Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD-associated drug targets for PH.

Among congenital cyanotic heart diseases (CHDs), situs inversus totalis with transposition of great vessels with a large ventricular septal defect (VSD) has a very low incidence of around 1 in 10,000. Hereby, we present a 16-year-old man with the aforementioned cardiac anomaly with cardiac arrhythmias, septic shock, and a history of road traffic accident-causing osteomyelitis of the left thigh requiring incision and drainage. The patient was admitted to the intensive care unit with a high-grade fever, narrow pulse pressure, and atrial fibrillation. The patient was operated on under general anesthesia with endotracheal intubation after optimization. Invasive monitoring, antiarrhythmics, and vasopressors were required intraoperatively, and surgery progressed uneventfully. Furthermore, the patient had undergone a series of debridements after 8 days, which were performed under regional anesthesia uneventfully. This case report represents a plan of action for perioperative anesthetic management and anticipates the difficulties for CHD patients in the course of surgery and subsequential prudence.

BACKGROUND: Myopathy, lactic acidosis and inherited sideroblastic anemia (MLASA) are a group of rare intriguing disorders with wider pathophysiological implications. One of the causes of MLASA is the mutation in PUS1 gene that encodes for pseudouridine synthase. This PUS1 mutation results in MLASA in which anemia and myopathy predominate. Severe pulmonary arterial hypertension has not been previously reported in patients with PUS1 gene mutation.
METHODS: A 17 year old girl with congenital sideroblastic anemia presented with worsening of breathlessness. Severe pulmonary artery hypertension was documented on investigations. A homozygous variant in exon 3 of gene PUS1,( chromosome 12:g.131932301 C > T c.430 C > T) was found on sanger sequencing.
CONCLUSIONS: We document severe pulmonary arterial hypertension in a patient of congenital sideroblastic anemia from PUS1 gene. We hypothesis that cross talk with TGFb pathways might occur in PUS1 mutation, and that might cause severe PAH. This observation might have therapeutic implications.

Atrial septal defects (ASDs), comprising a significant portion of congenital cardiac anomalies, encompass a rarer and more diagnostically challenging subset known as sinus venosus ASDs (SVASDs). ASDs are more prevalent in females, and the prognosis for patients under 40 years of age is generally favorable with advancements in surgical and transcatheter interventions. However, undiagnosed ASDs in adults above 40 years old, especially females, often lead to severe complications, including pulmonary hypertension, atrial fibrillation, Eisenmenger syndrome, and a mortality rate exceeding 50%. Our detailed case study focuses on an obese 42-year-old Hispanic migrant female with chronic respiratory failure misattributed to pulmonary hypertension, resulting in the progression of complications from undiagnosed SVASD. Further investigation using contrast-enhanced transesophageal echocardiography (TEE) elucidated the correct diagnosis four years after her initial presentation. This report explores the potential factors contributing to the patient\'s delayed diagnosis and development of advanced cardiac complications of pulmonary hypertension leading to Eisenmenger syndrome that precluded her from procedural intervention. Furthermore, this report pioneers the first thorough review of case reports in adults newly diagnosed with SVASD, revealing sex-based differences in complications.

OBJECTIVE: Vasopressin has systemic vasoconstrictive yet pulmonary vasodilatory effects, making it an ideal agent for hypotension management in infants with congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension. The side effects of vasopressin in this population, such as hyponatremia, are understudied. This study aims to characterize the effect of vasopressin on sodium concentrations in infants with and without CDH.
METHODS: This was a retrospective review of patients who received vasopressin while admitted to a level IV neonatal intensive care unit. The primary outcome was the incidence of hyponatremia (blood sodium <135 mmol/L) during vasopressin therapy. Secondary outcomes included time to hyponatremia, dose and duration of vasopressin, incidence of severe hyponatremia (blood sodium <125 mmol/L), and hypertonic saline use. Both blood serum and blood gas sample sodium concentrations were used to compare CDH vs non-CDH patients.
RESULTS: The average difference between baseline and lowest blood sodium was significant for both CDH and non-CDH patients for all samples (p < 0.001). There was no significant difference in the primary outcome, nor in the secondary outcomes of time to hyponatremia or duration of vasopressin infusion. The average dose of vasopressin was higher in the CDH vs non-CDH group (p = 0.018). The incidences of severe hyponatremia and hypertonic saline use were greater in the CDH vs non-CDH group for patients who had blood serum sodium samples collected (p = 0.049 and p = 0.033, respectively).
CONCLUSIONS: This study showed that severe hyponatremia occurred more frequently in CDH vs non-CDH patients. Extreme caution is necessary when managing total body sodium in patients with CDH.

Expanding upon the critical advancements brought forth by single-cell omics in pulmonary hypertension (PH) research, this review delves deep into how these technologies have been piloted in a new era of understanding this complex disease. By leveraging the power of single cell transcriptomics (scRNA-seq), researchers can now dissect the complicated cellular ecosystem of the lungs, examining the key players such as endothelial cells, smooth muscle cells, pericytes, and immune cells, and their unique roles in the pathogenesis of PH. This more granular view is beyond the limitations of traditional bulk analysis, allowing for the identification of novel therapeutic targets previously obscured in the aggregated data. Connectome analysis based on single-cell omics of the cells involved in pathological changes can reveal a clearer picture of the cellular interactions and transitions in the cellular subtypes. Furthermore, the review acknowledges the challenges that lie ahead, including the need for enhancing the resolution of scRNA-seq to capture even finer details of cellular changes, overcoming logistical barriers in processing human tissue samples, and the necessity of integrating diverse omics approaches to fully comprehend the molecular underpinnings of PH. The promise of these single-cell technologies is immense, offering the potential for targeted drug development and the discovery of biomarkers for early diagnosis and disease monitoring. Through these advancements, the field moves closer to realizing the goal of precision medicine for patients with PH.

Sickle cell disease (SCD) is associated with substantial morbidity and early mortality in afflicted adults. Cardiopulmonary complications that occur at increased frequency in SCD such as pulmonary embolism, pulmonary arterial hypertension, and acute chest syndrome can acutely worsen right ventricular function and lead to cardiogenic shock. Mechanical circulatory support including venoarterial extracorporeal membrane oxygenation (VA ECMO) is being increasingly utilized to treat hemodynamic collapse in various patient populations. However, a paucity of literature exists to guide the use of mechanical circulatory support in adults with SCD where disease-related sequela and unique hematologic aspects of this disorder may complicate extracorporeal therapy and must be understood. Here, we review the literature and describe three cases of adult patients with SCD who developed cardiogenic shock from acute decompensated right heart failure and were treated clinically with VA ECMO. Using an in vitro ECMO system, we investigate a potential increased risk of systemic fat emboli in patients with SCD who may be experiencing vaso-occlusive events with bone marrow involvement given the high-volume shunting of blood from venous to arterial systems with VA ECMO. The purpose of this study is to describe available extracorporeal life support experiences, review potential complications, and discuss the special considerations needed to further our understanding of the utility of VA ECMO in those with SCD.

UNASSIGNED: To evaluate the effectiveness of the surgical approach in patients with congenital heart disease and pulmonary hypertension (PH).
UNASSIGNED: This was a retrospective clinical review of patients with congenital heart disease and PH who underwent pulmonary artery banding (PAB) at our institution between January 2013 and January 2023.
UNASSIGNED: We identified 219 patients (53.4% males) with a median age of 7 (4.0-15.0) months and a median weight of 6.8 (5.2-9.0) kg at the time of PAB. The median hospital stay was 7.0 (5.0-10.0) days. The in-hospital mortality rate was 4.6%. The median follow-up was 33.0 (17.0-61.0) months. Survival rates were 96.9 ± 2.5% at 60 months and 92.1 ± 6.9% at 120 months post-PAB. 43.8% of patients had a de-banding procedure, and 147 (79.0%) patients received a second-stage procedure (34.7% univentricular, 65.3% biventricular). The mortality rate between stages was 4.3%. 21 (9.6%) patients reached a third-stage procedure. The overall mortality rate was 9.1%.
UNASSIGNED: PAB is an acceptable strategy for patients with congenital heart disease complicated with PH. The results and outcomes of subsequent univentricular or biventricular procedures are generally good.

Integrative multiomics can help elucidate the pathophysiology of pulmonary fibrosis (PF) associated pulmonary hypertension (PH) (PF-PH). Weighted gene co-expression network analysis (WGCNA) was performed on a transcriptomic dataset of explanted lung tissue from 116 patients with PF. Patients were stratified by pulmonary vascular resistance (PVR) and differential gene expression analysis was conducted. Gene modules were correlated with hemodynamics at the time of transplantation and tested for enrichment in the lung transcriptomics signature of an independent pulmonary arterial hypertension (PAH) cohort. We found 1,250 differentially expressed genes between high and low PVR groups. WGCNA identified that black and yellowgreen modules negatively correlated with PVR, while the tan and darkgrey modules positively correlated with PVR. Additionally, the tan module showed the strongest enrichment for an independent PAH gene signature, suggesting shared gene expression patterns between PAH and PF-PH. Pharmacotranscriptomic analysis using the Connectivity Map implicated the tan and darkgrey modules as potentially pathogenic in PF-PH, given their combined module signature demonstrated a high negative connectivity score for Treprostinil, a medication used in the treatment of PF-PH, and a high positive connectivity score for Bone morphogenetic protein loss of function. Pathway enrichment analysis revealed that inflammatory pathways and oxidative phosphorylation were downregulated, whereas epithelial mesenchymal transition was upregulated in modules associated with increased PVR. Our integrative systems biology approach to the lung transcriptome of PF with and without PH identified several PH-associated co-expression modules and gene targets with shared molecular features with PAH warranting further investigation to uncover potential new therapies for PF-PH.

Pulmonary hypertension (PH) is a chronic progressive disease with high mortality. There has been more and more research focusing on the role of AMPK in PH. AMPK consists of three subunits-α, β, and γ. The crosstalk among these subunits ultimately leads to a delicate balance to affect PH, which results in conflicting conclusions about the role of AMPK in PH. It is still unclear how these subunits interfere with each other and achieve balance to improve or deteriorate PH. Several signaling pathways are related to AMPK in the treatment of PH, including AMPK/eNOS/NO pathway, Nox4/mTORC2/AMPK pathway, AMPK/BMP/Smad pathway, and SIRT3-AMPK pathway. Among these pathways, the role and mechanism of AMPK/eNOS/NO and Nox4/mTORC2/AMPK pathways are clearer than others, while the SIRT3-AMPK pathway remains still unclear in the treatment of PH. There are drugs targeting AMPK to improve PH, such as metformin (MET), MET combination, and rhodiola extract. In addition, several novel factors target AMPK for improving PH, such as ADAMTS8, TUFM, and Salt-inducible kinases. However, more researches are needed to explore the specific AMPK signaling pathways involved in these novel factors in the future. In conclusion, AMPK plays an important role in PH.