Table 1.

Key inclusion and exclusion criteria

Key inclusion criteria

PLN p.Arg14del carriers

Age ≥ 18 and ≤ 65 years

New York Heart Association functional class ≤ 1

LV ejection fraction ≥ 45 (measured with MRI)

Key exclusion criteria

Palpitations necessitating treatment (at the discretion of the attending physician)

A diagnosis of DCM (according to the Mestroni criteria [19]). Note: regional LV wall motion abnormalities are acceptable

A diagnosis of ARVC (according to the task force criteria [18])

Global or regional RV dysfunction and/or structural alterations (according to task force criterion 1 [18])

Ventricular premature complexes > 2500 during 24-hour 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 ischaemic heart disease

Treatment with cardioactive medication

Hyperkalaemia (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

Concomitant use of NSAIDs

Concomitant use of potassium-sparing agents

Known intolerance or contraindication for aldosterone antagonists

Participation in another drug trial in which the last dose of drug was within the past 30 days

Contra-indications for CMR (claustrophobia, metal devices)

Subjects unable or unwilling to provide written informed consent

Note: presence of late gadolinium enhancement on CMR is not an exclusion criterion

PLN phospholamban, DCM dilated cardiomyopathy, LV left ventricular, ARVC arrhythmogenic right ventricular cardiomyopathy, RV right ventricular, eGFR estimated glomerular filtration rate, NSAIDs non-steroidal anti-inflammatory drugs, CMR cardiac magnetic resonance