Editor's note: Please see companion articles What is Sports Cardiology? and Exercise Physiology for the Sports Cardiology Fellow.

The field of sports cardiology has rapidly evolved over the last few decades. However, despite our growing understanding of the 'athlete's heart' and sudden cardiac death in this population, there remain significant evidence gaps which pose challenges in the clinical management of athletes or high-active people. In this article, the final section in a three-part series, we focus on a few key clinical dilemmas specific to each age group of athletes. Rather than provide an exhaustive list of all controversial areas in sports cardiology, of which there are many, our aim is to highlight common scenarios encountered in clinical cardiology and sports cardiology practices. In particular, we discuss the pre-participation evaluation, exercise prescriptions in young athletes with underlying cardiomyopathy and management of older athletes with atrial fibrillation and coronary artery calcification.

Variation in Pre-Participation Evaluation Protocols

What are current recommendations regarding pre-participation evaluation of young athletes?

Sudden cardiac death is a relatively infrequent event, both in the general population and among athletes.¹ The majority of sports-related sudden deaths occur among older athletes (>35 years of age), in whom atherosclerotic coronary artery disease (CAD) predominates as the cardiac cause of sudden death.^2,3 In the US, among athletes <35 years of age, hypertrophic cardiomyopathy is cited as a common cause of SCD. However, more recent data from college athletes has shown that a common finding at autopsy in cases of SCD is a structurally normal heart, implying that channelopathies and other electrical disorders may be a more common etiology than previously suspected.⁴ Notably, regional variations in the causes of SCD may exist, as ARVC has been reported to be a common cause of SCD from the Veneto region of Italy.⁶ Other causes of SCD include congenital coronary anomalies, commotio cordis, cardiomyopathies such as arrhythmogenic right ventricular cardiomyopathy (ARVC), myocarditis and valvular and aortic diseases. The data that report on the incidence of SCD come from disparate sources and include large, long-term, retrospective observational databases, but multiple studies have shown that male athletes have a three- to five-fold higher risk of SCD compared to female athletes.¹ Data from the National Collegiate Athletic Association (NCAA) indicate that black athletes in the US have a higher risk of sudden death sports-related deaths compared to white athletes.⁵

Pre-participation evaluation (PPE) prior to competing in competitive athletics has been recommended by multiple societies to identify possible cardiac abnormalities and risk factors that could result in SCD while engaging in sports.¹ The components of the PPE are highly variable among countries, leagues and levels of competition. Fourteen elements of the personal and family history and physical exam are recommended by the American College of Cardiology and the American Heart Association as part of a comprehensive medical questionnaire. The history portions of recommended PPE (Table 1) are based on expert consensus and have not been prospectively validated.⁷

Similarly, the addition of the resting 12-lead electrocardiogram (ECG) to the PPE has not been shown to prevent SCD in a randomized or prospective study. However, several associations do recommend its use and encourage standardization and adherence to consensus guidelines in interpretation for athletes, while recognizing its limitations.⁸ In the US, though the use of pre-participation ECG screening has been frequently debated, no mandate has been issued. In Italy and Israel, a PPE that includes a 12-lead ECG has been mandated nationally with conflicting findings. Corrado et al. published one of the first large, retrospective studies of SCD in athletes in the Veneto region of Italy and found a reduction in SCD with mandated pre-participation screening for athletes.⁹ This study formed the basis for guidelines from the European Society of Cardiology advocating mandatory ECG screening of athletes.¹⁰ However, another retrospective study in Israel found no difference in incidence of SCD between periods before and after implementation of a mandatory ECG screening program over a 30-year period.¹¹ In these countries, the rates of SCD after implementation of ECG screening were comparable to those observed elsewhere (e.g., Minnesota), where screening is not mandated.¹¹ Malhotra et al. conducted a study examining incidence and causes of SCD among adolescent boys playing soccer with the English Football Association, all of whom underwent screening with history, physical, 12-lead ECG and echocardiography. In this study, the rate of SCD among previously screened athletes was 6.8 per 100,000 athletes. The most commonly detected cardiomyopathy with screening was HCM; however, most deaths were due to cardiomyopathies undetected by pre-participation screening.¹² This appeared, on the surface at least, to suggest that the addition of an ECG and echocardiogram to the pre-participation screening protocol does not prevent SCD in athletes. However, a deeper analysis revealed that the pre-participation ECG and echocardiogram detected 42 cases of cardiac conditions associated with SCD (ECG alone identified 36 of the 42 cases). It must be considered that the subsequent appropriate management of these otherwise undiagnosed cases may have reduced their risk of SCD during the follow-up period. Furthermore, given that the mean time between screening and sudden cardiac death was 6.8 years, the authors note that age related penetrance of these inherited diseases is an important consideration in PPE. Indeed, exercise has been shown to accelerate the manifestation of certain cardiomyopathies, most notably ARVC, such that intensive training may "unmask" phenotypes that were not detected in screening at younger ages. Such age-related and exercise-accelerated phenotypic manifestations are critical considerations in assessing the sensitivity and specificity of pre-participation screening programs. They also raise the question of utility of serial ECGs for ongoing screening in athlete populations. Ultimately, while the inclusion of the ECG in routine PPE is subject to much debate, it is generally agreed that a thorough history and physical is critical in the initial evaluation.

Management of Young Athletes With Cardiovascular Conditions

Is my patient with underlying cardiomyopathy allowed to exercise?

There are particular populations of patients for whom consensus guidelines regarding participation in sports and activity have generally been restrictive. In these populations, limited data exists to guide recommendations, which have typically been made by expert opinion or consensus. It is important to realize that as newer data emerge, recommendations regarding restriction from sports are constantly evolving; here we discuss two such scenarios.

Among patients with implantable cardioverter defibrillators (ICDs), the basis for restricted activity recommendations include concern for lead dislodgement/failure to defibrillate, injury due to loss of consciousness from arrhythmia or damage to the ICD itself. Recent data, however, appears to allay some of the concerns regarding competitive sports participation in patients with ICDs. Lampert et al. established a multinational, prospective, observational registry of patients with ICDs (aged 10-60 years old) engaged in organized or high-risk sports to better understand risks associated with physical activity and ICDs. Among 372 patients in the registry, over a median follow-up of 31 months no patients experienced tachyarrhythmic death or had externally-resuscitated tachyarrhythmia during sports participation. Seventy-seven patients (21% of study population) experienced 121 shock episodes. Thirteen percent of the population received at least one appropriate shock and 11% experienced at least one inappropriate shock. Freedom from lead malfunction was 97% at five years after device implantation. Overall, this study demonstrated that patients with ICDs can engage in vigorous sports without increased risk of device malfunction or tachyarrhythmic death. However, the study did show that the risk of both appropriate and inappropriate ICD shocks must be weighed along with patient substrate in consideration of recommendations for engaging in physical activity.¹³

Among patients with HCM, guidelines have generally recommended avoiding vigorous or competitive sports as the risk of such activity in HCM is unknown.¹⁴ However, that previously undiagnosed HCM is an important underlying cause of SCD in young athletes increases the need to understand the risks associated with vigorous exercise in patients with HCM. As such, there is now an ongoing prospective, observational study, LIVE-HCM/LQT (Exercise in Genetic Cardiovascular Conditions) comparing outcomes between patients with HCM who exercise moderately to vigorously and sedentary controls with HCM. Based on a recent small study of symptomatic patients with HCM, as well as the large body of knowledge regarding the physiologic benefits of physical activity, it has been hypothesized that exercising with HCM may not only be low risk, but beneficial for symptom management.¹⁵

Management of Older Athletes With Common Cardiovascular Conditions

Older athletes represent a large proportion of patients seen in sports cardiology practices. The challenges in caring for this patient population are often significantly different than those of their younger counterparts, in whom the consultation may be focused on evaluation of symptoms, screening for inherited cardiomyopathies, and differentiating pathologic disease from common physiologic variants or adaptations to exercise. In the veteran or "masters" athlete (typically defined as >35 years of age), there is a greater prevalence of cardiovascular conditions seen in the general population, such as atrial fibrillation and CAD. In these instances, the clinical challenge often involves the significance, management and effects of such conditions on engagement in athletics in a population that is not as well studied as the general population.

How should I counsel my patient regarding the risk of atrial fibrillation and endurance exercise?

The major controversies regarding atrial fibrillation and exercise pertain to whether long term endurance sports can cause atrial fibrillation, the possible mechanisms by which this may be mediated, and the management of veteran athletes with atrial fibrillation. The association between atrial fibrillation and endurance sports is complex. Low to moderate levels of exercise are associated with a reduced risk of atrial fibrillation compared to sedentary controls;^16,17 however, more intense, high endurance activities are associated with an increased risk of developing atrial fibrillation.^18-25 Large case-control studies and meta-analyses have corroborated the hypothesis that there is a dose- and intensity- dependent association between endurance sports and atrial fibrillation.^25,26 Although there is no data to explicitly demonstrate causality between excess exercise and cardiac disease, atrial fibrillation represents the most compelling evidence for an overuse phenotype.²⁷ Furthermore, endurance athletes tend to exhibit left atrial dilatation,²⁸ exercise animal models demonstrate increased atrial fibrosis,²⁹ and high levels of exercise affect vagal tone which can increase the risk of atrial fibrillation.³⁰ Taken together, it is conceivable that high levels of exercise can result in an increased risk of atrial fibrillation.

The appropriate management of atrial fibrillation in athletes remains uncertain, in particular whether there is a difference between rate or rhythm control strategies, as well as whether ablation or medical therapies provide the most optimal outcome.^31-33 Given the overall decreased risk of cardiovascular disease in this active population, much of the data from management of this condition in the general population is not easily applicable to masters athletes. Management of atrial fibrillation in otherwise-healthy athletes also depends upon patient preference for taking medications regularly, particularly beta-blockers, which must be weighed against the risks of undergoing one or more invasive procedures. In addition, mitigating thromboembolic risk in athletes is challenging, as systemic anticoagulation may not be ideal depending on the sports in which such athletes engage.

Is it safe for my patient with coronary artery calcification to run a marathon?

Coronary artery disease in endurance athletes has been a fiercely debated topic over the past decade. The discussion is centered on two generally accepted observations. First, although the majority of veteran endurance athletes do not have coronary artery calcification, there is a higher prevalence of coronary artery calcification in veteran endurance athletes compared to age- and risk factor- matched controls.^34-36 Second, as mentioned earlier, vigorous exercise can transiently increase the risk of an acute cardiac event,^37-39 particularly in older athletes. Based on these findings, some argue that high levels of endurance exercise causes CAD, which in turn exposes one to an increased risk of an acute coronary event, particularly during bouts of intense physical exertion. While this is conceivable, it is equally plausible that calcification seen in athletes represents the exercise-induced favorable remodeling of previously unstable plaque that developed due to the presence of traditional risk factors such as dyslipidemia, glucose intolerance and genetic predisposition.²⁷ Furthermore, we currently do not completely understand the prognostic significance of this calcification, which recent work suggests may differ in athletes compared to sedentary individuals. This dilemma is becoming increasingly apparent in sports cardiology due to the increasing utilization of coronary calcium scoring in lower risk individuals. In turn, athletes may present more commonly with difficult questions regarding the significance of their coronary calcification, for which we do not have a clear mechanism or full understanding of the prognostic implications.⁴⁰ Until more definitive research focused on this unique population is performed, the significance of this phenomenon remains controversial and highly debated.^41,42 In the meantime, we recommend using coronary calcium scores in appropriate circumstances, and having an open dialogue with patients regarding the uncertainties with this particular finding in endurance athletes.

Conclusion

In this article, we have outlined some of the key questions, controversies and evidence gaps within the field of sports cardiology for the interested cardiology fellow. In order to develop a greater understanding of these issues it is imperative that we acquire more longitudinal, prospective data in this particular population of athletes and highly active people. While randomized controlled trials are difficult to conduct in small populations with rare diseases, large prospective observational trials can provide important insights into managing cardiovascular diseases in this population. In this way, we will be able to better identify optimal algorithms for pre-participation screening, ascertain the role and safety of exercise in athletes with underlying cardiac disease, and improve longevity in veteran athletes.

Table 1: AHA/ACC 14-Point Pre-Participation Evaluation for Cardiovascular Disease in a Young Athlete

Personal History	Exertional chest pain, discomfort or tightness
	Exertional syncope or near-syncope
	Excessive or unexplained fatigue/dyspnea associated with exercise
	Prior recognition of a heart murmur
	Elevated systemic blood pressure
	Prior restriction from sports participation
	Prior heart testing ordered by a physician
Family History	Premature death—sudden and unexpected before age 50 years of age due to heart disease—in one or more relatives
	Disability from heart disease in a close relative <50 years of age
	Specific knowledge of certain cardiac conditions in family members: hypertrophic or dilated cardiomyopathy, long-QT syndrome or other ion channelopathies, Marfan syndrome or clinically important arrhythmias
Physical Examination	Heart Murmur
	Femoral pulses to exclude aortic coarctation
	Physical stigmata of Marfan syndrome
	Brachial artery blood pressure (sitting)

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Keywords: American Heart Association, Arrhythmogenic Right Ventricular Dysplasia, Aortic Diseases, Athletes, Atrial Fibrillation, Calcium, Cardiomyopathies, Cardiomyopathy, Hypertrophic, Case-Control Studies, Channelopathies, Commotio Cordis, Cohort Studies, Coronary Artery Disease, Defibrillators, Implantable, Dilatation, Death, Sudden, Cardiac, Dyslipidemias, Echocardiography, Electrocardiography, Exercise, Electric Countershock, Expert Testimony, Follow-Up Studies, Football, Genetic Predisposition to Disease, Glucose Intolerance, Glucose Intolerance, Heart Atria, Mandatory Testing, Myocarditis, Penetrance, Incidence, Patient Preference, Phenotype, Physical Exertion, Prevalence, Prognosis, Prospective Studies, Referral and Consultation, Registries, Retrospective Studies, Risk Factors, Soccer, Sports, Tachycardia, Unconsciousness, Veterans

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