Quinidine Versus Verapamil in Short-coupled Idiopathic Ventricular Fibrillation

Inclusion Criteria:

1. At least one of the following 3 principal diagnostic criteria for short-coupled IVF: A. Diagnosis of short-coupled IVF, based on any documentation (i.e., ECG, Holtermonitor, device electrogram (EGM), or telemetry) of PVT of ≥3 consecutive beats or VFinitiated by a PVC with a coupling interval <350 ms B. Isolated PVCs with a couplinginterval <350 ms during the index admission after SCA based on a shockable rhythm or (presumed) arrhythmogenic syncope C. DPP6 haplotype carrier
2. Functioning transvenous or subcutaneous ICD in place
3. Sudden cardiac arrest, (near)syncope, appropriate ICD shock or nonsustained PVTdocumented by the ICD at least once in the past 2 years
4. Genetic testing has been initiated. Results are not required to be known at the timeof inclusion. In subjects who are family members of DPP6 carrying index patients,genes other than DPP6 are not required to be tested
5. Willing to undergo two assigned treatment periods with verapamil and quinidine
6. Age ≥ 18 years

Exclusion Criteria:

• Pregnancy or lactation
• Current treatment with class 1 antiarrhythmic medication (other than quinidine), class 3 antiarrhythmic medication, or digoxin, unless this medication is discontinued;patients who are currently treated with amiodarone will not be included due to thelong elimination half-life of amiodarone, unless amiodarone was only administeredintravenously for a short period of time
• Patients with a history of therapy refractory ventricular arrhythmia on an adequatedose of verapamil or quinidine, as determined by the treating cardiologist.
• Contra-indication to quinidine or verapamil (see section 7.6)
• Significant structural heart disease (left ventricular ejection fraction <50%,suspicion or definitive diagnosis of cardiomyopathy, moderate/severe pulmonary,mitral, or aortic valve stenosis or regurgitation)
• Suspicion or definitive diagnosis of another (heritable) arrhythmia syndrome, e.g. Brugada syndrome, early repolarization syndrome or catecholaminergic polymorphicventricular tachycardia
• Presence of a short (<350 ms) or prolonged (>480 ms) heart-rate corrected QT intervalon the resting ECG at baseline
• Presence of a pathogenic or likely-pathogenic ryanodine receptor 2 (RYR2) mutation
• Presence of ischemia-induced short-coupled ventricular arrhythmia in patient withdocumented coronary spasm
• Presence of pause-dependent torsade de pointes [preceding R-R interval prior to thetrigger PVC >1500 ms in individuals without pacemaker/ICD or >1300 ms in individualswith pacemaker/ICD] following a stable baseline rhythm. Initiation of ventriculararrhythmia by short-long-short cycles (R-R cycles <1300 ms) with a short-coupledtrigger PVC is allowed
• Significant coronary artery disease (≥50% narrowing of the diameter of the lumen ofthe left main coronary artery or ≥70% narrowing of the diameter of the lumen of theleft anterior descending coronary artery, left circumflex artery or right coronaryartery)
• Reversible metabolic or pharmacological/toxicological conditions that may causeelectrophysiological findings similar to short-coupled IVF
• Patients who are considered electrically unstable, at physician's discretion, due toactive electrical storm or very frequent nonsustained episodes of short-coupled IVFrequiring intravenous or invasive therapy
• Successful radiofrequency ablation of the PVC initiating short-coupled IVF and absenceof documented (non)sustained episodes of short-coupled PVT/VF afterwards. The patientwill, however, be eligible to participate in the study if ≥ 1 episode of short-coupledPVT/VF is documented after the ablation procedure
• Intention to perform radiofrequency ablation of the PVC initiating short-coupled IVFduring the course of the study
• Serious known comorbid disease with a life expectancy of less than two years
• Ongoing medical condition that is deemed by the principal investigator to interferewith the conduct or assessments of the study or safety of the subjects
• Circumstances that prevent follow-up
• Inability to take orally administered tablets
• Inability to provide informed consent