PET Imaging Finds Vulnerable Plaques That Cause MI

A new technique that can locate vulnerable coronary plaques at risk of rupturing and causing a myocardial infarction (MI) could help identify patients at high cardiovascular risk who might need more intensive treatment.

The technique uses sodium fluoride PET imaging to identify calcified areas on coronary plaques, which are an indication that the plaque is inflamed and vulnerable to bursting.

“This could represent a big change in the way coronary disease is detected,” saidDavid Newby, MD, University of Edinburgh, Edinburgh, United Kingdom, who is senior author of a new analysis evaluating the approach.

The analysis showed that vessel-specific coronary atherosclerotic plaque activity is associated with MI within the same coronary artery territory and that increased coronary atherosclerotic plaque activity is predominantly seen in coronary arteries without residual obstructive lesions.

“Our latest results confirm that individual vulnerable plaques are causing Mis, and we can identify these plaques with this new technique,” Newby said. “Our findings also suggest that just putting a stent into a narrowed artery doesn’t always fix the problem; there are other plaques that will cause future MIs that are not necessarily causing narrowing of the artery.”

These latest results come from an analysis of data from the PRE18FFIR or Prediction of Recurrent Events With 18F Sodium Fluoride to Identify Ruptured and High-Risk Coronary Artery Plaques in Patients With Myocardial Infarction study.

Previous results from that study showed that increased total coronary atherosclerotic plaque activity determined by ¹⁸F-sodium fluoride uptake across the entire coronary arterial tree is associated with a higher risk for cardiac death or MI, independent of obstructive coronary artery disease.

New Vessel-Level Analysis

The analysis shows that coronary atherosclerotic plaque activity tracks with MI at the vessel level. “This reaffirms and gives added plausibility to our prior patient-level results,” Newby said.

The new analysis of data from the PRE18FFIR study was published in the Journal of the American College of Cardiology (JACC).

“We know that a lot of MIs originate from plaques that are not causing stenosis. We talk about these plaques being vulnerable,” Newby explains, “but identifying which plaques are vulnerable is difficult. A normal coronary angiogram just shows lumen narrowing.”

For the PRE18FFIR study, the researchers evaluated whether ¹⁸F-sodium fluoride PET imaging could identify patients who would go on to have further cardiovascular events.

The trial, which involved patients who had multivessel cardiovascular disease and had had a recent MI showed that patients with a higher uptake of the sodium fluoride tracer on PET imaging were more likely to have another MI.

In the new analysis of PRE18FFIR data, the researchers looked at the relation between individual coronary atherosclerotic plaque activity in each coronary artery territory and MI and considered both vessel-specific and patient-centered perspectives.

Increased ¹⁸F-sodium fluoride uptake was seen in 679 of 2094 coronary arteries and in 414 of 691 patients. MI occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (hazard ratio [HR], 2.08; P = .013).

This association was not demonstrable in those treated with coronary revascularization (HR, 1.02) but was notable in untreated vessels (HR, 3.86).

Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk for cardiac death or MI (HR, 2.43; P = .002).

“We have shown in this study that this technique can identify patients with vulnerable plaques that can cause future MIs. The implication of this is that we may be able to treat patients with vulnerable plaques with increased lipid lowering and anti-inflammatory therapies to reduce their risk,” Newby said.

Less Invasive Technique

Although vulnerable plaques have been known about for many years, Newby believes that this new technique is an easier way to identify them.

Previously, patients had to undergo an invasive coronary angiogram with a camera inserted into all coronary arteries. “This is quite a complicated and invasive procedure. And it only gives an image of the plaque; it doesn’t give any real information about the biology of the plaques,” he explained.

“The new PET technique is much less invasive. The tracer is injected into the bloodstream. Then the patient undergoes a scan to see where the tracer has been taken up in the coronary arteries,” he said.

Although sodium fluoride PET imaging has been around for years, this is a new application for the technique.

“This is the first multicenter, randomized trial to show it can be used to identify vulnerable plaques and patients who will go on to have future cardiovascular events. I hope that this relatively simple technique can be used in clinical practice in the future to identify patients at high risk of MI and other cardiac events,” Newby said.

About 40% of the patients in this study — who all had a recent MI and multivessel disease — had vulnerable plaques and could benefit from intensified treatment, Newby estimated.

Randomized trials are necessary to determine whether prophylactic intervention with intensified treatment would improve outcomes in these patients.

The technique may also be useful in lower-risk patients, but more studies would have to be done to look at this, Newby said.

In the JACC analysis, the authors say their latest findings “support the central role of coronary atherosclerotic plaque activity in the development of MI and the importance of incorporating coronary atherosclerotic plaque activity in the prediction of coronary atherothrombotic events at both the vessel and the patient level.”

‘An Important Contribution’

This analysis is “an important contribution to our understanding of imaging vulnerable plaque,” Zahi A. Fayad, PhD, and Philip M. Robson, PhD, from the Icahn School of Medicine at Mount Sinai, New York City, and Valentin Fuster, MD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain, wrote in an editorial accompanying the JACC publication.

They pointed out that although the idea of identifying a vulnerable plaque whose imminent rupture will cause an MI is an attractive one, the development of atherosclerotic lesions and the processes of rupture have been shown to be more gradual and prolific; this detracts from the potential role that identifying vulnerable plaque may have for preventing coronary events.

The editorialists believe that patient-level risk, encompassing more traditional risk factors and disease burden, remains the most useful approach for predicting the possibility of an adverse event and for guiding intervention and medical therapy. “That is, it is preferable to consider the vulnerable patient rather than the vulnerable plaque,” they noted.

However, they acknowledged that this new analysis has shown that it is possible to identify a vulnerable plaque using molecular imaging.

“This important result, in addition to others that have confirmed that ¹⁸F-sodium fluoride PET can identify culprit plaque, predicts further disease burden progression as well as outcomes and serves a crucial role in aiding stratification of risk among a wider population of at-risk patients with previous myocardial infarction,” they said.

The impact of this study is broader because the data suggest that an indication of individual plaque vulnerability — based on an elevated ¹⁸F-sodium fluoride signal — could be a valuable component in determining patient-level risk, they added, calling for further studies that combine different markers of individual plaque vulnerability with more general markers of disease burden and patient-level risk to increase risk stratification for future coronary events.

“Although we anticipate the vulnerable-patient approach will continue to supersede the vulnerable-plaque approach for assessing coronary event risk, continued investigation of factors that determine and identify vulnerable plaque remain relevant because it adds to our understanding of biology, can provide immediate risk stratification within a population, can track treatment effects, and inform on patient-level risk as part of a multicomponent evaluation alongside conventional factor such as disease burden and medical history,” they said.