Long-Term Outcome Following Idiopathic Ventricular Fibrillation and Potential Emerging Etiologies

Unexplained cardiac death and cardiac arrest associated with idiopathic ventricular fibrillation (IVF) are heterogeneous pathologies responsible for significant mortality in young people.

This retrospective multicenter cohort study evaluated the natural history of a large cohort of IVF survivors including recurrence burden, emerging etiologies, and long-term management.

This study included IVF patients from 46 tertiary centers and followed for at least 5 years. Patients over the age of 15 years who had documented ventricular fibrillation and extensive negative investigations supporting the diagnosis of IVF were included. Patients were followed in each center with their outcome being established on data collection from subsequent clinical records, new investigations, genetic results, and implanted defibrillator recordings. Recurrent arrhythmias and mortality were assessed. Diagnoses were graded as definite (direct evidence) or probable (indirect criteria).

A total of 825 patients (37% women; age 35.7 ± 12 years) were followed for a median duration of 120 months (Q1-Q3: 78-180 months). Death occurred in 27 patients (3.3%) from cardiac (n = 10; 1.2%), noncardiac (n = 9; 1.1%), and unknown (n = 8; 1%) causes, and few patients (4.5%) developed overt cardiomyopathy. Overall arrhythmia recurrence increased steadily over 2 decades, reaching 52.7% of patients, with a median time to first recurrence of 20 months (Q1-Q3: 5-48 months) and a similar incidence in men and women. Emergent etiologies occurred in 68.8% of the total population, and were associated with new information during recurrences, structural changes, genetic results, and mapping procedures. They included reclassified inherited arrhythmia conditions in 73 (8.8%), focal sources in 272 (33.0%), and definite or probable microstructural myocardial alterations (MiCMs) with normal imaging in 223 (27.0%), while no diagnosis was identified in 257 (31.2%). Compared with MiCM, focal IVF included more women, occurred more frequently at rest/sleep, and was associated with narrow QRS complexes (90.1 ± 12 milliseconds vs 104.8 ± 16 milliseconds; P < 0.001). Quinidine appeared effective in preventing focal IVF (68.3%) whereas beta-blockers appeared effective (49.3%) in MiCM-IVF. Catheter ablation was performed in 181 patients with no recurrence observed in 75.7%.

This multicenter long-term cohort study of IVF survivors shows low cardiac mortality, a persistent risk of arrhythmia recurrences over time, and identifies potential emerging etiologies.