Imaging Coronary Microvascular Dysfunction (CMD) Study

NCT ID: NCT05634031

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-26
• Study Completion Date: 2027-03-01

Brief Summary

Angina is a common clinical symptom of ischemic heart disease, affecting up to 11 million people in the United States alone, and 112 million people globally. Despite this, 4 in 10 patients undergoing elective coronary angiography for angina and ischemia do not have evidence of obstructive coronary artery disease (CAD). This condition of ischemia with no obstructive CAD (INOCA) is associated with high clinical and economic morbidity, as these patients have a higher rate of repeat procedures and hospitalizations, worse quality of life, future adverse cardiovascular events and frequent time missed from work.

The overall objective of this study is to develop and validate a non-invasive algorithm for diagnosis and management of patients with INOCA and suspected microvascular dysfunction centered around cardiac PET MPI. A secondary goal of the study is to assess for improvement in patient symptoms, function and quality of life from PET-guided management of CMD in patients with INOCA.

This study will take place at Mount Sinai Morningside in the PET and CTunit on the 3rd floor. The sub-study will occur at Mount Sinai Morningside Cath Lab on the 3rd floor. The study will enroll an estimated total of 70 subjects, 12 of which will also participate in the sub-study. The study is estimated to last 2 years.

Detailed Description

All patients will be consented and will undergo Rb-82 rest-stress myocardial perfusion imaging PET with flow quantitation using vasodilator (regadenoson preferred) stressor and cold pressor test and an exercise treadmill test according to standard modified Bruce protocol (if able to exercise).

Only the patients who do not have a recent coronary CT angiography will be consented for undergoing a coronary CT angiography for measurement of plaque burden and quantification of extent and degree of epicardial stenosis.

A small subset of patients who have abnormal flow parameters on PET will be invited to participate in the invasive angiographic validation cohort and will undergo an invasive functional angiography with measurement of FFR, CFR, IMR and Ach-vasoreactivity testing to obtain validation data for PET-guided diagnosis of CMD. A short questionnaire of symptom, suspected diagnosis and planned management will be administered to the treating physician prior to and post-study enrollment.

Patient risk factors, symptoms, health status, medications will be collected using standardized data collection form on study enrollment.

For Aim 2, the cardiac PET findings will be made available to the treating clinician.

A positive PET result for endothelial-independent CMD will be defined as global MBFR <2. A positive PET result for endothelial-dependent CMD will be defined as MBF with cold-pressor test <=40%.

If there was evidence of CMD on cardiac PET, specific treatment recommendations will be made available to the treating physician. These recommendations will include consideration of aspirin, statin and ACE-inhibitors in all patients, beta-blockers (eg: carvedilol 6.25 mg BID with uptitration) as first line, non-dihydropyridine calcium channel blockers (cardizem and verapamil) as second line, and amlodipine (in combination with beta-blocker) or ranolazine as third-line therapy.

Patient symptoms and health status and downstream resource utilization (ER admissions for chest pain, use of other invasive or non-invasive diagnostic procedures for CAD) will be collected at 3 months.

Invasive physiology measurements will be made available to the treating clinician along with recommended management based on INOCA endotype (corMICA trial treatment algorithm) at completion of 3 months.

Conditions

Angina; Non-obstructive Coronary Artery Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Patients with INOCA

Patients to undergo coronary angiogram and/or coronary CT angiogram for suspected ischemic symptoms of angina and dyspnea but do not have obstructive epicardial coronary artery disease.

Group Type: EXPERIMENTAL

PET imaging

Intervention Type: RADIATION

PET imaging visit, which will take approximately 1-2 hours.

Coronary CT angiogram

Intervention Type: RADIATION

A coronary CT angiogram if the participant has not had one recently.

Functional Angiography

Intervention Type: PROCEDURE

A subset of patients with abnormal results on cardiac PET myocardial perfusion imaging study (estimated number of patients = 12) will be invited to participate in an invasive sub-study wherein they would undergo detailed invasive coronary physiology evaluation.

Functional Angiography (coronary reactivity test- CRT): is an angiography procedure done in the catheterization laboratory. It evaluates the coronary artery microcirculation and how the blood vessels respond to different medications.

Treadmill exercise stress study

Intervention Type: PROCEDURE

A treadmill exercise stress study

Interventions

PET imaging

PET imaging visit, which will take approximately 1-2 hours.

Intervention Type: RADIATION

Coronary CT angiogram

A coronary CT angiogram if the participant has not had one recently.

Intervention Type: RADIATION

Functional Angiography

A subset of patients with abnormal results on cardiac PET myocardial perfusion imaging study (estimated number of patients = 12) will be invited to participate in an invasive sub-study wherein they would undergo detailed invasive coronary physiology evaluation.

Functional Angiography (coronary reactivity test- CRT): is an angiography procedure done in the catheterization laboratory. It evaluates the coronary artery microcirculation and how the blood vessels respond to different medications.

Intervention Type: PROCEDURE

Treadmill exercise stress study

A treadmill exercise stress study

Intervention Type: PROCEDURE

Other Intervention Names

coronary reactivity test; CRT

Eligibility Criteria

Inclusion Criteria

• Patients with symptoms of exertional angina and/or dyspnea (confirmed on Seattle Angina Questionnaire and Rose Dyspnea Questionnaire)
• Evidence of non-obstructive CAD on CCTA or coronary angiography (no stenosis >50% and/or FFR if performed >0.80)

Exclusion Criteria

• Patients with reduced LVEF (<50%) or diagnosis of cardiomyopathy
• Patients with co-existent moderate or severe valve disease
• Patients with eGFR <30 ml/min/m2
• History of prior coronary revascularization
• Non-coronary indication for CCTA or coronary angiogram determining eligibility
• Contraindications to regadenoson (severe asthma/chronic obstructive pulmonary disease, brady-arrhythmias, or systolic blood pressure <90 mm Hg)
• Inability to provide informed consent
• Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Krishna Patel

Assistant Professor of Medicine (Cardiology) and Population Health Science and Policy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Krishna Patel, MBBS, MSc

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai Morningside

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Lilia Soriano, BS

Role: CONTACT

lilia.soriano@mountsinai.org

(929) 736-1828

Other Identifiers

IF2779994

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

STUDY-22-00774

Identifier Type: -

Identifier Source: org_study_id