Cardiac MRI for Severe Aortic Stenosis

A total of 80 participants will be enrolled into the study from site with the
protocol-required technology. The Pennsylvania Department of Health funding for this trial
is limited to sites in Pennsylvania. Participants will undergo pre- and post-operative
cardiac MRI, blood draws, a 6-minute walk test, arterial tonometry, medical history
assessment, and quality-of-life questionnaires to characterize the pathophysiologic factors
causing variability in regression after AVR. Researchers will evaluate the role of specific
hemodynamic abnormalities as determinants of post-AVR LV remodeling (LV hypertrophy and LV
myocardial fibrosis) as seen on contrast-enhanced cardiac MRI. The trial also will evaluate
a non-contrast-enhanced MRI approach (T1rho) potentially effective in assessing LV
myocardial fibrosis.

Inclusion Criteria:

- 18 years of age or older

- Severe symptomatic aortic stenosis (estimated aortic valve area <1 cm2) 1,2 as
documented on a transthoracic echocardiogram (ECG) performed within 4 months prior to
enrollment

- Planned for AVR within 8 weeks after enrollment

- Able to have a cardiac MRI within 3 weeks prior to the AVR surgery

- A preoperative coronary angiography demonstrating the absence of
hemodynamically-significant CAD in need of revascularization during AVR surgery

- Able to tolerate cardiac MRI with gadolinium contrast as required by protocol, to be
performed at an ACRIN-qualified facility using an ACRIN-qualified MR scanner

- Willing and able to provide a written informed consent

Exclusion Criteria:

- Not suitable to undergo cardiac MRI or use the contrast agent gadolinium because of:

- Claustrophobia

- Presence of metallic objects or implanted medical devices in body (i.e.,
implanted 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)

- Weight greater than that allowable by the MRI table

- Known LV ejection fraction <50%

- Previous aortic valve surgery

- Planned additional valve repair/replacement

- Infective endocarditis

- Moderate or severe aortic valve regurgitation

- Rhythm other than sinus rhythm (i.e., atrial fibrillation) that results in an
irregular heartbeat, compromising the quality of MRI and tonometry data acquisition,
as documented on an ECG performed within 8 weeks prior to enrollment

- Presence of hemodynamically-significant CAD that would require revascularization
during the AVR surgery

- Myocardial infarction or unstable angina in the previous month

- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 of body surface area
documented within 4 weeks prior to enrollment

NOTE: This threshold has been deemed appropriate for this study, rather than <30
mL/min/1.73m2, since eGFR is likely to decrease for participants between the baseline and
6-month examinations. The protocol calls for gadolinium administration in the 6-month
evaluation, and gadolinium administration is contraindicated in the presence of an eGFR
<30 mL/min/1.73m2. Therefore, initially excluding patients who have an eGFR < 60
mL/min/1.73m2 will minimize the presence of an eGFR <30 mL/min/1.73m2 at the time of the
6-month evaluation.

An eGFR < 30 mL/min/1.73m2 of body surface area or acute kidney injury will be a
contraindication to gadolinium contrast administration, and participants with insufficient
kidney function immediately before the 6-month cardiac MRI will undergo an MRI without
contrast-enhancement and will continue on-study.

- Presence of a bicuspid aortic valve, which is associated with an intrinsic aortopathy
that may affect arterial load in its own right;

- Resting heart rate >120 beats per minute, systolic blood pressure >180 mm Hg, or
diastolic blood pressure > 100 mm Hg

- Pregnancy or intent to become pregnant

- Conditions that would make the study measurements less accurate or unreliable (i.e.,
frequent premature beats that may affecting cardiac gating, anatomic neck
characteristics impeding arterial tonometry, inability to perform an adequate breath
hold for cardiac MRI acquisitions) or the reliable post-operative follow-up of
patients (for at least 6 months post-AVR) unlikely

- Known peripheral vascular disease, which may limit the ability to exercise
independently of cardiac status due to claudication

- Unwillingness of the patient to undergo a cardiac MRI

- Unwillingness of the patient to sign the consent form

- Any condition limiting life expectancy to <1 year