Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series).

Pulmonary vascular disease is not a single condition; rather it can accompany a variety of pathologies that impact the pulmonary vasculature. Applying precision medicine strategies to better phenotype, diagnose, monitor, and treat pulmonary vascular disease is increasingly possible with the growing accessibility of powerful clinical and research tools. Nevertheless, challenges exist in implementing these tools to optimal effect.

Carnitine consumption and effect of oral supplementation in human pulmonary arterial hypertension: A pilot study.

Carnitine is required to transport fatty acid across the mitochondrial membrane to undergo beta oxidation. In addition to disorders of fatty acid metabolism, a relative carnitine deficiency has been reported in pulmonary arterial hypertension (PAH). Here we performed an observational study in which food and supplement consumption were collected in an observation period followed by open label administration of a carnitine supplement to determine feasibility of increasing plasma carnitine levels in humans PAH.

Identifying consistent echocardiographic thresholds for risk stratification in pulmonary arterial hypertension.

Several indices of right heart remodeling and function have been associated with survival in pulmonary arterial hypertension (PAH). Outcome analysis and physiological relationships between variables may help develop a consistent grading system. Patients with Group 1 PAH followed at Stanford Hospital who underwent right heart catheterization and echocardiography within 2 weeks were considered for inclusion.

Frequency of acute vasodilator response (AVR) in incident and prevalent patients with pulmonary arterial hypertension: Results from the pulmonary vascular disease phenomics study.

The prevalence of acute vasodilator response (AVR) to inhaled nitric oxide (iNO) during right heart catheterization (RHC) is 12% in idiopathic pulmonary arterial hypertension (IPAH). AVR, however, is reportedly lower in other disease-associated pulmonary arterial hypertension (PAH), such as connective tissue disease (CTD). The prevalence of AVR in patients on PAH therapy (prevalent cases) is unknown.

Evolution and optimization of clinical trial endpoints and design in pulmonary arterial hypertension.

Selection of endpoints for clinical trials in pulmonary arterial hypertension (PAH) is challenging because of the small numbers of patients and the changing expectations of patients, clinicians, and regulators in this evolving therapy area. The most commonly used primary endpoint in PAH trials has been 6-min walk distance (6MWD), leading to the approval of several targeted therapies. However, single surrogate endpoints such as 6MWD or hemodynamic parameters may not correlate with clinical outcomes.

Clinical features do not identify risk of progression from isolated postcapillary pulmonary hypertension to combined pre- and postcapillary pulmonary hypertension.

Pulmonary hypertension is a common sequelae of left heart failure and may present as isolated postcapillary pulmonary hypertension (Ipc-PH) or combined pre- and postcapillary pulmonary hypertension (Cpc-PH). Clinical features associated with progression from Ipc-PH to Cpc-PH have not yet been described. We extracted clinical data from patients who underwent right heart catheterizations (RHC) on two separate occasions.

Rapid identification of sepsis in the emergency department.

Objectives: Recent research has helped define the complex pathways in sepsis, affording new opportunities for advancing diagnostics tests. Given significant advances in the field, a group of academic investigators from emergency medicine, intensive care, pathology, and pharmacology assembled to develop consensus around key gaps and potential future use for emerging rapid host response diagnostics assays in the emergency department (ED) setting.

Methods: A modified Delphi study was conducted that included 26 panelists (expert consensus panel) from multiple specialties.

Transpulmonary generation of cell-free hemoglobin contributes to vascular dysfunction in pulmonary arterial hypertension via dysregulated clearance mechanisms.

Circulating cell-free hemoglobin (CFH) is elevated in pulmonary arterial hypertension (PAH) and associated with poor outcomes but the mechanisms are unknown. We hypothesized that CFH is generated from the pulmonary circulation and inadequately cleared in PAH. Transpulmonary CFH (difference between wedge and pulmonary artery positions) and lung hemoglobin α were analyzed in patients with PAH and healthy controls.

Pulmonary Hypertension Association's 2022 International Conference Scientific Sessions Overview.

The considerable progress made in recent years in the diagnosis, risk stratification, and treatment of pulmonary hypertension was highlighted during the most recent edition of the Pulmonary Hypertension Association Scientific Sessions, which was held in Atlanta, Georgia from June 9 to 11, 2022, with the theme: Vision for the PHuture: The Evolving Science and Management of PH. Content presented over the 3-day conference focused on scientific and management updates since the last sessions were held in 2018 and included didactic talks, debates, and roundtable discussions across a broad spectrum of topics related to pulmonary hypertension. This article aims to summarize the key messages from each of the session talks.

Acute vasoreactivity testing during right heart catheterization in chronic thromboembolic pulmonary hypertension: Results from the pulmonary vascular disease phenomics study.

Chronic thromboembolic pulmonary hypertension (CTEPH) is believed to involve both vascular obstruction and vasoconstriction; hence, pulmonary vasodilators such as riociguat may be beneficial. Acute vasoreactivity testing (AVT) is seldom performed routinely in CTEPH patients, so there is limited understanding of the frequency and significance of an acute vasodilator response. Systematic vasodilator testing with oxygen (O) and oxygen plus inhaled nitric oxide (O + iNO) was performed as part of the Pulmonary Vascular Disease Omics (PVDOMICS) NHLBI project, providing an opportunity to examine AVT responses in CTEPH.

l-Carnitine therapy improves right heart dysfunction through Cpt1-dependent fatty acid oxidation.

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l-carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation.