Idiopathic ventricular fibrillation: Absence of evidence is not evidence of absence

Abstract

Sudden cardiac death is a major problem in the Western world. In young people, sudden cardiac arrest is often caused by ventricular fibrillation (VF). In most cases of VF, an underlying cause is found. However, in a small part of the patients, no cause for VF can be found. These patients are diagnosed with “idiopathic ventricular fibrillation” (IVF). Extensive diagnostic testing is necessary to exclude any underlying diseases. In this dissertation, we have attempted to further unravel the mystery surrounding IVF. Using a large national IVF database, we unraveled the characteristics of current IVF patients. Although adherence to (near-)complete diagnostic testing increased over the years, patients with IVF still undergo varying levels of diagnostic evaluation. This is problematic, as it leads to underdiagnosing of alternative disease. Unfortunately, as the substrate is absent in IVF, there are limited treatment options besides ICD implantation to prevent sudden cardiac death. In this thesis, we focussed on a specific phenotype in IVF, called short-coupled VF. We showed that this phenotype is prevalent in IVF. This is important, as previous research indicates that these patients can be treated effectively with class IA drugs. Another interesting region of interest in IVF patients is the mitral valve. Abnormalities in this region have been associated with ventricular arrhythmias. We were able to reveal abnormalities around the mitral valve using cardiac magnetic resonance imaging. In particular, we showed that mitral annulus disjunction is more prevalent in IVF patients compared to healthy controls. Patients with mitral valve disease proved to have a higher burden of ectopy than patients without mitral valve disease. We also applied echocardiographic deformation imaging to detect subtle myocardial abnormalities. Interestingly, both global and regional echocardiographic deformation abnormalities are more prevalent in IVF patients compared to healthy control subjects. Our research therefore indicates that subtle myocardial disease is present in a large subset of IVF patients. To search for cardiac abnormalities in family members of IVF patients, we performed familial cascade screening. We hypothesized that family members of IVF patients might reveal heritable cardiac diseases that were not apparent in the IVF patient. However, the yield of family screening in relatives of IVF patients appeared to be low when the patients was comprehensively investigated. This underlines the importance of systematic diagnostic testing in IVF. At last, we created a practical flowchart for diagnostic testing after sudden cardiac death of a young person. This is of utter importance as the current rate of diagnostic testing after sudden cardiac death in a young person is low in the Netherlands.