Risk Stratification and Prognosis of Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:Current guidelines for managing pulmonary arterial hypertension(PAH)recommend a risk strati-fication approach.However,the applicability and accuracy of these strategies for PAH associated with congenital heart disease(PAH-CHD)require further validation.This study aims to validate the reliability and predictive accuracy of a simplified stratification strategy for PAH-CHD patients over a three-year follow-up.Additionally,new prognostic variables are identified and novel risk stratification methods are developed for assessing and managing PAH-CHD patients.Methods:This retrospective study included 126 PAH-CHD patients.Clinical and biochemical variables across risk groups were assessed using Kruskal-Wallis and Fisher’s exact tests.Indepen-dent risk factors were identified using ordered logistic regression,while Kaplan-Meier and Cox proportional hazards regression analyses evaluated their impact on all-cause mortality.A new stratification model for the PAH-CHD population was constructed based on these analyses.Results:Significant survival differences across stratified risk groups were observed(p<0.001),validating the effectiveness of the simplified risk stratification method in PAH-CHD patients.Prothrombin activity was a strong independent predictor of adverse outcomes of PAH-CHD patients(Hazard ratio 0.95,p<0.001,C-index 0.70).A model combining N-terminal pro-brain natriuretic peptide,prothrombin activity,albumin,and right atrial area achieved an area under the curve of 0.89 and a C-index of 0.85.Conclusions:The simplified risk stratification method is applicable to PAH-CHD patients.Prothrombin activity is a strong independent predictor of adverse outcomes.A comprehensive risk stratification approach,incorporating both established and novel biomarkers,enhances accessibility and offers predictive efficacy during follow-up for PAH-CHD patients,comparable to established models.

Selexipag as Add-on Therapy for Patients with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease:A Single-Center Retrospective Study

Purpose:This study examined the efficacy and safety of selexipag in treating pulmonary arterial hypertension(PAH)associated with congenital heart disease(CHD).Materials and Methods:We conducted a retrospective study of patients with CHD-associated PAH,treated with selexipag since December 2017.Thirteen adult patients(mean age,45.4 years;women,77%)were treated with selexipag as add-on therapy.Baseline characteristics,World Health Organization functional class,6-minute walking distance(6MWD)test results,N-terminal pro-B-type natriuretic peptide levels,echocardiographic data,and incidence of side effects were assessed.Results:The majority of patients(12/13,92.3%)experienced more than one treatment-associated complication;one patient dropped out of the study due to intolerable myalgia.The results of 6MWD test(from 299.2±56.2 m to 363.8±86.5 m,p=0.039)and tricuspid regurgitation(TR)pressure gradient(from 84.7±20.5 mmHg to 61.6±24.0 mmHg,p=0.018)improved and remained improved after selexipag treatment in 12 patients.Based on the results of a non-invasive risk assessment,8(66.7%)patients showed improvement,3(25.0%)showed no interval change,and the status of one patient(8.3%)deteriorated.Moreover,compared to patients treated with a low dosage,patients treated with a medium-to-high dosage showed a greater increase in 6MWD results(88.3±26.4 m vs.55.3±27.6 m,p=0.043)and a greater reduction in the TR pressure gradient(-33.7±10.9 mmHg vs.-12.5±12.0 mmHg,p=0.015).Conclusion:Selexipag is an efficient pulmonary vasodilator as add-on therapy in treating CHD-associated PAH.

NOTCH3 Mutations and CADASIL Phenotype in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.

Transgelin as a potential target in the reversibility of pulmonary arterial hypertension second to congenital heart disease

Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.

Pulmonary Arterial Hypertension Medical Management of the Adult Patient with Congenital Heart Disease

Congenital heart disease(CHD)-associated pulmonary arterial hypertension(PAH)includes a heterogeneous patient population that can be characterized by the underlying cardiac malformation.CHD-associated PAH has an estimated prevalence of 5– 10% in adult patients,with an increasing number of patients surviving to adulthood because of advances in the surgical management and the development of pulmonary arterial hypertension(PAH)-targeted pharmacotherapy.Although limited data exist,targeted PAH pharmacotherapy has proven to be benefi cial in patients with CHD-associated PAH,with observed improvement in functional class,increase in exercise capacity,and improvement in quality of life and cardiopulmonary hemodynamics.Additionally,there has been increasing interest in the“treat-to-close”strategy.PAH-targeted pharmacotherapy may be used to optimize cardiopulmonary hemodynamics so as to improve patients’operability in repairing the cardiac defect.Although there have been signifi cant advances in the management of this disease state in the past 2 decades,mortality remains high,and ongoing clinical trials are needed to better understand the treat-to-close strategy.

Perioperative Nursing for Adult Congenital Heart Disease with Severe Pulmonary Arterial Hypertension

Objectives: To explore the main points of perioperative nursing for adult congenital heart disease with severe pulmonary arterial hypertension. Methods: A retrospective study of 13 patients with congenital heart disease and severe pulmonary arterial hypertension who admitted to the perioperative period of care from January 2018 to December 2019. To prevent perioperative complications of the patients, the focus is on respiratory and circulatory system care, followed by blood coagulation monitoring, digestive system protection and psychological care. Results: All 13 patients passed the perioperative period and were discharged from ICU. Conclusion: Adult congenital heart disease with severe pulmonary arterial hypertension has high perioperative risk, respiratory and circulatory system care is the key.

Treatment of patients with bosentan in postoperation of congenital heart disease with pulmonary arterial hypertension:a double-blind,randomized controlled trial

Objective Endothelin is a key role in the pathogenic of pulmonary arterial hypertension. High concentrations of endothelin 1 have been recorded in plasma and lungs of patients with pulmonary artery hypertension associated with congenital heart disease,and the concentrations of endothelin-1 was correlated with severity degree

The Potential of Circular RNAs as Biomarkers in Pulmonary Arterial Hypertension Related to Congenital Heart Disease

A particular type of endogenous noncoding RNAs known as circular RNAs(circRNAs)has now become possible biomarkers for several diseases because of their stability and tissue-specific expression patterns.CircRNAs might play a role in various of biological processes.The identification of particular circRNAs dysregulated in pulmonary arterial hypertension(PAH)raises the possibility of these molecules serving as biomarkers for the disease’s early diagnosis and treatment.This review mainly summarizes the role and potential of circRNA as a future biomarker in PAH related to congenital heart disease.This study presented several potential circRNA targets as diagnostic biomarkers for PAH,discussed their biological functions,and addressed the challenges that need to be considered for their application in clinical settings.

Bosentan Is Associated with a Reduction in Right Ventricular Systolic Pressure N-Terminal Pro-Hormone B-Type Natriuretic Peptide Levels in Young Patients with Pulmonary Hypertension

Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population;however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg;p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037;p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements;however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.

Pulmonary Hypertension Crisis in Patient with Tetralogy of Fallot and Mixed Total Anomalous Pulmonary Vein Connection after the Primary Correction:A Rare Case Report

Tetralogy of Fallot(TOF)with total anomalous pulmonary vein connections(TAPVC)is a rare type of complex congenital heart disease among all TOF cases.Co-presentation of major aortopulmonary collateral arteries(MAPCAs)compensates for the lack of central pulmonary bloodflow and decreases the severity of right-to-left shunting in TOF.We present a case of a 2-year-old child with complex diagnoses of TOF,TAPVC,a large secun-dum atrial septal defect(ASD),and intraoperatively identified MAPCAs.She underwent surgery to repair the TAPVC,valve-sparing reconstruction of the right ventricular outflow tract,interventricular defect closure,and the creation of patent foramen ovale(PFO).After the operation,hemodynamic instability happened along with sudden blood pressure drop,desaturation,and increased central venous pressure,which subsided after adminis-tering inhalational nitric oxide(NO).A postoperative pulmonary hypertension crisis was suggested when the patient experienced recurrent symptoms after the termination of NO.Echocardiographicfindings of a D-shaped left ventricle(LV),right-to-left PFO shunt and high tricuspid valve gradientfirmly established the diagnosis.It was subsequently managed with continuous NO inhalation and sildenafil,which rendered a satisfactory outcome.Repaired TOF and TAPVC could be at particular risk of developing pulmonary hypertension crisis,especially in the presence of MAPCAs due to possible remodeling of the pulmonary vasculature.Furthermore,a relatively non-compliant LV function and small left atrial size may exacerbate the risk of developing postcapillary pulmonary hypertension after TAPVC repair.A successful postoperative outcome calls for a meticulous preoperative analysis of the anatomical lesions,as well as careful monitoring.

Interventional closure operation increases angiotensin-(1-7) level in pulmonary arterial hypertension due to congenital heart disease

Background Recent studies have demonstrated that angiotensin(Ang)-(1-7) plays an important role in the development of pulmonary arterial hypertension(PAH). Our previously study showed that serum Ang-(1-7) level was decreased in patients with PAH due to congenital heart disease(CHD). The present study aimed to investigate the changes of serum Ang-(1-7) before and after intervention closure. Methods fifty-nine patients with CHD were included. The patients were divided into non-PAH(group A), mild PAH(group B) and moderate PAH(group C). The serum Ang-(1-7) was detected by enzyme-linked immunosorbent assay(ELISA) at 1 day before operation and 2 days after operation. Results Before intervention closure, serum angiotensin-(1-7) level was significantly lower in group C than that in group A and group B. After intervention closure operation, serum Ang-(1-7) level was increased in group B and group C. Conclusion Serum Ang-(1-7) level is increased in PAH patients after interventional closure operation of CHD, which might be used as potential clinical biomarkers to evaluate the postoperative prognosis for these patients.[S Chin J Cardiol 2019;20(4):264-268]

Comparative analysis of early and middle outcomes of the arterial switch operation in children with complete transposition of the great arteries with ventricular septal defect and severe pulmonary artery hypertension

Background The best age for the arterial switch operation （ASO） in complete transposition of great arteries with ventricular septal defect is usually considered to be within six months. This is because of severe pulmonary arterial hypertension and pulmonary arterial obstructive pathological changes. There are few reports on ASO surgery in children older than three years old. Methods We studied 41 children, including 24 males and 17 females, from January 2010 to December 2011. They were divided into three groups by operation age; 15 patients were 〈1 year old, 13 were 1-3 years old, and 13 were 〉3 years old. Associated cardiac abnormalities included patent ductus arteriosus in six cases, atrial septal defect in five cases, and mitral regurgitation in two cases. All the patients had echocardiography before the operation. Seventeen patients underwent a coronary computed tomography examination and five patients underwent right heart catheterization. All ASO surgeries were performed under inhalation anesthesia and hypothermic cardiopulmonary bypass. Results Three operative deaths occurred. Two were in the 〈1 year old group, who died from severe postoperative low cardiac output. The other was two years old and died of postoperative multiple organ failure. There was no significant difference in postoperative mortality and the recent mid-term survival rate among the three groups. Thirty-eight cases were followed up for an average of 11.2 months, ranging 6-20 months. One seven years old patient died of acute diarrhea and electrolyte disturbance arrhythmia caused by food poisoning. Three patients more than three years old still had residual pulmonary arterial hypertension. Conclusion Children older than three years old can still undergo the ASO procedure, but residual pulmonary hypertension is present.

超声心动图在成人先天性心脏病合并肺动脉高压手术时机评估中的应用

早期纠正先天性心脏病(congenital heart disease,CHD)患者心脏结构及功能的异常有益于患者的长期存活。肺动脉高压(pulmonary artery hypertension,PAH)的严重程度是决定成人CHD患者能否接受手术治疗及远期预后的重要影响因素。超声心动图作为一种无创、简便、有效的成像手段,在成人CHD及PAH患者中被广泛应用。基于超声心动图参数的预测模型不仅能提高无创参数量化血流动力学参数的准确性,而且还能对不同阶段CHD患者的手术可行性进行评估,从而避免反复进行有创的心导管检查,也提高了对成人CHD合并PAH患者的综合管理质量。

基于时频融合特征的肺动脉高压心音分类模型

先心病相关肺动脉高压是一种严重的心血管疾病,致死率高,对其进行早期筛查与识别对于治愈尤为重要。目前临床是通过右心导管术确诊,此为有创检查,不便于在大规模筛查中采用,研究一种无创便捷的识别方法迫在眉睫。文中建立了一种时频融合的心音分类模型。首先对心音信号进行预处理,然后使用融合滤波器组对信号进行转换并求取动态时频特征,最后将得到的融合特征参数输入表格式先验数据拟合网络(TabPFN)中进行分类识别。实验结果表明,该算法在正常、CHD-PAH和CHD中的平均准确率、精确率、灵敏度、特异度和F1分别为92.21%,92.15%,92.15%,96.11%,92.14%。对于先心病相关肺动脉高压的早期筛查与识别具有重要意义。

妊娠合并房间隔缺损并发醒后卒中1例报道

妊娠期缺血性卒中发病率低、致死率高。本文通过回顾1例妊娠合并有房间隔缺损并发醒后卒中患者的临床及影像学检查资料,探讨妊娠相关卒中的影像学表现、发病机制和治疗策略,旨在提高临床医师对合并有房间隔缺损的孕妇并发急性脑卒中的认识,为临床诊疗提供参考。

先天性心脏病合并肺动脉高压相关生物标志物的研究新进展

先天性心脏病合并肺动脉高压(CHD-PAH)是儿科肺动脉高压的重要类型,肺动脉高压影响右心功能,可导致右心室衰竭,是CHD-PAH患者死亡的主要原因。早期预测CHD-PAH患儿的不良预后对于积极改变相应的治疗策略,进而提高存活率至关重要。近年来,结缔组织生长因子、和肽素、内皮抑素及环状RNA等新兴的生物标志物被证明可对CHD-PAH患者的临床疗效及预后进行预测,对早期且准确的识别高危患者有重要作用。本文将通过讨论上述新型生物标志物与CHD-PAH的严重程度、疾病进展和临床疗效的相关性,以期为医师在临床诊治过程中运用相关生物标志物提供理论依据。

高原地区先天性心脏病相关性肺动脉高压的研究进展

高原地区先天性心脏病相关性肺动脉高压发病率明显高于平原地区,且进展迅速,其疾病临床特征及转归也不完全与平原地区相同,该领域研究甚少。现对高原地区先天性心脏病相关性肺动脉高压的流行病学、发病机制、治疗措施等方面的研究进行综述,以期为今后开展相关临床研究提供参考。

山西省2018~2021年先天性心脏病相关肺动脉高压患病率及流行病学特征分析

目的了解山西省先天性心脏病相关肺动脉高压(CHD-PAH)的患病率及流行病学特征,为制定CHD-PAH的防治策略提供科学依据。方法该研究为横断面回顾性研究,数据来源于2018~2021年山西省卫生健康统计直报系统住院患者病案首页信息,筛选出院诊断登记有“先天性心脏病(或先天性心脏畸形)和肺动脉高压”的患者。收集患者的年龄、性别、职业、婚姻状况等人口学资料、入院途径、入院医院等级、住院总费用等相关住院资料,分析流行病学特征。结果2018~2021年山西省病案首页出院诊断中有肺动脉高压患者65189例/人次,其中CHD-PAH 2147例/人次,CHD-PAH年均患病率为1.51/10万。CHD-PAH占肺动脉高压患者比例逐年下降。从2018~2021年总体来看,女性患病率均高于男性。0~6岁的患者历年均占比最高。不同年份患者职业分布不同,以农民及无业人员多见。患者入院途径以门诊为主,入院级别以省级医院多见。春夏季患者入院较多。患者平均住院日为9~10 d,住院总费用呈逐年增长趋势。疾病分类特征显示CHD-PAH患者中,房间隔缺损患者占比最多,其次为室间隔缺损,主动脉骑跨占比最少。结论通过详细描述山西省CHD-PAH的患病率及流行病学特征,对提高疾病认识,制定最佳预防策略、早期诊断、治疗时机和治疗选择具有重要意义。

波生坦联合雾化吸入硝普钠对先心病伴肺动脉高压患儿肺动脉血流动力学及心脏功能的影响分析

目的探究波生坦联合雾化吸入硝普钠对先天性心脏病(简称先心性)伴肺动脉高压患儿动脉血流动力学及心脏功能的影响。方法随机选取2021年12月—2023年2月贵阳市妇幼保健院收治的90例先心病伴肺动脉高压患儿为研究对象,根据不同治疗方法分为对照组和观察组,每组45例。对照组予以雾化吸入硝普钠治疗,观察组予以波生坦联合雾化吸入硝普钠治疗,两组患儿均持续治疗2个月。对比两组患儿的临床疗效、肺动脉血流动力学水平、心脏功能水平、肺功能水平及不良反应发生情况。结果观察组治疗总有效率为97.78%(44/45),高于对照组的82.22%(37/45),差异有统计学意义(χ^(2)=4.444,P=0.035);观察组治疗后肺血管阻力、平均肺动脉压低于对照组,差异有统计学意义(P均<0.05);治疗后两组患儿的平均动脉压比较,差异无统计学意义(P>0.05);治疗后,观察组心功能指数、心排血量、每搏输出量高于对照组,差异有统计学意义(P均<0.05);治疗后,观察组动脉血氧分压、氧合指数高于对照组,差异有统计学意义(P均<0.05);两组患儿的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论在先心病伴肺动脉高压患儿中,使用波生坦联合雾化吸入硝普钠治疗可有效改善患儿的肺动脉血流动力学,促进心脏功能与肺功能恢复正常,且不良反应较小。

超声心动图、ECG及联合检查对PAH-CHD肺动脉压力的预测价值观察

目的探讨超声心动图、心电图(ECG)及联合检查对先天性心脏病相关性肺动脉高压(PAH-CHD)肺动脉压力的预测价值。方法选取我院2017年1月-2018年9月收治的80例CHD患者为研究对象并开展回顾性分析,所有患者均行超声心动图及ECG检查,依据是否并发PAH将以上研究对象分为PAH组(36例)和非PAH组(44例),比较两组的超声心动图指标(肺动脉收缩压)及心电图指标(RV5振幅),绘制肺动脉收缩压、RV5振幅预测PAH-CHD肺动脉压力的ROC曲线,分析两者分别检查及联合的预测价值。结果 PAH组的肺动脉收缩压与RV5振幅均显著高于非PAH组(P<0.05);超声心动图指标预测PAH-CHD的灵敏度为72.1%,特异度为77.8%,心电图指标预测PAH-CHD的灵敏度为62.8%,特异度为69.4%,两者联合预测PAH-CHD的灵敏度为67.4%,特异度为83.3%;ROC曲线显示,两种检查方法的曲线下面积AUC与0.5比较差异显著(P<0.05),两种方法联合诊断的曲线下面积AUC均大于超声心动图、心电图单独诊断。结论超声心动图联合心电图检查对于PAH-CHD具有一定预测价值,且相较于单独检查能够提高准确度。