Recently our group undertook a post-mortem examination of a 57-year-old, highly trained male runner who died while running a marathon. The man had been running for 20 years, and had completed multiple marathons (personal best 2 hours 30 minutes). At post-mortem examination, the heart was abnormal, with circumferential left ventricular (LV) hypertrophy. Heart weight was 480 g (expected 315–327 g, upper limit of 431 g). The LV lateral and anterior free wall measured 20 mm at the midventricular level, and both the interventricular septum and posterior wall measured 19 mm in thickness (normal <15 mm). There was also hypertrophy of the trabeculae and both papillary muscles. The diameter of the LV chamber was reduced to 10 mm (fig 1). Macroscopically, there was no obvious scarring, and the coronary arteries were normal. There was minimal floppy change observed in the anterior and posterior mitral valve leaflets, and the other valves were normal.

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Figure 1 Gross morphology of the heart demonstrating circumferential left ventricular hypertrophy. Heart weight was 480 g. The lateral and anterior free wall measured 20 mm at the midventricular level. Both the interventricular septum and posterior wall measured 19 mm in thickness. There was also hypertrophy of trabeculae and both papillary muscles. The diameter of the left ventricle chamber was reduced to 10 mm.

Histological examination of both ventricles found fibrosis throughout both chambers but predominating in the LV. There was widespread replacement fibrosis particularly in the lateral and posterior ventricular walls, and interstitial fibrosis in the inner layer of the myocardium (fig 2). Myocyte hypertrophy was observed around the areas of scarring, but no myocyte disarray indicative of hypertrophic cardiomyopathy was seen. There was no inflammation in the heart or any abnormal infiltrate including amyloid. The epicardial and intramural coronary arteries were normal, with no histological evidence of disease. There was no family history of note, including inherited cardiac disease and sudden death. All eight of the runners’ offspring have now been screened, and there is no evidence of cardiac pathology.

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Figure 2 Histology slide of the left ventricular myocardium following sirius red FB3 staining, showing idiopathic interstitial myocardial fibrosis in the deceased marathon runner.

A resting ECG trace obtained from the runner before death was normal for athletically trained individuals and the runner was otherwise well and entirely asymptomatic before starting the marathon. The cardiac pathological findings are consistent with idiopathic left ventricular hypertrophy in the presence of idiopathic interstitial fibrosis.

DISCUSSION

The beneficial effects of moderate physical activity are well recognised, however, exercise per se is associated with a 10-fold increase in the incidence of cardiovascular events in individuals with cardiovascular disease. The incidence of sudden cardiac death during marathon races has been estimated at 1 in 50 000 runners.1 In total, 10 deaths (4 coronary artery disease, 3 hypertrophic cardiomyopathy, 1 subarachnoid haemorrhage, 1 cerebral oedema associated with hyponatraemia, and the reported case) have occurred over 25 years of the London Marathon (1 death per 80 000 finishers). A further seven successful resuscitations have taken place during the London Marathon that would otherwise have resulted in death in the absence of rapid emergency care (SS is the London Marathon medical director).

A reduction in diastolic and systolic function concomitant, but unrelated, to a rise in humoral markers of cardiac myocyte damage, has been seen after endurance exercise.2 Previous studies have suggested that these acute changes are likely to be physiological in nature, indicated by their rapid (<24 hours) return to baseline values. The clinical implications of repeated bouts of prolonged arduous exercise are less well understood. It has been suggested that such exercise may result in pathological changes of the heart including myocardial fibrosis3 and heart failure.4 In support of these findings, several studies have reported an increased prevalence of arrhythmias in endurance-trained athletes,5 with myocardial damage proposed as a mechanism.6 Indeed, a recent study suggested that endurance exercise may act as a promoter for alterations in right ventricular function acting as a trigger for ventricular arrhythmias.7

Widespread myocardial fibrosis is observed in healed myocarditis, dilated cardiomyopathy,8 hypertrophic cardiomyopathy, non-infarcted myocardium from hearts with ischaemic scars,9 and systemic hypertension.10 It can also be linked rarely to small intramural coronary artery disease.

The runner reported in this paper was healthy and free from cardiovascular disease at time of death, with no documented evidence of diseases associated with widespread myocardial fibrosis. LV hypertrophy is a well-known adaptation to endurance training but has not previously been linked to fibrosis or permanent damage of the heart. Although the LV hypertrophy observed in this case study is above that expected in normal or athletic populations, the cause is unknown. Idiopathic LV hypertrophy has been previously documented in deceased athletes and is associated with sudden cardiac death in athletes, accounting for 7.5% of deaths.11

Although interstitial fibrosis may be associated with the idiopathic left ventricular hypertrophy observed, the aetiology of the fibrosis observed in the present study is unclear. The potential relationship between the raised levels of humoral markers of cardiac myocyte damage seen after acute bouts of prolonged exercise prompts us to propose that chronic exposure to repeated bouts of minimal cardiac damage may have resulted in the development of the interstitial myocardial fibrosis observed in the present case study.