title: Combined increased chemosensitivity to hypoxia and hypercapnia as a prognosticator in heart failure.
abstract: OBJECTIVE
  The aim of the present study was to investigate the prognostic significance of chemosensitivity to hypercapnia in chronic heart failure (HF).
  
  
  BACKGROUND
  Increased chemosensitivity to hypoxia and hypercapnia has been observed in HF. The potential value of enhanced chemosensitivity to hypercapnia to risk prediction in systolic HF has not been specifically evaluated.
  
  
  METHODS
  One hundred ten consecutive systolic HF patients (age 62 +/- 15 years, left ventricular ejection fraction [LVEF] 31 +/- 7%) underwent assessment of chemosensitivity to hypoxia and hypercapnia (rebreathing technique) and were followed up for a median period of 29 months (range 1 to 54 months). The end point was a composite of cardiac death and aborted cardiac death (ventricular tachyarrhythmia treated by cardioverter-defibrillator).
  
  
  RESULTS
  At baseline, 31 patients (28%) had enhanced chemosensitivity to both hypoxia and hypercapnia. Although they had the same LVEF as the 43 patients (39%) with normal chemosensitivity, they were more symptomatic (New York Heart Association functional class), had higher plasma brain natriuretic peptide and norepinephrine, steeper regression slope relating minute ventilation to carbon dioxide output (V(E)/V(CO2) slope), more Cheyne-Stokes respiration, and more ventricular arrhythmias (all p < 0.05). Four-year survival was only 49%, in marked contrast to 100% for patients with normal chemosensitivity (p < 0.001). On multivariate analysis, combined elevation in chemosensitivity was the strongest independent prognostic marker, even when adjusted for univariate predictors (V(E)/V(CO2) slope, Cheyne-Stokes respiration, LVEF, and brain natriuretic peptide, p < 0.05).
  
  
  CONCLUSIONS
  Increased chemosensitivity to both hypoxia and hypercapnia, eliciting neurohormonal derangement, ventilation instability, and ventricular arrhythmias, is a very serious adverse prognostic marker in HF.
authors.affiliation: Department of Cardiovascular Medicine, G. Monasterio Foundation CNR-Regione Toscana and CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Giannoni
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.forename: Francesca
authors.initials: F
authors.lastname: Bramanti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Iudice
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
authors.forename: Antonio
authors.initials: A
authors.lastname: Barsotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Piepoli
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
mesh_terms: D002628:Chemoreceptor Cells / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D006935:Hypercapnia / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017286:Polysomnography; D011379:Prognosis; D011446:Prospective Studies; D013318:Stroke Volume / Q000502:physiology; D013997:Time Factors
chemical_list: D020097:Natriuretic Peptide, Brain