门脉高压相关性肺动脉高压临床分析

doi:10.3877/cma.j.issn.1674-6902.2020.01.006

目的

探讨门脉高压相关性肺动脉高压(PoPH)的临床特点和经胸超声心动测量右心房线性指数同心功能或肝功能的关系。

方法

选择首都医科大学附属北京安贞医院呼吸与危重症医学科2012年1月至2018年12月收治的门脉高压相关性肺动脉高压患者11例，回顾性分析11例患者的临床症状和体征、影像检查资料、实验室检查结果、右心导管检查测算数据、心肺功能测定结果、治疗和转归等。所有患者进行NHYA分级与mMRC量表评分。实验室检查结果包括血常规、生化、凝血、B型脑钠肽、动脉血气分析等，用以计算Child-Pugh及MELD等评分。

结果

11例中男性5例，女性6例，肝硬化门脉高压者9例，非肝硬化门脉高压者2例，追溯病史发现肺动脉高压距离门脉高压诊断时间为0.5至19年，中位时间5年。NHYA分级与改良MRC呼吸困难(mMRC)评分存在正相关关系[r＝0.9608，95%CI(0.8460，0.9896), P<0.0001]，与Child-Pugh评分无相关关系。右心房线性指数与BNP存在相关关系[r＝0.7930，95%CI(0.3684，0.9439)，P＝0.0036]，与终末期肝脏疾病评分(MELD)无相关关系。所有患者均存在不同程度的低氧血症，肺泡-动脉血氧分压差值较预计值升高(t＝3.669，P＝0.0018)，具有显著性差异。就诊时已出现右心功能严重下降的患者预后差。

结论

PoPH患者多以运动性呼吸困难为首发症状，与心功能严重程度相关，与肝功能无显著线性关系，临床随访不能只评价肝功能。随访中超声心动图中右心房径线的测量有助于心功能评估。尽早干预肺动脉压力的升高，有助于右心功能的保护，改善预后。

关键词: 肝硬化, 门脉高压, 肺动脉高压, 临床分析

Objective

To explore the clinical features of portopulmonary hypertension (PoPH) and the relationship between the right atrial liner index and the heart function.

Methods

Eleven patients were diagnosed as PoPH in Beijing Anzhen Hospital, Capital Medical University in China from January 2012 to December 2018. The general information, clinical manifestation, medical imaging results, laboratory tests, right heart catheter data, cardiopulmonary exercise test, treatment and prognosis of the patients were analyzed retrospectively. The laboratory tests included the complete blood count, serum chemistry profile, coagulation function, B type brain natriuretic peptide, and arterial blood gas analysis, which were used to calculate the scales of Child-Pugh and Model for the end-stage liver disease (MELD).

Results

The patients (5 males and 6 females) aged from 29 to 85 years. Hepatocirrhosis was found in 9 cases and non-hepatocirrhosis was found in 2 cases. According to the medical history, the onset time of pulmonary hypertension was 0.5-19 years after portal vein hypertension, with the median time of 5 years. The scale of New York Heart Association (NYHA) was positively correlated with the modified Medical Research Council (mMRC) scale [r=0.9608, 95%CI (0.8460, 0.9896), P<0.0001], however, it had no correlation with Child-Pugh scale. The correlation coefficient was 0.7930 between the right atrial linear index and the BNP with the 95%CI of 0.3684-0.9439 (P=0.0036). However, no significant difference was found between the right atrial linear index and the MELD. All the patients suffered from hypoxemia. The alveolar-arterial oxygen differential pressure (PA-aO₂) was higher significantly than the predicted value (t=3.669, P=0.0018). The patients with severe heart failure had poor prognosis.

Conclusion

The patients with PoPH are more likely to experience exertional dyspnea, which is associated with the degree of the heart dysfunction. And it is a fact that all the patients have hypoxemia. Therefore, the clinical decision for the patients with PoPH should not be made only in the consideration of the liver function. The right atrial linear index is an available option to follow such patients.

Key words: Liver cirrhosis, Hypertension, portal, Pulmonary hypertension, Clinical analysis

表1 POPH患者的基本情况及临床特征(n＝11)

项　目		单位	数值
年龄		岁	55(47～74)
男性		[n(%)]	4(36.4)
女性		[n(%)]	7(73.6)
体重		kg	62.36±8.27
身高		m	1.66±0.10
BMI		kg/m²	22.63±2.41
原发性肝脏疾病
	病毒性肝炎肝硬化	[n(%)]	7(63.63)
	酒精性肝炎肝硬化	[n(%)]	1(9.09)
	自身免疫性肝炎肝硬化	[n(%)]	1(9.09)
	非原发肝脏疾病
	布加综合征	[n(%)]	1(9.09)
	门静脉闭锁	[n(%)]	1(9.09)
NYHA分级
	Ⅱ级	[n(%)]	6(54.55)
	Ⅲ级	[n(%)]	2(18.18)
	Ⅳ级	[n(%)]	3(27.27)
mMRC评分
	1分	[n(%)]	1(9.09)
	2分	[n(%)]	5(45.45)
	3分	[n(%)]	2(18.18)
	4分	[n(%)]	3(27.27)
Child-pugh分级
	A级	[n(%)]	2(18.18)
	B级	[n(%)]	7(63.63)
	C级	[n(%)]	2(18.18)

表1 POPH患者的基本情况及临床特征(n＝11)

项　目		单位	数值
年龄		岁	55(47～74)
男性		[n(%)]	4(36.4)
女性		[n(%)]	7(73.6)
体重		kg	62.36±8.27
身高		m	1.66±0.10
BMI		kg/m²	22.63±2.41
原发性肝脏疾病
	病毒性肝炎肝硬化	[n(%)]	7(63.63)
	酒精性肝炎肝硬化	[n(%)]	1(9.09)
	自身免疫性肝炎肝硬化	[n(%)]	1(9.09)
	非原发肝脏疾病
	布加综合征	[n(%)]	1(9.09)
	门静脉闭锁	[n(%)]	1(9.09)
NYHA分级
	Ⅱ级	[n(%)]	6(54.55)
	Ⅲ级	[n(%)]	2(18.18)
	Ⅳ级	[n(%)]	3(27.27)
mMRC评分
	1分	[n(%)]	1(9.09)
	2分	[n(%)]	5(45.45)
	3分	[n(%)]	2(18.18)
	4分	[n(%)]	3(27.27)
Child-pugh分级
	A级	[n(%)]	2(18.18)
	B级	[n(%)]	7(63.63)
	C级	[n(%)]	2(18.18)

图1 右心房线性指数、BNP及MELD评分的多元相关分析，*：P<0.05

表2 PoPH患者超声心动图结果、MELD评分及BNP数值

序	右心房短径mm	右心房长径mm	右心房面积cm²	TRVa cm/s	估测sPAP mmHg	BSA m²	右心房线性指数cm/m²	MELD评分	BNP pg/ml
1	39	56	21.8	480	100	1.62	3.46	11	150
2	52	59	30.7	347	55	1.72	3.44	14	162
3	57	64	36.5	417	86	1.98	3.23	11^a	374
4	41	52	21.3	366	79	1.47	3.54	9	128
5	43	53	22.8	379	63	1.60	3.31	13	969
6	51	54	27.5	436	85	1.77	3.05	13	72
7	50	64	32.0	342	85	1.53	4.20	11	1 570
8	57	66	37.6	426	63	1.56	4.22	10	1 788
9	50	60	30.0	367	64	1.80	3.33	11	466
10	54	67	36.2	370	67	1.72	3.90	9	1 219
11	44	57	25.1	290	42	1.85	3.08	12	686
	49	59	29.2	383	72	1.69	3.52	11	689
SD	6	5	60.0	54	13	0.15	0.41	2	613

表2 PoPH患者超声心动图结果、MELD评分及BNP数值

序	右心房短径mm	右心房长径mm	右心房面积cm²	TRVa cm/s	估测sPAP mmHg	BSA m²	右心房线性指数cm/m²	MELD评分	BNP pg/ml
1	39	56	21.8	480	100	1.62	3.46	11	150
2	52	59	30.7	347	55	1.72	3.44	14	162
3	57	64	36.5	417	86	1.98	3.23	11^a	374
4	41	52	21.3	366	79	1.47	3.54	9	128
5	43	53	22.8	379	63	1.60	3.31	13	969
6	51	54	27.5	436	85	1.77	3.05	13	72
7	50	64	32.0	342	85	1.53	4.20	11	1 570
8	57	66	37.6	426	63	1.56	4.22	10	1 788
9	50	60	30.0	367	64	1.80	3.33	11	466
10	54	67	36.2	370	67	1.72	3.90	9	1 219
11	44	57	25.1	290	42	1.85	3.08	12	686
	49	59	29.2	383	72	1.69	3.52	11	689
SD	6	5	60.0	54	13	0.15	0.41	2	613

图2 门脉高压相关性肺动脉高压患者胸腹部CT表现；注：A增粗的主肺动脉横径大于同层面升主动脉横径；B增大的右心房(右箭头)及右心室，增粗的右肺下叶动脉(上箭头)；C缩小且比例失调的肝脏(右箭头)，表明凹凸不平，增大的脾脏(左箭头)；D增粗的左肾静脉(下箭头)汇入下腔静脉(右箭头)

表3 3例PoPH患者的右心导管结果

序号	RAP mmHg	mPAP mmHg	POAP mmHg	PVR Dny·s/cm⁵	CO L/min	CI L/min/m²
1	6/1	30	2	789.47	3.04	1.86
2	8/0	36	6	591.99	4.86	2.89
3	10/1	36	15	449.49	6.40	3.22

表3 3例PoPH患者的右心导管结果

序号	RAP mmHg	mPAP mmHg	POAP mmHg	PVR Dny·s/cm⁵	CO L/min	CI L/min/m²
1	6/1	30	2	789.47	3.04	1.86
2	8/0	36	6	591.99	4.86	2.89
3	10/1	36	15	449.49	6.40	3.22

图3 肺泡血氧梯度t检验箱式图；注：D_(A-a)O₂：肺泡动脉血氧差值，D_(A-a)O₂ Pred：肺泡动脉血氧差值预计值；*：二者存在统计学差异

表4 POPH患者动脉血气分析结果(n＝11)

序号	PaCO₂ mmHg	PaO₂ mmHg	D_(A-a)O₂^a mmHg	D_(A-a)O₂ Pred^b mmHg
1	25.0	67.7	50.8	14.1
2	31.4	92.6	17.9	12.6
3	24.7	72.1	46.8	12.6
4	31.3	76.8	33.8	14.7
5	37.4	68.1	34.9	14.3
6	40.6	80.6	18.4	10.7
7	26.2	79.2	37.8	17.4
8	25.5	59.3	58.6	8.6
9	36.5	99.1	5.0	19.7
10	33.6	84.2	23.5	20.4
11	30.3	83.8	28.1	12.4
	31.1	78.5	32.3	14.3
s	5.5	11.5	15.9	3.6

表4 POPH患者动脉血气分析结果(n＝11)

序号	PaCO₂ mmHg	PaO₂ mmHg	D_(A-a)O₂^a mmHg	D_(A-a)O₂ Pred^b mmHg
1	25.0	67.7	50.8	14.1
2	31.4	92.6	17.9	12.6
3	24.7	72.1	46.8	12.6
4	31.3	76.8	33.8	14.7
5	37.4	68.1	34.9	14.3
6	40.6	80.6	18.4	10.7
7	26.2	79.2	37.8	17.4
8	25.5	59.3	58.6	8.6
9	36.5	99.1	5.0	19.7
10	33.6	84.2	23.5	20.4
11	30.3	83.8	28.1	12.4
	31.1	78.5	32.3	14.3
s	5.5	11.5	15.9	3.6

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Clinical analysis of portopulmonary hypertension

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Clinical analysis of portopulmonary hypertension