左西孟旦治疗慢性血栓栓塞性肺动脉高压并发右心衰竭患者的研究

徐杰; 黄冬冬; 赵慧; 孟芳芳; 徐本永; 马强; 赵勤华; 吴文汇

doi:10.16766/j.cnki.issn.1674-4152.004295

左西孟旦治疗慢性血栓栓塞性肺动脉高压并发右心衰竭患者的研究

doi: 10.16766/j.cnki.issn.1674-4152.004295

1.
连云港市立东方医院心内科，江苏连云港 222042
2.
同济大学附属上海市肺科医院肺循环科，上海 200433
3.
昆明市寻甸县第一人民医院PCCM科，云南昆明 655200

基金项目:

国家重点研发计划“常见病多发病防治研究”重点专项青年科学家项目 2023YFC2509500

上海市科学技术委员会自然科学基金项目 22ZR1452400

上海市浦江人才计划项目 22PJD064

上海市卫生健康委员会卫生行业临床研究专项青年项目 20204Y0384

上海市肺科医院临床研究项目 FKLY20005

上海市肺科医院临床研究项目 fk18003

中华国际医学交流基金会心血管多学科整合思维研究基金项目 2021LY0415

详细信息

通讯作者:
吴文汇，E-mail：wenhui5621006@126.com

中图分类号: R544.16 R541.6
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出版历程
- 收稿日期: 2024-09-16
- 网络出版日期: 2026-03-13

Study on levosimendan in the treatment of patients with chronic thromboembolic pulmonary hypertension complicated with right heart failure

1.
Department of Cardiology, Lianyungang Municipal Oriental Hospital, Lianyungang, Jiangsu 222042, China

摘要

摘要: 目的观察左西孟旦对并发右心衰竭的慢性血栓栓塞性肺动脉高压患者右心功能的改善作用及药物安全性。方法前瞻性选取2021年6月—2022年12月上海市肺科医院收治的54例慢性血栓栓塞性肺动脉高压并发右心衰竭患者，采用随机数字表法分为左西孟旦组(28例)和米力农组(26例)。2组患者在接受靶向药物和利尿等药物的基础上，分别加用左西孟旦或米力农。记录患者治疗前与治疗7 d后血压、心率、N末端B型利钠肽(NT-proBNP)等生物标志物，右心功能与结构等变化。结果左西孟旦治疗后患者NT-proBNP和总胆红素水平显著下降(P＜0.05)，动脉氧饱和度提高，超声心动图测得肺动脉收缩压、右房横径、右心室舒张末横径、三尖瓣环收缩期位移(TAPSE)和外侧三尖瓣环的收缩期峰值速度等参数均显著改善。与治疗前比较，米力农组治疗后TAPSE差异无统计学意义(P>0.05)，左西孟旦组治疗后TAPSE则显著升高(P＜0.05)。2种药物均可降低血压，但均未引起相关临床症状，且对肝肾功能均无明显影响(P>0.05)。结论左西孟旦能有效降低慢性血栓栓塞性肺动脉高压并发右心衰竭患者的NT-proBNP及胆红素水平，改善三尖瓣环收缩期位移，且安全性良好。
- 左西孟旦 /
- 慢性血栓栓塞性肺动脉高压 /
- 右心衰竭
Abstract: Objective To observe the effect and drug safety of levosimendan on improving the right heart function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) complicated by right heart failure (RHF). Methods Fifty-four patients diagnosed with CTEPH and RHF, admitted to the Department of Pulmonary Circulation in Shanghai Pulmonary Hospital Affiliated to Tongji University from June 2021 to December 2022 were prospectively included and randomly divided into two groups: levosimendan group (n=28) and milrinone group (n=26). Both groups received standard treatment for CTEPH and heart failure, including pulmonary hypertension targeted drugs, diuretics, and so on. In addition, levosimendan was administered intravenously in levosimendan group; milrinone was administered in the milrinone group. Key parameters such as blood pressure, heart rate, and N-terminal B-type natriuretic peptide (NT-proBNP), and changes in right heart function and structure were recorded before and 7 days after treatment. Results After treatment, the levosimendan group showed significantly reductions in NT-proBNP levels and total bilirubin levels (P < 0.05). Furthermore, improvements in arterial oxygen saturaion and echocardiographic parameters such as pulmonary artery systolic pressure, right atrial diameter, right ventricular end-diastolic diameter, tricuspid annular plane systolic excursion (TAPSE), and S' wave were observed. The increase in TAPSE after treatment was not significant in the milrinone group (P>0.05), while it was significantly elevated in the levosimendan group (P < 0.05). Both drugs were associated with reductions in systemic blood pressure, but no clinical symptoms due to hypotension were observed, and there were no significant impacts on liver and kidney function (P>0.05). Conclusion Levosimendan effectively reduces NT-proBNP and bilirubin levels, improves TAPSE, and enhances right heart function in patients with CTEPH and RHF, and demonstrating good safety.
- Levosimendan /
- Chronic thromboembolic pulmonary hypertension /
- Right heart failure

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表 1 2组CTEPH并发RHF患者一般资料比较

Table 1. Comparison of general data between the two groups of patients with CTEPH and concurrent RHF

组别	例数	性别[例(%)]		年龄 (x±s，岁)	BMI (x±s)
组别	例数	男性	女性	年龄 (x±s，岁)	BMI (x±s)
左西孟旦组	28	10(35.71)	18(64.29)	66.58±9.89	23.20±2.72
米力农组	26	9(34.62)	17(65.38)	62.96±8.23	22.10±2.88
统计量		2.000^a		1.456^b	1.443^b
P值		0.157		0.151	0.155
注：^a为χ²值，^b为t值。

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表 2 2组CTEPH并发RHF患者治疗前后尿酸比较(x±s, μmol/L)

Table 2. Comparison of uric acid between the two groups of patients with CTEPH and concurrent RHF before and after treatment (x±s, μmol/L)

组别	例数	治疗前	治疗后
左西孟旦组	28	471.86±149.87	464.27±122.63
米力农组	26	378.00±119.47	384.95±113.66
统计量		2.532^a	1.164^b
P值		0.014	0.350
注：^a为t值，^b为F值。

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表 3 2组CTEPH并发RHF患者治疗前后总胆红素、直接胆红素比较[M(P₂₅, P₇₅), mmol/L]

Table 3. Comparison of total bilirubin and direct bilirubin between the two groups of patients with CTEPH and concurrent RHF before and after treatment [M(P₂₅, P₇₅), nmmol/L]

组别	例数	总胆红素			直接胆红素
组别	例数	治疗前	治疗后	治疗前后差值	治疗前	治疗后	治疗前后差值
米力农组	26	15.35(13.90, 20.41)	15.60(12.64, 18.68)	-0.75(-4.96, -1.95)	5.95(5.11, 7.97)	5.00(4.02, 6.03)	-1.05(-3.01, -0.03)
左西孟旦组	28	20.05(18.16, 25.27)	17.71(15.42, 20.03)^a	-2.55(-6.98, -1.01)	7.55(6.76, 9.65)	6.30(5.52, 7.99)^a	-1.15(-2.70, -0.20)
Z值		4.282	-3.842	-1.004	-1.960	-2.074	-0.347
P值		0.039	0.063	0.315	0.050	0.038	0.729
注：与同组治疗前比较，^aP＜0.05。

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表 4 2组CTEPH并发RHF患者治疗前后血气分析与超声心动图指标比较(x±s)

Table 4. Comparison of blood gas analysis and echocardiographic indexes between the two groups of patients with CTEPH and concurrent RHF before and after treatment (x±s)

组别	例数	SaO₂(%)		PaO₂(mmHg)		PaCO₂(mmHg)		PASP(mmHg)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
左西孟旦组	19	90.64±4.34	93.81±3.42^b	64.10±18.70	73.06±19.27	33.33±7.42	35.76±3.44	90.64±4.34	93.81±3.42^b
米力农组	20	93.78±3.89	93.60±2.72	73.94±18.87	70.93±15.65	34.35±7.46	36.37±6.70	93.78±3.89	93.60±2.72
统计量		2.382^a	1.581^c	1.635^a	1.516^c	1.514^a	3.793^c	1.514^a	1.581^c
P值		0.022	0.158	0.111	0.182	0.670	0.003	0.138	0.160

组别	例数	RATD(cm)		RVEDD(cm)		TAPSE		S'(cm/s)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
左西孟旦组	19	5.02±1.02	4.07±0.95^b	4.80±0.82	4.11±0.96^b	1.56±0.30	1.94±0.36^b	10.07±2.10	12.46±3.30^b
米力农组	20	4.52±0.89	4.07±0.63	4.33±0.71	3.95±0.76	1.70±0.35	1.87±0.27	10.92±2.26	12.29±2.90
统计量		1.634^a	2.274^c	1.917^a	1.596^c	1.338^a	1.778^c	1.215^a	1.295^c
P值		0.111	0.999	0.063	0.154	0.189	0.105	0.232	0.285
注：^a为t值，^c为F值；与同组治疗前比较，^bP＜0.05。1 mmHg=0.133 kPa。仅纳入2组治疗前后血气分析和超声心动图资料完整的数据。

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表 5 2组CTEPH并发RHF患者治疗前后NT-proBNP比较[M(P₂₅, P₇₅), pg/mL]

Table 5. Comparison of NT-proBNP between the two groups of patients with CTEPH and concurrent RHF before and after treatment [M(P₂₅, P₇₅), pg/mL]

组别	例数	治疗前	治疗后	治疗前后差值
米力农组	26	1 851.00(1 369.75, 3 343.25)	676.70(203.10, 901.10)^a	-1 088.30(-1 682.07, -701.40)
左西孟旦组	28	2 027.50(1 068.25, 3 198.25)	356.00(119.40, 1 196.00)^a	-1 430.80(-2 791.75, -808.85)
Z值		-0.476	-0.224	-1.298
P值		0.634	0.823	0.194
注：与同组治疗前比较，^aP＜0.05。

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表 6 2组CTEPH并发RHF患者治疗前后安全性指标比较(x±s)

Table 6. Comparison of safety related indexes for evaluation between the two groups of patients with CTEPH and concurrent RHF before and after treatment (x±s)

组别	例数	收缩压(mmHg)		舒张压(mmHg)		心率(次/min)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
左西孟旦组	28	117.61±14.97	106.35±11.91^b	75.54±11.29	65.15±9.51^b	85.18±13.00	81.81±7.43
米力农组	26	121.38±18.92	108.35±12.41^b	74.12±10.77	66.12±9.40^b	85.69±10.30	78.81±8.11^b
统计量		0.815^a	0.604^c	0.472^a	0.377^c	0.159^a	1.419^c
P值		0.419	0.548	0.639	0.708	0.874	0.162

组别	例数	血红蛋白(g/L)		尿素氮(mmol/L)		肌酐(μmol/L)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
左西孟旦组	28	135.11±20.31	135.19±19.84	6.43±2.48	7.92±2.62^b	76.79±20.43	77.59±15.25
米力农组	26	128.58±21.86	123.42±19.56^b	6.53±1.74	6.77±2.76	71.81±16.30	74.35±18.02
统计量		1.138^a	2.193^c	0.170^a	1.571^c	0.985^a	0.715^c
P值		0.260	0.033	0.865	0.122	0.329	0.478
注：^a为t值，^c为F值。与同组治疗前比较，^bP＜0.05。

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表 7 2组CTEPH并发RHF患者治疗前后谷丙转氨酶比较[M(P₂₅, P₇₅), U/L]

Table 7. Comparison of alanine aminotransferase levels between the two groups of patients with CTEPH and concurrent RHF before and after treatment [M(P₂₅, P₇₅), U/L]

组别	例数	治疗前	治疗后	治疗前后差值
米力农组	26	19.00(15.44, 33.27)	17.00(14.65, 29.12)	-2.00(-14.21，9.27)
左西孟旦组	28	15.00(13.37, 23.48)	16.00(16.35, 25.86)	3.00(-1.26，6.61)
Z值		-1.655	-0.117	-1.232
P值		0.098	0.907	0.218

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