De Masi De Luca Gabriele, Palama Zefferino, Longo Simonetta, Barba Francesca, Robles Antonio Gianluca, Nesti Martina, Scara Antonio, Coluccia Giovanni, Colopi Marzia, De Masi De Luca Giuseppe, Minardi Simona, Fusco Liuba, Palmisano Pietro, Accogli Michele, Sciarra Luigi, Romano Silvio
Department of Life, Health and Environmental Science, University of L'Aquila, L'Aquila, Italy.
Cardiology Unit, Card. "G. Panico" Hospital, Tricase, Italy.
Cardiol Res. 2025 Apr;16(2):140-152. doi: 10.14740/cr2018. Epub 2025 Feb 18.
The aim of our study was to evaluate the effects of dapagliflozin on the ventricular arrhythmia burden (VAb) in patients with heart failure with reduced ejection fraction (HFrEF) and an implantable cardioverter defibrillator (ICD), correlating the possible reduction in arrhythmic events and ICD therapies with the basal functional capacity, as well as the remodeling parameters induced by treatment.
A total of 117 outpatient ICD patients with a known diagnosis of HFrEF who underwent treatment with dapagliflozin were evaluated according to a prospective observational protocol. VAb (including sustained ventricular tachycardia, non-sustained ventricular tachycardia, ventricular fibrillation, and total ventricular events) and specific ICD therapies (anti-tachycardia pacing (ATP) and ICD shocks) were extrapolated from the devices' memory (events per patient per month) by comparing events in the observation period before and after the introduction of dapagliflozin.
The VAb was significantly reduced after dapagliflozin introduction (2.9 ± 1.8 vs. 4.5 ± 2.0, P = 0.01). The burden of appropriate ATPs was significantly reduced (0.57 ± 0.80 vs. 0.65 ± 0.91, P = 0.03), but not for ICD shocks. In patients with a more advanced functional class, a greater reduction in VAb was observed than in patients with a better initial functional capacity (2.2 ± 0.8 vs. 5.5 ± 1.8, P = 0.001 in the New York Heart Association (NYHA) III/IV group; 3.5 ± 2.1 vs. 4.5 ± 2.2, P = 0.02 in the NYHA I/II group). Considering two independent groups according to reverse remodeling (Δleft ventricular ejection fraction (LVEF) > 15%), a significant reduction in VAb was observed only in those patients who presented significant reverse remodeling (2.5 ± 1.1 vs. 5.1 ± 1.6, P = 0.01). A statistically significant interaction between the variation of total ventricular arrhythmias (VTA) and the basal NYHA class (F(1,115) = 142.25, P < 0.0001, partial η = 0.553), as well as between the variation of VTA and the ΔLVEF (F(1,115) = 107.678, P < 0.0001, partial η = 0.484) has been demonstrated using a two-way analysis of variance (ANOVA) test.
In ICD outpatients with HFrEF, dapagliflozin treatment produces a reduction in arrhythmic ventricular events. This improvement is more evident in patients who have a worse functional class and thus a more precarious hemodynamic state, and in patients who present with significant ventricular reverse remodeling. Therefore, we can hypothesize that the hemodynamic and structural improvements induced by treatment represent, at least in the short-medium term, some of the principal elements justifying the significant reduction in VAb.
我们研究的目的是评估达格列净对射血分数降低的心力衰竭（HFrEF）且植入了植入式心律转复除颤器（ICD）的患者的室性心律失常负荷（VAb）的影响，将心律失常事件和ICD治疗的可能减少与基础功能能力以及治疗引起的重塑参数相关联。
根据前瞻性观察方案，对总共117例已知诊断为HFrEF且接受达格列净治疗的门诊ICD患者进行了评估。通过比较引入达格列净前后观察期内的事件，从设备内存中推断出VAb（包括持续性室性心动过速、非持续性室性心动过速、心室颤动和总室性事件）以及特定的ICD治疗（抗心动过速起搏（ATP）和ICD电击）（每位患者每月的事件数）。
引入达格列净后VAb显著降低（2.9±1.8对4.5±2.0，P = 0.01）。适当ATP的负荷显著降低（0.57±0.80对0.65±0.91，P = 0.03），但ICD电击未降低。在功能分级更高级的患者中，观察到VAb的降低比初始功能能力较好的患者更大（纽约心脏协会（NYHA）III/IV组中为2.2±0.8对5.5±1.8，P = 0.001；NYHA I/II组中为3.5±2.1对4.5±2.2，P = 0.02）。根据逆向重塑（左心室射血分数（LVEF）变化>15%）分为两个独立组，仅在那些出现显著逆向重塑的患者中观察到VAb显著降低（2.5±1.1对5.1±1.6，P = 0.01）。使用双向方差分析（ANOVA）检验证明，总室性心律失常（VTA）变化与基础NYHA分级之间（F(1,115)=142.25，P<0.0001，偏η=0.553）以及VTA变化与ΔLVEF之间（F(1,115)=107.678，P<0.0001，偏η=0.484）存在统计学显著交互作用。
在患有HFrEF的ICD门诊患者中，达格列净治疗可减少心律失常性室性事件。这种改善在功能分级较差且血流动力学状态更不稳定的患者以及出现显著心室逆向重塑的患者中更为明显。因此，我们可以假设，至少在中短期内，治疗引起的血流动力学和结构改善是VAb显著降低的一些主要原因。
