P3525Buspirone effect on chemoreflex and central apneas in heart failure

• Published in: European heart journal 2019-10, Vol.40 (Supplement_1)
• Main Authors: Borrelli, C, Giannoni, A, Mirizzi, G, Emdin, M, Passino, C
• Format: Article
• Language: English
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehz745.0389

Abstract Background Increased chemosensitivity to carbon dioxide (CO2) is an important trigger of central apneas in heart failure (HF), contributing to HF progression and mortality. We hypothesized that buspirone, a 5HT1A receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO2 chemosensitivity, thus preventing CA in patients with HF. Methods Sixteen patients with systolic HF (age 71.3±5.8 years, left ventricular ejection fraction 29.8±7.8%) and moderate-severe central apneas (nighttime apnea/hypopnea index AHI≥15 events/hour) underwent a double-blind, placebo-controlled, cross over, randomized study of oral buspirone administration (45 mg/day for 1 week). Results Buspirone reduced CO2 chemosensitivity compared to placebo (1.2 IR [1.1–1.5] vs. 2.0 [1.6–2.2] L/min/mmHg, p=0.008). Furthermore, buspirone improved: the AHI at nighttime (16.5 [8.5–24.7] vs. 27.5 [23.0–37.3] events/hour, p=0.002), and daytime (8.0 [2.3–11.5] vs. 11.5 [6.3–18.8] events/hour, p=0.006); the central apnea index at nighttime (4.0 [1.0–19.0] vs. 12.5 [8.3–27.3] events/hour, p=0.01) and daytime (1.0 [0.0–3.0] vs. 4.0 [1.3–6.0] events/hour, p=0.009); and the oxygen desaturation index at nighttime (4.7 [1.0–11.0] vs. 20.0 [8.7–26.5] events/hour, p=0.004) and daytime (0.2 [0.1–0.7] vs. 1.2 [0.3–4.8] events/hour, p=0.005). Buspirone showed a good safety profile and had no effect on neurohormones, arrhythmias, exercise capacity and mood/daytime sleepiness. Conclusion Buspirone reduces CO2 chemosensitivity and inhibits central apneas both during the day and the night in patients with systolic HF.