Effects of Inhaled Treprostinil on Exercise Performance in Exercise Induced Pulmonary Hypertension

Overview

This study aims to investigate therapies for exercise induced pulmonary hypertension (EiPH). This is a condition that effects the blood vessels in the lungs and causes shortness of breath with activity. Currently, there are very limited treatment options for this condition. Inhaled treprostinil, also known as Tyvaso, is a medication used to treat other forms of lung disease and is safe and well tolerated. This study will measure the ability of Tyvaso to improve symptoms related to EiPH and improve performance on exercise testing.

Exercise-induced pulmonary hypertension (EiPH) is defined by the presence of normal resting pulmonary hemodynamics with an abnormal elevation in mean pulmonary artery pressure (mPAP) for a given cardiac output with exercise. EiPH is typically characterized by exertional dyspnea, with the absence of other features of resting pulmonary arterial hypertension (PAH) such as elevated right atrial pressure at rest or lower extremity peripheral edema. Since patients with EiPH have normal resting echocardiograms, the disease is often underdiagnosed. Exercise right-heart catheterization remains the gold standard in diagnosing EiPH. Aside from subjective markers of clinical improvement with therapy, assessment for physiological improvement is challenging since most measures of PAH severity, including echocardiograms, biomarkers and risk calculators, are normal at baseline in this population with EiPH. The investigators have pioneered the use of non-invasive cardiopulmonary exercise testing (CPET) to assess patients with cardiopulmonary limitations during exercise. Changes in oxygen pulse (O2 pulse) during exercise on CPET have previously been validated as an accurate predictor of stroke volume augmentation, which is an important physiological adaptation to exercise, and may serve as an objective marker of improvement in patients with EiPH. While the guidelines agree that EiPH is real and under-diagnosed, there is no consensus on the management since these patients have not been included in high-quality clinical trials for PAH treatment. Given the lack of treatment guidelines for EiPH, many providers use PAH-targeted therapy off-label in EiPH. Specifically, generic phosphodiesterase-5 inhibitors are the typical first line agent due to insurance barriers to accessing other therapies. Inhaled treprostinil (Tyvaso DPI) would be an ideal medication for this population. Tyvaso DPI is a convenient, inhaled medication with quick onset. The favorable pharmacokinetic profile raises the potential of this medication for dosing prior to exertion for patients with EiPH.