Out-of-hospital cardiac arrest due to ventricular arrhythmia in patients without structural heart disease: underlying etiology and long-term outcomes from a multicenter registry

Background Out-of-hospital cardiac arrest (OHCA) due to ventricular arrhythmia (VA) in the absence of structural heart disease is rare but represents a significant life-threatening condition worldwide. Establishing the underlying etiology remains clinically challenging. Purpose To investigate the prevalence, clinical characteristics, and long-term outcomes of OHCA survivors without structural heart disease. Methods Patients who survived OHCA due to VA and had no evidence of structural heart disease after comprehensive evaluation were enrolled in a multicenter registry. A total of 51 patients (median age 58 years; 84% male) were included from four centers in Japan. Results An implantable cardioverter-defibrillator (ICD) was implanted in all patients. The underlying etiology was idiopathic ventricular fibrillation (IVF) in 21 patients (41%), Brugada syndrome in 16 (31%), early repolarization syndrome (ERS) in 8 (16%), severe coronary artery spasm in 3 (6%), catecholaminergic polymorphic ventricular tachycardia in 2 (4%), and short QT syndrome in 1 (2%). Exercise-related OHCA occurred in 11 patients with IVF (52%), whereas in the non-IVF group, cardiac arrest occurred predominantly at rest or during sleep (25 patients, 83%; P=0.013). Antiarrhythmic drug therapy for prevention of VA was prescribed at the discretion of the treating physicians in 26 patients (51%). The medications included beta-blockers in 8 patients (16%), calcium channel blockers in 9 (18%), quinidine in 5 (10%), cilostazol in 3 (6%), bepridil in 4 (8%), and amiodarone in 6 (12%); some patients received combination therapy. In addition, catheter ablation targeting triggering ventricular premature complexes was performed in 2 patients with IVF (4%). During a median follow-up of 165 months (interquartile range 135–177 months), 21 patients (41%) received appropriate ICD therapy and 5 (10%) received inappropriate ICD therapy. Among patients with appropriate ICD therapy, 15 (71%) had a cardiac channelopathy as the index diagnosis. Inappropriate ICD therapy was triggered by atrial fibrillation (n=1), sinus tachycardia (n=2), and supraventricular tachycardia (n=2). In all of these patients (median age 17 years; 80% male), the index cardiac arrest was exercise-induced IVF. Among patients initially diagnosed with IVF, one developed recurrent appropriate ICD therapies due to severe coronary artery spasm during follow-up, and another showed progressive J-wave augmentation on electrocardiography and was subsequently reclassified as ERS. One non-cardiac death occurred during follow-up. Conclusion ICD implantation for secondary prevention is essential in patients with OHCA due to VA. The high rate of appropriate ICD therapies among patients with cardiac channelopathies highlights the importance of comprehensive diagnostic evaluation. Younger patients initially diagnosed with IVF may be at increased risk of inappropriate ICD therapies due to non-lethal arrhythmias.