Katetrizační ablace versus antiarytmika u předčasných komorových stahů (CAAD-PVC)

Participants randomised to catheter ablation will be expected to undergo catheter ablation for PVCs within 2 weeks after randomisation. Medical therapy may be used as a temporising measure before ablation as standard care. If the participant is drug-naïve, initiation of sotalol is recommended but not mandated. Medical therapy for PVCs should be discontinued after ablation and at least five half-lives before ablation. Repeat ablation procedures will be discouraged during the 12-week monitoring period although if PVC quiescence prevents targeted ablation, one repeat ablation attempt may be undertaken within two weeks.

Ablation will be guided by a combination of standard mapping techniques, as per standard practice. Preference will be given to "activation mapping" of the PVCs (which may be stimulated by administration of intravenous isoprenaline) using a three-dimensional electroanatomic mapping system. If there is paucity of PVCs, then "pace-mapping" will be performed.

Catheter ablation (CA) of premature ventricular complexes (PVCs) will be performed in standard fashion as approved by international guidelines. CA aims to deliver therapeutic energy to the site of origin of the PVCs, rendering the tissue there incapable of causing the arrhythmia. Ablations will be performed under sedation or GA, guided by electroanatomic mapping and cardiac imaging. End point of CA will be abolition of all PVCs (with and without isoprenaline provocation) with a 30-minute waiting period.

Occasionally, patients may experience episodes of PVC quiescence and an absence of PVCs on the day of CA. This can be a result of changes in medication, stress, hormones, electrolytes and can be unpredictable. As at least one PVC occurring during the CA is required to perform a CA, an episode of PVC quiescence on the day of the procedure that inhibits the ablation from taking place will not preclude the patient from having a repeat attempt at the CA.

Participants randomised to medical therapy will be managed with medical therapy alone by their usual medical practitioners. The objective is to replicate standard care for patients with PVCs managed using a non-interventional approach.

The protocol recommends sotalol, starting at 40 mg twice daily and uptitrating to 80 mg twice daily after at least one week as tolerated; minimum total daily dose is 40 mg and maximum total daily dose is 320 mg. If sotalol is contraindicated or not tolerated, metoprolol is recommended, starting at 25 mg twice daily and uptitrating to a maximum total daily dose of 300 mg. Verapamil or diltiazem may be considered when beta blockers are contraindicated; flecainide may be considered if coronary artery disease and structural heart disease have been ruled out. AADs may be changed at any time according to clinical response. Ultimately, the choice of AADs will be left to the treating physician who does not need to follow the above recommendations.

This arm aims to replicate standard of care for patients with PVCs managed by a non-interventional approach, usually encompassing patients who have symptoms and have not previously been prescribed an AAD or BB, being commenced on an AAD and/or a BB. Choice of AAD/BB will be left to primary physician: If deferred to the trial team, clinical protocol suggests sotalol (which has both AAD and BB properties) 80mg twice daily, or a lower dose if indicated. If sotalol is contraindicated, an alternative BB may be initiated using standard doses (metoprolol, atenolol, bisoprolol). Clinicians may consider alternative AAD if BBs are contraindicated. For example, a dihydropyridine calcium channel blocker (verapamil or diltiazem) may be initiated if patient has concurrent asthma. If coronary artery disease and structural heart disease is ruled out, flecainide (class I anti-arrhythmic agent) may be used. As with clinical practice, AAD/BB can be changed at any time depending on clinical response.

Number of participants achieving at least an 80% reduction in PVC burden, measured by ≥24-hour heart rhythm monitoring and compared with baseline PVC burden.

Change in PVC burden measured by ≥24-hour heart rhythm monitoring compared with baseline.

Number of participants achieving at least a 99% reduction in PVC burden, measured by ≥24-hour heart rhythm monitoring and compared with baseline PVC burden.

Change in quality of life as measured by the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA). The ASTA is the primary quality-of-life measure.

Change in depression, anxiety and stress symptoms as measured by the Depression, Anxiety and Stress Scale - 21 items (DASS-21).

Change in health-related quality of life as measured by the EQ-5D-5L.

Assessment of tolerability of medical therapy, including adherence and adverse events.

Assessment of tolerability of catheter ablation, including complications and adverse events.

Incidence of hospital admissions during trial follow-up.