title: Peripheral chemoreceptor hypersensitivity: an ominous sign in patients with chronic heart failure.
abstract: BACKGROUND
  Peripheral chemoreceptor hypersensitivity is a feature of abnormal cardiorespiratory reflex control in chronic heart failure (CHF) and may contribute to sympathetic overactivity, attenuated baroreflex sensitivity (BRS), and excessive ventilation during exercise. We studied whether augmented peripheral chemosensitivity carries independent prognostic significance.
  
  
  RESULTS
  We assessed peripheral chemosensitivity (ventilatory response to hypoxia using transient inhalation of pure nitrogen) and BRS (phenylephrine and spectral methods) in 80 consecutive CHF patients (age 58+/-9 years; left ventricular ejection fraction [LVEF] 24+/-12%; peak oxygen consumption [peak VO(2)] 18+/-7 mL(-1). min(-1)). CHF patients demonstrated augmented peripheral chemosensitivity and decreased BRS (all P<0.01 versus reference values). During follow-up (median 41 months, >3 years in all survivors), 37 patients died. High peripheral chemosensitivity (>0.72 L. min(-1). %SaO(2)(-1)) predicted impaired survival (hazard ratio 3.2, 95% CI 1.6 to 6.0, P=0.0006). In the 27 patients (34%) with high peripheral chemosensitivity, 3-year survival was 41% (95% CI 22% to 60%) compared with 77% (66% to 89%) in 53 patients with normal chemosensitivity (P=0.0002). In multivariate analyses, augmented chemosensitivity independently predicted death (hazard ratio 2.8, 95% CI 1.5 to 5.5, adjusted for age, peak VO(2), and VE/VCO(2) [P=0.002]; hazard ratio 2.6, 95% CI 1.3 to 5.1, adjusted for age, LVEF, and peak VO(2) [P=0.008]). Depressed BRS was related to unfavorable prognosis in univariate analysis (P=0.05) but not in multivariate analyses.
  
  
  CONCLUSIONS
  Hypersensitivity of the peripheral chemoreceptors independently predicts adverse prognosis in ambulatory patients with CHF. This hyperactive excitatory reflex, through its inhibitory effect on the baroreflex, may be the reason for the previously observed prognostic association of the latter.
authors.affiliation: Clinical Cardiology, NHLI, London, UK. piotrponikowski@hotmail.com
authors.forename: P
authors.initials: P
authors.lastname: Ponikowski
authors.forename: T P
authors.initials: TP
authors.lastname: Chua
authors.forename: S D
authors.initials: SD
authors.lastname: Anker
authors.forename: D P
authors.initials: DP
authors.lastname: Francis
authors.forename: W
authors.initials: W
authors.lastname: Doehner
authors.forename: W
authors.initials: W
authors.lastname: Banasiak
authors.forename: P A
authors.initials: PA
authors.lastname: Poole-Wilson
authors.forename: M F
authors.initials: MF
authors.lastname: Piepoli
authors.forename: A J
authors.initials: AJ
authors.lastname: Coats
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D002628:Chemoreceptor Cells / Q000503:physiopathology*; D002908:Chronic Disease; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010101:Oxygen Consumption; D011379:Prognosis; D016019:Survival Analysis; D015996:Survival Rate