Cardiac MRI for Post-TAVR Paravalvular Leak Assessment

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.

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.