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Solving the puzzles of the unstable plaque

ESC Congress News 2015 - London

Developing methods for risk stratification of vulnerable plaques to identify patients likely to benefit from intensive therapy is ‘the holy grail of cardiology’, according to a Symposium yesterday. For, following treatment of the initial culprit lesion by PCI, the risk of a coronary event from a further lesion has been estimated at 10% during the following year, and 5% in each of the subsequent four years.

Vascular Biology and Physiology
Invasive Imaging and Functional Assessment
Risk Factors and Prevention

David Erlinge saw a potential benefit of bioresorbable stents in the treatment of vulnerable plaque. Maria Radu described three imaging technologies for their characterisation.Indeed, said David Erlinge from Skane University Hospital, Lund, Sweden, studies suggest that patients who have had an MI are very likely to have other vulnerable plaques, placing them at high risk of subsequent events.

The term ‘vulnerable plaque’ refers to a plaque at high risk of disruption leading to thrombosis. Retrospective autopsy studies suggest there are several histological types, one study showing that 55-60% of subjects had underlying plaque rupture as the aetiology; 30-35% erosion; and 2-7% thrombi attributed to calcified nodules. Another autopsy study in patients who had died from cardiac causes found that the most common underlying plaque morphology was a ruptured thin-cap fibroatheroma (TCFA) characterised by an overlying thin fibrous cap (measuring <65 μm) and large necrotic core.

But not all TCFAs will rupture, and neither will all ruptures result in cardiac events - and some vulnerable patients are likely to have vulnerable blood (prone to thrombosis) and a vulnerable myocardium (prone to arrhythmia).

The three major invasive imaging technologies used for evaluating vulnerable plaques, said Maria Radu, from Herlev Hospital and Rigshospitalet, Copenhagen, include intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near infrared spectroscopy (NIRS).

  • IVUS, which has a resolution of 100 to 200 μm, allows measurement of the lumen and external elastic membrane providing information on plaque volumes. The addition of radio-frequency signal analysis provides useful information about plaque composition.
  • OCT, based on near-infrared light rather than ultrasound, provides resolutions of 10-20 μm, which is to date the only modality to directly visualise the TCFA in vivo. However, at the expense of increased resolution, it does not penetrate the plaque far enough to provide information of deep morphology or the external elastic membrane in the presence of extensive plaque, and thus is unable to assess plaque burden and remodelling.
  • Unlike IVUS and OCT, NIRS does not provide structural information, but rather assesses the chemical composition of a plaque. More specifically, it provides a ’chemogram’ of the cholesterol signal, and is thus able to accurately identify large cholesterol accumulations within lipid and necrotic cores.

‘Each of these technologies has their pros and cons and so the dream scenario would be to have a catheter combining all three together to increase the accuracy of plaque characterisation,’ said Radu.

Secondary prevention of patients who have already suffered an MI currently includes systemic therapy with statins, ACE inhibitors, beta-blockers, aspirin and calcium-channel blockers. But in future, said Erlinge, local therapeutic options might include the deployment of coronary stents to ‘seal or stabilise’ the plaque and reduce the risk of future events.

‘The potential benefits of stent treatment need to be balanced against the risks of procedural complications, re-stenosis and stent thrombosis,’ said Erlinge. ‘These patients don’t have angina or flow-limiting stenosis, which makes their balance of risks different.’ The use of biodegradable stents in such circumstances, he added, was likely to be preferable. A recent study showed that implantation of the ABSORB bioresorbable vascular scaffold over vulnerable plaques led to the formation of a neointima layer resembling a thick fibrous cap known for its plaque stability.

In the PROSPECT trial after successful PCI of the target culprit lesions in nearly 700 patients, IVUS was used to examine the proximal 6-8 cm of all three coronary arteries, with patients followed for a median of 3.4 years. Results showed that plaque burden >70% in untreated non-culprit lesions was the most important characteristic associated with future events.

Now, the combined PROSPECT2 and PROSPECT ABSORB studies are building on the PROSPECT study to examine 900 patients with NIRS combined with IVUS and randomise 300 patients with a plaque judged to be at high risk of causing future coronary events to treatment with the Absorb bioresorbable vascular scaffold plus guideline directed medical therapy (GDMT) or GDMT alone. ‘We want to see whether MI and sudden death are reduced,’ said Erlinge.