Changes in myocardial inflammation and viral infection in adults with inflammatory cardiomyopathy following long-term left ventricular assist device

Numerous studies have identified the myocardial inflammation as an important prognostic factor in the development and progression of heart failure. However an acccurate histopathological characterization is currently limited, with scarce data addressing a direct comparison between the different stages of the disease. Some observations have led to the hypothesis that a decrease of the ventricular afterload with a mechanical circulatory support(VAD) may lead to remission of chronic inflammation. We retrospectively analyzed the histopathological(H) features of the myocardial specimens obtained from the apical segment of the LV extracted at the time of VAD implantation(H1) and compared it with a second specimens(H2) at the time of heart transplantation (HTX). The diagnosis of MY was based upon the HI Dallas criteria and the immunohistochemistry, including a large panel of specific antibodies and additional PCR analysis for viral infection. Results: Among 999 patients (p) who underwent VAD implantation, we included 249 p in whom the VAD was explanted due to HTX or LV recovery (82% men, 47±14 years, 66% non ischemic dilated cardiomyopathy (DCM)). The VAD could be explanted in 11% of the p after LV recovery. H1 showed active myocardial inflammation in 65% of the patients: 95% of them were classified as active lymphocytic inflammatory cardiomyopathy (LIC), defined as myocarditis with a predominant inflamatory T lymphocytes and macrophages infiltrate with replacement fibrosis; three cases corresponded with sarcoidosis, and one case with eosinophilic myocarditis. Viral infiltration was detected in 52% of LIC cases, with Parvovirus B-19 (47%) and Human Herpesvirus 6 type B (38%) being the most frequently identified agents. Notably, high viral DNA copy numbers (>500 DNA copies/mm²) were found in 37% of virus-positive specimens, and in all these cases, the detected virus was Parvovirus B-19. H2 showed complete resolution of viral infiltration in 36% of cases, occurring more frequently when the initial viral load in the myocardium was low (p<0.001). However, despite prolonged VAD support (mean duration: 823 days), H2 revealed no significant reduction in myocardial inflammation compared to H1, highlighting the persistence of myocardial inflammation independent of viral clearance. Conclusions: An active myocardial lymphocytic inflammation is observed in the majority of the myocardial specimens in patients with end-stage DCM undergoing VAD as bridge to HTX or recovery, with viral infiltration detected in more than half of the cases. The resolution of the viral infiltrate in more than one third of the patients, without a significant reduction in myocardial inflammation, underscores the complexity of inflammatory cardiomyopathy and further fuels the debate on the precise role of viral infections in its pathogenesis .