Phospholamban p.Arg14del cardiomyopathy:Clinical and morphological aspects supporting the concept of arrhythmogenic cardiomyopathy

In this thesis, we investigated the morphological aspects of PLN cardiomyopathy to understand the disease, we explored new techniques (echocardiographical strain imaging) for early diagnosis, techniques for risk-stratification (cardiac magnetic resonance imaging; CMR) and new treatment options for these patients (clinical iPHORECAST trial and treatment in our PLN p.Arg14del mouse model). We found biventricular fibrofatty replacement to be characteristic. Furthermore, we found echocardiographic strain imaging can detect subtle myocardial dysfunction when other standard investigative tools show no abnormalities yet. CMR imaging with late gadolinium enhancement revealed early myocardial fibrosis in asymptomatic PLN p.Arg14del mutation carriers with preserved ejection fraction. The presence of this fibrotic areas was an independent predictor for malignant ventricular arrhythmias. The clinical multicenter iPHORECAST trail (work package 3.1 of CVON PREDICT), which I set up and where we investigate if eplerenone can slowen or stop disease progression, is still ongoing. Finally, we are currently working on a new PLN p.Arg14del mouse model in an attempt to identify new therapeutic strategies in these patients