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Cardiac MRI for Post-TAVR Paravalvular Leak Assessment (Class-CMR)

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ClinicalTrials.gov Identifier: NCT03195114
Recruitment Status : Recruiting
First Posted : June 22, 2017
Last Update Posted : December 7, 2018
Sponsor:
Information provided by (Responsible Party):
Thomas Gleason, University of Pittsburgh

Brief 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 variability of both imaging methods; and c) correlate the severity of PVL with post-TAVR changes in LV remodeling and clinical outcomes.

Condition or disease Intervention/treatment
Paravalvular Leak Diagnostic Test: Multimodality Imaging and Biomarkers

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.


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Study Type : Observational
Estimated Enrollment : 55 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : January 1, 2017
Estimated Primary Completion Date : December 1, 2023
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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.
Diagnostic Test: Multimodality Imaging and Biomarkers
Cardiac MRI, Cardiac MDCT, Echocardiography and Biomarkers Testing




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Intra- and inter-observer variability of PVL severity assessment [ Time Frame: 1-month and 7-months post-TAVR ]
    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.


Other Outcome Measures:
  1. PVL severity change at 7-months post-TAVR is associated with LV mass regression and myocardial fibrosis [ Time Frame: up to 7-months post-TAVR ]
    To test that PVL severity change by CMR over 6-month period post-TAVR (comparing assessment at 1-month vs 7-months post-TAVR regurgitant fraction and regurgitant volume), is a determinant of LV reverse remodeling and negatively correlates with the regression of LV mass and myocardial fibrosis assessed by CMR.


Biospecimen Retention:   None Retained
Samples for future


Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
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.
Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03195114


Contacts
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Contact: Thomas L Gleason, MD 412-802-8529 gleasontg@upmc.edu
Contact: Gail Wallen, RN 412-647-2782 walleng@upmc.edu

Locations
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United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Thomas Gleason, MD    412-802-8529    gleasontg@upmc.edu   
Contact: Gail Wallen, RN    412-647-2782    walleng@upmc.edu   
United States, Texas
Houston Methodist DeBakey Heart & Vascular Center Recruiting
Houston, Texas, United States, 77030
Contact: Dipan J Shah, MD    713-441-3625    DJShah@HoustonMethodist.org   
Contact: Stephen H Little, MD    713-441-3625    SHLittle@houstonmethodist.org   
Canada
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec Recruiting
Quebec, Canada, G1V 4G5
Contact: Josep Rodes-Cabau, MD    418-656-8711 ext 3055    Josep.Rodes@criucpq.ulaval.ca   
Contact: Philippe Pibarot, DVM, PhD    418-656-8711 ext 5938    Philippe.Pibarot@med.ulaval.ca   
Sponsors and Collaborators
University of Pittsburgh

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Responsible Party: Thomas Gleason, Associate Professor of Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03195114     History of Changes
Other Study ID Numbers: PRO15050330
First Posted: June 22, 2017    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Thomas Gleason, University of Pittsburgh:
post TAVR quantification
cardiac MRI
echocardiography
biomarkers