DENVER – The added prognostic value gained by measuring coronary flow reserve in addition to myocardial perfusion for predicting the risk of cardiac events is a major emerging theme in cardiac nuclear imaging.

The impetus for developing PET quantitation of coronary flow reserve as a tool for evaluating cardiac event risk in patients with known or suspected CAD lies in the relatively recent recognition that a normal or low-risk conventional single-photon emission computed tomography (SPECT) myocardial perfusion imaging study is no guarantee of a low event risk, Dr. George A. Beller noted at the annual meeting of the American Society of Nuclear Cardiology.

"In order to identify those patients with normal or low-risk perfusion scans who really are high risk, we need to do more than just look at relative perfusion," he explained. "Myocardial flow reserve as assessed by PET is emerging now as a really good adjunct to just looking at relative uptake."

Italian investigators recently utilized dynamic SPECT imaging to assess coronary flow reserve in 58 patients with a normal myocardial perfusion study. In the 20 patients with normal coronary flow reserve as well as normal perfusion, the cardiac event rate was just 0.7% per year. In the 38 with normal perfusion along with an abnormally low coronary flow reserve, however, the event rate was 5.2% per year (J. Nucl. Cardiol. 2011;18:612-9).

"This is a substantial sevenfold increase in event rate in those with what we would consider a normal scan with normal perfusion," commented Dr. Beller of the University of Virginia, Charlottesville.

PET offers several key advantages over SPECT for assessment of coronary flow reserve, the most important being that it provides accurate quantification of the extent of abnormal regional myocardial blood flow reserve. In addition, it readily detects microvascular dysfunction, and it also picks up balanced ischemia, which often results in a false-negative SPECT myocardial perfusion imaging study, he continued.

"Myocardial flow reserve as assessed by PET is emerging now as a really good adjunct to just looking at relative uptake."

A recent study by investigators at the University of Ottawa Heart Institute National Cardiac PET Center showed that quantitation of coronary flow reserve using rubidium-82 PET predicted hard cardiac events independently of summed stress scores for myocardial ischemia.

In 704 consecutive patients prospectively followed for a median of 387 days after testing, those with a summed symptom score of less than 4, indicative of normal myocardial perfusion, plus normal coronary flow reserve had a 1.3% incidence of cardiac death or MI. In contrast, patients with a summed symptom score below 4 and abnormally low coronary flow reserve had a significantly higher 2.0% event rate, while those with a summed symptom score of 4 or higher plus abnormal coronary flow reserve had an 11.1% cardiac event rate. Patients with abnormal myocardial perfusion and normal coronary flow reserve had a 1.1% incidence of cardiac events (J. Am. Coll. Cardiol. 2011;58:740-8).

Similarly, investigators at Johns Hopkins University, Baltimore, recently demonstrated that a finding of globally impaired myocardial flow reserve was a potent independent predictor of near-term cardiovascular events.

They utilized rubidium-82 PET to quantify global myocardial flow reserve in 275 patients referred for perfusion imaging and subsequently followed for an average of 1 year. In an age-adjusted multivariate analysis, a finding of regional perfusion defects was independently associated with a 2.5-fold increased risk of cardiac events, confirming a long-established relationship. But in addition, a global myocardial flow reserve below the median value was also an independent predictor of cardiac events, with an associated 2.9-fold increased risk (J. Nucl. Med. 2011;52:726-32).

On the basis of these and other compelling studies reported in the last year or two, Dr. Beller offered the following algorithm for noninvasive testing to predict the risk of cardiac events in patients with stable CAD: Those who can perform more than 10 METs (metabolic equivalents) of exercise on the treadmill are at very low risk and warrant being placed on optimal medical therapy, with crossover to an invasive strategy only if symptoms worsen. Patients less than 5% left ventricular ischemia and normal coronary flow reserve also belong in this low-risk category.

A high-risk test is defined by 10%-15% left ventricular ischemia or markedly reduced coronary flow reserve, even in the presence of only a mild perfusion defect. These are patients for whom consideration should be given to an invasive strategy coupled with optimal medical therapy.

For patients with mild ischemia – that is, 5%-9% – a normal ejection fraction, and either a normal or only a small focal area of diminished coronary flow reserve, optimal medical therapy and follow-up stress imaging is an appropriate approach, Dr. Beller added.

He declared having no financial conflicts.

Coronary Flow Reserve Enhances Risk Assessment