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.