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.

Central role of carotid body chemoreceptors in disordered breathing and cardiorenal dysfunction in chronic heart failure

“…Most importantly, patients without augmented chemosensitivity did not exhibit CSR, and the incidence of CSR progressively increased with enhancement of the CB chemoreflex. In other studies, deactivation of CB chemoreceptors with transient hyperoxia, or pharmacological attenuation of chemosensitivity with dihydrocodeine or acetazolamide significantly reduced central apnea incidence in CHF patients (Ponikowski et al, 1999; Fontana et al, 2011). These findings indicate an important relationship between CSR or cyclical breathing patterns and enhanced CB chemoreflex sensitivity.…”

Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure

“…Although sleep diminishes chemosensitivity per se, ventilatory oscillations become even more prominent (9). Key contributing factors include changes to state (sleep-wake transitions, arousals) and upper-airway patency (e.g., swings in dilator muscle tone) (38).…”

Congestive Heart Failure and Central Sleep Apnea

“…Although CSR can be observed during wakefulness, it is greatly exacerbated by the transition to sleep (69), which may appear counter-intuitive given the reduced chemosensitivity during sleep. (70)(71)(72) However, accompanying the transition from wake to sleep is an abrupt reduction in ventilatory drive (for any given PaCO 2 ); likewise accompanying the transition from sleep to wake (arousal) is an abrupt increase in ventilatory drive.…”