Effect of sacubitril/valsartan on clinical outcomes in patients with persistent atrial fibrillation undergoing catheter ablation: a single-center cohort study using propensity score matching
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摘要: 目的 探讨沙库巴曲缬沙坦对持续性心房颤动(房颤)导管消融术后中远期预后的影响。方法 回顾性分析我院2019年1月—2022年11月因持续性房颤行导管消融术的患者210例，分为沙库巴曲缬沙坦组(ARNI组，93例)和ACEI/ARB组(117例)。采用1∶1倾向性匹配评分，比较匹配后两组手术相关参数(手术时间、术式、单圈隔离率、左心房基质、手术前后左心房脉冲压、平均左心房压)、手术并发症、复合终点事件和左心功能指标的差异。结果 倾向性评分后ARNI组和ACEI/ARB组共有72对匹配成功，两组手术时间、单圈隔离率、电复律率、手术前后左心房脉冲压、平均左心房压和术后并发症比较均差异无统计学意义。与ACEI/ARB组相比，ARNI组术后6个月的房颤复发率显著降低(25.00% vs 11.11%，P=0.048)，心力衰竭加重比例明显减少(11.11% vs 2.78%，P=0.044)；两组心血管死亡率和再住院率比较差异无统计学意义。亚组分析中，基质标测显示，两组存在低电压区域比例比较差异无统计学意义(65.28% vs 72.22%)；与ACEI/ARB组相比，ARNI组存在左心房基质不良的患者6个月房颤复发率显著降低(33.33% vs 12.00%，P=0.017)。6个月左心功能和生化指标随访发现，与ACEI/ARB组相比，ARNI组左心房直径(LAD)显著降低[(43.08±6.54) mm vs (40.71±4.50) mm，P=0.017]，N末端脑钠肽前体(NT-proBNP)水平显著降低[333.00(121.00，870.00) pg/mL vs 195.00(88.50，429.50) pg/mL，P=0.018]，纽约心功能分级显著减小(P=0.025)。多因素logistic回归分析显示，沙库巴曲缬沙坦为左心房基质不良的持续性房颤患者导管消融术后6个月无房颤复发的保护性因素(OR=0.291，95%CI：0.094~0.904，P=0.033)。结论 沙库巴曲缬沙坦可有效减少持续性房颤导管消融术后6个月的复发率，改善其左心功能，获益可能主要来自对左心房不良基质的改善作用。Abstract: Objective To investigate the effect of sacubitril/valsartan on the mid- and long-term prognosis in patients with persistent atrial fibrillation undergoing catheter ablation.Methods A retrospective analysis encompassed 210 patients who underwent catheter ablation for persistent atrial fibrillation at our medical facility between January 2019 and November 2022. Participants were categorized into two groups: the sacubitril/valsartan group (ARNI group, n=93) and the ACEI/ARB group (n=117). A 1∶1 propensity score matching method was employed to compare discrepancies in procedure-associated parameters (procedure duration, operative approach, single-loop isolation rate, left atrial substrate, pre- and post-surgery left atrial pulse pressure, mean left atrial pressure), complications, composite endpoint events, and indicators of left heart function between the two cohorts.Results After the application of propensity score matching, 72 matched pairs were successfully included in the study. No statistically significant differences were observed in terms of procedure duration, single-loop isolation rate, instances of electrical resuscitation, pre- and post-operative left atrial pulse pressures, mean left atrial pressure, and postoperative complications between the two groups. In comparison to the ACEI/ARB group, the ARNI group exhibited a significantly reduced recurrence rate of atrial fibrillation (25.00% vs 11.11%, P=0.048) and a decreased occurrence of heart failure exacerbation (11.11% vs 2.78%, P=0.044) after 6 months operation. No noteworthy disparities were detected in cardiovascular mortality and readmission rates between the two groups. Subgroup analysis indicated no substantial distinction in the proportion of low voltage areas in substrate mapping between the two groups (65.28% vs 72.22%). Furthermore, individuals with poor left atrial substrate within the ARNI group demonstrated a significantly lower 6-month atrial fibrillation recurrence rate in comparison to the ACEI/ARB group (33.33% vs 12.00%, P=0.017). Six months follow-up showed that left atrial diameter (LAD) [(43.08 ± 6.54) mm vs (40.71 ± 4.50) mm, P=0.017], NT-proBNP levels [333.00 (121.00, 870.00) pg/mL vs 195.00 (88.50, 429.50) pg/mL, P=0.018], and NYHA grade (P=0.025) were significantly reduced in the ARNI group compared with those in the ACEI/ARB group. Multiple logistic regression analysis showed that sacubitril/valsartan was a protective factor for freedom from atrial arrhythmia recurrent 6 months after catheter ablation in patients with persistent atrial fibrillation with poor left atrial substrate (OR=0.291, 95%CI 0.094-0.904, P=0.033).Conclusion Sacubitril/valsartan exhibits the potential to effectively mitigate the 6-month recurrence rate and enhance left heart function in patients with persistent atrial fibrillation undergoing catheter ablation. These benefits are likely derived from the improvement of poor left atrial atrial substrate.
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表 1 PSM前后ACEI/ARB组和ARNI组基线资料的比较
Table 1. Baseline data before and after PSM in the ACEI/ARB group and ARNI group
例(%), X±S, M(P25, P75) 项目 匹配前 χ2/Z/t P 匹配后 χ2/Z/t P ACEI/ARB组(117例) ARNI组(93例) ACEI/ARB组(72例) ARNI组(72例) 年龄/岁 68.90±9.06 70.37±9.03 1.407 0.161 70.47±6.90 70.08±8.88 0.031 0.975 男性 65(55.56) 53(56.99) 0.043 0.889 41(56.94) 41(56.94) 0.000 1.000 BMI/(kg/m2) 24.80 (22.98，26.76) 25.61 (22.43，28.03) -1.019 0.308 24.61 (22.86，26.17) 25.66 (22.72，28.11) -1.822 0.068 高血压 71(60.68) 73(78.49) 7.627 0.007 51(70.83) 53(73.61) 0.138 0.853 糖尿病 31(26.50) 29(31.18) 0.558 0.539 21(29.17) 16(22.22) 0.909 0.446 冠心病 18(15.38) 27(29.03) 5.732 0.019 13(18.06) 13(18.06) 0.000 1.000 COPD 12(10.26) 6(6.45) 0.957 0.458 6(8.33) 4(5.56) 0.430 0.745 吸烟 26(22.22) 23(24.73) 0.182 0.743 17(23.61) 17(23.61) 0.000 1.000 饮酒 12(10.26) 12(12.90) 0.359 0.663 7(9.72) 8(11.11) 0.074 1.000 ALT/(U/L) 20.00 (14.00，29.00) 18.00 (13.50，26.00) -1.414 0.254 19.00 (14.00，27.00) 17.00 (13.00，26.75) -1.078 0.281 Cr/(μmol/L) 69.10 (57.45，88.42) 63.52 (51.43，89.95) -1.317 0.188 78.00 (66.33，89.98) 79.80 (70.53，91.08) -0.947 0.344 Ccr/(mL/min) 66.94 (56.55，86.22) 66.01 (52.78，80.43) -0.872 0.383 67.60 (51.74，82.51) 66.96 (52.86，87.61) -0.260 0.795 NT-proBNP/(pg/mL) 535.00 (290.00，1 241.00) 824.00 (456.50，1 475.00) -1.995 0.046 556.50 (290.00，1 410.00) 843.00 (439.50，1 502.50) -1.307 0.191 CHA2DS2-VASc评分 3(2，4) 4(3，5) -2.337 0.019 3(3，4) 3(2.25，4) -0.342 0.732 NYHA分级 2(1，3) 2(2，3) -1.750 0.080 2(1，3) 2(1.25，3) -0.239 0.811 LAD/mm 44.00 (42.00，48.00) 44.00(42.00，48.00) -0.665 0.506 45.00(42.25，48.00) 44.00(41.25，48.00) -1.070 0.284 LVEDD/mm 49.00 (46.00，52.00) 50.00 (46.00，52.50) -0.016 0.987 49.00 (45.00，51.75) 48.00 (45.00，51.00) -1.136 0.256 LVEF/% 59.00 (53.00，63.00) 56.00 (45.00，61.00) -2.499 0.012 57.50 (48.50，62.00) 56.00 (53.00，62.00) -0.342 0.732 CO/(L/min) 5.39 (4.53，6.27) 5.07 (4.09，6.07) -1.699 0.089 5.23 (4.50，6.30) 5.07 (4.05，5.93) -1.820 0.069 TR分级 1(1，1) 1(1，1) -0.079 0.937 1(1，1) 1(1，1.75) 0.000 1.000 MR分级 1(1，1) 1(0，1) -0.089 0.929 1(0，1) 1(0，1) -0.086 0.932 ALT；谷丙转氨酶；Cr：血清肌酐。 
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表 2 ACEI/ARB组和ARNI组手术相关参数比较
Table 2. Operation-related parameters in the ACEI/ARB group and ARNI group
例(%), X±S, M(P25, P75) 参数 ACEI/ARB组(72例) ARNI组(72例) χ2/Z/t P 手术时间/min 265.00(217.50，313.75) 272.00(215.50，315.00) -0.334 0.739 右侧单圈隔离率 39(54.17) 43(59.72) 0.453 0.614 左侧单圈隔离率 38(52.78) 35(48.61) 0.250 0.739 电复律率 54(75.00) 51(70.83) 0.316 0.708 术中左心房30%以上面积存在基质不良 51(70.83) 50(69.44) 0.033 1.000 术中行基质改良 47(65.28) 52(72.22) 0.808 0.472 后壁BOX术式 58(80.56) 61(84.72) 0.436 0.661 线性消融 28(38.89) 32(44.44) 0.457 0.612 术前LAPmean/mmHg 10.53±5.27 10.98±4.37 0.399 0.691 术毕LAPmean/mmHg 13.53±4.94 13.17±5.37 -0.275 0.784 术前LApp/mmHg 11.31±5.32 10.42±4.23 -0.791 0.432 术毕LApp/mmHg 12.96±6.68 11.74±5.08 -0.843 0.402
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表 3 ACEI/ARB组和ARNI组术后并发症和复合终点事件比较
Table 3. Postoperative complications and composite endpoint events in the ACEI/ARB group and ARNI group
例(%) 事件 ACEI/ARB组(72例) ARNI组(72例) χ2 P 心包填塞 1(1.39) 0 1.000 心房食道瘘 0 0 1.000 消化道出血 1(1.39) 0 1.000 腹股沟区血肿 3(4.17) 4(5.56) 1.000 动静脉瘘 0 0 1.000 假性动脉瘤 0 0 1.000 脑栓塞 1(1.39) 0 1.000 低血压 4(5.56) 8(11.11) 1.455 0.367 感染 3(4.17) 2(2.78) 1.000 6个月复合终点事件 房颤复发 18(25.00) 8(11.11) 3.921 0.048 心衰加重 8(11.11) 2(2.78) 0.044 心血管死亡 1(1.39) 0 1.000 再住院 7(9.72) 3(4.17) 0.080
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表 4 左心房基质不良患者左心房压和6个月复合终点事件
Table 4. Left atrial pressure and 6-month composite endpoint events in patients with poor left atrial substrate
例(%), X±S 项目 ACEI/ARB组(51例) ARNI组(50例) χ2 P 术前LAPmean/mmHg 11.34±5.29 10.75±4.76 0.436 0.665 术毕LAPmean/mmHg 10.56±7.63 11.82±6.99 0.641 0.524 术前LApp/mmHg 12.00±5.52 9.82±4.65 1.600 0.115 术毕LApp/mmHg 10.96±8.75 10.76±6.59 -0.097 0.923 6个月复合终点事件 房颤复发 17(33.33) 6(12.00) 6.534 0.017 心衰加重 7(13.73) 2(4.00) 0.160 心血管死亡 1(1.96) 0 1.000 再住院 6(11.76) 3(6.00) 0.487
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表 5 左心房基质不良房颤患者6个月房颤复发的多因素logistic回归分析
Table 5. Risk factors of 6-month recurrence of atrial fibrillation in patients with poor left atrial substrate analyzed by multivariate logistic regression analysis
项目 B SE Wald df P OR 95%CI 年龄 -0.051 0.040 1.641 1 0.200 0.950 0.878~1.028 性别 0.009 0.581 0.000 1 0.987 1.009 0.323~3.152 LAD 0.137 0.053 6.742 1 0.009 1.147 1.034~1.271 沙库巴曲缬沙坦 -1.233 0.578 4.558 1 0.033 0.291 0.094~0.904 ln_NT-proBNP 0.239 0.313 0.583 1 0.445 1.270 0.688~2.347 LVEF 0.014 0.032 0.194 1 0.660 1.014 0.952~1.081
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表 6 ACEI/ARB组和ARNI组术后6个月心功能情况比较
Table 6. Cardiac function indexes 6 months after surgery in the ACEI/ARB group and ARNI group
例(%), X±S, M(P25, P75) 项目 ACEI/ARB组(72例) ARNI组(72例) χ2/Z/t P LAD/mm 43.08±6.54 40.71±4.50 2.419 0.017 LVEDD/mm 49.78±5.47 48.84±4.50 1.065 0.289 LVEF/% 59.19±6.68 60.17±5.07 -0.950 0.344 CO/(L/min) 5.37±1.47 5.27±1.32 0.415 0.678 TR分级 1(0，1) 1(0，1) -0.397 0.692 MR分级 1(0，1) 1(0，1) -0.297 0.767 NT-proBNP/(pg/mL) 333.00(121.00，870.00) 195.00(88.50，429.50) -2.369 0.018 NYHA分级 1(1，1) 1(1，1) -2.247 0.025
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