In 1958, British pathologist Donald Teare described a family in which eight victims of sudden death had marked asymmetric hypertrophy of the left ventricle,1 a condition now known as hypertrophic cardiomyopathy (HCM). Though much has been learnt about HCM, a number of problems remain unresolved, including how best to prevent HCM-related sudden cardiac death (SCD) in young athletes. As recently as the 2008 British Cardiovascular Society meeting, experts in cardiovascular medicine continued this lively debate.2 This editorial seeks to summarise the key factors relating to the detection and management of HCM in athletes.

CLINICAL MANIFESTATIONS OF HCM

Most of the work following Teare’s description of familial HCM took place in specialty research centres, which focused on patients with the highest burden of disease. These patients were generally young and most often presented with advanced heart failure, prior cardiac arrest, or SCD in an immediate family member. Such work established the classic clinical manifestations of HCM, including exertional chest pain and syncope, heart failure and SCD. This collective early experience led to the notion that HCM, though relatively rare, was a disease of youth commonly associated with significant morbidity and mortality.

In subsequent decades, a combination of heightened awareness and widespread use of non-invasive cardiac imaging revised many of these initial concepts. It is now clear that HCM is typified by its variability. Myocardial hypertrophy may be symmetric or asymmetric and may or may not be accompanied by left ventricular outflow obstruction. Several recent screening studies of asymptomatic subjects suggest that HCM is not rare, and that 1 in 500 Americans has echocardiographic evidence of unexplained left ventricular hypertrophy consistent with HCM.3 Furthermore, although HCM can cause SCD in young people, the disease affects people of all ages, and many people with HCM remain asymptomatic during an entirely normal lifespan.4

REDUCTION OF SUDDEN CARDIAC DEATH

The most nefarious HCM manifestation, SCD, has received a great deal of attention because it often affects young, seemingly healthy people in their physical prime. Among subjects with HCM, the likelihood of SCD appears to be associated with young age, race and vigorous physical activity.5 6 Indeed, HCM is associated with 30–50% of the SCDs during sports participation in the United States.7 The association between SCD and vigorous physical activity has received a great deal of attention because it is easily modifiable by activity restriction and because it is conceptually contrary to the vitality that generally characterises people who take part in sport. Strategies to reduce SCD in athletes have focused on three factors: (a) preparticipation screening for HCM; (b) risk stratification after HCM diagnosis; (3) determination of athletic eligibility for subjects with HCM.

Preparticipation screening

Preparticipation screening for HCM is theoretically attractive because it has the ability to identify subjects whose risk for HCM-related SCD might be reduced by intervention. Both the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) recommend screening for occult cardiovascular disease before athletic participation, but their screening protocols differ significantly. The ACC/AHA recommend screening via a medical history and physical examination with further testing reserved for athletes with abnormalities detected during this process.8 The most recent guidelines delineate a 12-element (eight medical history questions, four physical examination procedures) screening protocol. The ESC and subsequently the International Olympic Committee (IOC) also recommend screening with a history and physical examination.9 10 However, the ESC and IOC suggest a more comprehensive medical history (34 questions) and physical examination (six procedures) and mandate the inclusion of a resting 12-lead electrocardiogram (ECG). Proponents of the 12-lead ECG criticise the limited sensitivity of a screening programme confined to medical history and physical examination,11 whereas its opponents cite prohibitive cost and high false-positive rates associated with ECG screening.12

The data supporting ECG inclusive screening protocols have emerged from reports of the Italian experience. In 1971, Italian law mandated medical protection for athletes participating in organised sport.13 This was followed by legislation in 1982 outlining a preparticipation screening regimen, which included a 12-lead ECG and submaximal exercise testing.14 15 Data from the Italian experience were first published more than a decade ago.16 In this sentinel study, Corrado and colleagues reported data from an 18-year observational study of SCD in the Veneto region of Italy. Despite the use of a comprehensive preparticipation screening program, SCD occurred more frequently among athletes than among non-athletes (1.6 vs 0.75 deaths per 100 000 people/year, relative risk = 2.1, p<0.001). HCM was a relatively rare cause of death in this autopsy series, and caused only 2% of the deaths among Italian athletes compared with 7.3% of deaths among non-athletes. Simultaneously presented observational data from 33 735 screened Italian athletes suggested that the ECG was the key screening component for the detection of HCM.16 The authors concluded that ECG-based screening was effective in reducing the incidence of HCM-related SCD. Additional long-term observational data from Italy have recently been published and provide further support for an ECG-based screening protocol.17

These studies provide several important principles. First, because of either screening or disease prevalence, HCM appears to be less prevalent among Italian athletes and thus to account for a smaller percentage of SCDs among athletes than available data suggest for the United States. This regional heterogeneity requires that estimates of screening accuracy and cost effectiveness are tailored to the region of interest since both depend on disease prevalence. Second, 12-lead ECG does identify subjects with HCM who are missed by medical history and a focused physical examination. Although the Italian studies provide the best available data in support of preparticipation screening and the inclusion of an ECG, their observational design, absence of a direct comparison between ECG-based and non-ECG-based screening protocols and a surprisingly high prescreening mortality rate among Italian athletes are important limitations to these studies.18

Furthermore, the entire concept of preparticipation screening of athletes is based on expert consensus and not directly data driven. No random assignment clinical trials have evaluated preparticipation screening. Screening is intuitively attractive to prevent sports-related SCD, but assumes that the presence of HCM in asymptomatic athletes portends the same risk of SCD as that in patients with symptomatic HCM. Further it assumes that the medical management of these asymptomatic patients does not increase morbidity in people who would otherwise have been well. It is noteworthy that not one of the 22 athletes with HCM identified by Corrado et al16 died during 8.2 (5) years of follow-up. This may indicate that the medical management of these athletes, including disqualification from athletic participation, was successful in preventing SCD, but it is equally plausible that these asymptomatic athletes with HCM were are at low risk of SCD and thus unnecessarily barred from sport.

Risk stratification

Risk stratification for SCD in patients with HCM remains a challenge. The prognostic value of routine testing data (ie, echocardiography, exercise testing and ambulatory rhythm monitoring) and retrospective postmortem characterisation of sudden death victims have been examined for this purpose.19^–22 Established risk factors among people with HCM include: (a) prior cardiac arrest; (b) unexplained syncope; (c) maximum left ventricular wall thickness >30 mm; (d) family history of sudden death attributable to HCM; (e) reduction in systolic blood pressure during exercise; (f) non-sustained ventricular tachycardia during ambulatory rhythm monitoring.

These risk factors have proved clinically useful and have been endorsed by expert consensus committee clinical guidelines. Nevertheless, they were derived from a diverse population of patients with HCM and not from young asymptomatic subjects. In addition, these risk factors have all been studied as predictors of mortality and even SCD but not as predictors of activity-related SCD. Consequently, they may not predict SCD during sports participation in young asymptomatic athletes with HCM detected by screening. In addition, the prognostic significance of a complete absence of these risk factors and how to quantify SCD risk in their absence remain unknown.

Athletic eligibility

Present guidelines from both the ACC 36th Bethesda Conference and ESC recommend that athletes with unequivocal or probable HCM abstain from competitive sport and vigorous training with the exception of low-intensity activities.23 24 Justification for this recommendation is that vigorous exercise increases the risk of HCM-related SCD and that permanent withdrawal from sport may reduce this risk. Both guidelines acknowledge the inherent limitations of a universal disqualification mandate since it probably excludes many athletes with no actual risk of SCD. Such unnecessary prohibition can produce significant emotional and financial loss for some people. However, sport disqualification remains a cornerstone in the management of athletes with HCM and is the safest approach for these patients until more data are available.

As preparticipation screening gains popularity, clinicians will face more frequent difficult decisions about athletic eligibility. Among those with probable or definite HCM, available data leave little choice but to err on the side of caution and to recommend restricting physical activity. This course of action cannot be disputed in athletes with the classic SCD risk factors. Unfortunately, such subjects represent the minority of athletes with HCM and management decisions for individual patients with definite or suspected HCM but no clear risk factors for SCD must be made on an individual basis. Ultimately, sport prohibition is always the safest option, but this strategy may be unnecessarily cautious and may not be accepted by the patient. In such situations, other strategies including prophylactic defibrillator implantation have been proposed but lack sufficient efficacy data.25 At the very least, patients must be honestly informed about what is known and not known about the risk of SCD in asymptomatic athletes with HCM. Only then can a strategy that incorporates scientific data, individual patient characteristics and the patient’s preferences be developed.

SUMMARY

The debate at the 2008 British Cardiovascular Society meeting on managing athletes with HCM highlights the need for better data. Medicine is littered with intuitively appealing solutions that were ultimately proved to be ineffective or downright deleterious. Proposed screening practices require careful evaluation using controlled study designs that incorporate current technology and up-to-date cost–benefit analysis. We also need better criteria to differentiate HCM from physiological hypertrophy, and strategies to stratify the risk of SCD during vigorous exercise in asymptomatic, athletic patients with HCM. Most clinicians who deal with HCM know of middle-aged patients with definite HCM who survived successful high school and college athletic careers. Such observations suggest that we need better criteria to predict which patients with HCM are at real risk for exercise-related cardiac events. Only by examining these concerns will we move our strategies for preventing sport-related SCD from the realm of “expert” opinion to the certainty of data-driven treatments.