Pulmonary Hypertension in Women.

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by elevated pulmonary artery pressure and increased pulmonary vascular resistance. Females have a higher incidence of PAH, which is reflected globally across registries in the United States, Europe, and Asia. However, despite female predominance, women had better outcomes compared with male patients, a finding that has been labeled the "estrogen paradox." Special considerations should be given to women with PAH regarding sexual health, contraception, family planning, and treatment before, during, and after pregnancy. Pregnant women with PAH should be referred to a pulmonary hypertension care center; a multidisciplinary team approach is recommended, and Cesarean section is the preferred mode of delivery. While pregnancy outcomes have improved over the years with PAH-specific therapy, pregnancy portends a high-risk for those with PAH. Continued research is needed to tailor PAH treatment for women.

Exploring the pathogenesis of pulmonary vascular disease.

Pulmonary hypertension (PH) is a complex cardiopulmonary disorder impacting the lung vasculature, resulting in increased pulmonary vascular resistance that leads to right ventricular dysfunction. Pulmonary hypertension comprises of 5 groups (PH group 1 to 5) where group 1 pulmonary arterial hypertension (PAH), results from alterations that directly affect the pulmonary arteries. Although PAH has a complex pathophysiology that is not completely understood, it is known to be a multifactorial disease that results from a combination of genetic, epigenetic and environmental factors, leading to a varied range of symptoms in PAH patients. PAH does not have a cure, its incidence and prevalence continue to increase every year, resulting in higher morbidity and mortality rates. In this review, we discuss the different pathologic mechanisms with a focus on epigenetic modifications and their roles in the development and progression of PAH. These modifications include DNA methylation, histone modifications, and microRNA dysregulation. Understanding these epigenetic modifications will improve our understanding of PAH and unveil novel therapeutic targets, thus steering research toward innovative treatment strategies.

Acute Myocardial Infarction in the Setting of Pulmonary Hypertension due to a Patent Foramen Ovale and Paradoxical Embolism.

A 67-year-old woman with pulmonary hypertension (PH) presented with a 1-day history of worsening shortness of breath and pleuritic chest pain and was found to have a troponin T level of 3755 ng/L (ref. range 0-19 ng/L). An initial diagnostic workup in the emergency department (ED) led to an urgent left heart catheterization which revealed a 90% occlusive right coronary artery blood clot, even though a recent heart catheterization less than a month prior was completely unremarkable. Further workup led to the discovery of a patent foramen ovale (PFO) and an aneurysmal interatrial septum, suggesting the presence of a paradoxical embolism. While typically asymptomatic, a PFO is an important clinical entity that can lead to irreversible cardiac damage. Suspicion should be high for this finding in the case of an acute myocardial infarction (MI) with no clear cause, especially in a patient with elevated right heart pressures.

Clinical impact of pulmonary arterial hypertension on SARS-CoV-2 outcomes: U.S. pre-vaccination analysis.

Our retrospective study aimed to determine how pulmonary arterial hypertension (PAH) influences the clinical outcomes of COVID-19 admissions by using data from the 2020 nationwide inpatient sample (NIS). Among the 1,018,915 adults who were hospitalized with COVID-19 in 2020, 155 also had a PAH diagnosis. After adjusting for all baseline demographics and co-morbidities through multivariate analysis, we found that in patients admitted with a principal diagnosis of COVID-19, PAH was not associated with an increased risk of mortality compared to those without PAH. (adjusted OR 0.58 [95% CI 0.2-1.6] p=0.3). In addition, patients with both COVID-19 and PAH showed no statistically significant difference in the odds of requiring mechanical ventilation (adjusted OR 1.1 [95% CI 0.5-2.6] p=0.9), vasopressor needs (adjusted OR 0.4 [95% CI 0.1-3.5] p=0.4), acute kidney injury necessitating renal replacement therapy(adjusted OR 0.7 [95% CI 0.3-1.7] p=0.5), mean length of stay (LOS) (11.1 vs. 7.5 days), adjusted difference 3.1 [95% CI -3.8- 10.1] p=0.37) or mean total hospitalization charges ($195,815 vs $79,082, adjusted difference 107,146 [95% CI -93,939 - 308,232] p=0.29). Further studies are needed to investigate this subpopulation during the post-vaccination era to observe the effects of outcomes in these patients.

Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies.

INTRODUCTION: Portopulmonary hypertension (PoPH) carries a worse prognosis than other forms of pulmonary arterial hypertension (PAH). Data regarding use of PAH-specific therapies in patients with PoPH are sparse as they are usually excluded from clinical trials. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles in patients with PoPH newly initiating macitentan in the USA using the OPUS/OrPHeUS combined dataset. METHODS: OPUS was a prospective, US, multicenter, observational drug registry (April 2014-June 2020); OrPHeUS was a retrospective, US, multicenter chart review (October 2013-March 2017). Additional information regarding patients' liver disease was retrospectively collected for patients with PoPH in OPUS. RESULTS: The OPUS/OrPHeUS dataset included 206 patients with PoPH (median age 58 years; 52.4% female), with baseline cirrhosis and liver test abnormalities reported in 72.8% and 31.6% of patients respectively. Macitentan was initiated as combination therapy in 74.8% of patients and median (Q1, Q3) exposure to macitentan was 11.9 (3.1, 26.0) months. One-year Kaplan-Meier estimates (95% confidence limit, CL) of patients free from all-cause hospitalization and survival were 48.6% (40.7, 56.0) and 82.2% (75.1, 87.4). Of the 96 patients with PoPH in OPUS, 29.2% were classified as in need of liver transplant due to underlying liver disease during the study; transplant waitlist registration was precluded because of PAH severity for 32.1% and 17.9% were transplanted. Hepatic adverse events (HAE) were experienced by 49.0% of patients; the most common being increased bilirubin (16.0%), ascites (7.3%), and hepatic encephalopathy (5.8%); 1.5% and 21.8% of patients discontinued macitentan as a result of HAE and non-hepatic adverse events. CONCLUSION: There were no unexpected safety findings in patients with PoPH treated with macitentan. These data add to the evidence supporting the safety and tolerability of macitentan in patients with PoPH. A graphical abstract is available with this article. TRIAL REGISTRATION: OPsumit® Users Registry (OPUS): NCT02126943; OPsumit® Historical Users cohort (OrPHeUS): NCT03197688; www. CLINICALTRIALS: gov .