左心疾病相关肺高血压不同血流动力学分类方法与预后关系研究

Prognosis of different hemodynamic classifications in patients with pulmonary hypertension due to left heart disease

目的比较跨肺压差(TPG)、肺动脉舒张压差(DPG)和肺血管阻力(PVR)3种分类方法对左心疾病相关肺高血压(PH-LHD)患者预后的预测价值,探讨PH-LHD预后相关血流动力学和临床指标与患者全因死亡的关系。方法本研究为单中心前瞻性队列研究。连续入选2013年9月至2019年12月在南京医科大学第一附属医院心血管内科经右心导管确诊的PH-LHD住院患者,依据TPG(界值12 mmHg;1 mmHg=0.133 kPa)、DPG(界值7 mmHg)、PVR(界值3 Wood单位)和TPG联合PVR对入选患者进行分组,收集患者基线临床资料。所有患者随访至发生终点事件或2022年4月18日,终点事件定义为随访期间发生的全因死亡。采用受试者工作特征曲线比较3种分类方法对PH-LHD患者全因死亡的预测价值。根据约登指数计算最佳临界值,采用Kaplan-Meier曲线进行生存分析,并使用log-rank检验比较依据最佳临界值或指南推荐的界值的分类方法对PH-LHD患者生存率的预测效力。将单因素分析中与全因死亡有关的变量纳入多因素Cox回归模型,分析PH-LHD患者全因死亡的独立危险因素。结果共纳入243例患者,年龄(54.9±12.7)岁,男性169例(69.5%)。中位随访时间57个月,共101例(41.6%)发生终点事件。分组结果为:(1)依据TPG:TPG≤12 mmHg组115例,TPG>12 mmHg组128例;(2)依据DPG:DPG<7 mmHg组193例,DPG≥7 mmHg组50例;(3)依据PVR:PVR≤3 Wood单位组108例,PVR>3 Wood单位组135例;(4)依据TPG联合PVR:TPG≤12 mmHg且PVR≤3 Wood单位组89例,TPG>12 mmHg且PVR>3 Wood单位组109例。PVR(AUC=0.698,95%CI:0.631~0.766)较TPG(AUC=0.596,95%CI:0.523~0.669)和DPG(AUC=0.526,95%CI:0.452~0.601)对PH-LHD患者全因死亡有更好的预测价值(P<0.05)。根据约登指数计算的TPG、DPG和PVR的最佳临界值分别为13.9 mmHg、2.8 mmHg和3.8 Wood单位。Kaplan-Meier生存曲线分析显示,按PVR或TPG分组的患者生存率组间差异有统计学意义(P<0.05),按DPG分组的患者生存率组间差异无统计学意义(P>0.05)。多因素Cox回归分析结果显示,年龄、PVR和log 2N末端B型利钠肽原是PH-LHD患者全因死亡的独立危险因素(P均<0.05)。结论PVR分类方法对预测PH-LHD患者全因死亡最有价值,TPG分类方法表现出中等预测能力,DPG分类方法对PH-LHD患者全因死亡无预测价值。年龄、PVR和log 2N末端B型利钠肽原对预测PH-LHD患者全因死亡有价值。

Objective To compare the prognostic values of different classification by using transpulmonary pressure gradient(TPG),diastolic pressure gradient(DPG)and pulmonary vascular resistance(PVR)in patients with pulmonary hypertension due to left heart disease(PH-LHD),and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods This was a single-center prospective cohort study.In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology,the First Affiliated Hospital of Nanjing Medical University,from September 2013 to December 2019 were enrolled.Patients were divided according to TPG(cutoff value 12 mmHg;1 mmHg=0.133 kPa),DPG(cutoff value 7 mmHg),PVR(cutoff value 3 Wood Units),and the combination of TPG and PVR.Baseline characteristic was recorded.All patients were followed up until the occurrence of endpoint event,defined as all-cause death that occurred during the follow-up period,or until April 18,2022.Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients.The optimal cutoff values were calculated using Jorden index.Survival analysis was performed using Kaplan-Meier analysis,and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients.Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results A total of 243 patients were enrolled,aged(54.9±12.7)years old,including 169(69.5%)males.During a median follow-up of 57 months,there were 101(41.6%)deaths occurred.Grouping results were as follows:(1)TPG:TPG≤12 mmHg group 115 patients,TPG>12 mmHg group 128 patients;(2)DPG:DPG<7 mmHg group 193 patients,DPG≥7 mmHg group 50 patients;(3)PVR:PVR≤3 Wood Units group 108 patients,PVR>3 Wood Units group 135 patients;(4)TPG and PVR:TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients,TPG>12 mmHg and PVR>3 Wood Units group 109 patients.PVR(AUC=0.698,95%CI:0.631-0.766)had better predictive value for all-cause mortality than TPG(AUC=0.596,95%CI:0.523-0.669)and DPG(AUC=0.526,95%CI:0.452-0.601)(all P<0.05).The optimal cutoff values for TPG,DPG,and PVR were13.9 mmHg,2.8 mmHg,and 3.8 Wood Units,respectively.Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival(P<0.05),while DPG did not showed significance(P>0.05).Multivariate Cox regression analysis showed that age,PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients(all P<0.05).Conclusion Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients,while TPG showed moderate predictive ability and DPG had no predictive value.