PHOspholamban RElated CArdiomyopathy STudy - intervention (i-PHORECAST)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 150

Inclusion Criteria

PLN R14del mutation carriers
Age >=18 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)
•Global or regional RV dysfunction and/or structural alterations (according to
task force criterion 1).
•Ventricular premature complexes >2500 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/1.73m^2)
•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 highering/sparing-agents
•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
Note: presence of late gadolinium enhancement on MRI is not an exclusion criterion

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is a composite of at least one the following components:<br /><br>• LV enddiastolic volume, increase >10%<br /><br>• LV ejection fraction, absolute decrease >5%<br /><br>• RV enddiastolic volume, increase >10%<br /><br>• RV ejection fraction, absolute decrease >5%<br /><br>• late enhancement, absolute increase >5%<br /><br>(all the above parameters to be assessed with MRI)<br /><br>• QRS voltage, decrease >25% (ECG, measured in lead I, II and III in mV)<br /><br>• the occurrence of non-sustained ventricular tachycardia (Holter monitoring,<br /><br>exercise testing)<br /><br>• symptoms/signs of heart failure and/or arrhythmias necessitating treatment<br /><br>according to the attending physician and likely due to arrhythmogenic<br /><br>cardiomyopathy<br /><br>• cardiovascular death, including sudden death, likely due to arrhythmogenic<br /><br>cardiomyopathy</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Diagnosis of DCM<br /><br>• Diagnosis of ARVC (according to task force criteria)<br /><br>• Development of global or regional dysfunction and structural alterations,<br /><br>(according to task force criterion)<br /><br>• All individual components of the primary endpoint<br /><br>• QRS-axis on 12-lead ECG<br /><br>• Conduction intervals (PR-interval, QRS-duration) on 12-lead ECG and SA-ECG<br /><br>• STT-segment changes on 12-lead ECG<br /><br>• Change in biomarkers<br /><br>• Occurrence of sustained ventricular tachycardia or ventricular fibrillation<br /><br>• Hospitalization for a cardiovascular reason</p><br>