目的:血管紧张素受体-脑啡肽抑制剂(ARNI)沙库巴曲/缬沙坦(Sac/Val)在减少住院方面优于依那普利,动态心力衰竭和射血分数降低(HFrEF)患者的心血管和全因死亡率,特别是当它被最大限度地向上滴定时。不幸的是,不到50%的HFrEF患者达到目标剂量,从而破坏对结果的有益影响。在这项研究中,我们旨在评估Sac/Val及其滴定剂量在逆转心脏重塑中的作用,并确定哪种超声心动图指数最能预测向上滴定成功.
结果:从2020年1月至2021年6月,我们回顾性地确定了95例慢性HFrEF患者(65.6[59.1-72.8]岁;15.8%的女性),这些患者从5个意大利大学医院的HF诊所开了Sac/Val处方,并评估了Sac/Val高剂量的耐受性(患者达到并稳定耐受最大剂量的能力)作为队列的我们使用了多变量逻辑回归分析,使用逐步向后选择方法,确定Sac/Val最大剂量耐受性的独立预测因子,使用,作为候选预测因子,在单变量分析中,只有P值<0.1的变量。为多变量反向逻辑回归分析确定的候选预测因子是年龄,性别,体重指数(BMI),慢性肾脏病(CKD),慢性阻塞性肺疾病(COPD),血脂异常,心房颤动,收缩压(SBP),ACEi/ARBs最大剂量的基线耐受性,左心室整体纵向应变(LVgLS),左心室射血分数(EF),三尖瓣环平面收缩期偏移(TAPSE),右心室(RV)面积分数变化(FAC),RV全局和自由壁纵向应变(RVgLS和RV-FW-LS)。在多变量分析之后,只有一个分类(基线时的ACEi/ARBs最大剂量)和三个连续(年龄较小,更高的SBP,和更高的TAPSE),结果与研究结果变量显着相关,具有很强的判别能力(曲线下面积0.874,95%置信区间(CI)(0.794-0.954)来预测最大Sac/Val剂量耐受性。
结论:我们的研究首次分析了超声心动图的潜在作用,特别是,RV功能障碍,用TAPSE测量,预测Sac/Val最大剂量耐受性。因此,RV功能障碍患者(基线TAPSE<16mm,在我们的队列中)可能受益于不同的滴定Sac/Val的策略,例如从最低剂量开始和/或在尝试使用较高剂量之前等待更长时间的观察。
The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all-cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up-titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up-titration success.
From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1-72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P-value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV-FW-LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794-0.954) to predict maximum Sac/Val dose tolerability.
Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE <16 mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses.