Phenotypic Classification of FMR With CMR

Improving Phenotypic Classification and Prediction of Treatment Outcomes in Patients With Non-ischemic Cardiomyopathy and Functional Mitral Regurgitation

The goal of the current research is to develop personalized risk prediction for functional mitral regurgitation (FMR) patients through explainable unsupervised phenomapping enriched with advanced cardiac magnetic resonance (CMR) imaging biomarkers, and to determine the CMR predictors of reverse remodeling following modern therapies for FMR.

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 and will 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.

Study Overview

• Status: Recruiting
• Conditions: Functional Mitral Regurgitation; Nonischemic Congestive Cardiomyopathy
• Intervention / Treatment: Diagnostic test: Cardiac magnetic resonance (CMR)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 360

Contacts and Locations

• Study Contact: Name: Deborah Kwon, MD; Phone Number: 216-444-8526; Email: kwond@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Sub-Investigator: Wilson Tang, MD
      • Contact: Deborah Kwon, MD; Phone Number: 216-444-8526; Email: kwond@ccf.org
      • Sub-Investigator: Samir Kapadia, MD
      • Sub-Investigator: David Chen, PhD
      • Sub-Investigator: Xiaofeng Wang, PhD
      • Sub-Investigator: Marc Gillinov, MD
      • Sub-Investigator: Christopher Nguyen, PhD
      • Sub-Investigator: Nancy Obuchowski, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients referred to Cleveland Clinic Structural Interventional Cardiology Clinic for evaluation of possible percutaneous MV intervention are routinely referred for CMR as part of their clinical protocol, and will be recruited for this prospective study. Additionally, patients clinically referred for CMR for evaluation of cardiomyopathy, who are found to have FMR RF >20% for enrollment into this prospective study.

Description

Inclusion Criteria:

1 CMR LVEF <50% 2.FMR Fraction>20%, with adequate image quality and no evidence of severe obstructive CAD

Exclusion Criteria:

1. >moderate aortic regurgitation/stenosis,
2. <18 years of age,
3. acute myocarditis,
4. eGFR<15
5. HCM
6. cardiac amyloidosis/sarcoidosis
7. prior mitral valve intervention
8. myocardial infarction within 8 weeks of CMR
9. ischemic infarct pattern on CMR

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Optimize mGDMT; NICM patients referred for mGDMT optimization	Diagnostic test: Cardiac magnetic resonance (CMR); Cardiac magnetic resonance (CMR) at 6 months. If referred to MitraClip, CMR will be performed at 6 months from the procedure.
MitraClip and mGDMT; NICM patients who are fully medically optimized with significant FMR at the time of the baseline CMR and are referred for Mitraclip treatment	Diagnostic test: Cardiac magnetic resonance (CMR); Cardiac magnetic resonance (CMR) at 6 months. If referred to MitraClip, CMR will be performed at 6 months from the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of cardiac mortality, heart transplant, or LVAD implantation.	Occurrence of cardiac mortality and/or heart transplant and/or LVAD implantation	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FMR	a change of >5 units/percentage points compared to baseline	6 months
Change in NT-proBNP	30% change in NT-proBNP or decrease to level < 1000 compared to baseline	6 months
Change in KCQL score	5 point change in KCQL score compared to baseline	6 months
Change in 6-minute walk test	25 meter change in 6-minute walk test compared to baseline	6 months
Recurrent heart failure hospitalization	Occurrence of heart failure related hospitalization	up to 1 year
Arrhythmias	Occurrence of arrhythmia	up to 1 year
MI	Occurrence of myocardial infarction	up to 1 year
Stroke	Occurrence of stroke	up to 1 year
Heart transplant	Occurrence of heart transplant	up to 1 year
LVAD implantation	Occurrence of implant of left ventricular assisted device (LVAD)	up to 1 year
Mortality	Occurrence of mortality	up to 1 year

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Deborah Kwon, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 20, 2023
• First Submitted That Met QC Criteria: July 20, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Heart Valve Diseases; Cardiomegaly; Laminopathies; Mitral Valve Insufficiency; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: 23-702; 1R01HL170090-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No