Clinical trial NCT05634031: Imaging Coronary Microvascular Dysfunction (CMD) Study
Official title: Development and Validation of a Non-invasive Algorithm for Diagnosis of Microvascular Angina Among Patients With Ischemia and Non-obstructive Coronary Artery Disease (IMAGING-CMD Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Angina
Non-obstructive Coronary Artery Disease
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2022-12-01
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: The Seattle Angina Questionnaire (SAQ)
timeFrame: 3 months
measure: Rose Dyspnea Scale (RDS)
timeFrame: 3 months
measure: Euro-QOL 5 Dimension Visual Analog Scale (EQ5D-VAS)
timeFrame: 3 months
measure: Number of ER admissions for chest pain per participant
timeFrame: 3 months
measure: Number of use of other invasive or non-invasive diagnostic procedures for CAD
timeFrame: 3 months
Secondary outcomes:
measure: The Bruce protocol score
timeFrame: within 3 months of patient enrollment
measure: Number of participants with METs >=10 METS
timeFrame: within 3 months of patient enrollment
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Morningside
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Krishna Patel, MBBS, MSc
role: PRINCIPAL_INVESTIGATOR
References: