Pulmonary Circulation

Current predictors of clinical outcomes after pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are largely limited to preoperative clinical characteristics. N-terminal-pro-brain natriuretic peptide (NT-pro-BNP), a biomarker of right ventricular dysfunction, has not yet been well described as one such predictor. From 2017 to 2021, 816 patients with CTEPH referred to the University of California, San Diego for PTE were reviewed for differences in NT-pro-BNP to predict preoperative characteristics and postoperative outcomes up to 30 days post-PTE...

Lung transplantation remains an important therapeutic option for idiopathic pulmonary arterial hypertension (IPAH), yet short-term survival is the poorest among the major diagnostic categories. We sought to develop a prediction model for 90-day mortality using the United Network for Organ Sharing database for adults with IPAH transplanted between 2005 and 2021. Variables with a p  value ≤ 0.1 on univariate testing were included in multivariable analysis to derive the best subset model...

Information on factors leading to pulmonary arterial hypertension (PAH) treatment discontinuation is limited. This study analyzed 12,902 new PAH medication users to identify predictors of treatment discontinuation. Treatment by accredited pulmonary hypertension centers and combination therapy with PAH agents from different classes were less likely to result in discontinuation.

Pulmonary arterial hypertension (PAH) is driven by pathologies associated with increased metabolism such as pulmonary revascularization, vasoconstriction and smooth muscle cell proliferation in pulmonary artery wall. 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) is an imaging technique sensitive to glucose metabolism and might be considered as a non-invasive method for diagnosis due to significant role of inflammation in idiopathic pulmonary artery hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH)...

Cardiac catheterization remains the gold standard for the diagnosis and management of pediatric pulmonary hypertension (PH). There is lack of consensus regarding optimal anesthetic and airway regimen. This retrospective study describes the anesthetic/airway experience of our single center cohort of pediatric PH patients undergoing catheterization, in which obtaining hemodynamic data during spontaneous breathing is preferential. A total of 448 catheterizations were performed in 232 patients. Of the 379 cases that began with a natural airway, 274 (72%) completed the procedure without an invasive airway, 90 (24%) received a planned invasive airway, and 15 (4%) required an unplanned invasive airway...

Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor-κB (NF-κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF-κB activation on the serum levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in acute pulmonary microthromboembolism (APMTE) rats...

Reduced exercise capacity in pulmonary hypertension (PH) significantly impacts quality of life. However, the cause of reduced exercise capacity in PH remains unclear. The objective of this study was to investigate whether intrinsic skeletal muscle changes are causative in reduced exercise capacity in PH using preclinical PH rat models with different PH severity. PH was induced in adult Sprague-Dawley (SD) or Fischer (CDF) rats with one dose of SU5416 (20 mg/kg) injection, followed by 3 weeks of hypoxia and additional 0-4 weeks of normoxia exposure...

Right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) is associated with poor outcomes. Cardiac magnetic resonance imaging (cMRI) is the gold standard for volumetric assessment, and few reports have correlated 6-min walk distance (6MWD) and cMRI parameters in PAH. Cardiac Effort, (the number of heart beats used during 6-min walk test)/(6MWD), incorporates physiologic changes into walk distance and has been associated with stroke volume (SV) measured by nuclear imaging and indirect Fick...

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and critical malignancy-related disease characterized by acute progressive pulmonary hypertension (PH). In most cases of PTTM, the cancer can be diagnosed in advance. Identification of the primary cancer is valuable for PTTM diagnosis. Here, we present the case of a patient with PTTM due to early gastric carcinoma in whom the diagnosis of malignant cancer was not revealed until macroscopic autopsy findings. This case highlights the importance of recognizing causative occult early gastric cancer leading to PTTM in cases of acute progressive PH...

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study. I nhaled I m atinib P ulmonary A rterial H ypertension C linical T rial (IMPAHCT; NCT05036135) is a phase 2b/3, randomized, double-blind, placebo-controlled, dose-ranging, and confirmatory study. IMPAHCT is designed to identify an optimal AV-101 dose (phase 2b primary endpoint: pulmonary vascular resistance) and assess the efficacy (phase 3 primary endpoint: 6-min walk distance), safety, and tolerability of AV-101 dose levels in subjects with pulmonary arterial hypertension using background therapies...

Compared to healthy volunteers, participants with post-acute sequelae of SARS-CoV-2 infection (PASC) demonstrated increased plasma levels of the prothrombotic protein NEDD9, which associated inversely with indices of pulmonary vascular function. This suggests persistent pulmonary vascular dysfunction may play a role in the pathobiology of PASC.

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat)...

Pulmonary endarterectomy (PEA) is a standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH combined with bronchial obstruction by a tumor is rare but should be assessed carefully because PEA for obstructed segments can be less therapeutic and make the subsequent surgical resection challenging. This report describes a case of CTEPH with bronchial obstruction by a typical carcinoid tumor in a 75-year-old man. On-site evaluation and removal of the obstructive tumor were performed bronchoscopically, increasing the effectiveness of subsequent PEA for all affected pulmonary segments...

Genetic research and testing are increasingly important for understanding and treating pulmonary arterial hypertension. We aimed to explore how attitudes toward genetic research among clinical and research teams impacted the engagement in genetic research and the integration of genetic insights into clinical practice. We conducted 53 semistructured interviews and focus groups with patients, clinicians, and researchers from nine UK Pulmonary Hypertension centers, who had genetic research experience. Transcripts were thematically coded using inductive analysis...

Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator with a safety concern due to rebound pulmonary hypertension (PH) associated with its withdrawal. We report short-term pulsed iNO in patients with severe pulmonary arterial hypertension (PAH) and nonoperable chronic thromboembolic PH (nCTEPH). This is a retrospective analysis of 33 patients: 22 with PAH and 11 with nCTEPH. We assessed hemodynamic, echocardiographic, and other noninvasive variables to evaluate safety and efficacy of iNO...

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment...

Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono- vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open-label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America...

Observational studies have confirmed that 25-hydroxyvitamin D (25(OH)D) is associated with pulmonary hypertension (PH), but the causal association between each other is unclear. Therefore, Mendelian randomization (MR) method was performed to validate the causal association between PH and serum 25(OH)D levels. The summary data for 25(OH)D and PH were from the National Human Genome Research Institute-European Bioinformatics Institute. Catalog of human genome-wide association studies and FinnGen biobank consortium...

We analyzed the effect of respiratory swings on interpreting intravascular pulmonary vascular pressures (PVPs) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) candidates for lung transplantation (LTx) and the role of the alterations in pulmonary function tests on the dynamic respiratory variations. Twenty-eight consecutive patients were included. All patients underwent a complete hemodynamic study (right atrial, mean pulmonary arterial, and pulmonary arterial occlusion pressures [RAP, mPAP, and PAOP]-) and pulmonary function testing (force vital capacity [FVC], forced expiratory volume in the first second [FEV1], and residual volume [RV])...

Symptoms associated with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) impact patient's health-related quality of life (HRQoL). Studies on change and if a minimal clinically important difference (MCID) in HRQoL is reached within a year after diagnosis are lacking. The aim was to investigate the change in HRQoL as well as the proportion of patients that reached MCID at an early postdiagnosis visit. The study included adult patients from the Swedish PAH & CTEPH registry, diagnosed 2008-2021, with Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) at time of diagnosis and a follow-up...