Long-term Efficacy of Acetazolamide on Cheyne-Stokes Respiration in Congestive Heart Failure

Abstract

We very much appreciated Dr. Javaheri’s recent article concerning the effects of acetazolamide on Cheyne-Stokes respiration (CSR) in congestive heart failure (1). Since CSR in heart failure, characterized by repetitive central apneas alternating with a crescendo–decrescendo tidal volume, is acknowledged to behighly prevalent (2) and probably can also be a therapeutic target, the article has relevance not only for pulmonary/sleep specialists but cardiologists as well. According to this study, acetazolamide was taken 1 h before bedtime for a week by heart failure patients with CSR. The author reported that apnea–hypopnea and nocturnal oxygen desaturation were ameliorated, subjective perception of sleep quality and daytime symptoms were improved, and PaCO2 in arterial blood gases was decreased. Although Dr. Javaheri suggested that a changing apneic threshold might have played a major role (1), other mechanisms could be considered, including the changes in controller/plant gains and circulation time. A further decline in PaCO2 secondary to the metabolic acidosis produced by acetazolamide may pose a risk of exaggerating CSR by jeopardizing respiratory stability. In a recent case series, five heart failure patients with CSR were treated nightly for a year with continuous positive airway pressure (CPAP) of 5–8 cm H2O, resulting in improved central sleep apnea, sleep quality, and cardiac function (3). An additional data analysis of ventilatory response to rebreathing hypercapnia in four of five normocapnic patients revealed that the slope of the regression line of minute ventilation versus PaCO2 was significantly decreased after 3 mo of CPAP, suggesting that chemoreceptor sensitivity was diminished after appropriate treatment. Dr. Javaheri did not show changes in chemosensitivity, but had previously reported that an enhanced sensitivity to CO2 could predispose some heart failure patients to develop CSR (4). Although the central action of acetazolamide might have improved daytime symptoms in heart failure patients (1), acetazolamide is a second-line diuretic for treatment of heart failure due to its adverse effects (such as hyperpnea, numbness, and nocturia) and pharmacologic acclimatization, which would occur within a few months after starting administration. Nonetheless, the long-term efficacy and safety of acetazolamide in improving CSR in heart failure has not yet been established. Sleep-disordered breathing is a major public health problem (5), and its interactionwith cardiac function has been called a new cardiovascular frontier (6), as indicated by the fact that only 17 yr have passed since one of the earliest prevalence studies dealing with CSR in heart failure appeared in a journal for cardiologists (2).