Abstract：
BACKGROUND: Heart failure with reduced ejection fraction is associated with potentially deleterious imbalance of the cardiac autonomic nervous system. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) reduces cardiovascular mortality and hospitalization for heart failure with reduced ejection fraction. Whether ARNI affects the cardiac autonomic nervous system has not been studied.
RESULTS: This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds (P<0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds (P<0.001), HR decreased from 73±9 bpm to 67±4 bpm, (P<0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds (P<0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg2 versus 4.7 deg2, P=0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P<0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P<0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement.
CONCLUSIONS: Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by \"volume unloading\" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction.
BACKGROUND: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.
RESULTS: This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds (P<0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds (P<0.001), HR decreased from 73±9 bpm to 67±4 bpm, (P<0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds (P<0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg2 versus 4.7 deg2, P=0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P<0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P<0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement.
CONCLUSIONS: Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by \"volume unloading\" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction.
BACKGROUND: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.
摘要：
背景：射血分数降低的心力衰竭与心脏自主神经系统的潜在有害失衡有关。Sacubitril/缬沙坦（血管紧张素受体-脑啡肽抑制剂[ARNI]）可降低心血管死亡率和射血分数降低的心力衰竭住院率。ARNI是否影响心脏自主神经系统尚未研究。
结果：该研究者发起，prospective,单中心队列研究比较了心率(HR)变异性，HR,减速能力,和周期性复极动力学作为ARNI治疗开始前后心脏自主神经系统的非侵入性措施。患者接受标准化12导联动态心电图，治疗开始前和治疗后3个月的超声心动图和实验室检查。终点是HR变异性的变化(正常到正常间隔的SD，连续R-R间隔之间差异的平均平方)，HR,减速能力,和周期性复极动力学以及心室功能和NT-proBNP（N末端B型利钠肽原）。在63例射血分数降低的心力衰竭患者中，48例（76.2%）患者在随访时仍使用ARNI。正常到正常间隔的SD从25毫秒增加到36毫秒（P<0.001），连续R-R间期之间的平均方差从12毫秒增加到19毫秒（P<0.001），HR从73±9bpm下降到67±4bpm，（P<0.001），减速能力从2.1毫秒增加到4.4毫秒（P<0.001）。观察到周期性复极化动力学降低的趋势（5.6deg2对4.7deg2，P=0.09）。自主神经改变伴随左心室射血分数增加（29±6％对40±8％，P<0.001）和降低NT-proBNP（3548对685ng/L，P<0.001)。相关性分析显示容积卸载(如NT-proBNP降低所证明的)与自主神经改善之间存在显著关系。
结论：三个月的ARNI治疗导致心脏副交感神经张力显著增加。自主神经特性的改善可能由“容积卸载”介导，并可能有助于ARNI在射血分数降低的心力衰竭中的有益作用。
背景：URL：https://www。clinicaltrials.gov；唯一标识符：NCT04587947。
结果：该研究者发起，prospective,单中心队列研究比较了心率(HR)变异性，HR,减速能力,和周期性复极动力学作为ARNI治疗开始前后心脏自主神经系统的非侵入性措施。患者接受标准化12导联动态心电图，治疗开始前和治疗后3个月的超声心动图和实验室检查。终点是HR变异性的变化(正常到正常间隔的SD，连续R-R间隔之间差异的平均平方)，HR,减速能力,和周期性复极动力学以及心室功能和NT-proBNP（N末端B型利钠肽原）。在63例射血分数降低的心力衰竭患者中，48例（76.2%）患者在随访时仍使用ARNI。正常到正常间隔的SD从25毫秒增加到36毫秒（P<0.001），连续R-R间期之间的平均方差从12毫秒增加到19毫秒（P<0.001），HR从73±9bpm下降到67±4bpm，（P<0.001），减速能力从2.1毫秒增加到4.4毫秒（P<0.001）。观察到周期性复极化动力学降低的趋势（5.6deg2对4.7deg2，P=0.09）。自主神经改变伴随左心室射血分数增加（29±6％对40±8％，P<0.001）和降低NT-proBNP（3548对685ng/L，P<0.001)。相关性分析显示容积卸载(如NT-proBNP降低所证明的)与自主神经改善之间存在显著关系。
结论：三个月的ARNI治疗导致心脏副交感神经张力显著增加。自主神经特性的改善可能由“容积卸载”介导，并可能有助于ARNI在射血分数降低的心力衰竭中的有益作用。
背景：URL：https://www。clinicaltrials.gov；唯一标识符：NCT04587947。
