Aggravation of left ventricular dysfunction in patients with biopsy-proven cardiac human herpesvirus A and B infection

BACKGROUND: Human herpesvirus 6 (HHV-6) A and B are lymphotropic viruses with life-long persistence, primarily associated with non-cardiac diseases, and discussed as a possible etiologic factor of myocarditis and cardiomyopathy.

OBJECTIVE: To analyze the long-term spontaneous course of cardiac patients suffering from suspected inflammatory cardiomyopathy (CMi) with persisting HHV-6 A and B infections by follow-up biopsies.

STUDY DESIGN: We prospectively evaluated patients (n=73) with biopsy-proven viral HHV-6 A and B infection in endomyocardial biopsies (EMBs), followed up by reanalysis of EMBs and left ventricular ejection fraction (LV-EF) measurements after a median period of 8.8 months (range 4-73 months). Beyond, we studied HHV-6 prevalence in isolated peripheral blood cells (PBCs) and HHV-6 species in EMBs. HHV-6 species-specific cellular infection sites within the myocardium were identified by immunohistochemistry (IHC).

RESULTS: We identified 73 patients with cardiac HHV-6 A and B persistence or newly detected in follow-up EMB (95.0% B). Proof of HHV-6 in PBCs was primarily associated with A. Persistence of cardiac HHV-6 B genome was significantly associated with cardiac dysfunction at follow-up (LV-EF deteriorated from 58.2±16.0 to 51.8±17.2%, p<0.001), and LV improvement was observed when HHV-6 B persistence resolved (LV-EF increased from 54.9±15.4 to 60.7±13.1%, p<0.001).

CONCLUSIONS: Persistence of cardiac HHV-6 B genomes was significantly associated with cardiac dysfunction, and hemodynamic parameters improved in association with HHV-6 B clearance.