title: Effect of acetazolamide on chemosensitivity, Cheyne-Stokes respiration, and response to effort in patients with heart failure.
abstract: Increased chemosensitivity to hypoxia and hypercapnia, together with a prolonged circulatory time, are the main determinants of Cheyne-Stokes (C-S) respiration in heart failure. To evaluate the effect of acetazolamide, a carbonic anhydrase inhibitor, on chemosensitivity and respiratory dynamics in patients with heart failure with C-S respiration, 12 patients (mean age 62 ± 9 years, mean left ventricular ejection fraction 24 ± 9%) and C-S respiration (mean apnea-hypopnea index 23 ± 13) who underwent 4 consecutive days of oral acetazolamide treatment (250 mg twice daily) were enrolled in this study. Assessment of chemosensitivity to hypoxia and hypercapnia, cardiopulmonary stress testing, 24-hour cardiorespiratory polygraphy, and neurohormonal characterization were performed at baseline and at the end of treatment. Acetazolamide improved central apneas (apnea-hypopnea index 23 ± 13 to 15 ± 9, p = 0.012) and the percentage of time spent below an arterial oxyhemoglobin saturation of 90% (16 ± 23% to 10 ± 18%, p = 0.005). Chemosensitivity to hypoxia was blunted (1.03 ± 0.69 to 0.78 ± 0.55 L/min/mm Hg, p = 0.032), while chemosensitivity to hypercapnia increased after acetazolamide (1.27 ± 0.71 to 1.54 ± 0.78 L/min/% arterial oxygen saturation, p = 0.023); patients achieved a lower workload (90 ± 30 to 81 ± 30 W, p <0.001), with no differences in peak oxygen consumption, while there was an increment in the regression slope relating minute ventilation to carbon dioxide output (39 ± 10 to 43 ± 9, p = 0.010). In conclusion, in patients with heart failure, acetazolamide diminishes C-S respiration and improves oxyhemoglobin saturation, likely by decreasing chemosensitivity to hypoxia. However, it is associated with reduced maximal workload achieved during effort and increased chemosensitivity to hypercapnia, inducing a reduction in the ventilatory efficiency.
authors.affiliation: Division of Cardiovascular Medicine, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Fontana
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.forename: Alberto
authors.initials: A
authors.lastname: Giannoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Iudice
authors.forename: Resham
authors.initials: R
authors.lastname: Baruah
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000368:Aged; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002639:Cheyne-Stokes Respiration / Q000188:drug therapy*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006935:Hypercapnia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide