Role of Testosterone and Physical Activity in ARVC Pathogenesis
Testosterone, the hormone generally found in higher amounts in males, has been shown to have pro-arrhythmic effects, accelerate ARVC pathogenesis including myocardial apoptosis and lipogenesis, independent of age, BMI, ventricular function and desmosome mutation status.22 Other concomitant factors that may have accelerated his phenotypical expression, particularly with left sided involvement, include (male) gender and the degree of physical activity including strenuous exercise. The patient’s rigorous exercise capacity (evident by his exercise treadmill study reaching Bruce Stage 5) and recent physical training for becoming a firefighter/EMT (which is generally 18 weeks in duration), we feel, are likely to have progressed his disease process in the short time with recurrent hospitalizations. High intensity exercise is of particular importance in ARVC as it increases wall stress, increases sympathetic stimulation, predisposes to greater incidence of fatal ventricular arrhythmia, and is correlated with reduced LV (and RV) function.23 Those with ARVC are encouraged to avoid competitive sports, especially endurance or high intensity sports due to the arrhythmic risk and accelerated disease progression.24,25 Endurance training studies of plakoglobin deficient mice (similar to the protein deficiency produced by the JUP gene mutation in our patient), have demonstrated alterations in right ventricular dilation/dysfunction and electrophysiological function (increased spontaneous ventricular ectopy).26 To the best of our knowledge, we could not find similar documented reports demonstrating structural leftventricular changes within such a short time period with this isolated gene mutation. Ultimately, our recommendation for exercise cessation may also help explain his improvement in scar/fibrotic burden seen in his third CMR scan.