Survivors of idiopathic ventricular fibrillation (IVF) had a low rate of cardiac mortality despite a persistent risk of arrhythmia recurrence over time, according to research presented at the Ventricular Arrhythmias Symposium 2026 and simultaneously published Oct. 10 in JACC: Clinical Electrophysiology.

The retrospective multicenter cohort study led by Michel Haïssaguerre, MD, and colleagues followed 825 patients with documented VF and extensive negative investigations supporting a diagnosis of IVF (mean age at index event, 36 years; 37% women) across 46 tertiary care centers in 16 countries. Eligibility required at least five years of follow-up; mortality estimates were thus limited to patients who survived at least five years after the initial cardiac arrest.

Over a median follow-up period of 120 months, 27 patients (3.3%) died: 10 from cardiac causes (1.2%), nine from noncardiac causes (1.1%) and eight from unknown causes (1.0%). Median time to first arrhythmia recurrence was 20 months, with recurrence increasing steadily over two decades, eventually reaching 53% of patients. Within the cohort, 4.5% developed overt cardiomyopathy.

During follow-up, new information from recurrences, structural changes, genetic results and mapping procedures led to the identification of potential emerging etiologies in 69% of the cohort; 257 patients (31%) remained undiagnosed. The most common etiologies were focal sources (33%), definite or probable microstructural myocardial alterations with normal imaging (MiCM; 27%) and reclassified inherited arrhythmia conditions (9%). Compared with patients with MiCM, patients with focal IVF were more likely to be women. Focal IVF occurred more frequently at rest or during sleep and was associated with narrower QRS complexes (90.1 ms vs. 102.8 ms; p<0.001).

Apparent treatment effectiveness differed between focal IVF and MiCM. Among patients with focal IVF, 68% had no arrhythmia recurrence with quinidine treatment compared with 19% during beta-blocker treatment. In MiCM-IVF, 49% had no recurrence with beta-blockers compared with 31% with quinidine. The authors caution that these observational comparisons may be affected by center-specific practices, recurrence timing, exercise restrictions and individual patient characteristics.

Regarding the clinical implications of these differing etiologies, "clinical differences between focal IVF and MiCM-IVF could point towards a presumptive diagnosis at initial presentation. Narrow QRS complexes (without microvoltage) suggest a higher probability of focal origin... Widened QRS complexes justify thorough investigation for myocardial abnormalities, such as optimized imaging and electrophysiological mapping; or to assess arrhythmogenicity during isoprenaline infusion," write Haïssaguerre, et al., noting, however, that these observations should be considered exploratory and hypothesis-generating.