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CLINICAL RESEARCH: HEART FAILURE

Combined Increased Chemosensitivity to Hypoxia and Hypercapnia as a Prognosticator in Heart Failure

Alberto Giannoni, MD^_*,,, Michele Emdin, MD, PhD^_*,_*, Francesca Bramanti, BSc^_*, Giovanni Iudice, BSc^_*, Darrel P. Francis, MD, PhD, Antonio Barsotti, MD, PhD, Massimo Piepoli, MD, PhD and Claudio Passino, MD^||

^_* Department of Cardiovascular Medicine, G. Monasterio Foundation CNR-Regione Toscana and CNR Institute of Clinical Physiology, Pisa, Italy
Department of Cardiology, University of Genova, Genova, Italy
International Centre for Circulatory Health, St. Mary's Hospital and Imperial College, London, United Kingdom
Heart Failure Unit, Cardiology Department, G. da Saliceto Polichirurgico Hospital, Piacenza, Italy
^|| Scuola Superiore Sant'Anna, Pisa, Italy

Manuscript received September 29, 2008; revised manuscript received February 9, 2009, accepted February 16, 2009.

^_* Reprint requests and correspondence: Dr. Michele Emdin, Cardiovascular Medicine Department, G. Monasterio Foundation, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy (Email: emdin{at}ifc.cnr.it).

Objectives: 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 (VE/VCO ₂ 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 (VE/VCO ₂ 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.

Key Words: heart failure • prognosis • chemoreflex • arrhythmia • brain natriuretic peptide • Cheyne-Stokes respiration

Abbreviations and Acronyms   BNP = brain natriuretic peptide   CI = confidence interval   CSR = Cheyne-Stokes respiration   HCVR = hypercapnic ventilatory response   HF = heart failure   HR = hazard ratio   HVR = hypoxic ventilatory response   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   VE/VCO 2 slope = regression slope relating minute ventilation to carbon dioxide output   VO 2 = oxygen uptake

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J. Am. Coll. Cardiol. 2009 53: A32. [Full Text] [PDF]