Gut Microbiome and Pulmonary Arterial Hypertension - A Novel and Evolving Paradigm.

Pulmonary arterial hypertension is characterized by perivascular and systemic inflammation. The gut microbiome influences the host immune system. Here we review the emerging preclinical and clinical evidence that strongly suggests that alterations in the gut microbiome may either initiate or facilitate progression of established pulmonary arterial hypertension by modifying the systemic immune responses.

Restructures the Micro/Mycobiome to Combat Glycoprotein-130 Associated Microtubule Remodeling and Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.

Emerging data demonstrate systemic and local inflammation regulate right ventricular (RV) adaption in preclinical and human pulmonary arterial hypertension (PAH). Pathological RV inflammation is targetable as antagonism of glycoprotein-130 (GP130) signaling counteracts pathological microtubule remodeling and improves RV function in rodents. Microtubules control several aspects of cardiomyocyte biology including cellular and nuclear size/structure, t-tubule homeostasis, and the proper localization of connexin-43.

Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results.

Background: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.

Extrapulmonary manifestations of pulmonary arterial hypertension.

Introduction: Extrapulmonary manifestations of pulmonary arterial hypertension (PAH) may play a critical pathobiological role and a deeper understanding will advance insight into mechanisms and novel therapeutic targets. This manuscript reviews our understanding of extrapulmonary manifestations of PAH.

Areas Covered: A group of experts was assembled and a complimentary PubMed search performed (October 2023 - March 2024).

Ketone bodies in right ventricular failure: A unique therapeutic opportunity.

Background: Ketone bodies are pleotropic metabolites that play important roles in multiple biological processes ranging from bioenergetics to inflammation regulation via suppression of the NLRP3 inflammasome, and epigenetic modifications. Ketone bodies are elevated in left ventricular failure (LVF) and multiple approaches that increase ketone concentrations exert advantageous cardiac effects in rodents and humans. However, the relationships between ketone bodies and right ventricular failure (RVF) are relatively unexplored.

Sex differences in right ventricular function between Groups 1 and 3 pulmonary hypertension.

Group 3 pulmonary hypertension (PH) patients have disproportionate right ventricular dysfunction (RVD) compared to pulmonary arterial hypertension. We evaluated how sex and PH etiology modulated RVD. Strain echocardiography showed no intrasex differences between PH types.

Pulmonary tumor thrombotic microangiopathy: Exploration into current diagnostic aids and therapeutics.

Pulmonary tumor thrombotic microangiopathy (PTTM) is an under-recognized cause of pulmonary hypertension and fulminant right ventricle failure. It is associated with a high mortality due to delay in diagnosis. We present two cases of PTTM, both diagnosed postmortem, highlighting the importance of timely identification and initiation of treatment for this near-fatal condition.

Effect of Combination of Balloon Pulmonary Angioplasty and Medical Therapy on Reverse Right Ventricular Remodeling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive and debilitating disorder that results from incomplete resolution of vascular obstructions resulting in pulmonary hypertension. Surgical pulmonary thromboendarterectomy (PTE) is the treatment of choice for CTEPH. Unfortunately, many CTEPH patients are ineligible for PTE or do not have access to an expert surgical center.

Ketone Bodies in Right Ventricular Failure: A Unique Therapeutic Opportunity.

Ketone bodies are pleotropic metabolites that play important roles in multiple biological processes ranging from bioenergetics to inflammation regulation via suppression of the NLRP3 inflammasome, and epigenetic modifications. Ketone bodies are elevated in left ventricular failure (LVF) and multiple approaches that increase ketone concentrations exert advantageous cardiac effects in rodents and humans. However, the relationships between ketone bodies and right ventricular failure (RVF) are relatively unexplored.

Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study.

Introduction: The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD). The open-label extension (OLE) evaluated long-term effects of inhaled treprostinil in PH-ILD.

Methods: Of 258 eligible patients, 242 enrolled in the INCREASE OLE and received inhaled treprostinil.

Effect of Chronic Digoxin Use on Mortality and Heart Failure Hospitalization in Pulmonary Arterial Hypertension.

Background Digoxin acutely increases cardiac output in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, the effects of chronic digoxin use in PAH are unclear. Methods and Results Data from the Minnesota Pulmonary Hypertension Repository were used. The primary analysis used likelihood of digoxin prescription.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Riociguat and the right ventricle in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive diseases that can lead to right heart failure and death. Right ventricular dysfunction, hypertrophy and maladaptive remodelling are consequences of increased right ventricular (RV) afterload in PAH and CTEPH and are indicative of long-term outcomes. Because RV failure is the main cause of morbidity and mortality in PAH and CTEPH, successful treatments should lead to improvements in RV parameters.

Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR).

Background: Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population.

Outcomes of Patients Referred for Cardiac Rehabilitation After Left Ventricular Assist Device Implantation.

A single-center continuous-flow left ventricular assist device (LVAD) cohort (n = 503) was reviewed for patients with information on cardiac rehabilitation (CR) participation (n = 273) over a 13-year period. The analysis was then limited LVAD recipients who fit into three main CR categories: those who graduated CR (n = 138), those who were able to but declined participation (n = 61), and those who were too sick to complete or start CR (n = 28). To assess the association between CR categories and mortality and hospitalizations on LVAD support, multivariate cox regression and negative binomial regression analyses were performed, respectively.

Hypotension on cardiopulmonary stress test predicts 90 day mortality after LVAD implantation in INTERMACS 3-6 patients.

Aims: Cardiopulmonary stress test (CPX) is routinely performed when evaluating patient candidacy for left ventricular assist device (LVAD) implantation. The predictive value of hypotensive systolic blood pressure (SBP) response during CPX on clinical outcomes is unknown. This study aims to determine the effect of hypotensive SBP response during to clinical outcomes among patients who underwent LVAD implantation.

Elucidating the Clinical Implications and Pathophysiology of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Call to Action: A Science Advisory From the American Heart Association.

This science advisory focuses on the need to better understand the epidemiology, pathophysiology, and treatment of pulmonary hypertension in patients with heart failure with preserved ejection fraction. This clinical phenotype is important because it is common, is strongly associated with adverse outcomes, and lacks evidence-based therapies. Our goal is to clarify key knowledge gaps in pulmonary hypertension attributable to heart failure with preserved ejection fraction and to suggest specific, actionable scientific directions for addressing such gaps.