Integrated Diagnostics Characterization of Right Ventricular Diastolic Flow Dynamics in Pulmonary Arterial Hypertension

This study has been completed.
Sponsor:
Collaborator:
Siemens Medical Solutions USA, Inc
Information provided by (Responsible Party):
Brett Fenster, National Jewish Health
ClinicalTrials.gov Identifier:
NCT01491646
First received: December 12, 2011
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

Pulmonary hypertension (PH) is a condition in which high blood pressure develops in the lungs and right side of the heart. People with PH suffer from shortness of breath, chest pain, heart failure, heart rhythm problems, and fainting. PH is diagnosed using a test called a cardiac catheterization where blood pressure is measured directly using a tube placed in the right side of the heart and lung arteries. Because a cardiac catheterization is invasive, researchers are investigating ways to diagnose PH using imaging tests that are not invasive. The study will evaluate whether or not a magnetic resonance image (MRI) of the heart, and blood tests can detect PH.


Condition
Pulmonary Hypertension

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Integrated Diagnostics Characterization of Right Ventricular Diastolic Flow Dynamics in Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by National Jewish Health:

Primary Outcome Measures:
  • Correlation between RV diastolic function and vorticity [ Time Frame: 2 years ]

Biospecimen Retention:   Samples Without DNA

plasma, serum


Enrollment: 25
Study Start Date: November 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pulmonary Hypertension
Previous diagnosis of PH by right heart catheterization
Healthy Controls
Healthy controls without lung/heart conditions

Detailed Description:

The adaptive changes that result from chronic pressure overload in pulmonary arterial hypertension (PAH) lead to myocardial hypertrophy, stiffening, and right ventricular diastolic dysfunction (RVDD). A growing body of evidence has identified RVDD as an important prognostic indicator for PAH.1 Diagnosis of RVDD relies upon 1) elevated brain natriuretic peptide (BNP), which correctly identifies RVDD in the PAH population but remains a nonspecific marker, and 2) echocardiography, as defined by reduced early (E') tricuspid annular velocity, elevated ratio of early filling tricuspid inflow peak velocity to E' (E/E'), and prolonged relaxation time (RT). 2 However, the right ventricle's unusual anatomy and susceptibility to altered loading conditions have raised questions about the ability of echo indices to accurately reflect complex diastolic mechanics. The development of a robust non-invasive application for RV diastolic assessment may improve the understanding, diagnosis, and management of RVDD and therefore PAH.

Similar to the left ventricle, rheological analysis of right ventricular inflow in canine models has identified the formation of diastolic vortex rings.3 Vortex rings develop from high velocity diastolic jet emanating from the valvular annulus interacting with stationary blood in the ventricle. Vortex ring formation time has successfully identified left ventricular diastolic dysfunction.4 Numerous additional vortex properties exist, including depth, transverse position, length, width, and sphericity index, that offer novel and robust diastolic flow characterization with the potential incremental diagnostic value to existing echo parameters. Vortex formation and analysis in RVDD has yet to be studied.

Vortex measurement can be performed using dimensional (4D) (time-resolved three-dimensional) cardiac MRI (CMR). 4D CMR captures the complex multidirectional nature of flow through volumetric rendering of fluid vectors and velocity using blood flow streamlines and particle traces. In contrast to echocardiography, 4D CMR is not limited by poor acoustic windows commonly seen in patients with respiratory disease and PAH, making it an ideal noninvasive modality for vortex characterization.

The biological adaptations resulting from chronic pressure overload in PAH might be correlated to the blood levels of different categories of biomarkers. They might play a role in the screening, diagnosis, monitoring or prognosis of patients with PAH and RVDD. Special mention can be made to the natriuretic peptides (BNP, NT-proBNP) based on their clinical value as hemodynamic markers in congestive heart failure. Cardiac markers of necrosis (asTroponin-I, and particularly the high sensitivity assays) might identify even minimal areas with such myocardial cell damage. The biological evaluation of cardiac fibrosis, might be assessed by markers of fibrosis, as Hyaluronic acid (HA), Procollagen III amino terminal peptide (PIIINP) and Tissue inhibitor of metalloproteinase 1 (TIMP-1). The potential role of the inflammatory component, can be evaluated with MPO (myeloperoxidase, pro-inflammatory enzyme), IL-6 (pro-inflammatory cytokine), C-RP (C-reactive protein)

The present study aims to:

  1. Characterize and quantify RV vortex flow in normal subjects and PAH subjects with RVDD
  2. Assess the feasibility of 4D CMR right ventricular diastolic vortex analysis for diagnosis of RVDD Hypothesis: 4D CMR vortex analysis accurately identifies RVDD, and the information provided by biomarkers helps by adding diagnostic information.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

specialist clinics community

Criteria

Inclusion Criteria:

  • previous diagnosis of PH by right heart catheterization
  • RV diastolic dysfunction by echo
  • normal RV systolic function
  • age 18-75 years old
  • no contraindication to MRI

Exclusion Criteria:

  • absence of PH
  • absence of RV diastolic dysfunction by echo
  • RV systolic dysfunction
  • age < 18 years
  • contraindication to MRI
  • pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01491646

Locations
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
Sponsors and Collaborators
National Jewish Health
Siemens Medical Solutions USA, Inc
Investigators
Principal Investigator: Brett Fenster, MD, FACC, FACP National Jewish Health
  More Information

Publications:
Responsible Party: Brett Fenster, Assistant Professor of Medicine, National Jewish Health
ClinicalTrials.gov Identifier: NCT01491646     History of Changes
Other Study ID Numbers: HS 2512
Study First Received: December 12, 2011
Last Updated: November 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Jewish Health:
pulmonary hypertension
cardiac magnetic resonance imaging
Characterize and quantify RV vortex flow
Assess feasibility of cardiac MR for RVDD diagnosis
Biomarker information to help diagnose

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 29, 2014