Phenotypic Classification of FMR With CMR

Functional Mitral Regurgitation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05965258
• Other study ID #: 23-702
• Secondary ID: 1R01HL170090-01
• Status: Recruiting
• Start date: August 29, 2023
• Est. completion date: December 31, 2028

Study information

• Verified date: October 2023
• Source: The Cleveland Clinic
• Contact: Deborah Kwon, MD
• Phone: 216-444-8526
• Email: kwond[@]ccf.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2028
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Functional Mitral Regurgitation
• Mitral Valve Insufficiency

Intervention

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.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
The Cleveland Clinic	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

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