| Autor: |
Evan L. Brittain, Kevin Niswender, Vineet Agrawal, Xinping Chen, Run Fan, Meredith E. Pugh, Todd W. Rice, Ivan M. Robbins, Haocan Song, Christopher Thompson, Fei Ye, Chang Yu, He Zhu, James West, John H. Newman, Anna R. Hemnes |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 9, Iss 22 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2047-9980 |
| DOI: |
10.1161/JAHA.120.018349 |
| Popis: |
Background Metabolic dysfunction is highly prevalent in pulmonary arterial hypertension (PAH) and likely contributes to both pulmonary vascular disease and right ventricular (RV) failure in part because of increased oxidant stress. Currently, there is no cure for PAH and human studies of metabolic interventions, generally well tolerated in other diseases, are limited in PAH. Metformin is a commonly used oral antidiabetic that decreases gluconeogenesis, increases fatty acid oxidation, and reduces oxidant stress and thus may be relevant to PAH. Methods and Results We performed a single‐center, open‐label 8‐week phase II trial of up to 2 g/day of metformin in patients with idiopathic or heritable PAH with the co‐primary end points of safety, including development of lactic acidosis and study withdrawal, and plasma oxidant stress markers. Exploratory end points included RV function via echocardiography, plasma metabolomic analysis performed before and after metformin therapy, and RV triglyceride content by magnetic resonance spectroscopy in a subset of 9 patients. We enrolled 20 patients; 19/20 reached the target dose and all completed the study protocol. There was no clinically significant lactic acidosis or change in oxidant stress markers. Metformin did not change 6‐minute walk distance but did significantly improve RV fractional area change (23±8% to 26±6%, P=0.02), though other echocardiographic parameters were unchanged. RV triglyceride content decreased in 8/9 patients (3.2±1.8% to 1.6±1.4%, P=0.015). In an exploratory metabolomic analysis, plasma metabolomic correlates of ≥50% reduction in RV lipid included dihydroxybutyrate, acetylputrescine, hydroxystearate, and glucuronate (P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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