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Anti-β1-adrenoreceptor auto-antibodies in elderly heart failure patients

Authors

  • T.D. Trippel
  • D.N. Mueller
  • D. Obradovic
  • F. Edelmann
  • E. Tahirovic
  • N. Wilck
  • G. Riemekasten
  • D. Dragun
  • A. Busjahn
  • H. Heidecke
  • J. Junker
  • B. Pieske
  • H.D. Dungen
  • R. Dechend

Journal

  • Frontiers in Bioscience

Citation

  • Front Biosci 24: 1037-1049

Abstract

  • An autoimmune reaction directed against the cardiac b1-adrenergic receptor (β1-ADR) leading to the generation of autoantibodies (AA) against this G-coupled receptor has been described in patients with heart failure (HF). Agonist-like β1-ADR-AA are associated with morbidity in HF patients and even predict mortality. Standardised and valid diagnostic tools to detect β1-ADR-AA in clinical routine are lacking. We used a novel ELISA approach to investigate β1-ADR-AA in a cohort of 574 HF patients of the CIBIS-ELD trial with follow up. The CIBIS-ELD trial compared the titration of bisoprolol and carvedilol to recommended target doses in regard to BB tolerability in patients aged 65 years and older. Patient with left ventricular (LV) ejection fraction (EF) less than 50% or LV diameter end diastolic (DED) more than 55 cm showed significantly higher levels of β1-ADR-AA. Although not yet fully validated, this ELISA allowed for a negative correlation of β1-ADR-AA with the EF at baseline and at the follow up, β1-ADR-AA further correlated positively with basal heart rate at follow up 12 weeks later. β1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (p<0.01). Changes in β1-ADR-AA between F-Up and baseline were significantly higher in patients who used beta blockers (p=0.016) before study inclusion. The type of beta-blocker titrated in this study did not affect log β1-ADR-AA levels at baseline (p=0.132), follow-up (p=0.058), nor the change (p=0.426). β1-ADR-AA levels were estimated using a novel, commercially available ELISA. Although not yet fully validated, this ELISA allowed for pathophysiological insights: β1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (p<0.01), irrespective of type of BB. Higher levels of β1-ADR-AA at baseline are associated with higher heart rates, lower ejection fraction and enlarged left ventricles. The relevance of the β1-ADR-AA biomarker should be further evaluated.


DOI

doi:10.2741/4766