scholarly journals Angiostatic Peptide, Endostatin, Predicts Severity in Pediatric Congenital Heart Disease–Associated Pulmonary Hypertension

2021 ◽  
Author(s):  
Caroline M. Daly ◽  
Megan Griffiths ◽  
Catherine E. Simpson ◽  
Jun Yang ◽  
Rachel L. Damico ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Artery ◽  
Risk Stratification ◽  
Disease Severity ◽  
Congenital Heart ◽  
Adverse Outcomes ◽  
Right Atrial ◽  
Free Survival ◽  
Over Time

Background Endostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH. Methods and Results Serum endostatin was measured in cross‐sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH‐CHD, N=185). Outcomes, assessed by regression and Kaplan‐Meier analysis, included hemodynamics, change in endostatin over time, and transplant‐free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH‐CHD. In APAH‐CHD, endostatin was associated with a shorter 6‐minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant‐free survival. Addition of endostatin to an NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells. Conclusions Endostatin is associated with disease severity, disease improvement, and worse survival in APAH‐CHD. Endostatin with NT‐proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH‐CHD.

scholarly journals Pulmonary arterial hypertension associated with congenital heart disease in children: clinical characterisation, outcomes and changes in demographics over time

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Constantine ◽  
K Dimopoulos ◽  
R Condliffe ◽  
P Clift ◽  
G Chaplin ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Free Survival ◽  
Paediatric Cohort ◽  
Group A ◽  
Pulmonary Arterial ◽  
Group B ◽  
Group D ◽  
Over Time

Abstract Background/Introduction Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD) in children and is associated with significant morbidity and mortality. The impact of different phenotypes on management and survival remains unclear. Purpose To examine the clinical features, management and outcomes of paediatric PAH-CHD patients based on the 20-year experience of the UK National Paediatric Pulmonary Hypertension (PH) Service. Methods Consecutive PAH-CHD patients entering the service between January 2001 and January 2021 were included and classified into: Eisenmenger syndrome (ES, group A), PAH related to a significant systemic-pulmonary shunt (group B), PAH with small or co-incidental CHD (group C) and PAH following defect repair (group D). Incident patients (without pre-existing PAH) were included in survival analysis. Results Of the overall PH paediatric cohort of 1104 patients, 819 (74.2%) had co-existing CHD and 354 (32.1%) patients received a diagnosis of PAH-CHD: 57.1% female, median [IQR] 4.6 [1.7–10.9] years. Group D PAH-CHD was the commonest subgroup, accounting for 36%, while the least frequent subtype was group C (14%). Group A and group B PAH-CHD represented 26% and 24%, respectively. Down syndrome was present in over one third (122, 34.5%) of PAH-CHD patients and was more commonly associated with ES (p=0.02). PAH therapy was started in 79.9% of PAH-CHD patients. At the end of follow-up, patients with group C PAH-CHD were more likely to be on combination therapy than any other group (64.6% vs. 28.4%, p<0.0001). Prostanoid therapy was used in a minority (11%) of patients. The subgroup distribution of PAH-CHD at diagnosis changed from the early (2000–2005) to late (2015–2020) period (Figure 1). The proportion of ES patients decreased from 43.4% to 14.6% of PAH-CHD (p<0.0001). The proportion of group B PAH-CHD patients increased (9.4% vs. 33.3%, p<0.0001), with the majority (59.3%) deemed “operable” on specialist assessment. There was a trend for an increase in repaired PAH-CHD patients between the early and late era (31.1% vs. 43.8%, p=0.09). Transplant-free survival in PAH-CHD was 90.9% (95% CI: 87.8–94%) at 1 year, 77.9% (95% CI: 73.1–83.1%) at 5 years, and 74.9% (95% CI: 69.6–80.7%) at 10 years (Figure 2). Group C PAH-CHD had a lower transplant-free survival than the other 3 groups (HR 2.54, 95% CI: 1.51–4.28, p=0.0005). There was no difference in outcome between group A and group D PAH-CHD (HR 1.19, 95% CI: 0.62–2.28, p=0.6). Conclusions Repaired PAH-CHD, not ES, was the most common subtype in this large paediatric cohort. Over time, there were fewer ES patients and more “operable” patients with left-right shunts, suggesting an improvement in early diagnosis and management. Despite widespread use of PAH therapy, PAH-CHD remains a life-limiting disease with the poorest outcomes in PAH with co-incidental CHD. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Constantine received a personal PhD fellowship grant (CHAMPION PhD Fellowship) Figure 1 Figure 2

scholarly journals Results of Right Atrial to Right Ventricular and Right Atrial to Pulmonary Artery Conduits for Complex Congenital Heart Disease

1980 ◽  
Vol 192 (3) ◽  
pp. 382-389 ◽  
Author(s):  
HILLEL LAKS ◽  
WILLIAM G. WILLIAMS ◽  
WILLIAM E. HELLENBRAND ◽  
ROBERT M. FREEDOM ◽  
NORMAN S. TALNER ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Congenital Heart ◽  
Right Atrial ◽  
Complex Congenital Heart Disease

Abstract 14979: Endostatin as a Predictor of Severity and Survival in Pediatric Congenital Heart Disease Associated Pulmonary Hypertension

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Caroline Daly ◽  
Megan Griffiths ◽  
Jun Yang ◽  
Melanie Nies ◽  
Rachel L Damico ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Disease Severity ◽  
Congenital Heart ◽  
Right Atrial ◽  
Pulmonary Vascular Disease ◽  
Multiple Time ◽  
Angiogenic Inhibitor ◽  
Kaplan Meier ◽  
Increased Risk

Introduction: Pediatric pulmonary arterial hypertension (PAH) is a multifactorial pulmonary vascular disease with high mortality. Endostatin (ES), an angiogenic inhibitor, is associated with disease severity and mortality in adults with PAH and poor lung growth in children. Hypothesis: Increased ES is associated with worse disease severity and outcomes in pediatric PAH. Methods: Serum ES levels were measured in two cohorts of pediatric PAH (IPAH, FPAH and APAH) patients; the cross-sectional CCHMC PAH Biobank (PAHB, N=175) and a longitudinal cohort from Children’s Hospital of Colorado (CHC, N=61). Outcomes included medical therapy, functional and hemodynamic measures, and survival (death, transplant, palliative shunt). Adjusted logistic and linear regressions and Kaplan-Meier analysis were used to assess the relationship between ES and clinical outcomes. Results: In both cohorts, ES was significantly higher in PAH associated with congenital heart disease (APAH-CHD, PAHB n=70, p=0.002; CHC n=29, p=0.007) and was highest in those with a ventricular shunt (n=24, p=0.001). In APAH-CHD, ES was associated with a decreased 6MWD (-108m, -187- -30, p=0.01) and increased mean right atrial pressure (mRAP 1.8mmHg, 0.3-3.3, p=0.02). Longitudinally, in the APAH-CHD subgroup when adjusted for age, sex, and multiple time points, higher ES was associated with increased PVRi and mPAP (PVRi 2.5WU*m 2 , 0.7-4.3, p=0.007; mPAP 10mmHg, 4.5-15, p<0.001). Kaplan-Meier analysis (Figure 1) demonstrated that ES was associated with worse outcomes in both cohorts, with an adjusted Cox proportional hazard ratio of 4.3 (1.13-16, p=0.03) in the PAHB. Conclusions: ES was associated with worse functional measures, pulmonary vascular hemodynamics, and survival in pediatric APAH-CHD. These observations suggest that serum ES could act as a pulmonary vascular specific biomarker to identify those who are at increased risk of developing PAH and predict poor outcomes in APAH-CHD.

scholarly journals Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cuilan Hou ◽  
Junmin Zheng ◽  
Wei liu ◽  
Lijian Xie ◽  
Xiaomin Sun ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Artery ◽  
Molecular Mechanism ◽  
Protein Level ◽  
Congenital Heart ◽  
Artery Stenosis ◽  
Pulmonary Artery Stenosis ◽  
Functional Component ◽  
Functional Changes

AbstractCongenital heart defects, one of the most common birth defects, affect approximately 1% of live birth globally and remain the leading cause of infant mortality in developed countries. Utilizing the pathogenicity score and inheritance mode from whole exome sequencing results, a heterozygous mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) in elastin (ELN) was identified among 6,440 variants in a female proband born with an atrial septal defect accompanied by pulmonary artery stenosis. Results of RT-PCR showed that the mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) did not affect the expression levels of ELN mRNA but increased protein level. The content of ELN truncate (functional component) was significantly lower in both the intracellular and extracellular compartments after mutation. These results indicate that the ELN mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) affected the protein truncate, which may be a functional component of ELN and play crucial roles for this pedigree. Here we report of an ELN heterozygous variant associated with congenital heart disease accompanied with pulmonary artery stenosis, which is less common. Based on our results, we speculate that this may be the main molecular mechanism underlying the mutation-led functional changes, and propose that the decrease of ELN protein level may cause this pedigree vascular abnormality, especially pulmonary artery stenosis, and reinforce the view that ELN insufficiency is the primary cause of these vascular lesions. This may be the main molecular mechanism underlying the mutation-led functional changes. Thus, systematic analysis not only enables us to better understand the etiology of this disease but also contributes to clinical and prenatal diagnosis.

scholarly journals Anomalous Origin of the Left Anterior Descending Coronary Artery in an Adult

2021 ◽  
Vol 10 (01) ◽  
pp. e9-e10
Author(s):  
Keisuke Shibagaki ◽  
Chikara Shiiku ◽  
Hiroyuki Kamiya ◽  
Yoichi Kikuchi
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Coronary Artery ◽  
Pulmonary Artery ◽  
Congenital Heart ◽  
Left Coronary Artery ◽  
Internal Thoracic Artery ◽  
Artery Bypass ◽  
Anomalous Origin ◽  
Bypass Grafting

AbstractAn anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart disease. Among the variants, an anomalous origin of the left anterior descending coronary artery from the pulmonary artery (ALADPA) is extremely rare. Here, we report a case of ALADPA in an adult that was treated with coronary artery bypass grafting using the left internal thoracic artery.

Pulmonary Artery Banding Still Has an Important Role in the Treatmant of Congenital Heart Disease: Reply

2005 ◽  
Vol 79 (4) ◽  
pp. 1463-1464
Author(s):  
Hiroo Takayama ◽  
Masahide Chikada ◽  
Shinichi Takamoto ◽  
Akihiko Sekiguchi ◽  
Akira Ishizawa
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Artery ◽  
Congenital Heart ◽  
Pulmonary Artery Banding

Submitral Aneurysm After Pulmonary Artery Banding—A Case Report

2017 ◽  
Vol 9 (3) ◽  
pp. 364-367
Author(s):  
Abid Iqbal ◽  
Sabarinath Menon ◽  
Baiju S. Dharan ◽  
Kapilamoorthy Tirur Raman ◽  
Jayakumar Karunakaran
Keyword(s):  
Congenital Heart Disease ◽  
Young Adults ◽  
Heart Disease ◽  
Case Report ◽  
Pulmonary Artery ◽  
Congenital Heart ◽  
Interatrial Septum ◽  
Pulmonary Artery Banding ◽  
Complex Congenital Heart Disease ◽  
Unique Case

Submitral aneurysms are rare clinical entities occurring predominantly in young adults of African descent. A host of etiologies have been proposed for this entity. We present a unique case of submitral aneurysm which developed after pulmonary artery banding in a three-year-old girl with complex congenital heart disease. The aneurysmal sac was burrowing into the interatrial septum.

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