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Vulnerable Plaque
Ramesh Kawar

A vulnerable plaque is an atheromatous plaque which is particularly prone to produce sudden major problems, such as heart attack or stroke. It has been qualified by descriptive terms like unstable, thrombosis prone, culprit, dangerous, high risk etc.

Generally an atheroma becomes vulnerable if it grows more rapidly and has a thin cover separating it from the blood stream inside the arterial lumen, tearing of cover is called “plaque rupture”.

Because artery wall typically enlarge in response to enlarging plaques (positive remodelling) these plaques do not usually produce much stenosis of the artery lumen. Therefore, they are typically not detected by cardiac stress test.

The Problem
Coronary artery stenosis is generally asymptomatic until stenosis exceeds 70 to 80%. The large lesions can produce a critical reduction in blood flow to myocardium, resulting in typical symptoms of Angina pectoris. However, acute coronary and cebebro-vascular syndromes are often due to ruptures of plaques which have less than 50% stenosis. The ischaemic syndrome results from subsequent thrombus formation, leading to concept of “Vulnerable Plaque”. It is important to identify these coronary atherosclerotic plaques that might become unstable and thus bigger ACS.

Approximately 70% of fatal myocardial infarction and/or sudden cardiac death occur due to plaque rupture.

Characteristics of Vulnerable Plaque
Thin cap (< 100 mm), large lipid core (> 40%).

Endothelial denudation with superficial platelet aggregation.

Fissured plaque

Superficial calcified nodule

Intraplaque haemorrhage

Positive (outward) remodelling.

Identification of Vulnerable Plaque
Conventional coronary angiography is unable to detect nonobstructive culprit plaques or lesions. Also the phenomenon of positive remodelling makes it a false negative test even in presence of significant atherosclerotic plaque burden.

Various newer modalities of imaging and catheter base techniques have been developed to identify these culprit plaques/lesions.

Most commonly used and useful techniques are

  1. Optical Coherence Tomography (OCT)
  2. Thermography
  3. MR, Plaque Imaging
  4. Targeted contrast enhanced MRI Other less useful Techniques are :-
  5. IVUS
  6. Angioscopy
  7. Spectroscopy
  8. CT Plaque Imaging
  9. Nuclear Scintigraphy

1.Optical Coherence Tomography
This is a catheter based technique whereby Michelson Interferometer light is split into two signals, one is sent into the tissue and the other to a reference arm. The intensity of back reflected light and dynamic mirror translation is used to produce images with resolution of 4-20 mm with a penetration depth of 2 mm. It is better in detecting thin caps and tissue proliferation. The limitation of this technique include low penetration and light absorbance by blood (requiring saline infusion/proximal balloon occlusion).

2. Thermography
The rise in temperature due to increased metabolic activity as a result of inflammation in the atherosclerotic millieu gives rise to hot plaque concept. With the help of a thermistor with temperature accuracy of 0.050 C, a time constant of 300 ms and a spatial resolution of 0.5 mm, thermography catheter is used to differentiate between hot plaque (increased vulnerability) and normal vessel wall. Its use as a prognostication techniques has been validated. This is again a catheter based technique.

3. MRI Plaque Imaging and Targeted Contrast Enhanced MRI
Various MRI techniques including multicontrast approach, Fast Spin Echo (FSE) based MR sequences and magnetization transfer and water diffusion weighting techniques are in vogue for in vivo plaque characterization.

A special resolution to the degree of 0.7 x 0.7 x 0.8 mm3 has been achieved. MRI Imaging identifies calcifications as signal loss in all sequences, fibrocellular regions as intermediate to high signal intensities in all sequences and fatty lesions as areas of low signal intensity in T2s and hyperintense signal in T1w sequences.

In order to reduce signal to noise ratio in MRI, the use of ultra small super paramagnetic particles of iron oxide (USPIO) which are avidly taken by macrophage is being used. Thus macrophage dense plaque (increased vulnerability) detection and use of other contrast agents with enzyme activity will augment the spatial resolution available today with routine MRI.

Concept of “Vulnerable Patient”
Atherosclerotic cardiovascular disease result in more than 19 million deaths annually and coronary heart disease accounts for majority of these. Despite major advances in treatment of CHD patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify these victims before event occurs.

Besides the vulnerable plaque, other factors like vulnerable blood and vulnerable myocardium prone to arrhythmia forms a triad of “Cardiovascular Vulnerable Patient” and makes the subject susceptible to Acute Coronary Syndrome or sudden cardiac death.

The detection of Vulnerable Blood revolves around the serological evidence of vulnerability. They include :

  1. Abnormal Lipoprotein Profile ( ­ LDL, ¯ HDL small dense LDL particles).
  2. Raised inflammation sensitive plasma proteins (Fibrinogen, a - 1 antitrypsin, haptoglobin ceruloplasmin).
  3. Non specific markers of Inflammation (­ CRP, IL – 6, ICAM –1, VCAM –2, Soluble CD 40 Ligand, Homocystiene, P and E – Selection etc.)
  4. ­ levels of MMP – 2 and MMP – 9 (Matrix Metaloprotinase Inhibitors and PAPP-A (pregnancy associated plasma protein – A).

None of these tests have specificity and sensitivity levels in detecting vulnerability or predicting an acute coronary event commensurate with clinical utility.

Management of Vulnerable Plaque
Stabilization of vulnerable plaques can be achieved with the help of various approaches.

Drug Therapy
The only agents found to have definitive benefit in reducing the risk of plaque rupture are HMG CoA reductase inhibitors (statins) They have mortality benefits over and above its lipid lowering effects and may be more effective than revascularization in preventing Myocardial Infarction in patients with coronary artery disease.

Other drugs with definite use as plaque stabilising agents are cardiac drugs like ACE inhibitors, b-blockers and antiplatelet agents. Others with purported benefit but inconclusive benefits include PPAR- agents like Pioglitazone, antiinflammatory agents, Antibiotics etc.

Photodynamic therapy is a non-thermal photochemical process that involves the administration of a photosensitizer followed by light activation, which leads to photo-chemical reaction producing the desired cytotoxic effect at the desired site. Two system under evaluation are :

a) AntrinR Phototherapy – Motexafin Lutetium.
b) Photopoint TM – MV0611
3) Plaque Stabilization with Drug Eluting Stents

The concept revolves around the idea that controlled balloon rupture of a vulnerable plaque in the safe setting of cath lab followed by Drug Eluting Stent implantation is far superior to catastrophic event of acute plaque rupture causing an acute coronary syndrome at home.

This controlled splitting then stimulates new tissue proliferation (smooth muscle cell) covering the former vulnerable plaque thereby sealing it and transforming it into a fibrous layer immune to fissure or rupture.

But the risk vs benefit ratio of such a procedure in an asymptomatic patient is debatable considering the aspects of acute/subacute stent thrombosis, restenosis, huge economic burden.

BCG is a live-attenuated vaccine derived from a strain of Mycobacterium bovis, and is given to neonates and young infants throughout much of the world. Although vaccine efficacy has been a source of controversy over the years, it is now generally accepted that BCG, although it may not prevent infection or adult pulmonary disease, highly effective in preventing severe childhood tuberculosis (tuberculous meningitis and miliary tuberculosis).

The Lancet, 2006; 367 : 1122.


Interventional Cardiologist, Bombay Hospital Institute of Medical Sciences, Mumbai - 400 020.