Effect of Preload Reducing Therapy on Right Ventricular Size and Function in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract Background Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an important cause of sudden cardiac death in young people and athletes. Thus far, no treatment has proven to slow the progression of the disease. Preload reducing agents such as nitrates and diuretics have shown promising results in preventing training-induced development of ARVC in a murine model. Objective To describe our experience with using preload reducing therapy in patients with ARVC and symptomatic RV dysfunction. Methods We performed retrospective chart review of prospectively collected registry data and included 20 patients with definite ARVC, who had serial echo measurements and an implantable cardioverter defibrillator. Six of the 20 with RV end diastolic area (RVEDA) above median (>25cm2), and NYHA class II-IV symptoms were successfully treated with long-term isosorbide dinitrate 5-40 mg TID (at maximum tolerated dose) and hydrochlorothiazide-spironolactone 25-25 mg daily. The main outcomes of interest were RVEDA, fractional area change (RV FAC) and RV outflow tract measurements. Generalized Estimating Equations with repeated measures were used to identify the association between preload reducing agents and echocardiographic structural progression. Results Patients who received preload reducing agents (n=6) were older, had larger RVs with lower FAC at baseline, however, treatment with preload reducing agents was associated with less RVEDA enlargement during mean (range) 3.3 (1-6.7) years of treatment in a multivariate analysis (%change in RVEDA associated with treatment (95% confidence interval (CI)): -7.71 (-13.29, -2.13), P-value:0.007). Conclusion Preload reducing agents show promising results in slowing RV enlargement in patients with ARVC showing possible disease modifying potential.