三维超声评价沙库巴曲缬沙坦治疗慢性心力衰竭疗效的研究
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摘要
目的:利用三维超声评价射血分数减低慢性心力衰竭(HFrEF)患者应用沙库巴曲缬沙坦(LCZ696)治疗6个月后左心室协调性及左心房功能变化。方法:25例心功能Ⅲ-Ⅳ级左心室射血分数≤40%的慢性心力衰竭患者纳入本研究。应用实时三维超声(RT-3DE)分析服用LCZ696初始及服药后6个月左心室舒张末容积(LVEDV-3D),左心室整体射血分数(GLVEF-3D)变化。分析左心室各节段到达最小收缩容积时间(Tmsv)标准差和最大差值被标准化为心动周期的百分比(Tmsv 16-SD%、Tmsv 12-SD%、Tmsv 6-SD%、Tmsv 16-Dif%、Tmsv 12-Dif%、Tmsv6-Dif%)作为评价左心室收缩同步性的指标。二维超声心动图测量左心房最大容积指数(LAVImax),多普勒超声测定舒张早期跨二尖瓣血流速度E峰与二尖瓣环组织速度e’的比值(E/e’)作为评价左心室充盈压指标。结果:25例患者服用沙库巴曲缬沙坦6个月后LVEDV-3D、GLVEF-3D、LAVImax及E/e’较前明显减小(P<0. 05),Tmsv 16-SD%、Tmsv 12-SD%、Tmsv 6-SD%、Tmsv 16-Dif%、Tmsv 12-Dif%、Tmsv6-Dif%均明显缩短(P<0. 05),氨基末端脑钠肽前体(NT-proBNP)较前明显降低(P<0. 05)。结论:LCZ696可显著改善HFrEF患者的左心室协调性及心房辅助功能,从而改善左心室功能。
Objective: using real-time three-dimensional echocardiography(RT-3 DE) to assess the left ventricle synchrony in patients with heart failure with reduced ejection fraction(HFrEF) after sacubitril/valsartan treatment. Methods: We included 25 symptomatic patients with HFrEF(left ventricular ejection fraction≤40%) and New York Heart Association(NYHA) classⅢ/Ⅳ and N-terminal pro-BNP(NT-proBNP) ≥400 pg/ml. All the patients underwent examinations with 2 D and Full volume RT-3 DE at baseline and 6 month after taking Sacubitril/Valsartan via TITRATION. With RT-3 DE the left ventricle end-diastolic volume(LVEDV-3 D) and global eject fraction(GLVEF-3 D) were acquired. Analysis of the difference(Dif) and stand deviation(SD) of the time to the point with minimal systolic volume(Tmsv) in 16, 12, and 6 segments were performed and adjusted by interval R-R interval(Tmsv SD%, Tmsv Dif%). The maximal Left atrial volume index were measured with 2 dimensional echocardiography. The ratio of trans-mitral flow velocity of early diastolic filling wave(E) to tissure doppler myocardial velocity e'(E/e') were acquired. Results: After 6 month initiation of LCZ696, the Tmsv 16-SD%,Tmsv 16-Dif%,Tmsv 12-SD%,Tmsv 12-Dif%, Tmsv6-SD%, and Tmsv6-Dif% decerased significantly(P<0.05). The LVEDV-3 D, GLVEF-3 D, LAVImax, E/e', NT-proBNP also reduced significantly(P<0.05) 6 month later(P<0.05) compared with baseline. Conclusions: LCZ696 can improve the left ventricle systolic synchrony in HFrEF, decrease the filling pressure of left ventricle and improve the left ventricle function.
Objective: using real-time three-dimensional echocardiography(RT-3 DE) to assess the left ventricle synchrony in patients with heart failure with reduced ejection fraction(HFrEF) after sacubitril/valsartan treatment. Methods: We included 25 symptomatic patients with HFrEF(left ventricular ejection fraction≤40%) and New York Heart Association(NYHA) classⅢ/Ⅳ and N-terminal pro-BNP(NT-proBNP) ≥400 pg/ml. All the patients underwent examinations with 2 D and Full volume RT-3 DE at baseline and 6 month after taking Sacubitril/Valsartan via TITRATION. With RT-3 DE the left ventricle end-diastolic volume(LVEDV-3 D) and global eject fraction(GLVEF-3 D) were acquired. Analysis of the difference(Dif) and stand deviation(SD) of the time to the point with minimal systolic volume(Tmsv) in 16, 12, and 6 segments were performed and adjusted by interval R-R interval(Tmsv SD%, Tmsv Dif%). The maximal Left atrial volume index were measured with 2 dimensional echocardiography. The ratio of trans-mitral flow velocity of early diastolic filling wave(E) to tissure doppler myocardial velocity e'(E/e') were acquired. Results: After 6 month initiation of LCZ696, the Tmsv 16-SD%,Tmsv 16-Dif%,Tmsv 12-SD%,Tmsv 12-Dif%, Tmsv6-SD%, and Tmsv6-Dif% decerased significantly(P<0.05). The LVEDV-3 D, GLVEF-3 D, LAVImax, E/e', NT-proBNP also reduced significantly(P<0.05) 6 month later(P<0.05) compared with baseline. Conclusions: LCZ696 can improve the left ventricle systolic synchrony in HFrEF, decrease the filling pressure of left ventricle and improve the left ventricle function.
引文
[1] Zucker IH, Xiao L, Haack KK.The central renin-angiotensin system and sympathetic nerve activity in chronic heart failure. Clin Sci (Lond), 2014,126(10):695-706.
[2] Vardeny O, Miller R, Solomon SD. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail, 2014,2(6):663-670.
[3] McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med, 2014,371(11):993-1004.
[4] Cho GY, Park WJ, Han SW, et al. Myocardial systolic synchrony measured by Doppler tissue imaging as a role of predictor of left ventricular ejection fraction improvement in severe congestive heart failure. J Am Soc Echocardiogr, 2004,17(12):1245-1250.
[5] Kusaka H, Sueta D, Koibuchi N, et al. LCZ696 Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Injury More Than Valsartan Alone. Am J Hypertens, 2015, 28(12):1409-1417.
[6] Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet,2012,380(9851):1387-1395.
[7] Senni M, McMurray JJ, Wachter R, et al. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail,2016,18(9):1193-1202.
[8] Packer M, McMurray JJ, Desai AS, et al. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation, 2015,131(1):54-61.
[9] von Lueder TG, Sangaralingham SJ, Wang BH, et al. Renin-angiotensin blockade combined with natriuretic peptide system augmentation: novel therapeutic concepts to combat heart failure. Circ Heart Fail, 2013,6(3):594-605.
[10] 师彦虎,杨玲,杨晓瑜. 血浆N末端-脑钠肽前体在舒张性心力衰竭中的意义. 心肺血管病杂志,2017,36(10):829-831.
[11] Ojala T, Mathur S, Vatanen A, et al. Repeatability and agreement of real time three- dimensional echocardiography measurements of left ventricular mass and synchrony in young patients. Echocardiography, 2015,32(3):522-527.
[12] Driessen MM, Kort E, Cramer MJ, et al. Assessment of LV ejection fraction using real-time 3D echocardiography in daily practice: direct comparison of the volumetric and speckle tracking methodologies to CMR. Neth Heart,2014,22(9):383-390.
[13] Kompa AR, Lu J, Weller TJ, et al. Angiotensin receptor neprilysin inhibition provides superior cardioprotection compared to angiotensin converting enzyme inhibition after experimental myocardial infarction. Int J Cardiol,2018,258:192-198.
[14] von Lueder TG, Wang BH, Kompa AR, et al. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy.Circ Heart Fail,2015,8(1):71-78.
[15] Marchese P, Malavasi V, Rossi L, et al. Indexed left atrial volume is superior to left atrial diameter in predicting nonvalvular atrial fibrillation recurrence after successful cardioversion: a prospective study. Echocardiography, 2012,29(3):276-284.
[16] Jhund PS, Claggett B, Packer M, et al. Independence of the blood pressure lowering effect and efficacy of the angiotensin receptor neprilysin inhibitor, LCZ696, in patients with heart failure with preserved ejection fraction: an analysis of the PARAMOUNT trial. Eur J Heart Fail, 2014,16(6):671-677.
[17] Senni M, McMurray JJV, Wachter R, et al. Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study. Eur J Heart Fail, 2018,20(3):491-500.
[18] Solomon SD, Rizkala AR, Gong J, et al. Angiotensin receptor neprilysin inhibition in heart failure with preserved ejection fraction: rationale and design of the PARAGON-HF trial. JACC Heart Fail, 2017,5(7):471-482.
[2] Vardeny O, Miller R, Solomon SD. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail, 2014,2(6):663-670.
[3] McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med, 2014,371(11):993-1004.
[4] Cho GY, Park WJ, Han SW, et al. Myocardial systolic synchrony measured by Doppler tissue imaging as a role of predictor of left ventricular ejection fraction improvement in severe congestive heart failure. J Am Soc Echocardiogr, 2004,17(12):1245-1250.
[5] Kusaka H, Sueta D, Koibuchi N, et al. LCZ696 Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Injury More Than Valsartan Alone. Am J Hypertens, 2015, 28(12):1409-1417.
[6] Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet,2012,380(9851):1387-1395.
[7] Senni M, McMurray JJ, Wachter R, et al. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail,2016,18(9):1193-1202.
[8] Packer M, McMurray JJ, Desai AS, et al. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation, 2015,131(1):54-61.
[9] von Lueder TG, Sangaralingham SJ, Wang BH, et al. Renin-angiotensin blockade combined with natriuretic peptide system augmentation: novel therapeutic concepts to combat heart failure. Circ Heart Fail, 2013,6(3):594-605.
[10] 师彦虎,杨玲,杨晓瑜. 血浆N末端-脑钠肽前体在舒张性心力衰竭中的意义. 心肺血管病杂志,2017,36(10):829-831.
[11] Ojala T, Mathur S, Vatanen A, et al. Repeatability and agreement of real time three- dimensional echocardiography measurements of left ventricular mass and synchrony in young patients. Echocardiography, 2015,32(3):522-527.
[12] Driessen MM, Kort E, Cramer MJ, et al. Assessment of LV ejection fraction using real-time 3D echocardiography in daily practice: direct comparison of the volumetric and speckle tracking methodologies to CMR. Neth Heart,2014,22(9):383-390.
[13] Kompa AR, Lu J, Weller TJ, et al. Angiotensin receptor neprilysin inhibition provides superior cardioprotection compared to angiotensin converting enzyme inhibition after experimental myocardial infarction. Int J Cardiol,2018,258:192-198.
[14] von Lueder TG, Wang BH, Kompa AR, et al. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy.Circ Heart Fail,2015,8(1):71-78.
[15] Marchese P, Malavasi V, Rossi L, et al. Indexed left atrial volume is superior to left atrial diameter in predicting nonvalvular atrial fibrillation recurrence after successful cardioversion: a prospective study. Echocardiography, 2012,29(3):276-284.
[16] Jhund PS, Claggett B, Packer M, et al. Independence of the blood pressure lowering effect and efficacy of the angiotensin receptor neprilysin inhibitor, LCZ696, in patients with heart failure with preserved ejection fraction: an analysis of the PARAMOUNT trial. Eur J Heart Fail, 2014,16(6):671-677.
[17] Senni M, McMurray JJV, Wachter R, et al. Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study. Eur J Heart Fail, 2018,20(3):491-500.
[18] Solomon SD, Rizkala AR, Gong J, et al. Angiotensin receptor neprilysin inhibition in heart failure with preserved ejection fraction: rationale and design of the PARAGON-HF trial. JACC Heart Fail, 2017,5(7):471-482.