Autoantibodies against β1-Adrenergic Receptors: Response to Cardiac Resynchronization Therapy and Renal Function

Pacing Clin Electrophysiol. 2016 Jan;39(1):65-72. doi: 10.1111/pace.12757. Epub 2015 Oct 26.

Abstract

Background: Cardiac resynchronization therapy (CRT) nonresponse remains a major clinical problem. Autoantibodies specific for the β1-adrenergic (β1-AAbs) and muscarinic (M2-AAbs) receptors are found in patients with chronic heart failure (HF) of various etiologies.

Materials and methods: We retrospectively analyzed 73 HF patients (median age 67 years, 84% males, New York Heart Association II-IV, in sinus rhythm, left ventricular ejection fraction <35%) who received CRT defibrillator (CRT-D) from 2010 to 2013. β1-AAbs and M2-AAbs were measured by enzyme-linked immunosorbent assay. Echocardiography was used to assess CRT response (reduction >15% in left ventricular end-systolic volume at 6 months follow-up). Renal function (RF) parameters (creatinine [Cr], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR Modified Diet in Renal Disease], cystatin C [Cys-C], and neutrophil gelatinase-associated lipocalin [NGAL]) were also evaluated.

Results: A significantly higher percentage of patients positive for β1-AAbs (OD sample/OD reference ratio >2.1) in nonresponders than in responder patients was observed (57% vs 27%, P = 0.004). No influence of M2-AAbs on CRT-D response was demonstrated. β1-AAbs were predictive of a poor CRT-D response (odds ratio [OR] [95% confidence interval (CI)] 3.64 [1.49-8.88], P = 0.005), also after adjustment for RF parameters (OR [95% CI] 4.95 [1.51-16.26], P = 0.008) observed to influence CRT-D response (Cr P = 0.03, BUN P = 0.009, Cys-C P = 0.02). The positive rates of β1-AABs in patients with abnormal blood level of Cr, eGFR, Cys-C, and NGAL were significantly higher than those with normal levels (P = 0.03, P = 0.02, P = 0.001, P = 0.007, respectively).

Conclusions: Our study suggests that (1) the evaluation of β1-AAb is useful to identify responders to CRT-D; (2) the presence of β1-AAbs is in relationship with elevated renal function parameters.

Keywords: CRT; congestive heart failure.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / immunology*
  • Biomarkers / blood
  • Cardiac Resynchronization Therapy / methods*
  • Female
  • Glomerular Filtration Rate / immunology*
  • Heart Failure / blood
  • Heart Failure / immunology*
  • Heart Failure / prevention & control*
  • Humans
  • Male
  • Middle Aged
  • Receptors, Adrenergic, beta-1 / immunology*
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Autoantibodies
  • Biomarkers
  • Receptors, Adrenergic, beta-1