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
|Condition or disease||Intervention/treatment|
|Paravalvular Leak||Diagnostic Test: Multimodality Imaging and Biomarkers|
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 Type :||Observational|
|Estimated Enrollment :||55 participants|
|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|
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
- 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).
- 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.
- 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
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
|Contact: Thomas L Gleason, MDfirstname.lastname@example.org|
|Contact: Gail Wallen, RNemail@example.com|
|United States, Pennsylvania|
|University of Pittsburgh Medical Center||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Thomas Gleason, MD 412-802-8529 firstname.lastname@example.org|
|Contact: Gail Wallen, RN 412-647-2782 email@example.com|
|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|
|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|