Clinical impact of subcutaneous treprostinil in trisomy 21 patient with pulmonary arterial hypertension associated with CHD

Subcutaneous treprostinil is commonly used to improve idiopathic pulmonary arterial hypertension in children. However, its effectiveness has not been reported in trisomy 21. We report the case of 9-year-old boy in trisomy 21 with CHD-pulmonary artery hypertension after surgical correction of CHD. Haemodynamics and exercise capacity dramatically improved with a transition from oral selexipag to subcutaneous treprostinil.

Multiscale modelling of Potts shunt as a potential palliative treatment for suprasystemic idiopathic pulmonary artery hypertension: a paediatric case study

Potts shunt (PS) was suggested as palliation for patients with suprasystemic pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. PS, however, can result in poorly understood mortality. Here, a patient-specific geometrical multiscale model of PAH physiology and PS is developed for a paediatric PAH patient with stent-based PS. In the model, 7.6mm-diameter PS produces near-equalisation of the aortic and PA pressures and $$Q_p/Q_s$$ Q p / Q s (oxygenated vs deoxygenated blood flow) ratio of 0.72 associated with a 16% decrease of left ventricular (LV) output and 18% increase of RV output. The flow from LV to aortic arch branches increases by 16%, while LV contribution to the lower body flow decreases by 29%. Total flow in the descending aorta (DAo) increases by 18% due to RV contribution through the PS with flow into the distal PA branches decreasing. PS induces 18% increase of RV work due to its larger stroke volume pumped against lower afterload. Nonetheless, larger RV work does not lead to increased RV end-diastolic volume. Three-dimensional flow assessment demonstrates the PS jet impinging with a high velocity and wall shear stress on the opposite DAo wall with the most of the shunt flow being diverted to the DAo. Increasing the PS diameter from 5mm up to 10mm results in a nearly linear increase in post-operative shunt flow and a nearly linear decrease in shunt pressure-drop. In conclusion, this model reasonably represents patient-specific haemodynamics pre- and post-creation of the PS, providing insights into physiology of this complex condition, and presents a predictive tool that could be useful for clinical decision-making regarding suitability for PS in PAH patients with drug-resistant suprasystemic PAH.

Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies

Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.

Can Severity of Pulmonary Hypertension Affect Success Rate of Balloon Mitral Commissurotomy?

Introduction: Rheumatic heart disease is responsible for the most prevalent pathological causes of mitral stenosis and is closely coupled with pulmonary hypertension. Balloon mitral commissurotomy as an alternative method for mitral valve replacement leads to a reduction in pulmonary pressure. All grades of pulmonary hypertension usually regress after mitral commissurotomy; however, the insignificant changes of pulmonary artery hypertension following balloon mitral valvuloplasty are not uncommon. Methods: This retrospective observational study was carried out on 160 patients with significant symptomatic mitral stenosis (mitral valve area [MVA] <1.5 cm ) who underwent successful percutaneous transvenous mitral commissurotomy (PTMC) within 2016-2020 at Shaheed Rajaie Cardiovascular, Medical and Research Center, Tehran, Iran. Results: In this study, 89.4% of the patients were female, and the mean age of the participants was 47.2±12.4 years. Most (74%) patients presented with dyspnea on exertion functional class II. The mean basic MVA was 1±0.20 cm that increased to 1.43±0.23 cm , and the mean basic systolic pulmonary artery pressure (PAP) was 43.84±11.93 mmHg that decreased to 35.13±7.7 mmHg. Persistent PAP after successful PTMC was observed in 34% of the patients. This group of patients showed smaller MVA gain and PAP reduction after the procedure. Pulmonary vascular resistance (PVR) > 2 Wood units was correlated to 91.7% of the post-procedural success rate. Conclusion: The PTMC plays an important role in the reduction of PAP; nevertheless, the chronicity and severity of PAP can lead to persistent pulmonary hypertension. The assessment of initial PAP and basic PVR can help select patients with more likely intended results.

CTRP9 Mitigates the Progression of Arteriovenous Shunt-Induced Pulmonary Artery Hypertension in Rats

The present study is aimed at investigating the molecular mechanism of C1q/TNF-related protein 9 (CTRP9) and providing a new perspective in arteriovenous shunt-induced pulmonary arterial hypertension (PAH). PAH was established by an arteriovenous shunt placement performed in rats. Adenovirus(Ad)-CTRP9 and Ad-green fluorescent protein viral particles were injected into the rats through the tail vein. Following 12 weeks, the mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured and morphological analysis was conducted to confirm the establishment of the PAH model. The systemic elevation of CTRP9 maintained pulmonary vascular homeostasis and protected the rats from dysfunctional and abnormal remodeling. CTRP9 attenuated the pulmonary vascular remodeling in the shunt group by decreasing the mPAP and RVSP, which was associated with suppressed inflammation, apoptosis, and extracellular matrix injury. In addition, CTRP9 dramatically increased the phosphorylation of AKT and p38-MAPK in the lung tissues of shunt-operated animals. These findings suggest a previously unrecognized effect of CTRP9 in pulmonary vascular homeostasis during PAH pathogenesis.

Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension

Once perceived as a disorder treated by vasodilation, pulmonary artery hypertension (PAH) has emerged as a pulmonary vascular disease with severe endothelial cell dysfunction. In the absence of a cure, many studies seek to understand the detailed mechanisms of EC regulation to potentially create more therapeutic options for PAH. Endothelial dysfunction is characterized by complex phenotypic changes including unchecked proliferation, apoptosis-resistance, enhanced inflammatory signaling and metabolic reprogramming. Recent studies have highlighted the role of epigenetic modifications leading to pro-inflammatory response pathways, endothelial dysfunction, and the progression of PAH. This review summarizes the existing literature on epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, which can lead to aberrant endothelial function. Our goal is to develop a conceptual framework for immune dysregulation and epigenetic changes in endothelial cells in the context of PAH. These studies as well as others may lead to advances in therapeutics to treat this devastating disease.

Assessing the spectrum of pulmonary hypertension identified at an Egyptian expert referral center

Background and objective Pulmonary hypertension is an assorted state that encompasses a spectrum of diseases and is categorized into five groups. The registries are necessary for the identification of risk factors, progression of the disease, outcomes, and effect of treatment strategies on the progression of the disease. The aim of this work was to identify different groups of PH identified at an Egyptian referral center and to compare the demographic and clinical characteristics of each group. Patients and methods This study included 132 patients who were diagnosed with a right heart catheter in the Chest Department, Kasr El-Aini Hospital, Faculty of Medicine, Cairo University, in the period from January 2017 to January 2019. Patients were classified into different groups, then received medical treatment accordingly. Demographic and clinical data were documented. Arterial blood gases, spirometry, and 6-minute walk test (6MWT) were performed. Results The mean age of cases was (43.9±13.69) years; the majority of them were females (72.7%). More than half of the patients (57.5%) had pulmonary artery hypertension (PAH), while 22.7% and 18.3% had pulmonary hypertension due to chronic thrombo-embolic cause and lung cause respectively. The 1-year survival rate was 81.8%. Conclusions The results of the study showed female predominance, the PAH type was the commonest, and the overall 1-year survival rate was 81.8%.