Pulmonary HypertensionNCT01491646
Integrated Diagnostics Characterization of Right Ventricular Diastolic Flow Dynamics in Pulmonary Arterial Hypertension
An observational study of Pulmonary Hypertension, run by National Jewish Health at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Hypertension
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2010to Oct 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: specialist clinics community
Who may be able to join
- 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
Who cannot join
- absence of PH
- absence of RV diastolic dysfunction by echo
- RV systolic dysfunction
- age < 18 years
- contraindication to MRI
- pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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:
- Characterize and quantify RV vortex flow in normal subjects and PAH subjects with RVDD
- 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.
- Conditions
- Pulmonary Hypertension
- Keywords
- 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
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pulmonary Hypertension | Previous diagnosis of PH by right heart catheterization | |
| Healthy Controls | Healthy controls without lung/heart conditions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between RV diastolic function and vorticity
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2011 (estimated)
- Study startNov 2010
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Jewish Health
- Sponsor type
- University, hospital or other
- Collaborators
- Siemens Medical Solutions
- Responsible party
- Sponsor
- Investigators
- Brett Fenster, MD, FACC, FACP, Principal investigator, National Jewish Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01491646
- Sponsor's protocol ID
- HS 2512
- Status last verified
- Oct 2020
- First submitted
- 12 Dec 2011
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Shiina Y, Funabashi N, Lee K, Daimon M, Sekine T, Kawakubo M, Sekine Y, Takahashi M, Yajima R, Wakatsuki Y, Tanabe N, Kuriyama T, Komuro I. Doppler imaging predicts cardiac events in chronic pulmonary thromboembolism. Int J Cardiol. 2009 Apr 3;133(2):167-72. doi: 10.1016/j.ijcard.2007.12.017. Epub 2008 Feb 1.
PubMed 18242738Shiina Y, Funabashi N, Lee K, Daimon M, Sekine T, Kawakubo M, Takahashi M, Yajima R, Tanabe N, Kuriyama T, Komuro I. Right atrium contractility and right ventricular diastolic function assessed by pulsed tissue Doppler imaging can predict brain natriuretic peptide in adults with acquired pulmonary hypertension. Int J Cardiol. 2009 Jun 12;135(1):53-9. doi: 10.1016/j.ijcard.2008.03.090. Epub 2008 Sep 14.
PubMed 18793807Pasipoularides AD, Shu M, Womack MS, Shah A, Von Ramm O, Glower DD. RV functional imaging: 3-D echo-derived dynamic geometry and flow field simulations. Am J Physiol Heart Circ Physiol. 2003 Jan;284(1):H56-65. doi: 10.1152/ajpheart.00577.2002. Epub 2002 Sep 12.
PubMed 12388220Kheradvar A, Gharib M. On mitral valve dynamics and its connection to early diastolic flow. Ann Biomed Eng. 2009 Jan;37(1):1-13. doi: 10.1007/s10439-008-9588-7. Epub 2008 Nov 4.
PubMed 18982451Hong GR, Pedrizzetti G, Tonti G, Li P, Wei Z, Kim JK, Baweja A, Liu S, Chung N, Houle H, Narula J, Vannan MA. Characterization and quantification of vortex flow in the human left ventricle by contrast echocardiography using vector particle image velocimetry. JACC Cardiovasc Imaging. 2008 Nov;1(6):705-17. doi: 10.1016/j.jcmg.2008.06.008. Epub 2008 Nov 18.
PubMed 19356506
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Integrated Diagnostics Characterization of Right Ventricular Diastolic Flow Dynamics in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01491646
- Acronym / sponsor ID
- HS 2512
- Conditions
- Pulmonary Hypertension
- Keywords
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Jewish HealthUniversity, hospital or other
- Collaborators
- Siemens Medical Solutions
- Study start
- Nov 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 14 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- Characterize and quantify RV vortex flow in normal subjects and PAH subjects with RVDD
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pulmonary Hypertension | – | –Previous diagnosis of PH by right heart catheterization |
| Healthy Controls | – | –Healthy controls without lung/heart conditions |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- specialist clinics community
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- absence of PH
- absence of RV diastolic dysfunction by echo
- RV systolic dysfunction
- age < 18 years
- contraindication to MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation between RV diastolic function and vorticity
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Background: PubMed 18242738Shiina Y, Funabashi N, Lee K, Daimon M, Sekine T, Kawakubo M, Sekine Y, Takahashi M, Yajima R, Wakatsuki Y, Tanabe N, Kuriyama T, Komuro I. Doppler imaging predicts cardiac events in chronic pulmonary thromboembolism. Int J Cardiol. 2009 Apr 3;133(2):167-72. doi: 10.1016/j.ijcard.2007.12.017. Epub 2008 Feb 1.
- Background: PubMed 18793807Shiina Y, Funabashi N, Lee K, Daimon M, Sekine T, Kawakubo M, Takahashi M, Yajima R, Tanabe N, Kuriyama T, Komuro I. Right atrium contractility and right ventricular diastolic function assessed by pulsed tissue Doppler imaging can predict brain natriuretic peptide in adults with acquired pulmonary hypertension. Int J Cardiol. 2009 Jun 12;135(1):53-9. doi: 10.1016/j.ijcard.2008.03.090. Epub 2008 Sep 14.
- Background: PubMed 12388220Pasipoularides AD, Shu M, Womack MS, Shah A, Von Ramm O, Glower DD. RV functional imaging: 3-D echo-derived dynamic geometry and flow field simulations. Am J Physiol Heart Circ Physiol. 2003 Jan;284(1):H56-65. doi: 10.1152/ajpheart.00577.2002. Epub 2002 Sep 12.
- Background: PubMed 18982451Kheradvar A, Gharib M. On mitral valve dynamics and its connection to early diastolic flow. Ann Biomed Eng. 2009 Jan;37(1):1-13. doi: 10.1007/s10439-008-9588-7. Epub 2008 Nov 4.
- Background: PubMed 19356506Hong GR, Pedrizzetti G, Tonti G, Li P, Wei Z, Kim JK, Baweja A, Liu S, Chung N, Houle H, Narula J, Vannan MA. Characterization and quantification of vortex flow in the human left ventricle by contrast echocardiography using vector particle image velocimetry. JACC Cardiovasc Imaging. 2008 Nov;1(6):705-17. doi: 10.1016/j.jcmg.2008.06.008. Epub 2008 Nov 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brett Fenster, MD, FACC, FACP principal investigator
National Jewish Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Hypertension, run by National Jewish Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between RV diastolic function and vorticity (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01491646, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.