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![Management algorithm for patients with Eisenmenger syndrome. PAH: pulmonary arterial hypertension; CHD: congenital heart disease; MRI: magnetic resonance imaging; CT: computed tomography; 6MWT: 6-min walk test; NYHA: New York Heart Association. Reproduced from [52] with permission from the publisher.](profile/Rafael-Alonso-Gonzalez/publication/47459137/figure/fig3/AS:669174867185669@1536555129196/Management-algorithm-for-patients-with-Eisenmenger-syndrome-PAH-pulmonary-arterial.png)
Management algorithm for patients with Eisenmenger syndrome. PAH: pulmonary arterial hypertension; CHD: congenital heart disease; MRI: magnetic resonance imaging; CT: computed tomography; 6MWT: 6-min walk test; NYHA: New York Heart Association. Reproduced from [52] with permission from the publisher.
Source publication
Pulmonary arterial hypertension (PAH) commonly arises in patients with congenital heart disease (CHD). Greater numbers of patients with PAH associated with CHD (PAH-CHD) are now surviving into adulthood, many with increasingly complex cardiac defects. Patients with cardiac defects which result in left-to-right shunting are at risk of developing PAH...
Context in source publication
Context 1
... consensus for optimal management of patients with Eisenmenger syndrome has recently been updated ( fig. 5) and its multidisciplinary nature is clear. The importance of patient education and engagement also cannot be over- emphasised, especially in terms of endocarditis prophylaxis, lifestyle issues (especially exercise, contraception and the risks of pregnancy), and frank discussion about future prospects and prognosis. Historically, there ...
Similar publications
Pulmonary arterial hypertension (PAH) is a serious complication of congenital heart disease, causing an increase in morbidity and mortality. The progressive and irreversible pulmonary vascular disease is more often the consequence of a significant, uncorrected, left-to-right shunt. The rise in pulmonary vascular resistance may lead to the reversal...
Citations
... The development of PAH is an important factor affecting the prognosis of children after CHD surgery/intervention (17). As VSD is the most common congenital heart disease, early identification of VSD patients who may develop pulmonary hypertension after surgery/intervention is important to improve the success rate of treatment (18). ...
Background
The mechanism of pulmonary arterial hypertension (PAH) after surgery/intervention for isolated venticlular septal defect (VSD) in children is unknown. Reliable prognostic indicators for predicting postoperative PAH are urgently needed. Prognostic nutration index (PNI) is widely used to predict postoperative complications and survival in adults, but it is unclear whether it can be used as an indicator of prognosis in children.
Methods
A total of 251 children underwent VSD repair surgery or interventional closure in Hunan Children's Hospital from 2020 to 2023 were collected. A 1:1 propensity score matching (PSM) analysis was performed using the nearest neighbor method with a caliper size of 0.2 Logistics regression analysis is used to examine factors associated with the development of PAH.
Results
The cut-off value for PNI was determined as 58.0. After 1:1 PSM analysis, 49 patients in the low PNI group were matched with high PNI group. Children in the low PNI group had higher risk of postoperative PAH (P = 0.002) than those in the high PNI group. Multivariate logistics regression analysis showed that PNI (RR: 0.903, 95% CI: 0.816–0.999, P = 0.049) and tricuspid regurgitation velocity (RR: 4.743, 95% CI: 1.131–19.897, P = 0.033) were independent prognostic factors for the development of PAH.
Conclusion
PNI can be used as a prognostic indicator for PAH development after surgery/intervention in children with isolated VSD.
... Prior studies on patients with pulmonary arterial hypertension secondary to congenital cardiac disorders, including PAPVC, showed clinical and hemodynamic improvements with endothelin receptor antagonists, phosphodiesterase inhibitors, and prostaglandins [8]. After initiation of pharmacotherapy, the patient needs to be closely monitored for disease progression. ...
Partial anomalous pulmonary venous connection (PAPVC) occurs when any pulmonary vein, but not all, drains directly into the right atrium or its venous tributaries. PAPVC can very rarely present as an individual cause of pulmonary artery hypertension. Here we are presenting a case of a 41-year-old farmer with a history of exertional dyspnoea for the past three years, which increased over 6 months. Chest high-resolution computed tomography (HRCT) was suggestive of non-fibrotic hypersensitivity pneumonitis. Hence the patient was started on systemic steroids, with which the patient's oxygen saturation improved. On 2D-ECHO, the right ventricle systolic pressure was 48+RAP. Right heart catheterization showed mean pulmonary artery pressure of 73 mmHG, PVR 8.7. On further evaluation, CTPA was done, which surprisingly revealed the left superior pulmonary vein draining into the left brachiocephalic vein.
... The majority of patients are born with acyanotic CHD (ACCHD), while approximately 10% of patients have CCHD. If ACCHD with significant left-to-right shunt is left untreated, patients may become cyanotic later in life, mostly due to the development of severe, progressive pulmonary vascular disease and subsequent Eisenmenger syndrome [19]. The resulting chronic hypoxemia, which can be severe, leads to multisystemic complications. ...
... The mean duration of hypoxemia in CCHD was 25 (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) years. Duration of hypoxemia was not associated with plasma normetanephrine and metanephrine levels (ρ = 0.130, p = 0.480 and ρ = −0.001, ...
Purpose
The co-occurrence of cyanotic congenital heart disease (CCHD) and PHEO/PGL has been reported, but the role of the hypoxic environment in the pathogenesis of PHEO/PGL remains unclear. Our aim was to compare plasma metanephrine and normetanephrine levels between patients with CCHD and patients with acyanotic congenital heart disease (ACCHD).
Methods
We performed a cross-sectional study in a prospective cohort of 44 patients with congenital heart disease (CHD) (31 (70.5%) females) with a median age of 37.5 (31.0–55.6) years at the time of evaluation. Thirty-two (73%) patients had CCHD and 12 (27%) patients had ACCHD. Morning blood samples for plasma determination of metanephrine and normetanephrine were collected.
Results
Plasma normetanephrine levels were significantly higher in patients with CCHD compared to ACCHD (p = 0.002). Ten (31.3%) patients with CCHD had plasma normetanephrine levels elevated above the reference range, while all ACCHD patients had normal levels. Patients with lower oxygen saturation and higher proBNP had significantly higher normetanephrine levels (ρ = −0.444, p = 0.003 and ρ = 0.449, p = 0.002, respectively). No chromaffin cell tumors were detected.
Conclusion
Increased plasma normetanephrine levels in patients with CCHD can be explained by the effect of hypoxia. Future research is needed to better understand the impact of chronic hypoxia in CCHD on increased sympathetic outflow, hyperplastic response of chromaffin tissue, and the role of somatic mutations in CCHD-PHEO/PGL pathogenesis related to hypoxia.
... Surgical repair with ASD patching, anomalous vein anastomosis and other methods may be warranted depending on symptoms and shunt fraction. Patients who are unable to undergo surgery may see improvement with prostaglandins and phosphodiesterase inhibitors [9] . ...
Partial anomalous pulmonary venous return (PAPVR) is a congenital heart anomaly in which some of the pulmonary veins return to the right atrium or one of its supplying veins instead of normally connecting with the left atrium. Oftentimes it is concurrent with a secundum atrial septal defect. PAPVR is typically asymptomatic, however symptoms of pulmonary hypertension can arise at higher degrees of left-to-right shunting. An 80-year-old male presented with exertional dyspnea and was found to have a secundum atrial septal defect on echocardiogram. A subsequent contrast enhanced computed tomography of the chest revealed a concomitant PAPVR.
... Patients with cardiac defects which result in left-to-right shunting are at risk of developing PH, owing to the increased shear stress and circumferential stretch induced by increased pulmonary blood flow, which leads to endothelial dysfunction and progressive vascular remodeling and, thus, increased pulmonary vascular resistance [6]. For large VSD, there is a large left-to-right shunt at the ventricular level, leading to early increased pulmonary artery pressure, often with repeated pneumonia, congestive heart failure and growth retardation, and even life-threatening [7,8]. ...
Background: Real-time three-dimensional echocardiography (RT-3DE) could obtain ventricular volume and ejection fraction rapidly and non-invasively without relying on ventricular morphology. This study aims to use RT-3DE to evaluate the changes in biventricular volume and systolic function in children with ventricular septal defect (VSD) and moderate to severe pulmonary hypertension (PH) before surgery. Methods: In this study 18 children with VSD and moderate to severe PH (VSD + PH Group) and 18 healthy children of the same age (Control Group) were recruited. Biventricular volume and systolic function were evaluated by RT-3DE. The measurements included: left and right ventricular volume indexed to body surface area (BSA), stroke volume (SV) indexed to BSA, and ejection fraction (EF). Results: The results showed left and right ventricular volume indexed to BSA and SV indexed to BSA were significantly increased in VSD + PH Group (VSD + PH Group vs. Control Group), LVEDV/BSA (ml/m²): 48.67 ± 21.46 vs. 25.59 ± 6.96, RVEDV/BSA (ml/m² ): 55.98 ± 15.35 vs. 27.69 ± 4.37, LVSV/BSA (ml/m²): 24.08 ± 9.30 vs. 15.14 ± 4.29, RVSV/BSA (ml/m²): 26.02 ± 8.87 vs. 14.11 ± 2.89, (P < 0.05). While for EF in VSD + PH Group decreased (VSD + PH Group vs. Control Group), LVEF: 50.93 ± 7.50% vs. 59.38 ± 7.24%, RVEF: 45.84 ± 7.71% vs. 51.05 ± 6.90% (P < 0.05). Conclusion: In children with VSD and moderate to severe PH, increased biventricular volume and decreased systolic function were observed with RT-3DE, but biventricular systolic function remained within acceptable limits. The children in this study recovered well after surgery without serious perioperative complications, suggesting that biventricular systolic function may help facilitate the surgical decision-making process in children with VSD and moderate-to-severe PH.
... The progress in surgical strategies and personalized treatments was witnessed in CHD-PAH, both in basic research and clinical applications, and the qualities of life and survival rates of patients were significantly improved [7][8][9]. However, those who survive surgery may remain at risk of persistent PAH and the prognosis may be considerably worse for patients with postoperative PAH than those unoperated [10,11]. ...
The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD–PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD–PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO3), bicarbonate in superior vena cava (svcHCO3), and the partial pressure of dissolved CO2 gas in radial artery (aPCO2) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO3, svcHCO3, and aPCO2, would be of great value in disease monitoring and evaluating future therapeutic interventions.
... The incidence of PAH secondary to congenital heart disease is estimated as 1.6-12.5 case/million/ year. The increased pulmonary blood flow in Congenital Heart Disease (CHD) with left-to-right shunts induces endothelial cell injury and apoptosis and increases pulmonary arterial pressure with neo-intimal development and pulmonary vascular remodeling [3] . Specific PAH-target drugs have improved the quality of life and survival by preventing pulmonary vascular remodeling [4] . ...
... The mechanisms of shear stress on EVs secretion relate to the response of membrane tension (69). Besides, calcium could enhance exosomes secretion from a microenvironment perspective (70), whereas arterial hypertension was also associated with the increase of shear stress from a macro perspective (71). Evidence proved that exercise training could increase EVs release under high shear stress, and decrease the risk of thrombosis correspond to stenotic arteries (72). ...
Exosomes, with an diameter of 30~150 nm, could be released from almost all types of cells, which contain diverse effective constituent, such as RNAs, proteins, lipids, and so on. In recent years, exosomes have been verified to play an important role in mechanism, diagnosis, treatment, and prognosis of cardiovascular disease, especially coronary artery disease (CAD). Moreover, it has also been shown that exosomes derived from different cell types have various biological functions based on the cell stimulation and microenvironment. However, therapeutic exosomes are currently far away from clinical translation, despite it is full of hope. In this review, we summarize an update of the recent studies and systematic knowledge of therapeutic exosomes in atherosclerosis, myocardial infarction, and in-stent restenosis, which might provide a novel insight into the treatment of CAD and promote the potential clinical application of therapeutic exosomes.
... Murmurs associated with valvular regurgitation might be present but murmurs due to shunts and due to an increased flow (distal to the shunt) disappear upon the development of Eisenmenger syndrome. 3 Cardiomegaly, congestive heart failure, the presence of a third heart sound and flow-related murmurs favor operability. Cardiac catheterization is an important tool in the assessment of PVD in these patients with borderline evidence of operability. ...
... This implies that the pruning of the distal pulmonary vasculature in PAH may be a way for the lung to preserve microvascular perfusion by increasing microvascular resistance and elevating shear stress [74]. However, like congenital heart disease, the microvasculature in PAH may also experience high shear stress or high oscillations in flow, sue to increased stiffness in the pulmonary arteries [75]. Despite the lower shear stress in the main pulmonary arteries, the pulsatility may elevate in the microvasculature and the stiffness of the arteries increases, which explains the coupling of microvascular dysfunction with macrovascular dysfunction. ...
Pulmonary arterial hypertension (PAH) is a rare, complex, and progressive disease that is characterized by the abnormal remodeling of the pulmonary arteries that leads to right ventricular failure and death. Although our understanding of the causes for abnormal vascular remodeling in PAH is limited, accumulating evidence indicates that endothelial cell (EC) dysfunction is one of the first triggers initiating this process. EC dysfunction leads to the activation of several cellular signalling pathways in the endothelium, resulting in the uncontrolled proliferation of ECs, pulmonary artery smooth muscle cells, and fibroblasts, and eventually leads to vascular remodelling and the occlusion of the pulmonary blood vessels. Other factors that are related to EC dysfunction in PAH are an increase in endothelial to mesenchymal transition, inflammation, apoptosis, and thrombus formation. In this review, we outline the latest advances on the role of EC dysfunction in PAH and other forms of pulmonary hypertension. We also elaborate on the molecular signals that orchestrate EC dysfunction in PAH. Understanding the role and mechanisms of EC dysfunction will unravel the therapeutic potential of targeting this process in PAH.
