Detection of Early Pulmonary Vascular Disease in Scleroderma

Johns Hopkins University, Baltimore MD

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Abstract

? DESCRIPTION (provided by applicant): Pulmonary arterial hypertension (PAH) is a frequent complication of systemic sclerosis (SSc), and carries with it a poor prognosis and median survival of less than 4 years, even on PAH specific therapy. Despite its clinical significance, PAH with SSc (SSc-PAH) is diagnosed late in disease progression, which is associated with a further decrease in survival. Current methods of detecting PAH fail to detect early pulmonary vascular disease, as they depend on detecting elevations of resting pulmonary arterial pressures, which only occurs after 50-70% of the pulmonary vasculature is affected. Thus, there is an urgent need for identification of early pulmonary vascular disease in SSc. An abnormal pulmonary vascular response to exercise, or exercise-induced pulmonary hypertension (Ex-PH) signifies the loss of the pulmonary vasculatures normal ability to dilate and recruit previously closed pulmonary vessels, and is an indicator of early pulmonary vascular disease. Measurement of exercise hemodynamics is not uniformly performed, thus the use of more readily available metrics to define the presence of Ex-PH may improve detection of early pulmonary vascular disease. By defining Ex-PH as a ?mPAP/?CO > 3.0mmHg*min*L-1 with exercise (mPAP= mean pulmonary artery pressure, CO= cardiac output), we have preliminary data implicating a decrease in pulmonary arterial compliance and stroke volume index as predictors of Ex-PH, as well as differences in non-invasive measures, such as serum NT-pro-BNP, six minute walk test (6MWT), and right ventricular (RV) SVI and RV end diastolic volume (EDV) as assessed by cardiac magnetic resonance imaging (CMR). Therefore, we hypothesize that both resting invasive and non-invasive measures can predict early pulmonary vascular diseases in SSc. To test this hypothesis, we propose a prospective observational cohort study, where we will enroll SSc patients at the Johns Hopkins Pulmonary Hypertension Program who undergo resting and exercise right heart catheterization (RHC) as part of their clinical care or an ongoing NIH-funded study assessing RV dysfunction in PAH, the latter of which also includes a CMR. Patients without resting PAH will be included, and stratified into those with and without Ex-PH, and analyzed to accomplish two aims. The first aim is to determine if a decreased resting pulmonary arterial compliance predicts the presence of Ex-PH, and thus early pulmonary vascular disease in SSc. The second aim will include demographic, anthropometric, pulmonary function, functional capacity, and CMR measures into multivariate regression models to identify non-invasive markers of Ex-PH, and thus early pulmonary vascular disease.