SNOWMASS, COLO. – Mounting evidence attests to the value of noninvasive measurement of coronary flow reserve as a means of classifying cardiovascular risk in patients with stable coronary artery disease (CAD) more accurately than is possible via coronary angiography or measurement of fractional flow reserve, Marcelo F. Di Carli, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“We use CFR [coronary flow reserve] as a way to exclude coronary disease. It’s a good practical measure of multivessel ischemic CAD. When the CFR is normal, you can with high confidence exclude the possibility of high-risk CAD,” according to Dr. Di Carli, executive director of the cardiovascular imaging program and chief of the division of nuclear medicine and molecular imaging at Brigham and Women’s Hospital, Boston.

When the CFR is markedly low, however, a patient with stable CAD is at high risk for cardiovascular events, even if angiography shows no clinically significant stenosis, added Dr. Di Carli, who is also professor of radiology and medicine at Harvard Medical School, Boston.

Most recently, he and his coinvestigators utilized CFR to provide new insight into the paradox that women have a higher cardiovascular disease death rate than men, even though their prevalence of obstructive CAD is lower.

Their NIH-sponsored study included 329 consecutive patients with a left ventricular ejection fraction greater than 40% – 43% of them women – who underwent coronary angiography several days after noninvasive assessment of CFR via myocardial perfusion positron emission tomography. The women had a lower burden of angiographic CAD and a lower pretest clinical risk score than the men. Nevertheless, during a median of 3 years of follow-up, the women had an adjusted twofold greater risk of the composite endpoint of cardiovascular death, nonfatal MI, or heart failure.

This excess cardiovascular risk in women was independently associated with a very low CFR, defined as less than 1.6. Dr. Di Carli and his coinvestigators calculated that this impaired CFR mediated 40% of the excess risk in women. Thus, a low CFR represents a novel hidden biologic risk for ischemic heart disease (Circulation. 2017 Feb 7;135[6]:566-77).

CFR is defined as the ratio of absolute coronary flow or myocardial perfusion between drug-induced hyperemia and rest. It can be quantified noninvasively using positron emission tomography or MRI.

CFR integrates into a single measure the three components of CAD: the focal stenosis, the diffuse atherosclerotic plaque typically present to a varying degree throughout a target vessel, and microvascular dysfunction.

CFR is a measure of coronary physiology, as is invasive fractional flow reserve (FFR). However, FFR measures only the severity of stenosis and extent of diffuse disease; it doesn’t assess microvascular dysfunction. This is a limitation because it means FFR can give false-negative readings in patients without significant obstructive coronary disease who have severe microvascular dysfunction.

As for angiography, Dr. Di Carli continued, it’s now evident that this purely anatomic assessment is of limited value as a marker of clinical risk and is inadequate to guide management decisions in the setting of stable CAD. After all, angiographically guided revascularization has not reduced cardiovascular events in clinical trials comparing it with optimal medical therapy, as in the COURAGE and BARI-2D trials.

“It’s clear that there’s been a paradigm shift in how we manage patients with stable CAD. For many years the coronary angiogram was the cornerstone of what we did: how we understand the symptoms, the patient’s risk, and ultimately how we proceed with treatment. But there is no benefit in basing treatment solely on what the lesions look like anatomically. That’s why we’ve turned to functional testing of coronary physiology,” he said.

CFR has opened a window on the importance of microvascular dysfunction, which is present in about half of patients with stable CAD and has been shown to predict cardiovascular risk independent of whether or not severe obstructive disease is present.

In an earlier study, Dr. Di Carli and coworkers demonstrated that quantification of CFR enhances stratification for risk of cardiac death among diabetes patients (Circulation. 2012 Oct 9;126[15]:1858-68). The study included 2,783 patients, of whom 1,172 were diabetic, who underwent measurement of CFR and were subsequently followed for a median of 1.4 years, during which 137 cardiac deaths occurred.

Diabetes patients without known CAD who had a low CFR had a high cardiac death rate of 2.8%/year, similar to the 2.0%/year rate in nondiabetic patients with a history of acute MI or revascularization. On the other hand, diabetes patients with a normal CFR and without known CAD had a cardiac mortality rate of only 0.3%/year, comparable to the 0.5% rate in nondiabetics without known CAD who had preserved systolic function and a normal stress perfusion study.

In the future, CFR may aid in decision making as to whether an individual with stable CAD is best treated by percutaneous coronary intervention, surgical revascularization, or guideline-directed medical therapy. For example, if CFR indicates the presence of an isolated severe focal stenosis, and this is confirmed by angiography and FFR, PCI may be the best option, while diffuse disease as demonstrated by CFR may be better treated surgically or using optimal medical therapy. But this needs to be established in prospective clinical trials, added Dr. Di Carli.

He reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

Coronary flow reserve reveals hidden cardiovascular risk