Blood myeloid dendritic cell reduction and differences between myocarditis and dilated cardiomyopathy

Abstract

Aims: The role of dendritic cells (DCs) in cardiomyopathies is unknown yet. Dilated cardiomyopathy (DCM) is often preceded by myocarditis, hence the two conditions often clinically overlap. In order to investigate the role of DCs in diagnosing myocarditis/DCM, we prospectively investigated the circulating DC precursors (DCPs) as well as mature DCs in endomyocardial biopsies (EMBs) from patients with acute myocarditis and newly diagnosed DCM. Methods: Blood myeloid (mDCPs) and plasmacytoid (pDCPs) DC precursors were flow cytometrically analyzed in patients with newly onset heart failure (HF) and biopsy proven DCM (n=43, mean EF 29±10%) and patients with MRI confirmed myocarditis (n=23). Individuals with excluded heart disease were used as controls (n=52). Left-ventricular EMBs were performed when clinically indicated (n=45) and were immunohistologically analyzed for the presence of mature myeloid DCs (CD83+) and tissue fibrosis (Sirius red). Analyses of circulating DCPs were performed initially and at repeated follow-up intervals of 6 months. Correlation analysis was performed between circulating DCPs and mature DCs in EMBs, as well as clinical, echocardiographic and invasive left-ventricular parameters. Results: Relative and absolute numbers of circulating mDCPs were reduced in patients with myocarditis compared to controls (0.065% vs 0.2%,p<0.001). Following clinical recovery of myocarditis, circulating mDCPs tended to normalise (0.015% vs 0.2%,p=0.008). Circulating mDCPs of DCM patients were at initial presentation unchanged compared to controls (0.18% vs 0.2%,p=0.258), but were significantly reduced at 6- and 12-month-follow-up (0.16% vs 0.2%,p=0.047 and 0.14% vs 0.2%,p=0.021). No statistical significance was observed for pDCPs. Correlation analysis revealed inverse correlation of blood mDCPs with myocardial mature DCs in EMBs (r=-0.522,p=0.026). We also found an inverse correlation of blood mDCPs with cTNI (r=-0.826,p<0.001), CRP (r =-0.388,p=0.014), invasively measured EF (r=-0.383,p=0.026), but not BNP (p=0.921). Blood mDCPs positively correlated with tissue fibrosis (r=0.395,p=0.05), mitral and tricuspid regurgitation (r=0.395,p=0.012 and r=0.47,p=0.002). Conclusions: Circulatory mDCs migrated into the myocardium of these patients. While their peripheral reduction was acute in myocarditis, it was delayed and chronic/progressive in DCM. Thus, inflammatory processes in DCM were not causative, but rather secondary to structural myocardial changes. DCs could prove to be discriminatory between myocarditis and DCM in early diagnosis.