Cardiology and Cardiovascular Pathophysiology, University of Perugia, Italy.
Cardiac, Thoracic and Vascular Department, University of Pisa, Italy.
Int J Cardiol. 2022 Mar 1;350:62-68. doi: 10.1016/j.ijcard.2022.01.004. Epub 2022 Jan 5.
Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect.
To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome.
In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/m) were combined to determine 4 hemodynamic profiles: profile-A (normal-flow/normal-pressure); profile-B (low-flow/normal-pressure); profile-C: (normal-flow/high-pressure); profile-D: (low-flow/high-pressure). Changes among categories were recorded, and their associations with rates of the composite of death/HF-hospitalization were assessed by multivariable Cox analysis.
At baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P < 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4-16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0-37.3) or worsened (31.2%, 20.7-46.9, P < 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45-0.95, P < 0.05).
In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.
沙库巴曲缬沙坦可改善射血分数降低的心力衰竭（HF，HFrEF）患者的预后。然而，对于这种有利影响的潜在机制知之甚少。
评估沙库巴曲缬沙坦引起的超声心动图血流动力学特征的变化及其对预后的影响。
本项多中心、开放标签研究共纳入 727 例 HFrEF 门诊患者，在基线（开始沙库巴曲缬沙坦治疗前）和 12 个月后进行全面超声心动图检查。通过组合估计的左心室充盈压（E/e'）和心输出量（CI，l/min/m）来确定 4 种血流动力学特征：特征 A（正常流量/正常压力）；特征 B（低流量/正常压力）；特征 C：（正常流量/高压力）；特征 D：（低流量/高压力）。记录类别之间的变化，并通过多变量 Cox 分析评估其与复合死亡/心力衰竭住院的发生率之间的关系。
基线时，29%的患者存在特征 A，15%的患者存在特征 B，32%的患者存在特征 C，24%的患者存在特征 D。12 个月后，53%的患者血流动力学特征得到改善（所有特征 A 达标，或特征 D 的患者达标为 C 或 B 特征），39%的患者保持不变，9%的患者恶化。沙库巴曲缬沙坦剂量越高，特征改善的比例越高（P<0.0001）。第二次超声心动图检查后，患者平均随访 12.6±7.6 个月：特征改善的患者的事件发生率较低（12.3%，95%CI：9.4-16.1），与血流动力学特征保持不变（29.9%，24.0-37.3）或恶化（31.2%，20.7-46.9，P<0.0001）的患者相比。改善的血流动力学特征与 LVEF 及其他混杂因素无关，是有利预后的独立预测因素（HR 0.65，95%CI：0.45-0.95，P<0.05）。
在 HFrEF 患者中，沙库巴曲缬沙坦的有益预后作用与血流动力学状况的改善相关。
