Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.
Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
Cardiovasc Ther. 2018 Aug;36(4):e12435. doi: 10.1111/1755-5922.12435. Epub 2018 Jun 7.
Major classes of medical therapy for heart failure with reduced ejection fraction (HFrEF) induce reverse remodeling. The revere remodeling response to sacubitril/valsartan remains unstudied.
We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients with a class I indication (New York heart Association [NYHA]-class II-IV, Left ventricular ejection fraction [LVEF] < 35%, optimal dose with Renin-Angiotensin-System-Blocker [RAS-blocker]). Doses of sacubitril/valsartan were optimized to individual tolerance. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms.
One-hundred-twenty-five HFrEF patients (66 ± 10 years) were prospectively included. The amount of RAS-blocker before and after switch to sacubitril/valsartan was similar(P = .290), indicating individual optimal dosing of sacubitril/valsartan. Over a median(IQR) follow-up of 118(77-160) days after initiation of sacubitril/valsartan, LVEF improved (29.6 ± 6% vs 34.8 ± 6%; P < .001) and Left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) decreased (LVESV; 147 ± 57 mL vs 129 ± 55 mL; P < .001 and LVEDV; 206 ± 71 mL vs197 ± 72 mL; P = .027). Volumetric remodeling was associated with a reduction in the degree of mitral regurgitation (1.59 ± 1.0 vs 1.11 ± 0.8; P < .001; [scale from 0-4]). Metrics of diastolic function improved; including a drop in the E/A-wave ratio (1.75 ± 1.13 vs 1.38 ± 0.88; P = .002) and diastolic filling time (% of cycle length) prolonged (48 ± 9% vs 52 ± 1%; P = .005). The percent of patients with a restrictive mitral filling pattern dropped from 47% to 23% (P = .004). A dose-dependent effect was noted for changes in LVEF (P < .001) and LVESV (P = .031), with higher doses of sacubitril/valsartan leading to more reverse remodeling.
Switching therapy in eligible HFrEF patients from a RAS-blocker to sacubitril/valsartan induces beneficial reverse remodeling of both metrics of systolic as diastolic function.
治疗射血分数降低的心力衰竭（HFrEF）的主要药物类别可诱导逆向重构。沙库巴曲缬沙坦的逆向重构反应仍未得到研究。
我们进行了一项单中心、前瞻性评估者盲法研究，以确定沙库巴曲缬沙坦在 I 类适应证（纽约心脏协会[NYHA]心功能分级 II-IV 级，左心室射血分数[LVEF]＜35%，最佳剂量的肾素-血管紧张素-系统阻滞剂[RAS 阻滞剂]）的 HFrEF 患者中的逆向重构反应。沙库巴曲缬沙坦的剂量优化至个体耐受。通过 2 位对临床数据和超声心动图时间均不知情的研究人员离线评估超声心动图图像。
125 例 HFrEF 患者（66±10 岁）被前瞻性纳入。在转换为沙库巴曲缬沙坦前后，RAS 阻滞剂的剂量相似（P=0.290），这表明沙库巴曲缬沙坦的剂量为个体最佳剂量。在开始沙库巴曲缬沙坦治疗后的中位（IQR）随访 118（77-160）天，LVEF 改善（29.6±6% vs 34.8±6%；P＜0.001），左心室收缩末期（LVESV）和舒张末期容积（LVEDV）降低（LVESV：147±57 mL vs 129±55 mL；P＜0.001 和 LVEDV：206±71 mL vs 197±72 mL；P=0.027）。容积重构与二尖瓣反流程度降低相关（1.59±1.0 vs 1.11±0.8；P＜0.001；[0-4 级]）。舒张功能的指标改善，包括 E/A 波比值下降（1.75±1.13 vs 1.38±0.88；P=0.002）和舒张充盈时间（心动周期长度的百分比）延长（48±9% vs 52±1%；P=0.005）。限制型二尖瓣充盈模式的患者比例从 47%降至 23%（P=0.004）。LVEF（P＜0.001）和 LVESV（P=0.031）的变化呈剂量依赖性，沙库巴曲缬沙坦的高剂量导致更多的逆向重构。
在符合条件的射血分数降低的心力衰竭患者中，从 RAS 阻滞剂转换为沙库巴曲缬沙坦治疗可导致收缩和舒张功能的多项指标有益的逆向重构。
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