In an animal study Benito et al. compared rats that were trained to run strenuously and without resting for 60 minutes daily for 16 weeks to sedentary rats.41 The running rats developed bi-ventricular hypertrophy, diastolic dysfunction, bi-atrial dilation and had increased collagen deposition and fibrosis in the RV and in both atria. Ventricular tachycardia was inducible in 42% of the running rats versus only 6% of the sedentary rats (P=0.05). Importantly, the fibrotic changes caused by 16 weeks of intensive ET had largely regressed back to normal by eight weeks after the daily running regimen was ceased. Excessive strenuous daily running in this animal study replicated the adverse cardiac structural remodeling and pro-arrhythmia substrate noted in observational studies of extreme endurance human athletes. These findings support the hypothesis that long-term strenuous daily endurance ET such as marathon running or professional long-distance cycling may cause cardiac fibrosis (especially in the atria and the RV), diastolic dysfunction, and increased susceptibility to atrial and ventricular arrhythmias (VA). However, it should be noted that animal studies are of uncertain clinical relevance due to the excessively stressful nature of the imposed exercise.
Running is a prototypical natural physical activity and often plays an integral and important role in an active healthy lifestyle.1,2 However, continuous running such as is required for training and participating in a marathon may be detrimental to cardiovascular health. Several serological markers of cardiac damage have been documented to rise during and after marathon running.13, 17, 42 These markers include cardiac troponin-I, creatine kinase and creatine kinase myocardial band (CK-MB), myoglobin, and BNP (See Figure 4). Additionally, transient renal dysfunction has been observed with EEE efforts causing volume depletion and diminished renal filtration with elevations in blood urea nitrogen, serum creatine, and cystatin-C.43 Abnormally increased levels of cardiac biomarkers including troponin after extreme aerobic endurance events, such as marathons, in all probability reflect myocardial cell damage and stretch at the sites of myocyte slippage of one cell along another due to loss of integrity of desmosomal connections.
Chronic EEE imposes increased hemodynamic demands which alter the loading conditions of the heart, particularly among athletes participating in sports requiring sustained large elevations in cardiac work such as long-distance running, rowing, and cycling.44 Highly trained individuals develop cardiac adaptations including enlarged left ventricular (LV) and RV volumes, increased LV wall thickness and cardiac mass, and increased left atrial (LA) size.38-40 These structural alterations, together with a preserved LV ejection fraction (EF), have been considered typical findings of the “athlete’s heart.”35-37 Accumulating information suggest that some of the remodeling that occurs in endurance athletes may be pathological rather than entirely benign and adaptive.34
Repetitive sustained intense aerobic exercise induces remodeling of the RV with dilation of RV end diastolic dimension, however, the RVEF remains normal in asymptomatic athletes without evidence for arrhythmia.25,26 In a recent study,13 forty athletes were studied at baseline, immediately following an endurance race (three to eleven hours duration) and one week after the race (See Figures 5, 6).
Figure 5. Repetitive sustained intense aerobic exercise induces remodeling of the RV with dilation of RV end diastolic dimension, however, the RVEF remains normal in asymptomatic athletes without evidence for arrhythmia.
Figure 6. Repetitive sustained intense aerobic exercise induces remodeling of the RV with dilation of RV end diastolic dimension, however, the RVEF remains normal in asymptomatic athletes without evidence for arrhythmia.
Relative to baseline, RV volumes increased and all functional measures decreased post-race; RVEF decreased with increasing race duration. RV function was mostly recovered by one week. On cardiac magnetic resonance imaging (CMR), delayed gadolinium enhancement (a marker of myocardial fibrosis) localized to the interventricular septum was identified in athletes who had greater cumulative exercise exposure and lower RVEF than those with normal CMR (See Figure 7).
In a study of 102 ostensibly healthy male runners ranging from 50 to 72 years old, who had completed at least five marathons during the past three years compared to 102 age-matched control subjects, CMR was used to assess the effects of chronic long distance running on myocardial structure.45 Approximately 12% of these apparently healthy marathon runners showed evidence for patchy myocardial scarring, a rate three-fold higher than that in age-matched control subjects. This study indicates that in endurance athletes, CMR with late gadolinium enhancement can reliably detect areas of patchy fibrosis.45 Of additional concern, the CAD event rate during two-year follow up was significantly higher in the marathon runners than in controls (P < .0001).
Figure 7. delayed gadolinium enhancement (a marker of myocardial fibrosis) localized to the interventricular septum was identified in athletes who had greater cumulative exercise exposure and lower RVEF than those with normal CMR.
A recent study also reported that long-term marathon runners had increased aortic stiffness compared with recreational exercisers.46 This study assessed blood pressure and aortic elasticity among 47 individuals who chronically trained for and competed in marathons, and compared them to 46 others who did not participate in chronic endurance ET. The chronic marathoners showed significantly higher systolic blood pressures compared with the control group (126 mm Hg vs. 115 mm Hg). Pulse-wave velocity, utilized to assess aortic stiffness, was significantly higher in the marathoner group compared to controls.20,46 Thus, sustained shear stress over a long period of time may induce fibrotic changes in the arterial wall, potentially similar to that in the myocardium, and over time leads to decreases in compliance. It should be noted that aortic stiffness and atrial pulse wave reflections have been established as independent predictors of CV risk.47
Schwartz et al. reported that long-term marathon runners, defined as individuals who have completed at least 25 marathons over the past 25 years, showed higher than expected levels of coronary artery calcium (CAC) and calcified coronary plaque volume.26 This study, utilizing CT coronary angiography, found that the chronic marathoners had significantly more calcified plaque volume, 274 mm3, versus 169 mm3 for the sedentary controls. CV risk factors such as age, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were similar between the marathoners and controls, but heart rate and weight were lower, and high-density lipoprotein cholesterol levels were higher in the runners. A similar study in a different population found increased CAC in 108 middle-aged marathon runners compared with non-runners who had matched risk factors, and CV event rates in the marathoners were equivalent to a CAD population.48 In a case report, Goel et al.49 observed a 49-year-old marathoner who had significant obstructions in all three major epicardial coronary arteries with no associated risk factors, and who generated protracted oxidative stress with prolonged running.
Increases in LV mass typically develop in response to high-level, intense long-term ET, particularly in cyclists, cross-country skiers, and rowers.50 The “physiological” LV hypertrophy that is a common feature of “athlete’s heart” is thought to be a functional adaptation to chronic ET. LV mass, as determined by CMR, was significantly greater in the marathoners.51 In this study, increased LV mass correlated with higher CAC scores. Specifically, marathon runners with a mass above 150 grams had a significantly higher CAC score than those with LV masses below 150 grams.51 These investigators also found a mismatch between the risk-factor profiles and the amount CAC particularly in those with a LV muscle mass above 150 grams.