about one-third either male, ≤50 years of age, without a stress trigger, or with in-hospital death, nonfatal recurrence, embolic stroke, or delayed normalization of ejection fraction. Beta-blocking drugs were not absolutely protective and SC was a marker for increased noncardiac mortality. These data support expanded management and surveillance strategies including CMR imaging and consideration for anticoagulation.
Objectives This study sought to assess the impact of body mass index (BMI) on cardiac phenotypic and clinical course in a multicenter hypertrophic cardiomyopathy (HCM) cohort. Background It is ...unresolved whether clinical variables promoting left ventricular (LV) hypertrophy in the general population, such as obesity, may influence cardiac phenotypic and clinical course in patients with HCM. Methods In 275 adult HCM patients (age 48 ± 14 years; 70% male), we assessed the relation of BMI to LV mass, determined by cardiovascular magnetic resonance (CMR) and heart failure progression. Results At multivariate analysis, BMI proved independently associated with the magnitude of hypertrophy: pre-obese and obese HCM patients (BMI 25 to 30 kg/m2 and >30 kg/m2 , respectively) showed a 65% and 310% increased likelihood of an LV mass in the highest quartile (>120 g/m2 ), compared with normal weight patients (BMI <25 kg/m2 ; hazard ratio HR: 1.65; 95% confidence interval CI: 0.73 to 3.74, p = 0.22 and 3.1; 95% CI: 1.42 to 6.86, p = 0.004, respectively). Other features associated with LV mass >120 g/m2 were LV outflow obstruction (HR: 4.9; 95% CI: 2.4 to 9.8; p < 0.001), systemic hypertension (HR: 2.2; 95% CI: 1.1 to 4.5; p = 0.026), and male sex (HR: 2.1; 95% CI: 0.9 to 4.7; p = 0.083). During a median follow-up of 3.7 years (interquartile range: 2.5 to 5.3), obese patients showed an HR of 3.6 (95% CI: 1.2 to 10.7, p = 0.02) for developing New York Heart Association (NYHA) functional class III to IV symptoms compared to nonobese patients, independent of outflow obstruction. Noticeably, the proportion of patients in NYHA functional class III at the end of follow-up was 13% among obese patients, compared with 6% among those of normal weight (p = 0.03). Conclusions In HCM patients, extrinsic factors such as obesity are independently associated with increase in LV mass and may dictate progression of heart failure symptoms.
Controversy has evolved over the most practical and effective strategy for preparticipation cardiovascular screening of competitive athletes to detect unsuspected cardiovascular disease and prevent ...sudden death on the athletic field. Athlete screening in the Veneto region of Italy is part of a national program (with 12-lead electrocardiography) that has reported the detection of previously undiagnosed hypertrophic cardiomyopathy and a decrease in the cardiovascular death rate in young athletes. In this study, over time periods of similar length, cardiovascular-related mortality rates in Veneto athletes were compared with those of a demographically similar region of the United States (Minnesota) in which screening is limited to history and physical examination. There were 55 sudden cardiovascular deaths reported in Veneto over 26 years (2.1/year), compared with 22 deaths in 23 years (0.96/year) in Minnesota. Over the recent and comparable 11-year period, 1993 to 2004, 12 deaths were reported in Veneto and 11 in Minnesota. When analyzed as deaths per 100,000 person-years, Veneto exceeded Minnesota for all years combined (1.87 for 1979 to 2004 vs 1.06 for 1985 to 2007, respectively, p = 0.006), although the 2 regions did not differ significantly for 1993 to 2004 (0.87 vs 0.93, respectively, p = 0.88) or most recently for 2001 to 2004 (0.43 vs 0.90, respectively, p = 0.38). In conclusion, sudden cardiovascular deaths in young competitive athletes occurred at a low rate in both Veneto and Minnesota. Despite different preparticipation screening strategies, athlete sudden death rates in these demographically similar regions of the United States and Italy have not differed significantly in recent years. These data do not support a lower mortality rate associated with preparticipation screening programs involving routine electrocardiography and examinations by specially trained personnel.
In hypertrophic cardiomyopathy (HC), atrial fibrillation (AF) is an important determinant of clinical deterioration due to heart failure or embolic stroke. This study characterizes left atrial (LA) ...structural and functional parameters to establish markers predictive of AF risk, using cardiovascular magnetic resonance (CMR) imaging. We studied 427 consecutive patients with HC in sinus rhythm with CMR (age 44 ± 18 years), including 41 who developed clinically overt AF after study entry (2.6 ± 2.1 years), 49 patients with AF before CMR, 337 patients with HC but without AF, and 244 normal controls. LA chamber was assessed for absolute and indexed end-diastolic volume (LAEDV), end-systolic volume, and percent ejection fraction (LAEF). In the 41 prospectively studied patients with HC who developed AF during follow-up, LAEDV was significantly greater than in patients without AF (146 ± 48 vs 107 ± 37 ml) or in normal controls (81 ± 24 ml, p <0.001). Percent LAEF was lower in patients developing AF (36 ± 10%) than without AF (46 ± 12%) or controls (55 ± 9%, p <0.001). Multivariate analysis identified LAEF (<38%), LAEDV (≥118 ml), and age (≥40 years) as independently associated with AF occurrence. In conclusion, CMR measures of LA remodeling and dysfunction reliably identified patients with HC at risk for future development of AF. Decrease in LAEF represents a strong novel marker of susceptibility to AF in this disease.
Patients with hypertrophic cardiomyopathy (HC) are reported to have a mortality rate of about 1.0% per year, and those patients without sudden death risk factors and with no or mild symptoms are ...generally considered to have a benign clinical presentation. However, the risk of sudden death and the outcome in this latter subgroup have not been investigated systematically and remain unresolved. We assessed the risk of sudden death and outcome in 653 consecutive patients with HC without risk factors and with no or mild symptoms. Over a median follow-up of 5.3 years, 35 patients (5.4%) died of HC-related causes. Mean age at death was 46 ± 20 years in patients who died suddenly and 66 ± 15 and 72 ± 9 years, respectively, in patients who died of heart failure or stroke. Event rate was 0.6% per year for sudden death, 0.2% per year for heart failure death, and 0.1% per year for stroke-related death. Sudden death risk was independently and inversely related to age, and risk of heart failure or stroke death was directly related to age (p = 0.020). At 10 years after the initial evaluation, sudden death risk was 5.9%, with sudden death rate being the lowest (0.3% per year) in patients with normal left atrial dimension (≤40 mm). In conclusion, in patients with HC without conventional risk factors and with no or mild symptoms, the risk of sudden death was not negligible, with an event rate of 0.6% per year. Heart failure and stroke-related death were less common and largely confined to older patients. These results underscore the need for a more accurate assessment of the sudden death risk in patients with HC.
The issue of sudden death in young athletes and consideration for the most practical and optimal strategy to identify those genetic and/or congenital heart diseases responsible for these tragic ...events continues to be debated. However, proponents of broad-based and mandatory national preparticipation screening, including with 12-lead electrocardiograms have confined the focus to a relatively small segment of the youthful population who choose to engage in competitive athletic programs at the high school, college, and elite-professional level. Therefore, lost in this discussion of preparticipation screening of athletes is that the larger population of young people not involved in competitive sports (and, therefore, a priori are excluded from systematic screening) who nevertheless may die suddenly of the same cardiovascular diseases as athletes. To substantiate this hypothesis, we accessed the forensic Hennepin County, Minnesota registry in which cardiovascular sudden deaths were 8-fold more common in nonathletes (n = 24) than athletes (n = 3) and threefold more frequent in terms of incidence. The most common diseases responsible for sudden death were hypertrophic cardiomyopathy (n = 6) and arrhythmogenic right ventricular cardiomyopathy (n = 4). These data raise ethical considerations inherent in limiting systematic screening for unsuspected genetic and/or congenital heart disease to competitive athletes.
Preparticipation screening of athletes with 12-lead electrocardiography has been promoted for the detection of asymptomatic cardiovascular disease, particularly hypertrophic cardiomyopathy (HC). ...Although false-positive electrocardiographic (ECG) results for HC are well recognized in athlete screening, expected false-negative rates are unknown. The aim of this study was to characterize the rate of false-negative ECG findings in a cohort of young asymptomatic patients with phenotypically expressed HC, defined by cardiovascular magnetic resonance, using the 2010 European Society of Cardiology recommended ECG criteria for the identification of suspected heart disease in trained athletes. Cardiac magnetic resonance studies and 12-lead electrocardiography were performed in 114 consecutive asymptomatic patients with HC aged ≤35 years (mean age 22 ± 8 years; 77% male patients). Electrocardiograms were analyzed to distinguish pathologic ECG patterns from alterations considered nonpathologic and physiologic consequences of athletic training. Among the 114 patients with HC, 103 (90%) demonstrated ≥1 pathologic ECG abnormality, while the remaining 11 patients (10%) had normal or nonpathologic ECG patterns and therefore defined a subgroup in whom ECG screening would not be expected to raise suspicion of heart disease (i.e., false-negative results). In this false-negative ECG results group, maximal left ventricular wall thickness was 17 ± 2 mm (range 15 to 21), compared to patients with pathologic ECG patterns, in whom maximal left ventricular wall thickness was 22 ± 5 mm (p = 0.003). In conclusion, a substantial minority of young asymptomatic patients with HC with phenotypically expressed left ventricular hypertrophy have nonpathologic ECG findings on the basis of the 2010 European Society of Cardiology guidelines. In principle, this high false-negative rate of 10% represents an important limitation in applying 12-lead electrocardiography to large, apparently healthy athletic populations for the detection of HC.
End-stage hypertrophic cardiomyopathy (ES-HC) has an ominous prognosis. Whether genotype can influence ES-HC occurrence is unresolved. We assessed the spectrum and clinical correlates of ...HC-associated mutations in a large multicenter cohort with end-stage ES-HC. Sequencing analysis of 8 sarcomere genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1) and 2 metabolic genes (PRKAG2 and LAMP2) was performed in 156 ES-HC patients with left ventricular (LV) ejection fraction (EF) <50%. A comparison among mutated and negative ES-HC patients and a reference cohort of 181 HC patients with preserved LVEF was performed. Overall, 131 mutations (36 novel) were identified in 104 ES-HC patients (67%) predominantly affecting MYH7 and MYBPC3 (80%). Complex genotypes with double or triple mutations were present in 13% compared with 5% of the reference cohort (p = 0.013). The distribution of mutations was otherwise indistinguishable in the 2 groups. Among ES-HC patients, those presenting at first evaluation before the age of 20 had a 30% prevalence of complex genotypes compared with 19% and 21% in the subgroups aged 20 to 59 and ≥60 years (p = 0.003). MYBPC3 mutation carriers with ES-HC were older than patients with MYH7, other single mutations, or multiple mutations (median 41 vs 16, 26, and 28 years, p ≤0.001). Outcome of ES-HC patients was severe irrespective of genotype. In conclusion, the ES phase of HC is associated with a variable genetic substrate, not distinguishable from that of patients with HC and preserved EF, except for a higher frequency of complex genotypes with double or triple mutations of sarcomere genes.
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