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

ESC Heart Fail. 2018 Oct;5(5):846-857. doi: 10.1002/ehf2.12298. Epub 2018 Aug 31.

Abstract

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.

Keywords: Anaphylatoxin receptors; Complement; Myocarditis; Non-ischaemic heart failure; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Echocardiography
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation*
  • Heart Failure / diagnostic imaging
  • Heart Failure / genetics*
  • Heart Failure / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Prognosis
  • RNA / genetics*
  • Receptors, Complement / biosynthesis
  • Receptors, Complement / genetics*
  • Retrospective Studies
  • Young Adult

Substances

  • Receptors, Complement
  • complement C3a receptor
  • RNA