PV Loop and Pulmonary Hypertension

Non-Invasive Evaluation of Right Ventricular - Pulmonary Arterial Coupling in Children With Elevated Pulmonary Vascular Resistance

The right ventricular (RV) systolic function is a key determinant of outcome in patients with pulmonary hypertension and elevated pulmonary vascular resistance. As the pulmonary artery pressure and vascular resistance increase (i.e. RV afterload) in these patients, so does the right ventricular contractility in an attempt to maintain cardiac output. This is response of a ventricle to its afterload is termed ventriculo-arterial (VA) coupling. However, there is a limit to this increase in contractility after which VA uncoupling occurs ultimately leading to decrease cardiac output and right ventricular failure. The accepted gold standard for measurement of VA coupling is the ratio of the end systolic ventricular elastance (Ees) to the end systolic arterial elastance (Ea) measured invasively via high fidelity conductance catheters during cardiac catheterization. In this study, the aim is to devise a non-invasive scoring system that can identify VA uncoupling in patients with elevated pulmonary vascular resistance using echocardiography, cardiac MRI, cardiopulmonary exercise testing and brain natriuretic peptide levels. The hypothesis is that a group of morphologic and functional variables obtained noninvasively can differentiate an RV with VA coupling from that with VA uncoupling.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Vascular Resistance Abnormality
• Intervention / Treatment: Procedure: Measuring VA Coupling

• Study Type: Observational
• Enrollment (Estimated): 65

Contacts and Locations

• Study Contact: Name: Brittany Faanes, MPH, CCRP; Phone Number: 612-625-5929; Email: grego318@umn.edu
• Study Contact Backup: Name: Jasmine Becerra, BS; Phone Number: 415-476-2649; Email: jasmine.becerra@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • Pediatric Pulmonary Hypertension Program
      • Contact: Jasmine Becerra, BS; Phone Number: 415-476-2649; Email: jasmine.becerra@ucsf.edu
      • Principal Investigator: Hythem Nawaytou, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Brittany Faanes, MPH, CCRP; Phone Number: 612-625-5929; Email: grego318@umn.edu
      • Principal Investigator: Gurumurthy Hiremath, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children with Elevated Pulmonary Arterial Hypertension

Description

Inclusion Criteria:

• Children 1-21 years of age
• Patients referred for cardiac catheterization for hemodynamic evaluation due to concern for pulmonary hypertension
• Structurally normal heart

Exclusion Criteria:

• Pulmonary hypertension secondary to pulmonary venous hypertension defined as pulmonary capillary wedge pressure of more than or equal to 15mmHg
• Pulmonary hypertension secondary to mixed pulmonary arterial and venous hypertension
• Patient will be excluded from performing an MRI if they have:

claustrophobia, metal implants or allergy to contrast

• Patients will be excluded from performing a cardiopulmonary exercise test (CPET) if they are: 1) less than 8 years or 2) unable to follow instructions to run on a treadmill.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observational Group; Subjects will undergo clinically indicated investigations and tests. The research part of the study is measuring the VA coupling using high fidelity catheters. That is expected to increase the duration of the cardiac catheterization for 30 minutes.	Procedure: Measuring VA Coupling; Subjects will undergo clinically indicated investigations and tests. The research part of the study is measuring the VA coupling using high fidelity catheters. That is expected to increase the duration of the cardiac catheterization for 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify echocardiographic measurements of right ventricular systolic function and pulmonary blood flow and their cutoff values contemporaneous that can identify VA uncoupling	Yes/No result: Can echocardiographic measurements allow non-invasive identification of VA uncoupling (defined as Ees/Ea <0.805). Three ratios: tricuspid annular plane systolic excursion to the pulmonary artery acceleration time, right ventricular free wall strain to the pulmonary artery acceleration time and, right ventricular fractional area change to the pulmonary artery acceleration time.	within one week of measurement of ventriculo-arterial coupling ratio during cardiac catheterization
Identify cMRI measurements of right ventricular systolic function and pulmonary blood flow and their cutoff values contemporaneous that can identify VA uncoupling.	Yes/No result: Can cMRI measurements allow non-invasive identification of VA uncoupling (defined as Ees/Ea <0.805). Two ratios: right ventricular ejection fraction to right ventricular end systolic volume and right ventricular ejection fraction to pulmonary artery acceleration time (by echocardiography).	within one week of measurement of ventriculo-arterial coupling ratio during cardiac catheterization
Identify 6-minute walk distance cutoff that can identify VA uncoupling	Yes/No: Can 6-minute walk distance identify VA uncoupling (defined as Ees/Es<0.805)	within one week of measurement of ventriculo-arterial coupling ratio during cardiac catheterization
Identify brain natriuretic peptide cutoff value that can identify VA uncoupling	Yes/No: Can brain natriuretic peptide identify VA uncoupling (defined as Ees/Es<0.805)	within one week of measurement of ventriculo-arterial coupling ratio during cardiac catheterization

Collaborators and Investigators

• Sponsor: Hythem Nawaytou
• Collaborators: University of Minnesota
• Investigators: Principal Investigator: Gurumurthy Hiremath, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: July 8, 2022
• First Submitted That Met QC Criteria: July 29, 2022
• First Posted (Actual): August 2, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: pediatric; pulmonary vascular resistance; VA uncoupling
• Additional Relevant MeSH Terms: Congenital Abnormalities
• Other Study ID Numbers: PEDS-2020-29351

Drug and device information, study documents

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