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

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. (J Am Coll Cardiol 2009; 53: 193-9) (C) 2009 by the American College of Cardiology Foundation