Over the last decade, parvovirus B19 (B19V) has frequently been linked to the pathogenesis of myocarditis (MC) and its progression towards dilated cardiomyopathy (DCM). The exact role of the presence of B19V and its load remains controversial, as this virus is also found in the heart of healthy subjects. Moreover, the prognostic relevance of B19V prevalence in endomyocardial biopsies still remains unclear. As a result, it is unclear whether the presence of B19V should be treated. This review provides an overview of recent literature investigating the presence of B19V and its pathophysiological relevance in MC and DCM, as well as in normal hearts. In brief, no difference in B19V prevalence is observed between MC/DCM and healthy control hearts. Therefore, the question remains open whether and how cardiac B19V may be of pathogenetic importance. Findings suggest that B19V is aetiologically relevant either in the presence of other cardiotropic viruses, or when B19V load is high and/or actively replicating, which both may maintain myocardial (low-grade) inflammation. Therefore, future studies should focus on the prognostic relevance of the viral load, replicative status and virus co-infections. In addition, the immunogenetic background of MC/DCM patients that makes them susceptible to develop heart failure upon presence of B19V should be more thoroughly investigated.

Truncating titin variants lead to pronounced cardiac alterations in mitochondrial function, with increased interstitial fibrosis and reduced hypertrophy. Those structural and metabolic alterations in TTNtv hearts go along with increased ventricular arrhythmias at long-term follow-up, with a similar survival and overall cardiac function.

Background - Genetic analysis is a first-tier test in dilated cardiomyopathy (DCM). Electrical phenotypes are common in genetic DCM but their exact contribution to the clinical course and outcome is unknown. We determined the prevalence of pathogenic gene variants in a large unselected DCM population, and determined the role of electrical phenotypes in association with outcome. Methods - This study included 689 DCM patients from the Maastricht Cardiomyopathy Registry, undergoing genetic evaluation using a 48 cardiomyopathy-associated gene-panel, echocardiography, endomyocardial biopsies and Holter monitoring. Upon detection of a pathogenic variant in a DCM patient, familial segregation was performed. Outcome was defined as cardiovascular death, heart transplantation, heart failure hospitalization and/or occurrence of life-threatening arrthymias. Results - A (likely) pathogenic gene variant was found in 19% of patients, varying from 36% in familial to 13% in non-familial DCM. Family segregation analysis showed familial disease in 46% of DCM patients who were initially deemed non-familial by history. Overall, 18% of patients with a non-genetic risk factor had a pathogenic gene variant. Almost all pathogenic gene variants occurred in just 12 genes previously shown to have robust disease association with DCM. Genetic DCM was independently associated with electrical phenotypes such as atrial fibrillation (AF), non-sustained ventricular tachycardia (NSVT) and AV-block (AVB), and inversely correlated with the presence of a left bundle branch block(p<0.01). After a median follow-up of 4 years, event-free survival was reduced in genetic versus non-genetic DCM patients(p=0.01). This effect on outcome was mediated by the associated electrical phenotypes of genetic DCM(p<0.001). Conclusions - One in five patients with an established non-genetic risk factor or a non-familial disease still carries a pathogenic gene variant. Genetic DCM is characterized by a profile of electrical phenotypes (AF, NSVT and AVB), which carries increased risk for adverse outcomes. Based on these findings, we envisage a broader role for genetic testing in DCM.

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To conclude, this study suggests that immunosuppressive therapy in infl-CMP patients results in an improved heart transplantation-free survival as compared with standard heart failure therapy alone, underscoring the urgent need for a large prospective multicenter trial.