image-based multi-scale modeling framework of the cardiopulmonary system: longitudinal calibration and assessment of therapies in pediatric pulmonary hypertension

Conditions: Pulmonary Hypertension; Congenital Heart Disease; Pediatric Congenital Heart Disease

Summary: this study looks to develop a multi-scale computational model of pulmonary hypertension, this clinical model will be calibrated using longitudinal, retrospectively and prospectively acquired human clinical data.

pulmonary hypertension (ph) is a complex disorder associated with elevated pulmonary arterial pressure. unlike systemic hypertension, ph is difficult to detect in routine physical examinations and the current gold standard for diagnosing ph is through invasive right heart catheterization. prolonged ph results in functional, structural and anatomical changes in the right ventricle (rv), large pulmonary arteries, and the pulmonary micro-circulation that ultimately lead to decompensated rv failure and death. unlike in systemic hypertension, for which patients have effective pharmacological management of blood pressure for decades, ph prognosis remains poor with 15% mortality within 1 year on modern therapy. our current understanding of ph has largely been obtained through animal models and clinical studies. however, surgical banding or chronic hypoxia animal models do not fully reproduce the etiology of human ph, whereas invasive clinical measurements of pulmonary vascular resistance (pvr), stiffness and ventricular elastance provide limited insight into disease progression. therefore, there is a pressing need to develop a multi-scale (ms) computational model that can couple the short term (e.g. hemodynamics) and long-term g\&r interactions between the rv and the pulmonary circulation. the overall goals of this project are to use the framework to (1) describe the time course of the biomechanical alterations and (2) identify the key mechanical culprits associated with ph-induced heart failure so that clinical interventions can be targeted against them.

Eligibility criteria:
inclusion criteria: * patients has been clinically diagnosed with pulmonary hypertension (\>25 mmhg) or patient is a biopsy-proven non-rejecting cardiac transplant recipient * receiving partial or full care from pediatric cardiology team at mott children's hospital (may have a primary cardiologist elsewhere). exclusion criteria: * girls and women who are pregnant or actively trying to become pregnant * patients with significant neurocognitive impairment that precludes their ability to sign a consent form * patient has a contraindication to right-heart catheterization (rhc) examination, which includes patients with hypoxia and those who have difficulty maintaining supine position for the procedure. * patients with the following genetic syndromes:trisomy 21 if unable to assent or consent, trisomy 18,trisomy 13, other genetic syndromes at the discretion of the primary investigator * patients with unrepaired single ventricles (i.e., pre-fontan physiology) * patients who have heart failure and are deemed to be high risk to undergo tests that require sedation/anesthesia. * patients who require iv sedation or general anesthesia for research only mri * patients with a pacemaker/internal defibrillator will be excluded from mri portion only