“Heart attack risk identified by new scan,” is the BBC News headline, reporting on the development of a scan that could help doctors identify fatty build-ups (plaques) in the arteries. These plaques are characteristic of atherosclerosis and coronary heart disease and can trigger a heart attack if they rupture.
The news comes from a study that tested the use of a PET-CT scanner to identify “high-risk” plaques that had, or could, rupture. The PET-CT scan uses a radioactively labelled chemical to produce 3D images. The chemical normally used is a glucose-like substance called fludeoxyglucose (FDG), which is taken up by body tissues. However, recent studies suggest that sodium fluoride (NaF) is a more effective way of identifying plaques.
The current study involved 40 people who recently had a heart attack and 40 people with stable angina. The patients had PET-CT scans using either FDG or NaF as the radioactively labelled chemical. They were also tested using coronary angiography, which is currently the gold-standard method of looking at blockages in the heart arteries.
In almost all of the people who had had a heart attack, NaF was taken up by the “culprit” fatty deposits that had caused the blockage. The results also confirmed that NaF was better than FDG at showing these blockages. Almost half of the people with stable angina were found to have high-risk deposits using the NaF technique.
While this sounds promising, only a small number of patients have been studied. It remains to be seen whether the new test improves outcomes for people with coronary heart disease.
Where did the story come from?
The study was carried out by researchers from the University of Edinburgh, the Royal Infirmary of Edinburgh and the University of Cambridge, and was funded by the Scottish Chief Scientist Office and the British Heart Foundation.
It was published in the peer-reviewed medical journal The Lancet.
The UK media’s reporting of the study was generally accurate and appropriate.
What kind of research was this?
This was a diagnostic study that aimed to see whether a certain type of imaging scan can identify fatty deposits (atherosclerosis) in the heart arteries, which are at high risk of causing a heart attack.
If one of these fatty deposits (plaques) ruptures and breaks apart, it can lead to a blood clot (thrombus). If a clot completely blocks the artery, it prevents blood from reaching the heart muscle and causes a heart attack.
The difficulty is in knowing which fatty deposits are “unstable” and likely to rupture, and so cause a heart attack. Unstable deposits are known to have certain characteristics, such as a large, fatty centre made up of necrotic (“dead”) material and a thin outer covering. The development of imaging techniques that are able to detect these high-risk features would be a useful medical advance.
The current study involved PET-CT scans, a combination of CT (computerised tomography) and PET (positron emission tomography) imaging that uses a radioactively labelled chemical to produce 3D images.
Normally, radioactively labelled FDG is used to produce the 3D images. This approach is often used in cancer cases because FDG has a similar structure to glucose. This means it is taken up by body tissues, which can be detected by the scan and can therefore help identify abnormal tissue growths.
However, recent research has shown that radioactively labelled NaF could be a better marker for looking at the fatty deposits of atherosclerosis.
The study involved 40 people who had recently suffered a heart attack and 40 people who had stable angina. They were given three diagnostic tests:
- Two non-invasive imaging PET-CT scans – one using the standard radioactively labelled chemical FDG, and one using NaF.
- The gold-standard invasive method of looking at blockages in the artery – coronary angiography. In coronary angiography, a long thin tube (catheter) is entered into a blood vessel in the arm or groin and fed through to the heart arteries. A dye is then injected and an X-ray is taken to view the heart arteries.
The study aimed to see how well a PET-CT scan using NaF detected fatty deposits that had either already ruptured or were at high risk of rupturing. Researchers compared the performance against the standard non-invasive method (PET-CT using FDG) and the standard invasive method (coronary angiography).
The study also looked at some people who were at risk of stroke and were having surgery to remove a fatty deposit from the carotid artery in their neck. It compared PET-CT scans with laboratory findings after the deposit was removed.
What did the research involve?
The research included patients treated at the Royal Infirmary of Edinburgh between February 2012 and January 2013, including 40 people who had experienced a heart attack and 40 people with stable angina who were undergoing coronary angiography to look at the blockages in their heart arteries.
A further nine people were included who were at risk of stroke and were having a carotid endartectomy to remove a clot from the main carotid artery in their neck.
The study had various exclusion criteria, including only looking at those over the age of 50 and excluding those with poorly controlled diabetes or kidney failure.
The 40 patients with heart attack and 40 patients with stable angina underwent the three PET-CT scan imaging techniques using either radioactively labelled FDG or NaF, or coronary angiography.
For the PET-CT scans, the researchers measured uptake of the chemicals (tissue to background ratios) and looked at whether this was above or below a reference cut-off. This was so they could class the fatty deposits as either positive or negative for uptake – that is, whether or not there was a significant uptake of the chemical.
An independent expert reviewed the PET-CT images, looking for fatty deposits that were positive or negative for uptake of the radioactive chemical, and determined the severity of stenosis (narrowing of the artery caused by atherosclerosis), the composition of the fatty deposits (whether calcified, non-calcified, or mixed) and the presence of high-risk features.
For the nine people who had carotid endartectomy, the composition of the removed fatty deposits was examined in the laboratory. In the people with stable angina, intravascular ultrasound (where an ultrasound probe is advanced through the catheter in the groin or arm) was also used to look at the fatty deposits in the heart arteries.
The main analysis of the study was to compare the uptake of NaF in “culprit” and “non-culprit” fatty deposits in people who had had a heart attack – in other words, to look at how the chemical had been taken up by fatty deposits leading up to the heart attack.
The other outcomes examined included comparing imaging and laboratory examination features of positive and negative deposits in people with coronary artery disease and people with carotid artery disease.
What were the basic results?
In the 93% of people who had had a heart attack (37/40), NaF uptake was seen in the culprit fatty deposit responsible for the heart attack. The culprit fatty acid deposits were identified by coronary angiography as being those plaques that blocked the arteries.
The average NaF uptake in the culprit deposits was significantly higher than in non-culprit deposits (average tissue to background ratio 1.66, compared with 1.24). NaF was better than the standard chemical marker of FDG at identifying culprit deposits.
When FDG was used, there was no significant difference in the average uptake of culprit versus non-culprit deposits (1.71 versus 1.58).
When they looked at fatty deposits removed from the necks of people at high risk of stroke, NaF uptake had occurred at the site of the carotid deposits and was associated with characteristic laboratory examination findings, including calcification and necrosis (dead tissues).
Just under half of the people with stable angina (18/40) had fatty deposits positive for NaF uptake. These deposits had more high-risk features identified by intravascular ultrasound than those negative for NaF uptake, such as having a necrotic (dead tissue) core.
How did the researchers interpret the results?
The researchers conclude that PET-CT using radioactively labelled NaF “is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque”.
They say that further studies are now needed to see whether this method can improve the management and treatment of patients with coronary artery disease.
This is a valuable study which shows the promise of using PET-CT with radioactively labelled sodium fluoride (NaF) as a way of identifying fatty deposits in the heart arteries that could be at risk of rupturing and causing a heart attack. The results confirmed that the marker used in this study (NaF) was better than the chemical marker normally used in PET-CT scans (FDG).
The technique has the principal value of being a non-invasive technique compared with coronary angiography, which is the standard method used to look at blockages in heart arteries. As it does not involve surgical intervention, this could have advantages not only for patients, but also in terms of resources.
But so far only a small number of patients with coronary artery disease have been studied at one hospital in Edinburgh. Also, as the researchers say, the chemical was not taken up by all high-risk or ruptured deposits: in three of the people who had a heart attack, the uptake of NaF by the culprit plaques fell below threshold. And in people with stable angina, high-risk deposits with increased NaF uptake were seen in almost half of patients.
Ultrasound evaluation of the structure and composition of the arteries with NaF uptake found the characteristic features of high-risk deposits, though it is unknown whether they would have definitely gone on to cause a heart attack. This suggests that the technique could be potentially refined to provide more accurate results.
Further studies are awaited to see whether this new technique can improve outcomes in people with angina and heart attack.
The most important goal for such a diagnostic test would be to see whether it actually improves outcomes for people with coronary heart disease, leading to earlier treatment and ultimately improved survival.