Quinidine versus verapamil in short-coupled idiopathic ventricular fibrillation: An open label, randomized crossover pilot trial.

• At least one of the following 3 principal diagnostic criteria for
short-coupled VF:
1. Diagnosis of short-coupled IVF, based on any documentation (through
electrocardiogram (ECG), Holter monitor, device electrogram (EGM), or
telemetry) of PVT of >=3 consecutive beats or VF initiated by a PVC with a
coupling interval <350 ms
2. Isolated PVCs with a coupling interval <350 ms during the index admission
after SCA based on a shockable rhythm or presumed arrhythmogenic syncope
3. DPP6 haplotype carrier (also without documentation of short-coupled IVF)
• Functioning transvenous or subcutaneous ICD in place
• Sudden cardiac arrest, (near)syncope, appropriate ICD shock or nonsustained
PVT documented by the ICD at least once in the past 2 years
• Genetic testing has been initiated. Results are not required to be known at
the time of inclusion. In subjects who are family members of DPP6 carrying
index patients, others genes than DPP6 are not required to be tested.
• Willing to undergo two assigned treatment periods with verapamil and quinidine
• Age >= 18 years

• Pregnancy or lactation
• Current treatment with amiodarone
• Patients with a history of therapy refractory ventricular arrhythmia on an
adequate dose of verapamil or quinidine, as determined by the treating
cardiologist.
• Contra-indication to quinidine or verapamil (see section 7.5)
• 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
polymorphic ventricular tachycardia
• Presence of a short (<350 ms) or prolonged (>480 ms) heart-rate corrected QT
interval on the resting ECG at baseline
• Presence of a pathogenic or likely-pathogenic RYR2 mutation. DPP6 carrier
family members are not required to be tested for RYR2 carrier status.
• Presence of ischemia-induced short-coupled ventricular arrhythmia in patient
with documented coronary spasm
• Presence of pause-dependent torsade de pointes [preceding R-R interval prior
to the trigger PVC >1500 ms in individuals without pacemaker/ICD or >1300 ms in
individuals with pacemaker/ICD] following a stable baseline rhythm. Initiation
of ventricular arrhythmia by short-long-short cycles (R-R cycles <1300 ms) with
a short-coupled trigger PVC is allowed
• Significant coronary artery disease (>=50% narrowing of the diameter of the
lumen of the left main coronary artery or >=70% narrowing of the diameter of the
lumen of the left anterior descending coronary artery, left circumflex artery
or right coronary artery)
• Reversible metabolic or pharmacological/toxicological conditions that may
cause similar electrophysiological findings
• Patients who are considered electrically unstable, at physician*s discretion,
due to active electrical storm or very frequent nonsustained episodes of
short-coupled IVF requiring intravenous or invasive therapy
• Successful radiofrequency ablation of the PVC initiating short-coupled IVF
and absence of documented (non)sustained episodes of short-coupled PVT/VF
afterwards. The patient will, however, be eligible to participate in the study
if >= 1 episode of short-coupled PVT/VF is documented after the ablation
procedure
• Intention to perform radiofrequency ablation of the PVC initiating
short-coupled IVF during 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
interfere with the conduct or assessments of the study or safety of the
subject.
• Circumstances that prevent follow-up
• Is unable to take orally administered tablets
• Inability to provide informed consent