title: Autoantibodies against β1-Adrenergic Receptors: Response to Cardiac Resynchronization Therapy and Renal Function.
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.
  
  
  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.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Michelucci
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Pathology, University of Florence, Florence, Italy.
authors.forename: Mario Milco
authors.initials: MM
authors.lastname: D'Elios
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pieragnoli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ricciardi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Pathology, University of Florence, Florence, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Benagiano
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Pathology, University of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Niccolai
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Pathology, University of Florence, Florence, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Grassi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Attanà
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Nesti
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Grifoni
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Padeletti
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Pathology, University of Florence, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Prisco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D005260:Female; D005919:Glomerular Filtration Rate / Q000276:immunology*; D006333:Heart Failure / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D018342:Receptors, Adrenergic, beta-1
keywords: CRT; congestive heart failure