Comparative Imaging Assessment of Valvular Heart Disease

Assessment of Left Ventricular Volumes and Strain and Assessment of Valvular Lesions Using Two- and Three-dimensional Echocardiography and Cardiac MRI, a Correlation Study

The purpose of the study is to compare the various 2D and 3D methods of valvular heart disease quantification (Doppler, PISA, VCA, volumetric method) and strain with cardiac magnetic resonance (CMR) measurements of left and right ventricular systolic function strain and myocardial fibrosis assessment.

Study Overview

• Status: Recruiting
• Conditions: Aortic Stenosis; Aortic Regurgitation; Valve Heart Disease
• Intervention / Treatment: Diagnostic test: MRI with strain measurement; Diagnostic test: Echocardiography

Detailed Description

The objective of this study is to compare the accuracy of 3D TTE to 2D TTE in assessing the severity of valvular heart disease in patients with aortic stenosis, aortic regurgitation, and mitral valve regurgitation by comparing this to the reference standard of cardiac magnetic resonance (CMR) in subjects with different etiologies and mechanisms of valvular lesions and to the integrative method of valvular lesion grading as recommended by inter-societal guidelines. Another objective is to assess prevalence of focal and diffuse myocardial fibrosis as assessed by CMR in patients with aortic stenosis, aortic regurgitation and mitral regurgitation. In addition, the investigators aim to determine whether severity of myocardial fibrosis predicts onset of symptoms, referral for valve surgery and adverse ventricular remodeling. The investigators also aim to look at patients who will be undergoing CRT implant to predict their response to therapy.

At baseline, the Rapid Assessment of Physical Activity questionnaire and the Kansas City Cardiomyopathy Questionnaire will be completed. A 6-12 month follow-up is required and will include an abbreviated non-contrast research cardiac MRI and subject questionnaires.

Other follow-up will include using electronic medical records and the Social Security Death Index database for outcomes such as death, hospitalization for heart failure, mitral or aortic valve interventions and cardiovascular death.

Select patients will be asked to undergo a supine bicycle exercise stress MRI at enrollment. Approximately 40 subjects will be included in this substudy.

Additional exclusion criteria for this substudy:

• Unable to pedal a supine bicycle
• Require supplemental oxygen

During the exercise stress MRI, patients will be asked to cycle on a supine bike that will be mounted on the MRI platform. During this test, a caregiver will be present. An electrocardiogram (ECG) will be used to obtain tracings of cardiac activity. Respirations, blood pressure, and heart rate are also monitored during exercise. The test is continued until peak exercise level or target heart rate is achieved. As soon as the exercise portion is complete, MRI images will be acquired. When the test is complete, patients will be monitored until ECG, heart rate, and breathing have returned to baseline. Patients will be assessed for symptoms such as chest pain, dyspnea, leg pain, dizziness, or fatigue and may be given medications or instructed to stop the test early as necessary.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

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

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Deborah Kwon, M. D.; Phone Number: 216-444-8526; Email: kwond@ccf.org
      • Sub-Investigator: Richard Grimm, MD
      • Sub-Investigator: John Richard, MD
      • Sub-Investigator: Mina Chung, MD
      • Sub-Investigator: Wlson Tang, MD
      • Sub-Investigator: Tom Wang, MD
      • Sub-Investigator: Christopher Nguyen, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with suspected chronic AS, AR, MR or heart failure with reduced ejection fraction being evaluated for CRT implantation referred for clinically indicated CMR and echocardiography by their cardiologists.. CMR and echocardiography will be clinically indicated in this study group.

Description

Inclusion Criteria:

• Age 18-90 years of age
• Suspected moderate or severe MR,AR or AS on the basis of prior known clinical history or clinical exam.
• Suspected CRT "non-responder" with an implanted MRI compatible CRT device and reduced ejection fraction

Exclusion Criteria:

• Acute traumatic cardiac injury
• Aortic dissection or aortic root rupture
• Congenital heart diseases such as patent ductus arteriosus, coarctation of aorta, ASD and VSD
• Presence of A-V fistula or intracardiac shunts
• Any contraindications to CMR
• Moderate or severe dysfunction in multiple valves
• Patients with significant claustrophobia

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mitral Valve Regurgitation; Patients with moderate or severe (3+ or 4+) mitral valve regurgitation on the basis of prior known clinical history or clinical exam.	Diagnostic test: MRI with strain measurement; CMR measurements of left and right ventricular systolic function strain and myocardial fibrosis; Diagnostic test: Echocardiography; Doppler, PISA, VCA, volumetric method as performed during echocardiography
Aortic Valve Regurgitation; Patients with moderate or severe (3+ or 4+) aortic valve regurgitation on the basis of prior known clinical history or clinical exam.	Diagnostic test: MRI with strain measurement; CMR measurements of left and right ventricular systolic function strain and myocardial fibrosis; Diagnostic test: Echocardiography; Doppler, PISA, VCA, volumetric method as performed during echocardiography
Aortic Stenosis; Patients with moderate or severe (3+ or 4+) aortic stenosis on the basis of prior known clinical history or clinical exam.	Diagnostic test: MRI with strain measurement; CMR measurements of left and right ventricular systolic function strain and myocardial fibrosis; Diagnostic test: Echocardiography; Doppler, PISA, VCA, volumetric method as performed during echocardiography
Patients referred for CRT Implantation; Patients who meet clinical guideline criteria for CRT implantation with EF < 40%	Diagnostic test: MRI with strain measurement; CMR measurements of left and right ventricular systolic function strain and myocardial fibrosis; Diagnostic test: Echocardiography; Doppler, PISA, VCA, volumetric method as performed during echocardiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MRI Quantified LVEDVi	10% Change from Baseline - units of measure cc/m2	6 months
Change in MRI Quantified LVESVi	15% Change from Baseline - units of measure cc/m2	6 months
Change in MRI Quantified LV Strain	5% Change from Baseline	6 months
Change in MRI LVEF	5% Change from Baseline	6 Months
Change in Kansas City Cardiomyopathy Questionnaire Answers	Change in quality of life related to heart failure symptoms.	6 Months
Change in Physical Activity Questionnaire Answers	Change in physical activity level due to heart failure symptoms.	6 Months
All-cause mortality	number of patients expired	6 Months
Development of class I or IIa indication for valve surgery	The recommended indications for surgery include: development of symptoms, LV dysfunction (LV end-systolic diameter ≥45 mm or LV ejection fraction ≤60%), and new onset of atrial fibrillation or pulmonary hypertension (systolic pulmonary artery pressure >50 mm Hg at rest).	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of echocardiography as compared with MRI	Comparison of MRI measurements based on standard of care echocardiography.	6 Months

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Deborah Kwon, M. D., The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2019
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: October 11, 2019
• First Posted (Actual): October 14, 2019

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Aortic Valve Disease; Ventricular Outflow Obstruction; Heart Diseases; Aortic Valve Stenosis; Aortic Valve Insufficiency; Heart Valve Diseases
• Other Study ID Numbers: 19-549

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