06 December 2021

This week in PVD

Blood levels of 3 proteins may help distinguish HFpEF-PH from PAH

Elevated levels of three blood proteins — AMBP, LPL and glyoxalase I — may help identify and distinguish people with pulmonary hypertension linked to heart failure with preserved ejection fraction, called HFpEF-PH, from those with pulmonary arterial hypertension or PAH, a study suggests.

Differentiating between the two is key, researchers say, because PAH-specific therapies actually may worsen HFpEF-PH, which has no effective treatments.

The study, “Plasma tumour and metabolism related biomarkers AMBP, LPL and Glyoxalase I differentiate heart failure with preserved ejection fraction with pulmonary hypertension from pulmonary arterial hypertension,” was published in the International Journal of Cardiology.

Pulmonary arterial hypertension (PAH) is when high blood pressure occurs in arteries that supply blood to the lungs. It is associated with blood vessel tightening and structural alterations in pulmonary arteries. HFpEF-PH, meanwhile, is characterized by an inability of the heart’s lower left chamber to function properly, meaning that it pumps out less blood than the body needs.

Compared with those with PAH, people with HFpEF-PH are generally older and frequently have other health conditions.

Cardiac function changes shared with PAH often make the diagnosis of HFpEF-PH more challenging. But distinguishing between these types of hypertension is important, as life expectancy of PAH patients increases. Additionally, treatments specific to PAH have been shown to worsen HFpEF-PH, according to the researchers.

Notably, PAH has been labeled a “cancer-like” condition, since it involves cellular pathways that are cancer hallmarks, including cell proliferation and resistance to programmed-cell death (as opposed to death caused by injury).

Potential oral treatment reverses advanced PAH in rats, study shows

An orally available small molecule, BI113823, successfully reversed the progression of severe, advanced pulmonary arterial hypertension (PAH) in a rat model, a study demonstrated.

The experimental medicine lowered pulmonary blood pressure, reduced blood vessel thickening, suppressed inflammatory responses, and prevented right heart failure and death.

These findings support the further development of this therapy in people with established PAH, the scientists noted.

The study, “Reversal of pulmonary arterial hypertension and neointimal formation by kinin B1 receptor blockade,” was published in the journal Respiratory Research.

PAH is characterized by the thickening of the walls of the pulmonary arteries, which are blood vessels that transport blood from the heart to the lungs. This restricts blood flow and increases blood pressure (hypertension), which can lead to right heart failure.

Inflammation is a prominent feature of PAH, in which immune cells and elevated pro-inflammatory signaling proteins are often found in PAH patients’ lungs.

Kinins are short chains of amino-acids called peptides found in the bloodstream. They trigger inflammation by binding to and activating the kinin receptor called B1. This receptor is typically produced at low levels, but its level increases after injury or exposure to pro-inflammatory agents.

Recently, researchers based at the Chonbuk National University in South Korea demonstrated that the levels of kinin B1 receptors was enhanced in an experimental rat model of PAH and played an essential role in the development of PAH.

Inhaled pulmonary vasodilator therapies confer similar outcomes in adult lung transplant

Compared with inhaled nitric oxide, inhaled epoprostenol was associated with similar risk for primary graft dysfunction and other postoperative outcomes in patients undergoing lung transplant.

“The cost of inhaled nitric oxide exceeds millions of dollars annually for large health care systems nationwide, and inhaled nitric oxide is approximately 7-fold more expensive than inhaled epoprostenol. Accordingly, inhaled epoprostenol has emerged as a cost-saving inhaled nitric oxide alternative at several institutions. Although similar antioxidative and vasodilatory properties of inhaled epoprostenol have been reported in lung transplant, the evidence supporting its use is not based on robust comparisons with inhaled nitric oxide that assessed clinically meaningful outcomes,” Kamrouz Ghadimi, MD, MHSc, anesthesiologist and critical care specialist at Duke University School of Medicine, and colleagues wrote in JAMA Surgery. “Furthermore, available data interpretation is complicated by retrospective observational studies, differing epoprostenol formulations and aerosol-generating devices and lack of standardized criteria for discontinuing treatment with either agent.”

INSPIRE-FLO was a randomized, masked, parallel-designed, equivalence clinical trial that enrolled 201 adults who underwent single or bilateral lung transplant from May 2017 to March 2020. Patients were categorized into five strata based on prognostic clinical features and were randomly assigned to receive inhaled nitric oxide (n = 98; median age, 64 years; 60.2% men) or inhaled epoprostenol (n = 103; median age, 64 years; 68% men) during lung transplant.

Cardiopulmonary exercise testing valuable to assess unexplained dyspnea post-COVID-19

In a small study, cardiopulmonary exercise testing identified significant abnormalities, including dysfunctional breathing, resting hypocapnia and chronic fatigue syndrome, associated with post-acute sequelae of severe SARS-CoV-2 infection.

“The current clinical guidelines do not recommend cardiopulmonary exercise testing out of concern that this test could worsen the patients’ [long COVID] symptoms,” Donna M. Mancini, MD, advanced heart failure and transplant specialist at the Icahn School of Medicine at Mount Sinai, told Healio. “However, we found that cardiopulmonary exercise was able to identify reduced exercise capacity in about 46% of patients. This reduced functional capacity was from a circulatory abnormality. This may include changes involving the pulmonary or peripheral vasculature. We also found that nearly 90% of patients had ventilatory abnormalities during exercise.”

Utility of cardiopulmonary exercise testing

Mancini and colleagues aimed to assess the utility of cardiopulmonary exercise test to define unexplained dyspnea in patients with post-acute sequelae of SARS-CoV-2 (PASC) and also assessed patients for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome.

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