Low Coronary Flow Reserve During Stress MRI Predicts MACE

Marlene Busko

December 06, 2018

CHICAGO — Among patients undergoing a cardiac MRI stress test with coronary flow reserve (CFR) measured at the same time, those with CFR below the median had worse outcomes, a new study shows.

Specifically, they were twice as likely to have a major adverse cardiac event (MACE) — including death, nonfatal myocardial infarction (MI), heart failure hospitalization, sustained ventricular tachycardia or late revascularization — than those with a CFR above the median during a 2.1-year follow-up.

This increased risk remained significant even after adjustment for the extent of myocardial ischemia, ejection fraction, and the size of myocardial scar measured with late gadolinium enhancement (LGE).

The study, by Raksha Indorkar, MD, Division of Cardiology, Department of Medicine, University of Illinois at Chicago, and colleagues, was published online November 5 in JACC: Cardiovascular Imaging and presented November 10 at the American Heart Association Scientific Sessions 2018.

Global CFR is the ratio of total myocardial blood flow at stress to myocardial blood flow at rest, and mainly depends on the ability of the coronary microvasculature to dilate, so it "is a measure of the health of the coronary microcirculation," senior author Afshin Farzaneh-Far, MD, PhD, associate professor of medicine & radiology and director of the Cardiovascular MRI Laboratory at the University of Illinois at Chicago, explained to theheart.org | Medscape Cardiology.

"In this study we show that even if your stress test is normal — which previously you would have said 'Great! It's normal' — now we know that if your microcirculation is unhealthy, you're at increased risk of having subsequent adverse events."

"This could potentially allow us to look at...patients who have chest pain but who have normal coronary angiogram," he added. If they are found to have an abnormal microcirculation, this can explain their symptoms.

This study is the first to demonstrate the value of coronary sinus flow measurements at rest and during stress in addition to a routine stress cardiovascular magnetic resonance (CMR) protocol, Hajime Sakuma, MD, PhD, Department of Radiology, Mie University Hospital, Tsu, Japan, writes in an accompanying editorial.

"Global CFR measurement seems to be particularly useful in patients without myocardial ischemia or" scar, he notes.

"2D flow CMR is widely available in most MR scanners and can be easily used in clinical practice," he told theheart.org | Medscape Cardiology in an email.

However, "the prognostic value of global CFR measurement by CMR has not been recognized…in patients with suspected CAD."

The current study suggests it can improve risk stratification and influence patient management, "especially in patients with diffuse atherosclerosis and microvascular disease."

A "key point," according to Sakuma, "is education and training for MR technologists. Adequate positioning of the imaging slice for coronary sinus flow measurement may require a certain amount of experience or training."

A "Tiny Fraction" of Coronary Circulation

Currently, coronary artery disease (CAD) is managed primarily by detecting and treating stenosis in the epicardial coronary arteries, Indorkar and colleagues write.

However, these arteries "represent only a tiny fraction of the overall coronary circulation," and some patients, often women, with normal coronary angiograms still have chest pain.

Global CFR can shine a light on what is happening in the cardiac microcirculation.

To determine CFR during a stress MRI test, blood flow leaving the coronary sinus is measured at rest and then after the administration of a medication like adenosine or regadenoson that stimulates relaxation in the microcirculation.  

The researchers aimed to evaluate the incremental prognostic value of CFR in patients with known or suspected CAD who were undergoing stress cardiac MRI.

They prospectively enrolled 507 patients. Of these, 38 patients had uninterpretable images or were unable to complete the stress test.  

The patients had a mean age of 58 and 55% were women.

The main indications for stress testing were chest pain (68%), dyspnea (16%), and preoperative evaluation (11%). Fewer patients (11%) had abnormal ECG, nonsustained ventricular tachycardia, premature ventricular contractions, syncope, or new cardiomyopathy, and some patients had multiple indications.

Of the 469 patients who completed the test, 80 (17%) experienced a MACE during follow-up (19 patients died, 21 had an MI, 13 were hospitalized for HF, two had sustained ventricular tachycardia, and 25 had late revascularization).

Patients with CFR below the median of 2.2 had a significantly higher risk of having MACE than other patients.

Notably, in patients without myocardial ischemia, those with a CFR below the median had a much higher MACE event rate/year than other patients (8.6% vs 3.8%; = .002).

Similarly, in patients without myocardial scar, those with a CFR below the median had a much higher MACE event rate/year than other patients (9.3% vs 3.9%; = .001).

"These findings suggest a role for CMR-derived CFR in identifying patients at risk of adverse events following stress CMR, even in the absence of ischemia and LGE," Indorkar and colleagues conclude.

What is not clear, Farzaneh-Far said, is a "specific treatment" for the patients with normal coronary angiogram but an abnormal coronary microvascular function.

However, recent early evidence from the CorMicA study, which used invasive diagnostic methods, suggests that "targeting specific treatments to people that have abnormal microcirculation may result in better symptom improvement," he noted.

The next steps are to validate the current method in a multicenter setting, to establish normal values, and then to determine "how to specifically treat poor coronary microcirculation."

The researchers and editorialist have no relevant financial disclosures.

American Heart Association (AHA) Scientific Sessions 2018: Abstract 438. Presented November 10, 2018.

JACC: Cardiovascular Imaging. Published online November 5, 2018. Abstract, Editorial

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