Pulmonary arterial hypertension (PAH) is a devastating, rapidly progressive disease of the pulmonary vasculature that typically affects young women between the ages of 21 and 40. Untreated, the median survival time is 2.8 years. Only lung transplantation relieves the pulmonary hypertension. Methods currently used to assess the clinical course are either subjective or do not correlate well with symptoms and life expectancy. Right heart catheterization is widely-used to measure disease severity and response to therapy, but repeated catheterization causes morbidity and is a potential barrier to needed changes in therapy. Also, catheterization is performed at rest, not during exercise, when the patient is symptomatic. In contrast, preliminary data from the PI and his mentor show that noninvasive measures of aerobic function and ventilatory efficiency during exercise are closely related to disease severity and response to therapy in patients with PAH. This has broad implications for determining prognosis, selection of treatment, and making decisions on the timing of lung transplantation. The broad objectives of this proposal are to define optimal methods for noninvasively assessing patients with PAH, and to develop a prognostic model using cardiopulmonary exercise testing (CPET).
The specific aims are: 1) To establish peak exercise oxygen consumption (peak VOz) and other CPET measurements as independent predictors of survival time, need for tung transplantation, or hospitalization for symptoms of PAH. 2) To use CPET parameters to further subclassify patients with NYHA II and III functional class symptoms, and patients with 6-minute walk distances of 250-400 m 3) To establish the relationship between peak VO2 and other CPET measurements in tracking the response to vasodilator therapy. This study will help determine the most useful parameter(s) to follow for making critical clinical decisions, including determining the need for and timing of lung transplantation. From our large PAH referral clinic, we will perform CPET in 72 human subjects with PAH, as defined by the World Health Organization. We will examine how the pulmonary vasculopathy of PAH affects exercise aerobic capacity and ventilatory efficiency in PAH, and how these important reflections of cardiac and pulmonary vascular function relate to clinical indices used in the conventional evaluation of these patients. Our hypotheses are based on the concept that CPET measurements provide objective, quantitative measures of disease severity and response to therapy. Therefore important therapeutic decisions can be based on objective measures of the circulatory and ventilatory responses to exercise, This proposal will enable the PI to participate in a structured, graded career development program leading to the acquisition of skills needed for a career in patient-oriented cardiovascular research.
|Oudiz, Ronald J; Midde, Raghu; Hovenesyan, Arsen et al. (2010) Usefulness of right-to-left shunting and poor exercise gas exchange for predicting prognosis in patients with pulmonary arterial hypertension. Am J Cardiol 105:1186-91|
|Oudiz, Ronald J; Roveran, Giorgio; Hansen, James E et al. (2007) Effect of sildenafil on ventilatory efficiency and exercise tolerance in pulmonary hypertension. Eur J Heart Fail 9:917-21|
|Oudiz, Ronald J; Barst, Robyn J; Hansen, James E et al. (2006) Cardiopulmonary exercise testing and six-minute walk correlations in pulmonary arterial hypertension. Am J Cardiol 97:123-6|
|Resnick, Murray B; Gavilanez, Mariuxi; Newton, Eric et al. (2005) Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation. Hum Pathol 36:886-92|