Pharmacological inducibility of short-coupled Purkinje ectopy in patients with spontaneous short-coupled ventricular fibrillation

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In a subset of patients with idiopathic ventricular fibrillation (IVF), the cause is identified as short-coupled premature ventricular complexes (ScPVCs), which mostly originate from Purkinje cells, and are often short-living and undetected. There is no consistent test allowing identification of patients vulnerable to this malignant arrhythmia. We aimed at evaluating sodium channel blocker (NaBl) testing in patients who survived IVF associated with SCPVCs. Methods We retrospectively reviewed data of 112 patients at 3 centers, with the diagnosis of IVF associated with spontaneous and documented scPVCs. No patient from the previous report was included. We analyzed all patients who underwent NaBl tests during evaluation of IVF. An arrhythmogenic NaB test was defined as the occurrence of ≥10 scPVCs and/or ≥ 1 repetitive form (couplet, triplet, run) during the test, without spontaneous scPVC at baseline. We defined scPVCs as an R-on-T pattern PVC. We evaluated the occurrence of scPVC during NaB infusion, the arrhythmia pattern and we compared the characteristics of the arrhythmogenic versus non-arrhythmogenic response groups. Data regarding anti-arrhythmic drug treatment and follow-up were collected at each center. Results In total, 48 patients were included (Table). The NaB tests were performed using ajmaline 1mg/kg/5 or 10min, or flecainide 2mg/kg/10min. Overall, an arrhythmogenic NaB test occurred in 23 of 48 (48%) patients. Isolated ScPVCs were observed in 11 patients, couplet/triplets in 10, and runs in 6. The arrhythmogenic response was reproduced in 5/5 patients who had a second NaB test during scPVC mapping before catheter ablation. There were no significant differences between patients with arrhythmogenic or non-arrhythmogenic NaB tests in all baseline clinical variables tested including VF burden (Table). All patients were followed at least 1 year after initial diagnosis and NaB test. Under hydroquinidine (600 or 900mg/day), appropriate defibrillator shocks occurred in 7 of 8 patients with arrhythmogenic NaB test; whereas shocks occurred only in 2 of 11 patients with non-arrhythmogenic NaB test (P=0.02). Conclusion Sodium blockers unravel scPVCs in up to 50% of patients with IVF and may therefore represent a valuable tool to detect a potential cause for sudden cardiac death (SCD) or unexplained syncope. Additionally, the arrhythmogenic response to NaB may be associated with the success of hydroquinidine in preventing IVF recurrence, a finding that suggests the existence of distinct scPVCs phenotypes and that may have important therapeutic implications. Further functional and genetical investigations are warranted to explore the mechanisms underlying this association.