Heart Institute, University Hospital Germans Trias i Pujol, Badalona, Spain.
Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.
ESC Heart Fail. 2022 Aug;9(4):2170-2180. doi: 10.1002/ehf2.13952. Epub 2022 May 19.
Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS-HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF-PH treated with sacubitril/valsartan.
This single-arm, investigator-initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF-PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre-ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B-line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre-ARNI vs. ARNI ON, mPAP significantly declined by -4.99 mmHg [95% confidence interval (CI) -5.55 to -4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre-ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B-lines, and QoL. Mean loop diuretic management did not differ between periods.
Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF-PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH.
先前的研究并未充分描述血管紧张素受体-脑啡肽酶抑制剂（ARNI）沙库巴曲缬沙坦在射血分数保留的心力衰竭合并肺动脉高压（HFpEF-PH）患者中的血流动力学效应。治疗 PH 与血管紧张素 II 受体阻滞剂和 Neprilysin 抑制剂在 HFpEF 患者与 CardioMEMS 装置（ARNIMEMS-HFpEF）的研究目的是通过植入的肺动脉压（PAP）监测器评估 HFpEF-PH 患者的 PAP 动态，这些患者接受沙库巴曲缬沙坦治疗。
这项单臂、研究者发起的、干预性研究包括 14 名连续的有症状的 HFpEF-PH 患者，他们在入组前接受了 CardioMEMS 植入[平均射血分数 60.4±7.2%，基线平均 PAP（mPAP）33.9±7.6mmHg]。在三个时期检查了每日 PAP 值：CardioMEMS 植入后和沙库巴曲缬沙坦治疗前（ARNI 前）的 6 周期间、沙库巴曲缬沙坦治疗（ARNI ON）的 6 周期间和沙库巴曲缬沙坦停药（ARNI OFF）的 6 周期间。主要终点是有和没有沙库巴曲缬沙坦时 mPAP 的变化。次要终点包括 6 分钟步行距离、肺部超声 B 线总和和生活质量（QoL）的变化。在研究期间，记录了 1717 次 mPAP 测量值。与 ARNI 前相比，ARNI ON 时 mPAP 显著下降-4.99mmHg[95%置信区间（CI）-5.55 至-4.43]。与 ARNI ON 相比，ARNI OFF 时 mPAP 显著升高+2.84mmHg[95%CI+2.26 至+3.42]。与 ARNI 前相比，我们发现 6 分钟步行距离、B 线和 QoL 得到改善。各时期平均袢利尿剂管理无差异。
沙库巴曲缬沙坦显著降低了 HFpEF-PH 患者的 mPAP，独立于袢利尿剂管理，同时改善了功能能力、肺充血和 QoL。沙库巴曲缬沙坦可能是 HFpEF-PH 的一种治疗选择。
