PHOspholamban RElated CArdiomyopathy STudy - Intervention

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 appears to be an early manifestation of disease. The investigators hypothesize 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.

Inclusion criteria

• Phospholamban (PLN) R14del mutation carriers
• Age ≥30 and ≤ 65 years
• New York Heart Association functional class ≤ 1
• LV ejection fraction ≥.45 (measured with MRI)

Exclusion criteria

• Palpitations necessitating treatment (at the discretion of the attending physician)
• A diagnosis of DCM (see appendix 1). Note: regional LV wall motions abnormalities are acceptable.
• A diagnosis of ARVC (according to the task force criteria, see appendix 2)
• Global or regional RV dysfunction and/or structural alterations (according to task force criterion 1, see appendix 2).
• Ventricular premature complexes >1000 during 24hours Holter-monitoring
• Non-sustained ventricular tachycardia during Holter-monitoring or exercise-testing
• History of sustained ventricular tachycardia or ventricular fibrillation
• Hypertension requiring the use of antihypertensive drugs, or when this is anticipated within the coming 3 years
• Evidence of ischemic heart disease
• Treatment with cardioactive medication
• Hyperkaliemia (serum potassium >5.0 mmol/l)
• Severe renal dysfunction (eGFR <30 ml/min/1.73 m2)
• Severe hepatic impairment (Child-Pugh class C)
• Women who are currently pregnant or report a recent pregnancy (last 60 days) or plan on becoming pregnant.
• Concomitant use of CYP3A4-inhibitors (see appendix 5)
• Concomitant use of NSAIDs (see appendix 5)
• Concomitant use of potassium sparing-agents (see appendix 5)
• Known intolerance or contraindication to aldosterone antagonists
• Participation in another drug trial in which the last dose of drug was within the past 30 days.
• Contra-indications for MRI (claustrophobia, metal devices)
• Subjects unable or unwilling to provide written informed consent