Stegmann Tina, Parentin Luisa, Schirmer Stephan H, Lavall Philipp, Hagendorff Andreas, Laufs Ulrich, Lavall Daniel
Department of Cardiology, Leipzig University Hospital, Leipzig, Germany.
Kardiopraxis Kaiserslautern and Saarland University, Kaiserslautern, Germany.
Am J Physiol Heart Circ Physiol. 2024 Dec 1;327(6):H1477-H1489. doi: 10.1152/ajpheart.00410.2024. Epub 2024 Oct 25.
Sacubitril/valsartan improves outcomes in chronic heart failure (HF) with reduced ejection fraction (EF). The underlying mechanisms on left ventricular (LV) myocardial function are incompletely understood. In this study, 117 patients with symptomatic HF and LVEF ≤ 40% were enrolled prospectively. Noninvasive pressure-volume analysis was calculated from transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements. Primary outcome parameters were LV end-systolic elastance (; a measure of LV contractility), effective arterial elastance (; a measure of afterload), and the ventricular-arterial coupling ratio (/). The mean age was 65 ± 13 yr, 30% were female, and 54.7% had ischemic heart disease. During 6 mo of follow-up, eight patients died, three withdrew their consent, and four were lost to follow-up. About 102 patients were included in pressure-volume analyses. After 6 mo of sacubitril/valsartan treatment, increased (0.66 mmHg/mL [IQR 0.45-0.94] vs. 0.78 mmHg/mL [IQR 0.57-1.10], = 0.001), decreased (1.76 mmHg/mL [IQR 1.48-2.13] vs. 1.62 mmHg/mL [IQR 1.36-1.96], = 0.014), and the / ratio improved (2.52 [IQR 1.88-4.05] vs. 1.93 [IQR 1.50-2.63], < 0.001). LV end-diastolic pressure and LV volumes were reduced, and LVEF increased from 33% to 43% (both < 0.001). Clinical improvement occurred in NYHA functional class, NT-proBNP level, and 6-min walking distance. Change in LVEF correlated with change in ( = 0.33, = 0.0008), while change in NT-proBNP was associated with change in LV end-diastolic pressure (LVEDP) ( = 0.42, < 0.0001). In conclusion, sacubitril/valsartan is associated with improved ventricular-arterial coupling by enhancing LV contractility and reducing afterload. Beyond LV reverse remodeling, optimized ventricular-arterial interaction may contribute to the favorable outcome of sacubitril/valsartan treatment in HF with reduced EF. The study demonstrates that 6-mo treatment with sacubitril/valsartan in patients with heart failure with reduced ejection fraction is associated with increased left ventricular contractility, reduced afterload, and improved ventricular-arterial coupling. Together with reverse remodeling, these changes indicate a leftward shift of the operating left ventricular pressure-volume relationship. These data provide new insights into the understanding of pharmacological mechanisms in the failing heart and may facilitate tailored medical therapy.
沙库巴曲缬沙坦可改善射血分数降低的慢性心力衰竭（HF）患者的预后。其对左心室（LV）心肌功能的潜在机制尚未完全明确。在本研究中，前瞻性纳入了117例有症状的HF患者且左心室射血分数（LVEF）≤40%。通过经胸超声心动图同时测量袖带血压进行无创压力-容积分析。主要结局参数为左心室收缩末期弹性（；左心室收缩性的一种测量指标）、有效动脉弹性（；后负荷的一种测量指标）以及心室-动脉耦联比（/）。平均年龄为65±13岁，30%为女性，54.7%患有缺血性心脏病。在6个月的随访期间，8例患者死亡，3例撤回同意书，4例失访。约102例患者纳入压力-容积分析。沙库巴曲缬沙坦治疗6个月后，升高（0.66 mmHg/mL [四分位间距0.45 - 0.94] 对比0.78 mmHg/mL [四分位间距0.57 - 1.10]， = 0.001），降低（1.76 mmHg/mL [四分位间距1.48 - 2.13] 对比1.62 mmHg/mL [四分位间距1.36 - 1.96]， = 0.014），且/比值改善（2.52 [四分位间距1.88 - 4.05] 对比1.93 [四分位间距1.50 - 2.63]， < 0.001）。左心室舒张末期压力和左心室容积降低，LVEF从33%增至43%（均 < 0.001）。纽约心脏协会（NYHA）功能分级、N末端B型利钠肽原（NT-proBNP）水平及6分钟步行距离均有临床改善。LVEF的变化与的变化相关（ = 0.33， = 0.0008），而NT-proBNP的变化与左心室舒张末期压力（LVEDP）的变化相关（ = 0.42， < 0.0001）。总之，沙库巴曲缬沙坦通过增强左心室收缩性和降低后负荷改善心室-动脉耦联。除左心室逆向重构外，优化的心室-动脉相互作用可能有助于沙库巴曲缬沙坦治疗射血分数降低的HF取得良好预后。该研究表明，射血分数降低的心力衰竭患者接受6个月沙库巴曲缬沙坦治疗与左心室收缩性增加、后负荷降低及心室-动脉耦联改善相关。连同逆向重构，这些变化表明左心室压力-容积关系的工作曲线向左移位。这些数据为理解衰竭心脏的药理机制提供了新见解，并可能有助于制定个性化药物治疗方案。
