British Heart Foundation's Reflections of Research Competition

A video that we submitted to the British Heart Foundation's "Reflections of Research" competition has won in the best video category.

We made this video to highlight the variety of imaging methods that we have at our disposal to image atherosclerosis and its consequences.

Some more coverage on the Cambridge BRC website and the Addenbrooke's Hospital homepage.

Click here to view the other winning entries.

Imaging of progression of carotid atherosclerosis - case unproven

A study I recently read in the Lancet reports results of an individual patient data meta-analysis, which show that cIMT progression is not associated with incident myocardial infarction, stroke, or vascular death in the general population (hazard ratio 0·98, 95% CI 0·95–1·01, adjusted for age, sex, mean common carotid artery intima-media thickness, and vascular risk factors).

A single measure of carotid IMT may be useful for predicting risk in asymptomatic intermediate risk adults, although far less so than calcium scoring by CT according to the most recent guidelines.

Guidelines For Assessment Of Cardiovascular Risk In Asymptomatic Adults

ACCF/AHA guidelines - nice summary of current thoughts.

Similar guidelines were published recently by the European Society of Cardiology.

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Images above show non-invasive cardiac imaging using CT, compared (bottom) to invasive coronary angiography - 'A'. Note the distal left main stem 'soft' plaque visible on the contrast CT - 'C', invisible on the non-contrast calcium scoring CT scan in 'B'.

Dangerous plaques are missed by calcium scoring alone in maybe 5% scans in symptomatic subjects.

Non-invasive imaging of atherosclerosis review in EHJ

A very comprehensive review from an eminent group of authors appeared in EHJ recently.

Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque

It covers:

1. Pathobiology of plaque, including lipid accumulation, oxidation, inflammation, matrix breakdown, apoptosis and calcification (both macro- and micro-).

2. Imaging techniques PET, SPECT, CT, MRI and ultrasound

There were some interesting comments on the increasing use of FDG PET imaging for detection of inflammation in atherosclerosis : -

Despite these attractions, some issues require resolution before embracing FDG uptake in this regard. Firstly, only limited prospective data correlate FDG uptake, or changes in FDG uptake, with cardiovascular events or altered rates of such complications,42 and we eagerly await the results of larger prospective cohort studies, such as the High Risk Plaque Initiative and BioImage studies."

"In this regard, nuclear agents that image hypoxia, already in use in oncology, may be
useful in imaging atherosclerosis, as hypoxic conditions may prevail in the core of lesions."

I quite agree on point 1 and keep watching this space for point 2!

Day 3 ESC

A very well attended session at the ESC today concerned novel approaches to imaging the vulnerable plaque.

We heard from Zahi Fayad (New York), Jagat Narula (Orange, Ca) and Beat Kaufmann from Basel in Switzerland. I gave an over-view of vascular PET imaging, both with FDG and novel targeted ligands against plaque macrophages.

The session tried to communicate not only the state of play in 2010, but also to predict what may be around the corner for imaging. There seems to be a move towards more platform integration, with the appearance of combined PET/MR hardware. This will allow high sensitivity/high resolution imaging of the artery wall. I guess this will have large impact in brain imaging and likely also in cardiology for myocardial imaging.

For CT, as well as a move to lower radiation dose, Zahi Fayad talked about multi-color CT, something that holds great promise in separating out the various plaque elements, to a much greater extent than currently feasible with single energy imaging with iodine contrast agents. This work was recently published in Radiology (Cormode D et al - see image below).

We also heard a great review of ultrasound imaging of vulnerable plaque, using targeted microbubbles against selectins and adhesion molecules. Whilst very exciting, the field is confined right now to small animal models of disease, and to epitopes expressed on endothelial cells. But there is promise of eventual human translation.

What caught your eye in Stockholm today?

More prognostic data for cardiac CT and the limitations of virtual histology

As a follow up to a post here in December 2009, another paper confirming the prognostic ability of cardiac CT was just published in Circulation Cardiovascular Imaging (Russo et al, May 11th).

In a series of 441 patients imaged using 16 detector CT, the best predictor of events was a combination of risk score + calcium score + CT angiogram findings. Follow-up up was 32 months on average, and the number of hard CV events was 44.

Significant CAD on CT confered an annual event rate of 8.1%, mild CAD 3.9% and normal coronary arteries on CT meant a risk level very similar to that following a normal perfusion scan - 0.9% per year.

In the same Journal, Thim and colleagues tackled a related coronary issue, that of the reliable identification of necrotic core size in atheroma. This is thought to be related to risk of future CV events. They used an intravascular approach, IVUS-VH (virtual histology) and compared the findings with direct histology in a porcine model of atherosclerosis.There was no relationship at all between the true histology and the virtual histology findings.

I've discussed IVUS-VH before, in terms of the PROSPECT study.

What are your views on these two papers? Should we move away from intravascular coronary assessment towards a non-invasive imaging paradigm? Is the pig model of atheroma a reliable surrogate for human coronary disease (the IVUS-VH algorithm was based on human coronary lesions).

Let us know your views in the comments please.

Picking the plaques that go pop

Another exciting day in Barcelona. The highlight for me was a session dedicated to imaging of atherosclerosis, both from within the coronary arteries and non-invasively. My take-home message was that whilst we have many ways of quantifying the extent, structure and functional state of atherosclerosis in the coronary arteries and elsewhere, we are still in desperate need of prospective trials in this area. It is all very well to image atheroma; as clinicians we need to know more - we need to know which patients will suffer CV events in the future. We can choose from risk scores, such as Framingham. We can use circulating biomarkers - CRP, lipids and many others. And finally imaging of atherosclerosis. How to bring them all together?

Thankfully, there are a couple of very interesting trials underway. The first is the High Risk Plaque BioImage study, co-ordinated by BG Medicine in USA. This large, prospective, event-driven study in asymptomatic subjects has already recruited over 5000 patients for imaging (CT, MRI, FDG PET, IMT, calcium score) plus biomarkers. Over the next 3 years, CV events will occur in these patients; as a result we will discover the true 'predictability' of these modalities.

The second trial of huge interest is the PROSPECT study, due to be reported at TCT in San Francisco in late September. This focusses on invasive plaque assessment with coronary angiography, palpography and IVUS-VH and again attempts to predict events on the basis of imaging and circulating biomarkers over a 3 year period.

Let us know in the comments your thoughts on invasive and non-invasive plaque imaging.