达格列净对心力衰竭患者运动、心脏重塑、生物标志物以及肾脏和肺功能的影响：不如预期？
Dapagliflozin effects on exercise, cardiac remodeling, biomarkers, and renal and pulmonary function in heart failure patients: not as good as expected?
作者信息
Mapelli Massimo, Mattavelli Irene, Salvioni Elisabetta, Capra Nicolò, Mantegazza Valentina, Garlaschè Anna, Campodonico Jeness, Rubbo Filippo Maria, Paganin Chiara, Capovilla Teresa Maria, Nepitella Alessandro Alberto, Caputo Rebecca, Gugliandolo Paola, Vignati Carlo, Pezzuto Beatrice, De Martino Fabiana, Grilli Giulia, Scatigna Marco, Bonomi Alice, Sinagra Gianfranco, Muratori Manuela, Agostoni Piergiuseppe
机构信息
Centro Cardiologico Monzino, IRCCS, Milan, Italy.
Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy.
出版信息
Front Cardiovasc Med. 2025 Mar 17;12:1542870. doi: 10.3389/fcvm.2025.1542870. eCollection 2025.
BACKGROUND
Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) are standard therapy for heart failure (HF). We performed a holistic evaluation of dapagliflozin, including its effects on exercise performance, left ventricle (LV) reverse remodeling, cardiac biomarkers, fluid retention, and renal and pulmonary function.
METHODS
We enrolled HF reduced ejection fraction (LVEF) outpatients (EF <40%) eligible for SGLT2-i and performed cardiopulmonary exercise tests (CPET), pulmonary function tests, bioelectrical impedance vector analysis, and laboratory and echocardiographic assessments at baseline ( = 0), after 2-4 weeks (T1), and after 6 months of treatment (T2).
RESULTS
None of the patients interrupted SGLT2-i for adverse events albeit follow-up was completed by 67 of 75 enrolled patients. At T2, mean LVEF increased (from 34.6 ± 7.8 to 37.5 ± 9.2%; < 0.001) while end-diastolic (EDV) and end-systolic (ESV) volumes decreased [EDV: 186 (145-232) vs. 177 (129-225) mL, ESV: 113 (87-163) vs. 110 (76-145) mL; < 0.001]. Peak oxygen intake was unchanged [peakVO: 16.2 (13.4-18.7) vs. 16.0 (13.3-18.9) mL/kg/min; = 0.297], while exercise ventilatory efficiency (VE/VCO slope) improved [from 34.2 (31.1-39.2) to 33.7 (30.2-37.6); = 0.006]. Mean hemoglobin increased (from 13.8 ± 1.5 to 14.6 ± 1.7 g/dL; < 0.001), while renal function did not change after a transient worsening at T1. NT-proBNP, ST-2, and hs-TNI did not change as overall body fluids and quality of life assessed by KCCQ. NYHA class improved (=0.002), paralleled by a decrease of MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) score, from 3.3% (1.9-8.0) to 2.8% (1.2-5.7), suggestive of a positive impact on 2 years prognosis ( < 0.001).
CONCLUSIONS
Dapagliflozin induced positive LV remodeling, improvement of exercise ventilatory efficiency, and NYHA class but without peakVO fluid status and cardiac biomarkers changes.
背景
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2-i）是心力衰竭（HF）的标准治疗方法。我们对达格列净进行了全面评估，包括其对运动能力、左心室（LV）逆向重构、心脏生物标志物、液体潴留以及肾和肺功能的影响。
方法
我们纳入了符合SGLT2-i治疗条件的射血分数降低的HF门诊患者（LVEF<40%），并在基线（=0）、2-4周后（T1）和治疗6个月后（T2）进行了心肺运动试验（CPET）、肺功能测试、生物电阻抗矢量分析以及实验室和超声心动图评估。
结果
尽管75名入组患者中有67名完成了随访，但没有患者因不良事件中断SGLT2-i治疗。在T2时，平均LVEF升高（从34.6±7.8%升至37.5±9.2%；<0.001），而舒张末期（EDV）和收缩末期（ESV）容积降低[EDV：186（145-232）ml对177（129-225）ml，ESV：113（87-163）ml对110（76-145）ml；<0.001]。峰值摄氧量未改变[peakVO：16.2（13.4-18.7）ml/kg/min对16.0（13.3-18.9）ml/kg/min；=0.297]，而运动通气效率（VE/VCO斜率）有所改善[从34.2（31.1-39.2）降至33.7（30.2-37.6）；=0.006]。平均血红蛋白升高（从13.8±1.5g/dL升至14.6±1.7g/dL；<0.001），而肾功能在T1时短暂恶化后未发生变化。NT-proBNP、ST-2和hs-TNI没有变化，KCCQ评估的总体体液和生活质量也未改变。纽约心脏协会（NYHA）心功能分级改善（=0.002），同时MECKI（代谢运动试验数据与心脏和肾脏指数相结合）评分降低，从3.3%（1.9-8.0）降至2.8%（1.2-5.7），提示对2年预后有积极影响（<0.001）。
结论
达格列净可诱导左心室正向重构，改善运动通气效率和NYHA心功能分级，但不改变peakVO、液体状态和心脏生物标志物。
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