Functional mitral regurgitation (FMR) portends a bleak prognosis and is a common
consequence of ischemic and non-ischemic cardiomyopathy (ICM, NICM), where adverse
annular and left ventricular (LV) remodeling and/or infarction alters mitral valve (MV)
function.
Prior studies demonstrate significant increases in mortality risk as severity of FMR
increases; mortality rates range from 15-40% at 1 year. Furthermore, as the prevalence of
heart failure (HF) is rising, FMR is projected to double from over 2 million patients in
2000 to over 4 million patients in the United States by 2030. Defining FMR severity,
optimal timing of intervention, and most appropriate method for intervention remain
controversial. Recently, MITRA-FR and COAPT trials demonstrated contrasting survival
benefit with percutaneous MV repair, demonstrating the importance and need for more
optimal selection criteria. Currently, the patient selection criteria for Mitraclip
therapy are solely based on MV anatomy and controversial echocardiographic criteria for
FMR severity. Cardiac magnetic resonance (CMR) provides an exciting opportunity to
address numerous unmet needs regarding characterizing FMR and the need for more optimal
selection criteria for improving outcomes. Superior accuracy and reproducibility for
quantification of LV size and function, and gold standard tissue characterization,
positions CMR as the ideal imaging modality for comprehensively characterizing FMR and
the underlying myopathic processes that significantly impact response to FMR therapies.
The goal of the current research is to develop personalized risk prediction for FMR
patients through explainable unsupervised phenomapping enriched with advanced CMR imaging
biomarkers, and to determine the CMR predictors of reverse remodeling following modern
therapies for FMR.
The proposed research will leverage a large retrospective single center NICM CMR
database. Our CMR NICM database currently features 458 NICM patients, who underwent CMR
on a single CMR vendor platform from 2008-2017, who have been extensively curated with
contoured data for standard CMR measures. An additional 802 NICM patients have been
identified from our 2018-2021 CMR database with EF<50% with the same inclusion/exclusion
criteria, which will be extensively curated to enable phenomapping discovery. An external
400 NICM patient cohort will be used as an external validation cohort.
The prospective study entails aiming to recruit 360 adult patients (ages >18 years) with
EF 10-50% and FMR RF> 20%, who are clinically referred for CMR evaluation. Patients who
enroll in our study will be referred for optimization of mGDMT with Heart Failure
Pharmacist Clinic and followed every 2 weeks until optimized. All will return and undergo
follow-up CMR studies at 6months. NICM patients who are fully medically optimized with
significant FMR at the time of the baseline CMR and are referred for Mitraclip treatment
will undergo follow-up CMR 6 months from Mitraclip intervention. NICM patients referred
for mGDMT optimization, but have persistent or progressive FMR at the time of 6 month
follow-up CMR and referred for Mitraclip therapy, will undergo a 2nd follow-up CMR 6
months from Mitraclip therapy. CMR will be done on dedicated cardiac research MRI
scanner.
A ischemic cardiomyopathy subgroup will be assessed as a comparator cohort.