Abstract：
OBJECTIVE: We sought to evaluate the mechanism of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart failure with reduced ejection fraction (HFrEF).
RESULTS: The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II-III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11 C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (-4.5 mmHg; p = 0.026) and systolic blood pressure (-9.8 mmHg; p = 0.0007), myocardial perfusion (-0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (-296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088).
CONCLUSIONS: We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients.
RESULTS: The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II-III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11 C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (-4.5 mmHg; p = 0.026) and systolic blood pressure (-9.8 mmHg; p = 0.0007), myocardial perfusion (-0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (-296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088).
CONCLUSIONS: We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients.
摘要：
目的：我们试图评估血管紧张素转换酶抑制剂（ARNI）沙库巴曲/缬沙坦治疗HFrEF患者的机制，并将其与仅缬沙坦对照组进行比较。
结果：该研究为IV期，prospective,随机化，双盲,NYHAII-III级心力衰竭（HF）且左心室（LV）射血分数（EF）≤35％的患者的平行组研究。在为期6周的磨合期中，所有患者均接受缬沙坦治疗，将其上调至最高耐受剂量水平（80mgBID或160mgBID），然后随机分配至缬沙坦或沙库巴曲/缬沙坦。心肌耗氧量,心脏工作的能量效率，在55例患者（ARNI组-27例患者，治疗前和治疗6周（稳定剂量）后，使用超声心动图和11C-乙酸PET对心脏和全身血流动力学进行了定量，年龄63±10岁，EF29.2±10.4%，和缬沙坦唯一对照组-28例，年龄64±8岁，EF29.0±7.3%，所有的NS。）在两个治疗组中，心脏工作的能量效率保持不变。然而,舒张压（-4.5mmHg；p=0.026）和收缩压（-9.8mmHg；p=0.0007），心肌灌注（-0.054mL/g/min；p=0.045），与对照组相比，ARNI组的LV机械功（-296；p=0.038）显着降低。尽管与导入期相比，ARNI组的心肌耗氧量降低（-5.4％），而对照组（0.5％）保持不变，治疗组之间差异不显著(p=0.088)。
结论：我们发现，在HFrEF患者中，ARNI组和缬沙坦组之间心脏工作的能量效率没有差异。然而,在HF患者中，ARNI似乎对缬沙坦具有血液动力学和心脏机械作用。（EudraCT2017-002113-64）本文受版权保护。保留所有权利。
结果：该研究为IV期，prospective,随机化，双盲,NYHAII-III级心力衰竭（HF）且左心室（LV）射血分数（EF）≤35％的患者的平行组研究。在为期6周的磨合期中，所有患者均接受缬沙坦治疗，将其上调至最高耐受剂量水平（80mgBID或160mgBID），然后随机分配至缬沙坦或沙库巴曲/缬沙坦。心肌耗氧量,心脏工作的能量效率，在55例患者（ARNI组-27例患者，治疗前和治疗6周（稳定剂量）后，使用超声心动图和11C-乙酸PET对心脏和全身血流动力学进行了定量，年龄63±10岁，EF29.2±10.4%，和缬沙坦唯一对照组-28例，年龄64±8岁，EF29.0±7.3%，所有的NS。）在两个治疗组中，心脏工作的能量效率保持不变。然而,舒张压（-4.5mmHg；p=0.026）和收缩压（-9.8mmHg；p=0.0007），心肌灌注（-0.054mL/g/min；p=0.045），与对照组相比，ARNI组的LV机械功（-296；p=0.038）显着降低。尽管与导入期相比，ARNI组的心肌耗氧量降低（-5.4％），而对照组（0.5％）保持不变，治疗组之间差异不显著(p=0.088)。
结论：我们发现，在HFrEF患者中，ARNI组和缬沙坦组之间心脏工作的能量效率没有差异。然而,在HF患者中，ARNI似乎对缬沙坦具有血液动力学和心脏机械作用。（EudraCT2017-002113-64）本文受版权保护。保留所有权利。
