Image-based Multi-scale Modeling Framework of the Cardiopulmonary System: Longitudinal Calibration and Assessment of Therapies in Pediatric Pulmonary Hypertension

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension; Congenital Heart Disease; Pediatric Congenital Heart Disease
• Intervention / Treatment: Procedure: cardiac catheterization; Radiation: Cardiac MRI

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Mott Children's Hospital University of Michigan
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Pulmonary hypertension patients will be defined by a mean artery blood pressure >25 mmHg. Transplant patients are tested for pulmonary vascular resistance prior to transplant; if it is too high, transplant is contraindicated. So this group comprises patients who have normal right ventricular function and pulmonary vascular function to act as a control for the right-sided disease that we are testing, and in addition regularly undergo cardiac catheterization for clinical purposes.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pulmonary Hypertension; Participants diagnosed with pulmonary hypertension that will undergo a clinically indicated cardiac catheterization and cMRI.	Procedure: cardiac catheterization; cardiac catheterizations will be clinically indicated and the study will collect this clinical data.; Radiation: Cardiac MRI; If clinically indicated, the study will collect data from MRIs.
Heart Transplant; Successful cardiac transplant recipient without evidence of pulmonary hypertension, that will undergo clinically indicated cardiac catheterization.	Procedure: cardiac catheterization; cardiac catheterizations will be clinically indicated and the study will collect this clinical data.; Radiation: Cardiac MRI; If clinically indicated, the study will collect data from MRIs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3D volumetric data (mL/m2)	Modeling framework will be validated using 3D volumetric data (mL/m2) gathered via cardiac MRI	1 hour
Cardiopulmonary Flow (mL/beat)	Modeling framework will be validated using cardiopulmonary flow (mL/beat) gathered via cardiac MRI	1 hour
Mean Pressure (mmHg)	Modeling framework will be validated using pressures (mmHg) gathered via cardiac catheterization	2 hours

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Nationwide Children's Hospital; Michigan State University
• Investigators: Principal Investigator: Alberto Figueroa, Ph.D., University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): July 28, 2023

Study Registration Dates

• First Submitted: April 12, 2018
• First Submitted That Met QC Criteria: June 8, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Hypertension; Hypertension, Pulmonary; Heart Defects, Congenital
• Other Study ID Numbers: HUM00117706; U01HL135842 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No