New technique identifies ‘hot’ disease in arteries that can lead to CV events
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Using noninvasive 18F-sodium fluoride PET and coronary CTA to detect “hot” disease in arteries, researchers were able to predict which patients with recent MI would have recurrent coronary events.
PET “is often used in cancer; it uses positrons to produce a signal so you can see externally the biology of what’s going on in the body without inserting catheters,” David E. Newby, MD, British Heart Foundation Professor of Cardiology at the University of Edinburgh, U.K., said during a press conference at the European Society of Cardiology Congress. “What we’ve done is develop a technique using a slightly different tracer, 18F-sodium fluoride. What it does is bind to hardening within the coronary arteries and identify areas of active disease in the arteries. It’s not like a calcium score ... on a CT scan. This is activity of the plaque itself. This is potentially the first technique where we can actually see externally, using a PET CT scan, whether a patient’s coronary arteries are ‘hot’ and inflamed and might cause a heart attack. It’s lighting up just the area that’s got the nasty disease in it.”
Traditionally, prediction of future CV events in patients with MI is done by the GRACE score or by an invasive angiogram to assess for narrow arteries, he said. “The problem with these things is that scores are imprecise and the angiogram looks at narrowings, but we know that most recurrent heart attacks are from artery disease that is not narrowed.”
For the PRE18FFIR study, Newby and colleagues performed noninvasive 18F-sodium fluoride PET and coronary CTA on 704 patients with recent MI and multivessel disease (4% single-vessel, 55% two-vessel, 34% three-vessel, 7% left main). The clinical endpoints of interest were CHD death, MI, all-cause death and stenting or CABG. Median follow-up was 4 years.
There were 712 patients who attended the baseline visit. Six had an incomplete PET scan (three due to claustrophobia, one due to panic attack, one due to anxiety and one due to system malfunction) and two were lost to follow-up, according to the presentation.
“We showed that if we use this technique, we can actually predict the future risk of these patients of having a heart attack, of dying or of dying from heart disease in particular,” Newby said at the press conference. “What we didn’t see was whether somebody would have a stent put in.”
The patients were stratified by whether they had a lot of active disease (“hot arteries”) or not (“cold arteries”). Compared with those with cold arteries, those with hot arteries had elevated risk for CHD death/MI (HR = 1.82; 95% CI, 1.07-3.1; P = .03; log-rank P = .025) and all-cause death (HR = 2.43; 95% CI, 1.15-5.12; P = .02; log-rank P = .016), according to the researchers. There was no difference between the groups in revascularization.
“This is the first real demonstration in a robust, multicenter international study showing that we can see ‘hot’ plaques that are going to cause problems downstream,” Newby said at the press conference. “We’ve used a technique that is widely available in cancer but can now be applied readily to cardiology patients. And it picks out the people at the highest risk of a future event. It helps in terms of counseling the patient. It also helps in terms of escalating treatments, because we have an awful lot of treatments. And it also is a technique we potentially could use test new drugs against to see if we can prevent further recurrent heart attacks.”
Perspective
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Matthew I. Tomey, MD, FACC, FSCAI
As other presented studies explore the relative merits of angiographic vs. physiologic criteria to select nonculprit lesions for a localized intervention (PCI), the PRE18FFIR study provides an elegant reminder of the systemic nature of atherosclerosis and its critical third dimension of disease activity.
18F-sodium fluoride PET-CT is notable in its ability to noninvasively highlight inflammation of coronary arterial plaque.
In PRE18FFIR, patients with “hot arteries” after a myocardial infarction were significantly more likely than those with “cold arteries” to have a heart attack and die. While it is not yet clear that we need to image all our post-MI patients in this manner for risk stratification, the findings of PRE18FFIR should prompt us to ask for all our post-MI patients: Are we effectively maximizing medical therapy to “cool down” atherosclerosis progression?
We know that atherosclerosis disease progression accelerates after a MI and that inflammation is central to this process.
We now have multiple tools to modulate this inflammation, including but not limited to statins, anti-inflammatory agents, and, potentially, beta-blockers.
There remain significant gaps and disparities in delivery of evidence-based medical therapy after MI, and this constitutes a critical priority for quality improvement.
Our capacity to maximize medical therapy likely represents a critical effect modifier on the efficacy of nonculprit lesion PCI after acute MI, whether guided by angiography or physiology. Phrased otherwise: if we can “turn off” the progression of atherosclerosis medically, what is the residual benefit of nonculprit lesion PCI? In the answer to this question likely lies the reconciliation between studies of elective PCI for post-MI nonculprit lesions (eg, PRAMI, COMPLETE) and studies of elective PCI for stable CAD (eg, COURAGE, ISCHEMIA).
Perspective
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Samin K. Sharma, MD, FACC, FSCAI
There have been data in the past showing that plaque with more activity is more likely to rupture in the future and give rise to heart attacks. So far, all of those tests have been invasive: You put a catheter in the coronary artery and then make this prediction. What makes PRE18FFIR unique is to use a similar agent that oncologists use to look for cancer activity in the body. The technique enables you to see the inflammation activity in the body by injecting the agent with 18F-sodium fluoride and doing PET scanning. You also perform CTA to see if there is a blockage.
The researchers found that patients who had a high uptake of 18F-sodium fluoride, meaning “hot” arteries from fluoride binding to the plaque, had a lot of inflammation, and inflammatory arteries have a high chance of subsequent heart attack or death. In a nutshell, this is the first study to say that we can make this assessment noninvasively.
This is a unique concept, and its biggest advantage is that it can be more generalized than what we have been doing. The question is, even if you identify “hot” arteries, what are you going to do about them? Many of these patients are already on good medications — antiplatelet therapies, cholesterol medicines, etc. Now, we have no true anti-inflammatory medicines for coronary disease. Almost all have failed. Colchicine is the only one which is available, and maybe it will have a role. Importantly, once we see a patient has “hot” plaque, we will be more aggressive in reducing the cholesterol content to make the “hot” plaque become normal plaque. That can be accomplished with newer agents such as PCSK9 inhibitors and inclisiran (Leqvio, Novartis). Identifying “hot” plaque will make our therapy more aggressive and focused than usual. There are trials of anti-inflammatory medicines ongoing, but only colchicine has made it to the finish line, as it has been shown to reduce events in people with ACS and in people with chronic coronary syndrome.
These results will not change our policy right away. This study was the first of its kind. It will take more studies that duplicate these results before this technique is widely adopted, and that will take some time. Earlier adoption could occur in cases of patients who keep having recurrent events.
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Newby DE, et al. Hot Line 7. Presented at: European Society of Cardiology Congress; Aug. 26-29, 2022; Barcelona, Spain (hybrid meeting).
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