Pulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease, even with modern therapies. The cause of death is typically right ventricular failure. Recently, increased stiffness of the large pulmonary arteries was identified as a powerful predictor of mortality in PAH. Increased stiffness of the small arteries may also contribute to disease progression. The effects of proximal and distal arterial stiffening on a patient's exercise capacity and ability to benefit from exercise are unknown. We hypothesize that proximal arterial stiffening is responsible for right ventricular dysfunction via inefficient hemodynamic interactions. We also hypothesize that distal arterial stiffening limits exercise capacity. The goals of this study are to quantify right ventricular-pulmonary vascular interactions in different types of PAH, to determine the temporal changes in these interactions with PAH progression and to quantify the effects of exercise on right ventricular function. We have a particular interest in the subpopulation of PAH with systemic sclerosis (SSc) because we anticipate that this group has worse arterial stiffening than other groups, and consequently more inefficient right ventricular-pulmonary vascular interactions, which account for their worse prognosis.
Our aims are:
Aim 1. To quantify the relationships between pulmonary arterial stiffness, right ventricular function and the efficiency of ventricular-vascular interactions in patients with PAH.
Aim 2. To quantify the effects of exercise on pulmonary arterial stiffness, pulmonary vascular resistance, right ventricular function and the efficiency of ventricular-vascular interactions in patients with PAH.
Aim 3. To investigate the progression of loss of efficiency of ventricular-vascular interactions in canine models of IPAH and CTEPH. The clinical and scientific communities investigating PAH were recently charged with studying the cardiopulmonary system more comprehensively, especially in subpopulation of PAH with SSc. Our goals are to investigate the hemodynamic mechanisms of right ventricular-pulmonary vascular interactions in PAH, differences among PAH subtypes and the effects of exercise on ventricular and vascular function and interactions in PAH. Importantly, our results may lead to a novel "physiomarker" of disease that could enable clinicians to better identify PAH patients who are at risk for ventricular-vascular dysfunction and determine who will likely benefit from exercise training. 1
Pulmonary arterial hypertension (PAH) is a poorly understood disease of the arteries of the lung that ultimately leads to heart failure. The benefits of exercise in current clinical management of PAH are highly controversial, largely because its effects on heart function are unknown. We propose to measure the impact of exercise on blood flow and heart function to improve our understanding of this disease, identify patients who are likely to benefit from exercise, and develop novel predictors of disease progression.
|Freed, Benjamin H; Collins, Jeremy D; FranÃ§ois, Christopher J et al. (2016) MR and CT Imaging for the Evaluation ofÂ Pulmonary Hypertension. JACC Cardiovasc Imaging 9:715-32|
|Tian, Lian; Wang, Zhijie; Liu, Yuming et al. (2016) Validation of an arterial constitutive model accounting for collagen content and crosslinking. Acta Biomater 31:276-87|
|Brewis, Melanie J; Bellofiore, Alessandro; Vanderpool, Rebecca R et al. (2016) Imaging right ventricular function to predict outcome in pulmonary arterial hypertension. Int J Cardiol 218:206-11|
|Tian, Lian; Henningsen, Joseph; Salick, Max R et al. (2015) Stretch calculated from grip distance accurately approximates mid-specimen stretch in large elastic arteries in uniaxial tensile tests. J Mech Behav Biomed Mater 47:107-13|
|Barker, Alex J; RoldÃ¡n-Alzate, Alejandro; Entezari, Pegah et al. (2015) Four-dimensional flow assessment of pulmonary artery flow and wall shear stress in adult pulmonary arterial hypertension: results from two institutions. Magn Reson Med 73:1904-13|
|Forouzan, Omid; Warczytowa, Jared; Wieben, Oliver et al. (2015) Non-invasive measurement using cardiovascular magnetic resonance of changes in pulmonary artery stiffness with exercise. J Cardiovasc Magn Reson 17:109|
|Bellofiore, A; Henningsen, J; Lepak, C G et al. (2015) A novel in vivo approach to assess radial and axial distensibility of large and intermediate pulmonary artery branches. J Biomech Eng 137:044501|
|Bellofiore, A; Wang, Z; Chesler, N C (2015) What does the time constant of the pulmonary circulation tell us about the progression of right ventricular dysfunction in pulmonary arterial hypertension? Pulm Circ 5:291-5|
|Soydan, Lydia C; Kellihan, Heidi B; Bates, Melissa L et al. (2015) Accuracy of Doppler echocardiographic estimates of pulmonary artery pressures in a canine model of pulmonary hypertension. J Vet Cardiol 17:13-24|
|Forouzan, Omid; Flink, Evan; Warczytowa, Jared et al. (2014) Low Cost Magnetic Resonance Imaging-Compatible Stepper Exercise Device for Use in Cardiac Stress Tests. J Med Device 8:0450021-450028|
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