Arrhythmia mechanisms and effects of exercise training in CPVT and post-infarction heart failure

Abstract

Regular physical activity protects against cardiovascular disease. However, exercise can provoke fatal heart rhythm disturbances in some conditions. Patients with heart failure have increased risk of heart rhythm disturbances. On a cellular level, heart failure shares some alterations with the rare disease Catecholaminergic polymorphic ventricular tachycardia (CPVT). Both diseases have altered ryanodine receptor (RyR) function. Calcium release by RyR in the cardiomyocytes control electric activity and contraction of the heart. Dyssynchronous release of calcium in the diastole by RyR dysfunction in heart failure and CPVT, increases the propensity for arrhythmias, cardiac arrest and sudden cardiac death. Research has shown that exercise can modify RyR function. The thesis Arrhythmia mechanisms and effects of exercise training in CPVT and post-infarction heart failure investigates the mechanisms behind disrupted calcium handling in CPVT and the effect of exercise on RyR function in both CPVT and heart failure. The first paper found that stress-stimulation of the heart is the most important stimuli that leads to increased risk of rhythm disturbance in CPVT, due to dysfunctional calcium handling. However, our results also showed that increased heartrate could potentiate the release of calcium and further increase the risk of arrhythmias. In paper two and three, we investigated the anti-arrhythmic effect of exercise in CPVT and heart failure. We found that exercise stabilized the RyR function in both CPVT and heart failure. Exercise improved calcium handling in the cardiomyocytes, by lowering the calcium release through RyR in diastole. This could potentially decrease the propensity of rhythm disturbances, cardiac arrest and sudden cardiac death in CPVT and heart failure. More research is needed to explore the potential for anti-arrhythmic effect of exercise and how to perform exercise safely.