The Role of Noninvasive Endpoints in Predicting Long-Term Outcomes in Pulmonary Arterial Hypertension

Abstract

Background Until recently, many clinical trials in patients with pulmonary arterial hypertension (PAH) evaluated exercise capacity with 6-minute walk distance (6MWD) as the primary endpoint. Common secondary endpoints include PAH functional class (FC), which assesses symptoms, and either brain natriuretic peptide (BNP) or the inactive N-terminal cleavage product of its prohormone (NT-proBNP), which assesses cardiac function. Objective Examine the relationships among 6MWD, FC, and BNP/NT-proBNP measured at baseline or follow-up with long-term outcomes in PAH studies. Methods Relevant literature from January 1990 to April 2018 were obtained by searching PubMed, Embase, and Cochrane. Articles in English reporting on associations between 6MWD, FC, or BNP/NT-proBNP and outcomes in PAH were identified. Each endpoint was evaluated individually. Prespecified inclusion and exclusion criteria were applied at level 1 (titles/ abstracts) and level 2 (full-text review). Results The database search yielded 836 unique records; 65 full-text articles were reviewed. Twenty-five studies were eligible for inclusion. Findings supported the importance of measuring PAH noninvasive endpoints in predicting longterm outcomes. Patients with shorter or decreased 6MWD, poor (III/IV) or declining FC (e.g., from II to III), or elevated or increasing BNP/NT-proBNP had a higher risk of death and costly events (e.g., hospitalization, lung transplant). FC also predicted health care resource utilization and costs. Collectively, these endpoints establish risk groups that predict likelihood of complications from PAH or death. Conclusion Assessment of 6MWD, FC, and BNP/NT-proBNP provides low-cost, efficient, and noninvasive means of predicting long-term health and economic outcomes in patients with PAH.

Effect of Pomegranate Extract On N-Terminal Pro Brain Natriuretic Peptide and Asymmetric Dimetylarginine Levels in Children with Pulmonary Artery Hypertension in Acyanotic Congenital Heart Disease

“…This study, using 836 data and 65 journals explaining NT pro-BNP, 6MWD, and FC function as prognostic indicators of measurable outcomes, namely morbidity and mortality which, can be assessed early to determine the course of therapy and improve therapy outcomes. 27 Pomegranate (Punica Granatum. L) is a fruit with high antioxidant content.…”

Haemodynamic effects of riociguat in CTEPH and PAH: a 10-year observational study

“…Therefore, further large-sample multi-center studies are still needed to confirm our current findings. 6MWD was considered as correlates of risk of long-term health outcomes, although it can be affected by subjective factors such as patient motivation [28,29]. The improvement in 6MWD of riociguat was robust up to 8 years, which was apparently a continuation of the CHEST/PATENT-1 and 2-year follow-up study of CHEST/PATENT-2 [12][13][14][15][16][17].…”

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints

“… 98–100 Although circulating natriuretic peptide levels tend to be more influenced by left-sided cardiac disease, ventricular interdependence results in elevations of these markers in the setting of right heart failure. Natriuretic peptide levels have been shown to be predictors of outcomes in primary PH, 101 , 102 and a reduction in septal shift may improve left heart function and reduce pulmonary congestion. Because congestion is a dominant feature of right-sided heart failure associated with significant TR, CA125 may turn out to be a useful biomarker responsive to reductions in TR.…”