Angiotensin Receptor Neprilysin Inhibitor in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Regurgitation: The PRAISE-MR Randomized Trial.

Although sacubitril/valsartan reduces functional mitral regurgitation (MR) in HF with reduced EF (HFrEF), its impact on exercise hemodynamics and the dynamic burden of AFMR in HFpEF remains to be elucidated.

尽管沙库巴曲/缬沙坦在减少射血分数降低的心力衰竭（HFrEF）中的功能性二尖瓣反流（MR）方面有效，但其对HFpEF中运动血流动力学以及AFMR的动态负担的影响仍需进一步阐明。

Methods

This multicenter, randomized, open-label trial with blinded primary endpoint assessment assigned 84 patients with symptomatic HFpEF and at least moderate AFMR within the previous year to sacubitril/valsartan (n=41) or standard-of-care (SOC; n=43).

这项多中心、随机、开放标签试验，对84名在过去一年内至少有中度心房颤动相关二尖瓣反流（AFMR）症状的射血分数保留心力衰竭（HFpEF）患者进行了随机分组，分别接受沙库巴曲/缬沙坦治疗（n=41）或标准治疗（SOC; n=43）。

The primary outcome was the 6-month change in the exercise mean pulmonary arterial pressure to cardiac output (mPAP/CO) slope, assessed using cardiopulmonary exercise testing with simultaneous echocardiography (CPETecho).

主要结果是使用心肺运动测试联合超声心动图（CPETecho）评估的6个月运动平均肺动脉压与心输出量（mPAP/CO）斜率的变化。

Secondary outcomes included changes in peak oxygen consumption (peak VO2), Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, left atrial (LA) volume and function, and AFMR severity in rest and during stress.

次要结果包括峰值氧耗量（peak VO2）、堪萨斯城心肌病问卷（KCCQ）、N-末端前体脑钠肽（NT-proBNP）水平、左心房（LA）体积和功能以及静息和应激状态下的房颤相关微血管阻力（AFMR）严重程度的变化。

Results

At 6 months, sacubitril/valsartan significantly improved the mPAP/CO slope compared with SOC (adjusted between-group difference in change, -0.93 mm Hg/L/min; 95% CI, -1.80 to -0.07; P=0.035).

在6个月时，沙库巴曲/缬沙坦显著改善了mPAP/CO斜率，与标准治疗（SOC）相比（调整后的组间差异变化，-0.93毫米汞柱/升/分钟；95%置信区间，-1.80至-0.07；P=0.035）。

This hemodynamic benefit was accompanied by improvements in peak VO2 (mean change, +0.9 versus -0.6mL/kg/min; P=0.002) and KCCQ (median increase, 10 versus 2 points; P=0.002).

这种血流动力学益处伴随着峰值VO2的改善（平均变化量，+0.9对比-0.6mL/kg/min；P=0.002）和KCCQ的提高（中位数增加，10对比2点；P=0.002）。

Significant reductions in NT-proBNP and LA volume were observed (P<0.001 for both), alongside a significant blunting of the dynamic MR increase during exercise (P=0.020).

观察到NT-proBNP和左心房容积的显著减少（两者P<0.001），以及运动期间动态二尖瓣反流增加的显著抑制（P=0.020）。

Target dose was achieved in 60% of patients, with symptomatic hypotension as the primary titration-limiting factor.

60%的患者达到了目标剂量，其中症状性低血压是主要的剂量调整限制因素。

Conclusions

In HFpEF and AFMR, sacubitril/valsartan was associated with improvements in exercise hemodynamics and peak VO2, along with attenuation of the exercise-induced increase in AFMR.

在射血分数保留的心力衰竭（HFpEF）和心房颤动合并射血分数保留（AFMR）患者中，沙库巴曲/缬沙坦与运动血流动力学和峰值VO2的改善有关，同时减轻了运动引起的AFMR增加。

These findings suggest a phenotype-specific benefit, warranting confirmation in larger, placebo-controlled, clinical outcome trials.

这些发现表明存在特定表型的益处，需要在更大规模的、安慰剂对照的临床结果试验中得到证实。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05991284.

网址: https://www.clinicaltrials.gov; 唯一标识符: NCT05991284。

EudraCT: 2023-506634-70-00.

EudraCT: 2023-506634-70-00。