Myocardial expression of the anaphylatoxin receptor C3aR is associated with cardiac inflammation and prognosis in patients with non‐ischaemic heart failure

AIM: The aim of this study is to analyse the prognostic value of complement anaphylatoxin receptors in patients with non‐ischaemic cardiomyopathy undergoing endomyocardial biopsy. METHODS AND RESULTS: In 102 patients (72.5% male patients, median age 54 years) with non‐ischaemic cardiomyopathy, myocardial expression of C3aR was assessed among other parameters. The primary study endpoint was a composite of death, heart transplantation, heart failure‐related re‐hospitalization, and deterioration of left ventricular ejection fraction within a mean follow‐up of 11.9 months. The number of cells, which stained positive for C3aR, was significantly increased in patients with inflammatory compared with non‐inflammatory cardiomyopathy (1.75 ± 0.31 cells in inflammatory cardiomyopathy vs. 0.94 ± 0.26 in non‐inflammatory cardiomyopathy, P = 0.049). Subsequently, positive expression for C3aR was judged based on a semi‐quantitative scoring system. Significantly, more patients with positive MHCII and CD68 expression showed an increased number of C3aR‐positive cells. C3aR expression based on this score was more pronounced in patients with human herpesvirus 6 viral genome detection. Kaplan–Meier curves illustrate that the C3aR‐negative group reached the primary endpoint significantly more often (mean follow‐up 11.9 months, log rank 5.963, P = 0.015). Lack of C3aR expression was a strong independent predictor for the primary endpoint in Cox regression analysis [hazard ratio 0.46 (0.26–0.82, P = 0.009)]. CONCLUSIONS: C3aR‐positive cells are found more often in patients with inflammatory cardiomyopathy. The relevance of C3aR‐positive cells in patients with non‐ischaemic cardiomyopathy should be further evaluated as potential predictors or modulators of adverse cardiac remodelling, the substrate of progressive heart failure.