Application of Sacubitril/valsartan in Patients with Chronic Heart Failure Implanted with Implantable Cardioverter Defibrillators
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摘要:
目的 探讨沙库巴曲缬沙坦(S/V)对植入埋藏式心律转复除颤器(ICD)进行心脏性猝死(SCD)一级预防的射血分数下降性的慢性心力衰竭(HFrEF)患者心功能及室性心律失常的影响。 方法 纳入2017年9月至2022年12月期间在云南省第一人民医院心血管内科住院的接受S/V治疗并植入ICD进行SCD一级预防的HFrEF患者。(1)统计患者随访12个月时S/V剂量,治疗3月、6月、12月时心脏彩超指标(LVEF、LVEDD、LAD);(2)ICD记录的室性心律失常事件及治疗情况,动态心电图指标:平均每小时室性早搏次数、全部窦性心搏RR间期的标准差(SDNN)及校正后的平均QT间期(QTc)。 结果 共纳入56例患者。(1)随访1 a时,S/V的平均用药剂量为94.6 mg,bid。(2)随访3月LVEF、LVEDD、LAD均较治疗前改善;随访6月LVEF、LVEDD、LAD较治疗3月时改善;随访12月LVEF、LVEDD、LAD较治疗6月时改善,差异均有统计学意义(P < 0.05)。(3)与随访1~6月相比较,随访7~12月患者室性心动过速/心室颤动(VT/VF)、非持续性室性心动过速(NSVT)、监测室速发作次数均减少,差异有统计学意义(P < 0.05)。(4)与治疗前相比较,随访1 a患者SDNN由(94.38±26.42) ms增加至(102.23±20.36) ms;平均QTc由(441.92±10.64) ms缩短到(411.46±6.00) ms,差异均有统计学意义(P < 0.05)。 结论 (1)植入ICD进行SCD一级预防的HFrEF患者服用S/V治疗的1 a内心脏结构及功能持续改善;(2)随访期间S/V减少了室性心律失常的发生。 -
关键词:
- 慢性心力衰竭 /
- 埋藏式心律转复除颤器 /
- 沙库巴曲缬沙坦 /
- 心功能 /
- 室性心律失常
Abstract:Objectives To investigate the effects of sacubitril/valsartan (S/V) on cardiac function and ventricular arrhythmias in patients with chronic heart failure with reduced ejection fraction(HFrEF)who underwent primary prevention of sudden cardiac death (SCD) after implantation of an implantable cardioverter defibrillator (ICD). Methods HFrEF patients who were hospitalized in the Cardiovascular Department of the First People’ s Hospital of Yunnan Province from September 2017 to December 2022 and received S/V treatment and ICD implantation for primary prevention of SCD were included. ① We calculated the S/V dose of patients at 12 months of follow-up, as well as cardiac ultrasound indicators (LVEF, LVEDD, LAD) at 3, 6, and 12 months of treatment; ② ICD was used to record ventricular arrhythmia events and treatment status, dynamic electro-cardiogram indicators: average number of ventricular premature beats per hour, standard deviation (SDNN) of all sinus rhythm RR intervals, and corrected average QT interval (QTc). Results A total of 56 patients were included. (1) At one-year follow-up, the average medication dose for S/V in all patients was 94.6 mg bid. (2) Following up for 3 months, LVEF, LVEDD, and LAD improved compared to before treatment (P < 0.05); LVEF, LVEDD, and LAD improved after 6 months of follow-up compared to 3 months of treatment (P < 0.05); LVEF, LVEDD, and LAD improved after 12 months of follow-up compared to 6 months of treatment (P < 0.05). (3) Compared with 1-6 months of follow-up, the incidence of VT/VF, NSVT and monitored ventricular brachytherapy decreased during 7-12 months of follow-up (P < 0.05).(4) Compared with before treatment, SDNN increased from (94.38±26.42)ms to (102.23±20.36)ms and average QTc decreased from (441.92±10.64)ms to (411.46±6.00)ms during 1-year follow-up(P < 0.05). Conclusions (1) For HFrEF patients implanted with ICD for primary prevention of SCD, their cardiac structure and function was continued to improve within one year of receiving S/V treatment; (2) S/V reduced the occurrence of ventricular arrhythmias during the follow-up period of this study. -
表 1 S/V的使用情况[n(%)]
Table 1. Usage of S/V[n(%)]
时间 剂量( mg,bid) 12.5 25 50 100 200 初始 1(1.79) 22(39.29) 26(46.43) 6(10.71) 1(1.79) 1 a 0(0.00) 2(3.57) 24(42.86) 20(35.71) 10(17.86) 表 2 随访期间LVEF、LVEDD、LAD改善情况表(
$ \bar x \pm s $ )Table 2. The improvement of LVEF、LVEDD、LAD during the follow-up period(
$ \bar x \pm s $ )指标 时间 数值 t P LVEF(%) 基线 27.61±5.88 3月 34.09±7.17 7.666 <0.001* 6月 38.22±9.46 8.310 <0.001* 1 a 41.87±10.81 7.408 <0.001* LVEDD(cm) 基线 6.91±0.74 3月 6.38±0.80 −7.838 <0.001* 6月 6.09±0.81 −5.765 <0.001* 1 a 5.75±0.83 −9.629 <0.001* LAD(cm) 基线 4.36±0.65 3月 4.15±0.60 −4.630 <0.001* 6月 3.98±0.59 −4.541 <0.001* 1 a 3.81±0.57 −5.600 <0.001* 注:LVEF:左心室射血分数,LVEDD:左心室舒张末期内径,LAD:左房内径,*P < 0.05。 表 3 心律失常事件
Table 3. Arrhythmic events
观察指标 1~6月 7~12月 z P VT/VF发作总次数(次/6月) 22 8 −2.325 0.020* ≥1次NSVT发作的患者人数(n) 21 13 −2.000 0.046* NSVT发作总次数(次/6月) 833 168 −3.791 <0.001* Monitored VT(>4 beats,次/6月) 115 67 −2.154 0.031* PVC(个/h) 13(2,36) 11(0,30) −1.773 0.076 注:VT/VF:非持续性室性心动过速,VT-Mon:监测室性心动过速,VT/VF: 室性心动过速/心室颤动,PVC:室性期前收缩。*P < 0.05。 表 4 随访1 a与治疗前SDNN与平均QTc比较(ms,
$ \bar x \pm s $ )Table 4. SDNN and mean QTc were compared after 1-year follow-up and before treatment(ms,
$ \bar x \pm s $ )时间 SDNN 平均QTc 治疗前 94.38±26.42 441.92±10.64 1 a 102.23±20.36 411.46±6.00 t 2.328 −3.128 P 0.031* 0.026* 注:SDNN:全部窦性心率RR间期的标准差,QTc:校正后的平均QT间期,*P < 0.05。 -
[1] Wang H,Chai K,Du M,et al. Prevalence and incidence of heart failure among urban patients in China: A national population-based analysis[J]. Circ Heart Fail,2021,14(10):e008406. doi: 10.1161/CIRCHEARTFAILURE.121.008406 [2] Murphy S P, Ibrahim N E, Januzzi J L Jr. Heart failure with reduced ejection fraction: A review. [J] JAMA, 2020 , 324(5): 488-504. [3] Tsao C W,Lyass A,Enserro D,et al. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction[J]. JACC Heart Fail,2018,6(8):678-685. doi: 10.1016/j.jchf.2018.03.006 [4] McMurray J J,Packer M,Desai A S,et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure[J]. N Engl J Med,2014,371(11):993-1004. doi: 10.1056/NEJMoa1409077 [5] Writing Committee Members; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA guideline for the management of heart failure[J]. J Card Fail,2022,28(5):e1-e167. doi: 10.1016/j.cardfail.2022.02.010 [6] Martens P,Nuyens D,Rivero-Ayerza M,et al. Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction[J]. Clin Res Cardiol,2019,108(10):1074-1082. doi: 10.1007/s00392-019-01440-y [7] Curtain J P,Jackson A M,Shen L,et al. Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF[J]. Eur J Heart Fail,2022,24(3):551-561. doi: 10.1002/ejhf.2419 [8] 张常莹,刘晓宇,李晓燕,等. 沙库巴曲缬沙坦对植入了心脏除颤器的心力衰竭患者室性心律失常发生的影响[J]. 中国心脏起搏与心电生理杂志,2021,35(04):305-309. doi: 10.13333/j.cnki.cjcpe.2021.04.005 [9] El-Battrawy I,Pilsinger C,Liebe V,et al. Impact of sacubitril/valsartan on the long-term incidence of ventricular arrhythmias in chronic heart failure patients[J]. J Clin Med,2019,8(10):1582. doi: 10.3390/jcm8101582 [10] Vicent L,Juárez M,Martín I,et al. Ventricular arrhythmic storm after initiating sacubitril/valsartan[J]. Cardiology,2018,139(2):119-123. doi: 10.1159/000486410 [11] Vicent L,Méndez-Zurita F,Viñolas X,et al. Clinical characteristics of patients with sustained ventricular arrhythmias after sacubitril/valsartan initiation[J]. Heart Vessels,2020,35(1):136-142. doi: 10.1007/s00380-019-01454-6 [12] Vicent L,Martínez-Sellés M. Can sacubitril/valsartan have a proarrhythmic effect in some high-risk patients?[J]. Cardiology,2019,143(1):34-35. [13] Yancy C W,Jessup M,Bozkurt B,et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America[J]. J Card Fail,2017,23(8):628-651. doi: 10.1016/j.cardfail.2017.04.014 [14] Hubers S A,Brown N J. Combined angiotensin receptor antagonism and neprilysininhibition[J]. Circulation,2016,133(11):1115-1124. doi: 10.1161/CIRCULATIONAHA.115.018622 [15] Levine Y C,Rosenberg M A,Mittleman M,et al. B-type natriuretic peptide is a major predictor of ventricular tachyarrhythmias[J]. Heart Rhythm,2014,11(7):1109-1116. doi: 10.1016/j.hrthm.2014.04.024 [16] Primessnig U,Deißler P M,Wakula P,et al. Effects of BNP and sacubitrilat/valsartan on atrial functional reserveand arrhythmogenesis in human myocardium[J]. Front Cardiovasc Med,2022,9:859014. doi: 10.3389/fcvm.2022.859014 [17] Wang Z,Taylor L K,Denney W D,et al. Initiation of ventricular extrasystoles by myocardial stretch in chronically dilated and failing canine left ventricle[J]. Circulation,1994,90(4):2022-2031. doi: 10.1161/01.CIR.90.4.2022 [18] Sarrias A,Bayes-Genis A. Is sacubitril/valsartan (Also) an antiarrhythmic drug?[J]. Circulation,2018,138(6):551-553. doi: 10.1161/CIRCULATIONAHA.118.034755 [19] Eiringhaus J,Wünsche C M,Tirilomis P,et al. Sacubitrilat reduces pro-arrhythmogenic sarcoplasmic reticulum Ca2+ leak in human ventricular cardiomyocytes of patients with end-stage heart failure[J]. ESC Heart Fail,2020,7(5):2992-3002. doi: 10.1002/ehf2.12918 [20] Zhou Y,Rui S,Tang S,et al. Exploration ofmechanisms of sacubitril/ valsartan in the treatment of cardiac arrhythmias using a network pharmacology approach[J]. Front Cardiovasc Med,2022,9:829484. doi: 10.3389/fcvm.2022.829484 [21] Herring M P,Jacob M L,Suveg C,et al. Feasibility of exercise training for the short-term treatment of generalized anxiety disorder: A randomized controlled trial[J]. Psychother Psychosom,2012,81(1):21-28. doi: 10.1159/000327898 [22] Bardy G H,Lee K L,Mark D B,et al. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter defibrillator for congestive heart failure[J]. N Engl J Med,2005,352(3):225-237. doi: 10.1056/NEJMoa043399 [23] Al-Zaiti S S,Pietrasik G,Carey M G,et al. The role of heart rate variability,heart rate turbulence,and deceleration capacity in predicting cause-specific mortality in chronic heart failure[J]. J Electrocardiol,2019,52:70-74. doi: 10.1016/j.jelectrocard.2018.11.006 [24] Turrini P,Corrado D,Basso C,et al. Dispersion of ventricular depolarization- repolarization: a noninvasive marker for risk stratification in arrhythmogenic right ventricular cardiomyopathy[J]. Circulation,2001,103(25):3075-3080. doi: 10.1161/01.CIR.103.25.3075 [25] Okin P M,Devereux R B,Howard B V,et al. Assessment of QT interval and QT dispersion for prediction of all-cause and cardiovascular mortality in American Indians: The Strong Heart Study[J]. Circulation,2000,101(1):61-66. doi: 10.1161/01.CIR.101.1.61 [26] Monzo L,Gaudio C,Cicogna F,et al. Impact of sacubitril/valsartan on implantable defibrillator eligibility in heart failure: a real-world experience[J]. Eur Rev Med Pharmacol Sci,2021,25(18):5690-5700. [27] Guerra F,Ammendola E,Ziacchi M,et al. Effect of sacubitril/valsartan on left ventricular ejection fraction and on the potential indication for implantable cardioverter defibrillator in primary prevention: the SAVE-ICD study[J]. Eur J Clin Pharmacol,2021,77(12):1835-1842. doi: 10.1007/s00228-021-03189-8