Mapelli Massimo, Mattavelli Irene, Salvioni Elisabetta, Banfi Cristina, Mallia Alice, Galotta Arianna, Mantegazza Valentina, Garlaschè Anna, Campodonico Jeness, Rubbo Filippo Maria, Paganin Chiara, Capovilla Teresa Maria, Caputo Rebecca, Contini Mauro, Gugliandolo Paola, Vignati Carlo, Pezzuto Beatrice, Grilli Giulia, Scatigna Marco, Bonomi Alice, Sinagra Gianfranco, Muratori Manuela, Agostoni Piergiuseppe
Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy.
Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, 20122 Milan, Italy.
Int J Mol Sci. 2025 Aug 8;26(16):7696. doi: 10.3390/ijms26167696.
The mechanisms underlying the effects of dapagliflozin in heart failure with reduced ejection fraction (HFrEF) are not yet fully understood. This study aims to evaluate the effect of the drug on cardiorespiratory function by assessing alveolar-capillary membrane characteristics, sleep apnea, pulmonary and cardiac performance in stable HFrEF patients. Seventy-three patients with stable HFrEF were enrolled, with 66 completing the six-month follow-up. Analyses included assessment of the alveolar-capillary membrane by diffusion capacity, including its membrane diffusion and capillary volume components and measurements of proSP-B in the blood, an emerging biomarker of alveolar-capillary membrane function. Pulmonary function tests, overnight respiratory monitoring, and echocardiographic parameter collection were also conducted. After 6 months, a reduction in circulating proSP-B levels was observed (32.65 ± 13.36 at baseline vs. 30.86 ± 12.45 AU at 6 months, for trend 0.0092), accompanied by improvements in echocardiographic parameters (left ventricle ejection fraction and pulmonary pressures). Pulmonary function tests and overnight respiratory monitoring showed no significant changes in lung diffusion, spirometry, or obstructive sleep apnea (apnea hypopnea index from 5.0 [1.1-16.6] at baseline to 6.2 [0.7-13.8]/h; = n.s.). A significant reduction in central sleep apnea (CSA) was noted in the 13 patients with at least one CSA at baseline (15 [3-48] vs. 0 [0-18.5]/h, = 0.017). Dapagliflozin demonstrates both hemodynamic and non-hemodynamic effects, particularly improving alveolar-capillary membrane function. This study highlights the multifactorial benefits of dapagliflozin in patients with stable HFrEF and the potential of proSP-B as a sensitive marker for evaluating therapeutic response.
达格列净在射血分数降低的心力衰竭（HFrEF）中发挥作用的潜在机制尚未完全明确。本研究旨在通过评估稳定期HFrEF患者的肺泡-毛细血管膜特征、睡眠呼吸暂停、肺功能和心脏功能，来评价该药对心肺功能的影响。纳入73例稳定期HFrEF患者，其中66例完成了为期6个月的随访。分析内容包括通过弥散能力评估肺泡-毛细血管膜，包括其膜弥散和毛细血管容积成分，以及检测血液中的proSP-B（一种新兴的肺泡-毛细血管膜功能生物标志物）。同时还进行了肺功能测试、夜间呼吸监测和超声心动图参数收集。6个月后，观察到循环proSP-B水平降低（基线时为32.65±13.36，6个月时为30.86±12.45 AU，趋势检验P = 0.0092），同时超声心动图参数（左心室射血分数和肺压力）得到改善。肺功能测试和夜间呼吸监测显示，肺弥散、肺量测定或阻塞性睡眠呼吸暂停无显著变化（呼吸暂停低通气指数从基线时的5.0[1.1-16.6]次/小时变为6.2[0.7-13.8]次/小时；P = 无统计学意义）。在基线时至少有一次中枢性睡眠呼吸暂停（CSA）的13例患者中，CSA显著降低（从15[3-48]次/小时降至0[0-18.5]次/小时，P = 0.017）。达格列净具有血流动力学和非血流动力学效应，尤其能改善肺泡-毛细血管膜功能。本研究强调了达格列净对稳定期HFrEF患者的多方面益处，以及proSP-B作为评估治疗反应的敏感标志物的潜力。
