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CLINICAL RESEARCH: HEART FAILURE

Prognostic Implications of Baroreflex Sensitivity in Heart Failure Patients in the Beta-Blocking Era

Maria Teresa La Rovere, MD^_*,_*, Gian Domenico Pinna, MS^_*, Roberto Maestri, MS^_*, Elena Robbi, BS^_*, Angelo Caporotondi, MD^_*, Gianpaolo Guazzotti, MD^_*, Peter Sleight, MD, DM and Oreste Febo, MD^_*

^_* Divisione di Cardiologia, e Bioingegneria, Fondazione "Salvatore Maugeri," IRCCS Istituto Scientifico di Montescano, Montescano, Italy
Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

Manuscript received July 11, 2008; revised manuscript received August 28, 2008, accepted September 1, 2008.

^_* Reprint requests and correspondence: Dr. Maria Teresa La Rovere, Divisione di Cardiologia, Fondazione S. Maugeri, IRCCS, Istituto Scientifico di Montescano, 27040 Montescano (PV), Italy (Email: mariateresa.larovere{at}fsm.it).

Objectives: This study investigated the clinical correlates and prognostic value of depressed baroreceptor-heart rate reflex sensitivity (BRS) among patients with heart failure (HF), with and without beta-blockade.

Background: Abnormalities in autonomic reflexes play an important role in the development and progression of HF. Few studies have assessed the effects of beta-blockers on BRS in HF.

Methods: The study population consisted of 103 stable HF patients, age (median [interquartile range]) 54 years (48 to 57 years), with New York Heart Association (NYHA) functional class III in 22, and with a left ventricular ejection fraction (LVEF) of 30% (24% to 36%), treated with beta-blockers; and 144 untreated patients, age 55 years (48 to 60 years), with NYHA functional class III in 47%, and an LVEF of 26% (21% to 30%). They underwent BRS testing (phenylephrine technique).

Results: In both treated and untreated patients, a lower BRS was associated with a higher (III) NYHA functional class (p = 0.0002 and p < 0.0001, respectively); a more severe (2) mitral regurgitation (p = 0.007 and p = 0.0002), respectively; a lower LVEF (p = 0.0004 and p = 0.001, respectively), baseline RR interval (p = 0.0004 and p = 0.0002, respectively), and SDNN (p < 0.0001, p = 0.002, respectively); and a higher blood urea nitrogen (p = 0.004, p < 0.0001, respectively). Clinical variables explained only 43% of BRS variability among treated and 36% among untreated patients. During a median follow-up of 29 months, 17 of 103 patients and 55 of 144 patients, respectively, experienced a cardiac event. A depressed BRS (<3.0 ms/mm Hg) was significantly associated with the outcome, independently of known risk predictors and beta-blocker treatment (adjusted hazard ratio: 3.0 [95% confidence interval: 1.5 to 5.9], p = 0.001).

Conclusions: Baroreceptor-heart rate reflex sensitivity does not simply mirror the pathophysiological substrate of HF. A depressed BRS conveys independent prognostic information that is not affected by the modification of autonomic dysfunction brought about by beta-blockade.

Key Words: baroreceptors • beta-blocker • heart failure • autonomic nervous system • prognosis

Abbreviations and Acronyms   BRS = baroreceptor-heart rate reflex sensitivity   BUN = blood urea nitrogen   CI = confidence interval   CNES = cardiac norepinephrine spillover   HF = heart failure   ICD = implantable cardioverter-defibrillator   IQR = interquartile range   LVEDD = left ventricular end-diastolic diameter   LVEF = left ventricular ejection fraction   LVESD = left ventricular end-systolic diameter   MSNA = muscle sympathetic nerve activity   NSVT = nonsustained ventricular tachycardia   NYHA = New York Heart Association   SAP = systolic arterial pressure   SDNN = standard deviation of all normal-to-normal intervals   VPC = ventricular premature contraction

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