Clinical trial NCT03195114: Cardiac MRI for Post-TAVR Paravalvular Leak Assessment
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Paravalvular Leak
Keywords: post TAVR quantification
cardiac MRI
echocardiography
biomarkers
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2017-06-22
Enrollment: 15
Sex: ALL
Minimum age (years): 60
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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.

Primary outcomes:
measure: PVL severity regression
timeFrame: up to 7-months post-TAVR
Secondary outcomes:
measure: Intra- and inter-observer variability of PVL severity assessment
timeFrame: 1-month and 7-months post-TAVR
Other outcomes:
measure: PVL severity change at 7-months post-TAVR is associated with LV mass regression and myocardial fibrosis
timeFrame: up to 7-months post-TAVR
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist DeBakey Heart & Vascular Center
state: Texas
city: Quebec
country: Canada
facility: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Study officials:
References: