Exercise and Heart Disease

From Athletes and Arrhythmias to Hypertrophic Cardiomyopathy and Congenital Heart Disease

Abbas Zaidi; Sanjay Sharma


Future Cardiol. 2013;9(1):119-136. 

In This Article

Too Much of a Good Thing: Can Exercise Damage the Healthy Heart?

Whilst the health benefits of regular, moderate exercise are well established, the majority of highly trained athletes chronically engage in several times the exercise 'dose' proven to be of benefit for prevention of cardiovascular disease. The past quarter of a century has witnessed a dramatic upsurge in amateur endurance sports participation. In the USA, over half a million people completed a marathon last year, with more than 13 million runners competing in a race of 5 km or longer. Moreover, these numbers are projected to increase by approximately 5% per year. Cardiac event rates are low in athletes and amateur participants in endurance events, and are most frequently confined to those harboring hereditary or congenital abnormalities of the heart. Analogous with pharmacological treatments, it is recognized that exercise exhibits an inverted J-shaped dose–benefit response curve with respect to musculoskeletal injuries; however, the concept that intensive exercise may exert detrimental cardiovascular effects in individuals with normal hearts has never been systematically investigated in large cohorts. In recent years, a growing minority in the sports cardiology community have raised the question as to whether an optimal dose of exercise exists, beyond which its cardiovascular health benefits decrement at the expense of adverse effects.

A large number of studies have documented cardiac biomarker release immediately after endurance exercise, associated predominantly with transient impairment of LV myocardial relaxation.[56] As many as 50% of marathon runners have been reported to exhibit an acute rise in serum troponin concentration,[57] although this has traditionally been attributed to cytosolic leak rather than true myocyte necrosis. The precise significance of this transient phenomenon is uncertain, but limited CMR studies in small cohorts immediately post-race have failed to demonstrate obvious features of myocardial inflammation.[58] However, it has been postulated that repeated bouts of myocardial injury during intense exercise may lead to inflammation and fibrosis, resulting in chronic adverse cardiac remodeling and development of an arrhythmogenic substrate. This assertion is supported by a handful of post-mortem studies that have demonstrated idiopathic LVH and interstitial fibrosis in the hearts of veteran athletes who have been victims of sudden death.[59]

The benign nature of mild LVH and biventricular chamber enlargement commonly seen in athletes is supported by the preservation of systolic and diastolic function, as well as resolution of these changes with detraining, in the vast majority of studies. However, in one study of veteran Olympian athletes, significant LV dilatation persisted many years after cessation of high-level sporting activity in more than 20% of cases.[60] Perhaps the most compelling evidence that excessive exercise may be 'cardio-toxic' in predisposed individuals is the fivefold increase in the prevalence of atrial fibrillation in veteran endurance athletes,[61] as well as reports of sino-atrial disease,[62] ventricular arrhythmias[63] and advanced heart block.

The Right Ventricle: At Greater Risk of Arrhythmogenic Remodeling?

The focus of research relating to the athlete's heart has traditionally centered on LV physiology and structure. The right ventricle has been relatively neglected but is subject to the same preload as the LV during exercise. The substantial increase in cardiac output, coupled with a relatively minimal decrease in pulmonary vascular resistance during exercise, may be associated with exercise-induced pulmonary artery pressures exceeding 80 mmHg in some athletes, thereby exerting a disproportionately large afterload pressure on the thin-walled right ventricle.[64] In a recent study by La Gerche et al., echocardiography and cardiac biomarker assessment was performed in 40 athletes immediately before and after participation in endurance events of varying intensity.[65] Correlations were demonstrated between post-race biomarker elevations and RV systolic dysfunction, whilst LV systolic function was unaffected. In addition, the most profound post-race RV dysfunction was seen in athletes completing the most intense endurance event (ultra-triathlon), although almost all parameters of cardiac function had returned to normal within a week post-race. This study is cited as evidence that intense exercise might result in acute cardiac damage, which may disproportionately affect the right ventricle, and begs the question as to whether repetitive, long-standing bouts of arduous exercise could result in the development of an acquired form of the desmosomal gene disorder ARVC, phenotypically identical to the familial condition, but driven by training rather than a genetic substrate.

Several studies provide speculative evidence in support of this concept. Heidbuchel et al. studied 46 endurance athletes presenting with complex ventricular arrhythmias and demonstrated the primary arrhythmogenic focus to originate from the right ventricle in the majority of cases.[66] During a median follow-up period of 5 years, 18 of these athletes experienced major arrhythmic events, including sudden death in nine cases. A subsequent angiographic study by Ector et al. compared RV structure and function in a small number of endurance athletes with a history of symptomatic RV arrhythmias versus matched endurance athletes without RV arrhythmias. The results demonstrated significant reductions in RV ejection fraction in those athletes presenting with arrhythmias.[67] However, the patients reported by Heidbuchel and Ector represent a highly select group of symptomatic individuals presenting to a tertiary cardiac center with complex ventricular arrhythmias, and should not be considered to represent the usual asymptomatic endurance athletes. Furthermore, adverse events occurred in the youngest individuals, who would have expectedly trained for the lowest number of lifetime cumulative hours, thus refuting the hypothesis that chronic intensive exercise is the only mechanism for RV damage. In a further study, La Gerche et al. demonstrated desmosomal gene mutations in only 12.8% of athletes presenting with complex ventricular arrhythmias of RV origin, a figure much lower than that reported in familial ARVC, in which up to 60% of cases are genotype positive.[68] Once again, this should not be interpreted as conclusive evidence of an exercise-induced form of the disorder, since the yield of gene mutations in sporadic cases of ARVC is also low. Benito et al. have recently demonstrated training-dependant RV fibrosis and increased arrhythmia inducibility in a rat model of endurance exercise, although it should be noted that rats that were sacrificed after a brief period of detraining demonstrated complete regression of this fibrosis.[69]

Thus the evidence for the existence of an exercise-induced form of ARVC remains circumstantial, and requires detailed longitudinal assessment of large groups of endurance athletes before the concept can be unanimously accepted by the scientific community. Perhaps the most plausible theory is that chronic, intensive exercise may promote the expression of a latent arrhythmogenic substrate in genetically predisposed individuals. This concept is supported by an elegant series of studies by Kirchhof et al., in which the development of the ARVC phenotype in heterozygous plakoglobin-deficient mice was accelerated by an endurance training protocol,[70] and prevented by load-reducing therapy using nitrates and diuretics.[71] The concept of chronic exercise-induced cardiac damage is depicted in Figure 8.

Figure 8.

Theoretical model of chronic exercise-induced cardiac arrhythmogenic remodeling.
RV: Right ventricular.
Adapted from [73] with permission of the European Heart Journal.

The question of an optimal exercise dose is a pertinent and intriguing one, with a small but important signal in the literature that the linear relationship between exercise intensity and cardiovascular benefit may not stand up to scrutiny outside the realms of 'normal' activity. However, athletes in whom adverse cardiac events have been reported have almost without exception been those with underlying cardiac pathology, or those chronically engaging in levels of exercise many times that proven to improve cardiovascular health. In light of the burgeoning obesity epidemic in Western society and the rise in cardiac morbidity due to lack of habitual physical activity, regular moderate exercise must continue to be strongly advocated for the vast majority of the general population.