Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial

Farha, Samar; Saygın, Didem; Park, Margaret M.; Cheong, Hoi I.; Asosingh, Kewal; Comhair, Suzy; Stephens, Olivia R.; Roach, Emir Charles; Sharp, Jacqueline; Highland, Kristin B.; DiFilippo, Frank P.; Neumann, Donald R.; Tang, W.H. Wilson; Erzurum, Serpil C.

doi:10.1172/jci.insight.95240

Cited by 80 publications

(85 citation statements)

References 53 publications

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“…Effects of neurohormonal modulators (e.g., inhibitors of the renin-angiotensin/aldosterone system) and b-adrenergic receptor antagonists on RV contractile function require further study. In particular, the effect of the latter is of great interest, because currently available studies yielded conflicting results of these drugs on clinical outcomes and RV function (259)(260)(261)(262)(263). RV inotropic agents may improve shortand/or long-term outcomes in acute and/or chronic PH, but their role (and potential for adverse events) is incompletely explored.…”

Section: Assessment Of Contractile Signaling and Calcium Handlingmentioning

confidence: 99%

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

Lahm

Douglas²,

Archer³

et al. 2018

Am J Respir Crit Care Med

260

247

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Section: Assessment Of Contractile Signaling and Calcium Handlingmentioning

confidence: 99%

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

Lahm

Douglas²,

Archer³

et al. 2018

Am J Respir Crit Care Med

260

247

View full text Add to dashboard Cite

show abstract

“…11 Another trial of carvedilol in patients with PAH showed a decrease in heart rate and RV glycolysis, and proved to be safe in PAH patients, but did not show an increase in cardiac output or 6-minute walk distance (6MWD). 12 In light of the present data Dr Bogaard emphasized that he does not advocate use of beta-blockers in PAH patients, and that further clinical trials are needed with careful patient selection to identify patients who are most likely to respond to therapy. An alternative for targeting chronically activated sympathetic neurohormonal signaling in PAH may be to increase parasympathetic tone.…”

Section: Novel Therapies Targeting the Right Ventriclementioning

confidence: 87%

Basic Science and Clinical Trials: Accelerating the Future

Halliday

Brittain

2018

Advances in Pulmonary Hypertension

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The Scientific Sessions at the 2018 Pulmonary Hypertension Association International Conference began with presentations on the theme of “Basic Science and Clinical Trials: Accelerating the Future.” These presentations, by leading pulmonary hypertension researchers, focused on recent breakthroughs in understanding the pathobiology of the disease, preclinical models of new treatments, early-phase clinical trials, and future directions for the treatment of pulmonary arterial hypertension.

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“…The PAH Treatment with Carvedilol for Heart Failure (PAHTCH) trial was a double-blind, randomized, dose-ranging, 24-week trial of carvedilol in 30 patients with World Health Organization pulmonary hypertension (PH) Group 1, 3, or 4. 28 Carvedilol is a nonselective beta-blocker with vasodilator properties. Although carvedilol does not directly target a metabolic pathway, investigators assessed the effects of beta-blockade on RV glucose uptake as a maker of myocardial remodeling and hypoxia-inducible events.…”

Section: Carvedilolmentioning

confidence: 99%

Clinical Trials Targeting Metabolism in Pulmonary Arterial Hypertension

Brittain

2018

Advances in Pulmonary Hypertension

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Metabolic derangement is a pathologic feature of pulmonary arterial hypertension (PAH).1 Metabolic abnormalities such as aerobic glycolysis and impaired fatty acid oxidation are consistently observed across different animal models of PAH. Importantly, altered metabolism in human PAH and experimental models is not restricted to the pulmonary vasculature, raising the possibility that PAH is a systemic metabolic disease.2 For example, lipid accumulation is present in the myocardium and skeletal muscle of humans with PAH and the right ventricle exhibits increased glucose uptake compared with matched controls. As a result of these observations, targeting metabolic dysfunction has emerged as an important therapeutic approach for patients with PAH.3 This article will review key aspects of metabolism in PAH, existing metabolic data in humans, and will describe completed and ongoing clinical trials targeting metabolic dysfunction in patients with PAH.

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Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial

Abstract: ClinicalTrials.gov NCT01586156FUNDING. This project was supported by NIH R01HL115008 and R01HL60917 and in part by the National Center for Advancing Translational Sciences, UL1TR000439.

Cited by 80 publications

References 53 publications

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

Basic Science and Clinical Trials: Accelerating the Future

Clinical Trials Targeting Metabolism in Pulmonary Arterial Hypertension

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