Systematic assesment of patients with unexplained cardiac arrest: results from the FIVI-Gen study

Background and objectives: Idiopathic Ventricular Fibrillation (IVF) is a rare entity that might be due to subclinical underlying cardiomyopathies and channelopathies of genetic origin. We aim to assess the diagnostic yield of a novel systematic protocol in patients with IVF. Methods: IVF was defined as sustained VF episode which required external defibrillation, and with no pathological findings in basal electrocardiogram (EKG), echocardiogram, and coronary angiography. The diagnostic protocol consisted of three sequential steps: 1.- pharmacological tests with epinephrine and flecainide; 2.- first and second-degree relatives assesment with EKG and echocardiogram and 3.- genetic testing with next-generation sequencing method including 126 genes for cardiomyopathies and channelopathies. Results: Twenty three probands (69,6% males, mean age 40,5±14,5 years) and 87 first and second degree relatives from 7 spanish centres were assesed. Final diagnosis was obtained in 17 probands/families (73,9%). The most prevalent underlying etiology was Brugada Syndrome (30,4%), followed by Cathecolaminergic Polymorphic Ventricular Tachycardia (17,3%) and Long QT syndrome (13%). The way to reach the diagnosis and cumulative diagnostic rate of each sequential step of the protocol is summarized in table 1. Table 1. Diagnostic yield of each sequential step of the protocol CPVT, Cathecolaminergic Polymorphic Ventricular Tachycardia; HCM, Hypertrophic Cardiomyopathy; AC, Arrhythmogenic Cardiomyopathy. Conclusions: In patients with IVF the systematic application of a protocol that included next-generation sequencing rendered a definitive diagnosis in almost three-fourths of the cases. As expected, cardiac channelopathies were the main hidden etiology, but there were also cardiomyopathies with no expression in the EKG and imaging tests.