Paravalvular LeakClass-CMRNCT03195114
Cardiac MRI for Post-TAVR Paravalvular Leak Assessment
An observational study of Paravalvular Leak, run by University of Pittsburgh at 3 sites in 2 countries.
Trial summary
The objectives of this study are to: a) evaluate and correlate the severity of paravalvular leak (PVL) assessed by both cardiac MRI and transthoracic echocardiography (TTE) after transcatheter aortic valve replacement (TAVR) with Medtronic Evolut-R or Evolut PRO bioprostheses; b) assess the inter and intraobserver… Read more about this study
- Who is it for?
- Ages 60 to 100 years
- Conditions the study is for
- Paravalvular Leak
- What is being tested?
- Multimodality Imaging and Biomarkers
- How many people
- 15 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Jan 2017to 15 Feb 2019
- 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 60 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 55 men and women aged 60 or above who received Medtronic Evolut-R or Evolut PRO and have at least mild paravalvular leak on transthoracic echocardiogram performed 25-45 days after TAVR procedure.
Who may be able to join
- Subjects will be considered for study participation if they meet all of the following inclusion criteria:
- Patient ≥ 60 years of age has undergone commercial TAVR implant with Evolut R or Evolut PRO bioprosthesis within prior 25-45 days.
- Patient has ≥ mild PVL on TTE study performed at approximately the one (1) month post-TAVR (regular clinical follow-up visit taking place within prior 25-45 days post-TAVR)
- The patient and the treating physician agree that the subject will return for all required post-procedure follow-up visits.
- Eligible patients from the three (3) participating institutions (University of Pittsburgh, Pittsburgh, PA; Methodist Hospital, Houston, TX and Quebec Heart \& Lung Institute, Quebec, Canada) who have received TAVR with Evolut R or Evolut PRO will be screened for this study. All patients should be willing and able to provide a written informed consent for this study.
Who cannot join
- Patients with unstable condition and/or with implanted permanent cardiac device such as implantable cardiac defibrillators, cardiac resynchronization device, etc. MRI-conditional pacemaker devices would not represent an exclusion given the proven safety of these devices at 1.5 Tesla magnetic field strength.
- Patients treated with valve-in-valve implantation technique to address moderate-severe PVL and/or prosthetic aortic valve dysfunction.
- Patients with significant interval cognitive decline post-TAVR, unable to follow instructions required for both MDCT and CMR studies.
- Patients with metallic objects or implanted medical devices in the body (i.e. non-MRI conditional cardiac pacemaker or defibrillator, central nervous system aneurysm clips,implanted neural stimulators, cochlear implant, ocular foreign body [e.g., metal shavings], other implanted medical devices [e.g., drug infusion port], insulin pump, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) which would exclude the participant from participating in the study. Verification of safety for MRI study should be checked for each one of the implanted medical devices at the website www.mrisafety.com.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Houston Methodist DeBakey Heart & Vascular Center
Houston, Texas, 77030
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Canada1 site
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Québec, G1V 4G5
About this study
Official title: Multicenter Prospective CoreValve Study Using Cardiac MRI for Assessment of Paravalvular Aortic Regurgitation and Its Impact on LV Reverse Remodeling and Cardiovascular Outcomes
The objectives of this study are to: a) evaluate and correlate the severity of paravalvular leak (PVL) assessed by both cardiac MRI and transthoracic echocardiography (TTE) after transcatheter aortic valve replacement (TAVR) with Medtronic Evolut-R or Evolut PRO bioprostheses; b) assess the inter and intraobserver variability of both imaging methods; and c) correlate the severity of PVL with post-TAVR changes in LV remodeling and clinical outcomes.
Read the detailed description
Paravalvular leak (PVL) represents the most common complication post-transcatheter aortic valve replacement (TAVR). Presence of even mild PVL has been associated with unfavorable outcomes including late mortality, which is physiologically and hemodynamically hard to be reconciled.
Although transthoracic echocardiogram (TTE) is the first line test for the PVL quantification, it can be flawed due to poor acoustic windows, eccentricity of PVL, image degradation associated with the implanted prosthesis, irregular orifices, subjectivity and inconsistency of the assessment and grading. Furthermore, to date, most published studies do not use a uniform standardized way of quantifying the PVL. The Valve Academic Research Consortium (VARC) published the VARC II definitions and suggested the use of TAVR-specific criteria for the assessment of PVL. However, there has been no validation of this proposed criteria and how their selected cutoffs correlate to patient outcomes. All these issues contribute to uncertainty and imprecision of the current method, leading to difficulties and subjectivity in the assessment and quantification of PVL severity.
Cardiac MRI (CMR) is able to directly quantify aortic regurgitation with high accuracy and reproducibility by using the technique of phase-contrast velocity mapping when compared to TTE. CMR had lower intraobserver and interobserver variabilities for regurgitant volume assessment, suggesting that CMR may be superior for serial measurements. In addition, CMR quantification of aortic regurgitant fraction allows risk-stratification identifying patients at risk for development of heart failure and need for aortic valve surgery.
However, despite these advantages, the use of CMR for PVL assessment post-TAVR has been limited. A recent single center prospective pilot study (n=16) showed that CMR assessment of PVL was feasible using CoreValve prosthesis. In addition, CMR rather than TTE, correlated better with intra-procedural aortography. TTE underestimated the degree of PVL compared to CMR suggesting the opportunity of this modality to more reliably and accurately quantify PVL after TAVR. Another recent small and single-center CMR study (n=43) compared immediate post-TAVI CMR findings with those at 6-month follow-up. There were 32 patients (74%) treated with Medtronic CoreValve prosthesis and 11 (26%) treated with Edwards Sapien XT valve. The authors noted significant favorable LV remodeling at 6 months, but not in patients with > mild PVL. Furthermore, PVL quantified by CMR did not decrease over time. Given the small number of patients, the authors could not compare the temporal changes between the two prosthesis. In addition, the mechanisms associated with the changes in PVL severity were not able to be ascertained given the study design.
CMR provides exquisite tissue characterization using late-gadolinium enhancement imaging. Adverse myocardial response to pressure-overload causes maladaptive myocardial hypertrophy with increased LV mass and also myocardial fibrosis (MF), which has been associated with adverse outcomes despite aortic valve replacement. Newer CMR techniques such as T1 mapping and extracellular volume fraction quantification can now non-invasively quantify the extent of diffuse MF supported by histological validation. The interplay between PVL and MF and their impact of on the LV reverse remodeling is unknown. It is possible that PVL might exert its detrimental effects by slowing LV reverse remodeling, hampering the regression of LV hypertrophy and myocardial fibrosis post-TAVR.
Lastly, gated multi-detector computed tomography (MDCT) which has a critical role in the pre-procedural planning of patients undergoing TAVR evaluation, also has been found important in identifying predictors of PVL post-TAVR. However, the role of MDCT in the post-TAVR setting, for PVL evaluation, has not been yet established. Gated MDCT post-TAVR might be relevant to determine the interplay between the native aortic valve/annulus and the TAVR prosthesis aiding in the evaluation of possible mechanism(s) behind PVL changes over time.
- Conditions
- Paravalvular Leak
- Being tested
- Multimodality Imaging and Biomarkers
- Keywords
- post TAVR quantification, cardiac MRI, echocardiography, biomarkers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodality Imaging and BiomarkersDiagnostic test
Cardiac MRI, Cardiac MDCT, Echocardiography and Biomarkers Testing
| Study group | Role | What they receive |
|---|---|---|
| Multimodality Imaging and Biomarkers | Post-TAVR patients who received commercial Medtronic Evolut-R or Evolut PRO bioprosthesis implant and found to have at least mild PVL on 1-month post-TAVR echocardiogram will undergo multimodality imaging and biomarkers evaluation at 1-month and 7-months post-TAVR. Receives: Diagnostic Test: Multimodality Imaging and Biomarkers |
What is being measured
The primary outcome is the main question the study is designed to answer.
PVL severity regression
To test that PVL severity, assessed by CMR using regurgitant fraction and regurgitant volume, changes and regresses over a 6-month period post-TAVR (comparing those measurements at 1-month and 7-months post-TAVR).
Measured: up to 7-months post-TAVR
Secondary outcomes (1)
Intra- and inter-observer variability of PVL severity assessment
To test the hypothesis that PVL severity, assessed by CMR using regurgitant fraction and regurgitant volume, at both 1-month and 7-months post-TAVR has lower intra and inter-observer variability when compared to its assessment by TTE.
Measured: 1-month and 7-months post-TAVR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start1 Jan 2017
- Primary completion15 Feb 2019
- Study completion15 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paravalvular LeakStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Gleason, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03195114
- Sponsor's protocol ID
- PRO15050330
- Acronym
- Class-CMR
- Status last verified
- May 2020
- First submitted
- 12 Mar 2017
- Last updated
- 5 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Prospective CoreValve Study Using Cardiac MRI for Assessment of Paravalvular Aortic Regurgitation and Its Impact on LV Reverse Remodeling and Cardiovascular Outcomes
- ClinicalTrials.gov ID
- NCT03195114
- Acronym / sponsor ID
- Class-CMR / PRO15050330
- Conditions
- Paravalvular Leak
- Keywords
- post TAVR quantification, cardiac MRI, echocardiography, biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 15 Feb 2019 (actual)
- Study completion
- 15 Feb 2019 (actual)
- First posted
- 22 Jun 2017 (actual)
- 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.
The objectives of this study are to: a) evaluate and correlate the severity of paravalvular leak (PVL) assessed by both cardiac MRI and transthoracic echocardiography (TTE) after transcatheter aortic valve replacement (TAVR) with Medtronic Evolut-R or Evolut PRO bioprostheses; b) assess the inter and intraobserver variability of both imaging methods; and c) correlate the severity of PVL with post-TAVR changes in LV remodeling and clinical outcomes.
Detailed description
Paravalvular leak (PVL) represents the most common complication post-transcatheter aortic valve replacement (TAVR). Presence of even mild PVL has been associated with unfavorable outcomes including late mortality, which is physiologically and hemodynamically hard to be reconciled.
Although transthoracic echocardiogram (TTE) is the first line test for the PVL quantification, it can be flawed due to poor acoustic windows, eccentricity of PVL, image degradation associated with the implanted prosthesis, irregular orifices, subjectivity and inconsistency of the assessment and grading. Furthermore, to date, most published studies do not use a uniform standardized way of quantifying the PVL. The Valve Academic Research Consortium (VARC) published the VARC II definitions and suggested the use of TAVR-specific criteria for the assessment of PVL. However, there has been no validation of this proposed criteria and how their selected cutoffs correlate to patient outcomes. All these issues contribute to uncertainty and imprecision of the current method, leading to difficulties and subjectivity in the assessment and quantification of PVL severity.
Cardiac MRI (CMR) is able to directly quantify aortic regurgitation with high accuracy and reproducibility by using the technique of phase-contrast velocity mapping when compared to TTE. CMR had lower intraobserver and interobserver variabilities for regurgitant volume assessment, suggesting that CMR may be superior for serial measurements. In addition, CMR quantification of aortic regurgitant fraction allows risk-stratification identifying patients at risk for development of heart failure and need for aortic valve surgery.
However, despite these advantages, the use of CMR for PVL assessment post-TAVR has been limited. A recent single center prospective pilot study (n=16) showed that CMR assessment of PVL was feasible using CoreValve prosthesis. In addition, CMR rather than TTE, correlated better with intra-procedural aortography. TTE underestimated the degree of PVL compared to CMR suggesting the opportunity of this modality to more reliably and accurately quantify PVL after TAVR. Another recent small and single-center CMR study (n=43) compared immediate post-TAVI CMR findings with those at 6-month follow-up. There were 32 patients (74%) treated with Medtronic CoreValve prosthesis and 11 (26%) treated with Edwards Sapien XT valve. The authors noted significant favorable LV remodeling at 6 months, but not in patients with > mild PVL. Furthermore, PVL quantified by CMR did not decrease over time. Given the small number of patients, the authors could not compare the temporal changes between the two prosthesis. In addition, the mechanisms associated with the changes in PVL severity were not able to be ascertained given the study design.
CMR provides exquisite tissue characterization using late-gadolinium enhancement imaging. Adverse myocardial response to pressure-overload causes maladaptive myocardial hypertrophy with increased LV mass and also myocardial fibrosis (MF), which has been associated with adverse outcomes despite aortic valve replacement. Newer CMR techniques such as T1 mapping and extracellular volume fraction quantification can now non-invasively quantify the extent of diffuse MF supported by histological validation. The interplay between PVL and MF and their impact of on the LV reverse remodeling is unknown. It is possible that PVL might exert its detrimental effects by slowing LV reverse remodeling, hampering the regression of LV hypertrophy and myocardial fibrosis post-TAVR.
Lastly, gated multi-detector computed tomography (MDCT) which has a critical role in the pre-procedural planning of patients undergoing TAVR evaluation, also has been found important in identifying predictors of PVL post-TAVR. However, the role of MDCT in the post-TAVR setting, for PVL evaluation, has not been yet established. Gated MDCT post-TAVR might be relevant to determine the interplay between the native aortic valve/annulus and the TAVR prosthesis aiding in the evaluation of possible mechanism(s) behind PVL changes over time.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multimodality Imaging and Biomarkers | – | Diagnostic Test: Multimodality Imaging and BiomarkersPost-TAVR patients who received commercial Medtronic Evolut-R or Evolut PRO bioprosthesis implant and found to have at least mild PVL on 1-month post-TAVR echocardiogram will undergo multimodality imaging and biomarkers evaluation at 1-month and 7-months post-TAVR. |
Who may qualify
- Ages
- 60 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 55 men and women aged 60 or above who received Medtronic Evolut-R or Evolut PRO and have at least mild paravalvular leak on transthoracic echocardiogram performed 25-45 days after TAVR procedure.
Key inclusion criteria (5 listed)
- Subjects will be considered for study participation if they meet all of the following inclusion criteria:
- Patient ≥ 60 years of age has undergone commercial TAVR implant with Evolut R or Evolut PRO bioprosthesis within prior 25-45 days.
- Patient has ≥ mild PVL on TTE study performed at approximately the one (1) month post-TAVR (regular clinical follow-up visit taking place within prior 25-45 days post-TAVR)
- The patient and the treating physician agree that the subject will return for all required post-procedure follow-up visits.
- Eligible patients from the three (3) participating institutions (University of Pittsburgh, Pittsburgh, PA; Methodist Hospital, Houston, TX and Quebec Heart \& Lung Institute, Quebec, Canada) who have received TAVR with Evolut R or Evolut PRO will be screened for this study. All patients should be willing and able to provide a written informed consent for this study.
Key exclusion criteria (4 listed)
- Patients with unstable condition and/or with implanted permanent cardiac device such as implantable cardiac defibrillators, cardiac resynchronization device, etc. MRI-conditional pacemaker devices would not represent an exclusion given the proven safety of these devices at 1.5 Tesla magnetic field strength.
- Patients treated with valve-in-valve implantation technique to address moderate-severe PVL and/or prosthetic aortic valve dysfunction.
- Patients with significant interval cognitive decline post-TAVR, unable to follow instructions required for both MDCT and CMR studies.
- Patients with metallic objects or implanted medical devices in the body (i.e. non-MRI conditional cardiac pacemaker or defibrillator, central nervous system aneurysm clips,implanted neural stimulators, cochlear implant, ocular foreign body [e.g., metal shavings], other implanted medical devices [e.g., drug infusion port], insulin pump, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) which would exclude the participant from participating in the study. Verification of safety for MRI study should be checked for each one of the implanted medical devices at the website www.mrisafety.com.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multimodality Imaging and BiomarkersCardiac MRI, Cardiac MDCT, Echocardiography and Biomarkers Testing | Diagnostic test | Multimodality Imaging and Biomarkers |
Primary outcome
PVL severity regression
Time frame: up to 7-months post-TAVR
To test that PVL severity, assessed by CMR using regurgitant fraction and regurgitant volume, changes and regresses over a 6-month period post-TAVR (comparing those measurements at 1-month and 7-months post-TAVR).
1 secondary outcome
Intra- and inter-observer variability of PVL severity assessment
Time frame: 1-month and 7-months post-TAVR
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 5 May 2020.
- Individual participant dataSharing planned: No
Related trials for Paravalvular Leak
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Paravalvular Leak, run by University of Pittsburgh at 3 sites in 2 countries.
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 4 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 5 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Canada. 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?
PVL severity regression (time frame: up to 7-months post-TAVR). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 May 2020.