PHOspholamban RElated CArdiomyopathy STudy
In the Netherlands ≈15% of idiopathic dilated cardiomyopathy (DCM) and ≈10% arrhythmogenic right ventricular cardiomyopathy (ARVC) patients carry a single (founder) mutation in the gene encoding Phospholamban, PLN R14del. Analogous to other inherited cardiomyopathies, the natural course of the disease is age-related (“age-related penetrance”); after a presymptomatic phase of variable length many PLN R14del-carriers progress to overt disease, and are diagnosed with either DCM or ARVC.
PLN is a regulator of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) pump in cardiac muscle and thereby important for maintaining Ca2+ homeostasis. Cardiac fibrosis is an early manifestation of disease. The hypothesis of iPHORECAST is that treatment of presymptomatic PLN R14del-carriers with eplerenone, which by virtue of its mineralocorticoid(aldosterone)-blocking properties is a strong antifibrotic agent, reduces disease progression and postpones onset of overt disease. iPHORECAST is a multicenter, prospective, randomized trial, carried out in UMCG, Amsterdam UMC, UMCU and Antonius Hospital Sneek. Half of the subjects group receive a 50 mg tablet of eplerenone once daily and the other half receives no treatment. Duration of treatment is 3 years. The study started in 2014 and the last subject of the 84 asymptomatic PLN R14del-carriers that have been included will leave the study beginning 2021.The primary endpoint is a composite of MRI findings (LV and RV volumes and function, and gadolinium late enhancement), ECG findings and arrhythmias. The results of this innovative trial are expected in 2021.