Vulnerable Plaque: How Far are We From Applying an Interventional Strategy to Prevent Acute Events?

Login or register to view PDF.
Abstract

Considerable advances have been made in the last decade in the treatment of acute coronary syndromes. However, we are still unable to predict, and therefore prevent, their occurrence. The concept of vulnerable plaque has helped in understanding the pathogenesis of acute coronary occlusion but a preventative strategy remains elusive. A series of presentations at EuroPCR, 20–23 May 2014 (Paris, France) had the following objectives – to understand the concept of coronary plaques, to review available evidence linking vulnerable plaques with the development of future acute coronary events, and to give an update on diagnostic technology and ongoing clinical trials.

Received date
01 August 2014
Accepted date
26 September 2014
Citation
RadcliffeCardiology.com, August 2014.

Pages

Introduction
Considerable advances have been made in the last decade in the treatment of acute coronary syndromes. However, we are still unable to predict, and therefore prevent, their occurrence. The concept of vulnerable plaque has helped in understanding the pathogenesis of acute coronary occlusion but a preventative strategy remains elusive. A series of presentations at EuroPCR, 20–23 May 2014 (Paris, France) had the following objectives – to understand the concept of coronary plaques, to review available evidence linking vulnerable plaques with the development of future acute coronary events, and to give an update on diagnostic technology and ongoing clinical trials.

How Can We Identify Vulnerable Plaque?
Dr Lampros Michalis of the University of Ioannina (Ipiros, Greece) discussed the imitations of current means of imaging vulnerable plaque. Intravascular ultrasound (IVUS) allows identification of the lumen, stent and vessel wall but has low resolution and limited ability to detect plaque erosion, rupture and the presence of thrombus.1 Optical coherence tomography (OCT) can characterise plaques but has poor penetration and cannot see behind lipid tissue.2 Near infrared spectroscopy (NIRS) allows identification of the lipid component but provides no information on the lumen and plaque anatomy.3

New invasive imaging techniques are the focus of considerable research. Intravascular magnetic resonance imaging (MRI), still in preclinical development, is a promising technique that depicts vascular wall morphological features, atherosclerosis and calcification.4 Time resolved fluorescence spectroscopy (TRFS) allows detection of the biochemical components of the superficial plaque.5 Hybrid catheters also offer promise – utilising multi-modal intravascular imaging overcomes the limitations of individual techniques. The combination of IVUS and OCT is not yet clinically applicable because the probe is too big.6 An IVUS and TRFS catheter is not yet clinically available.7 A TRFS-US-PA catheter combines TRFS, ultrasound backscatter microscopy and photoacoustic imaging.8 A hybrid catheter combining OCT and NIRF is undergoing preclinical studies.9

Fusion of imaging data and IVUS data allows 3D reconstruction of the vessel morphology,10–12 and can be used to calculate endothelial sheer stress (ESS).13 Large plaque burden and low ESS predicted (with 41 % accuracy) worsening lumen obstruction requiring percutaneous coronary intervention (PCI). Fusion of angiographic and OCT data has also been reported,14 as has fusion of computerised tomography (CT) and IVUSNIRS. These imaging modalities represent progress but still require cardiac catheterisation, are interventional rather than predictive and have limited availability. There remains a need for noninvasive imaging. Coronary CT angiography can be used to assess endothelial shear stress (ESS) distribution in the coronary tree but has low resolution and does not permit assessment of vulnerable plaque characteristics.15 A combination of CT and positron emission tomography (PET) imaging using 18F-fludeoxyglucose (FDG) combines coronary anatomy with functional imaging for disease assessment.16 Recently, novel markers for PET such as 18F-sodium fluoride have been found to enhance sensitivity.17

In conclusion, detection of plaque vulnerability requires assessment of plaque morphology and composition as well as plaque activity, i.e. the substrate. However, the stimulus, i.e. the local haemodynamic milieu, also requires assessment. Noninvasive imaging offers the potential for population screening and improved risk assessment.

Prediction of an Acute Coronary Event
Dr Bernard de Bruyne of the Cardiovascular Center Aalst (Belgium) discussed predictive factors for acute coronary syndrome (ACS). The Prospective natural-history study of coronary atherosclerosis (PROSPECT) study concluded that events are more frequent at the site of lesions associated with IVUS virtual histology (VH) criteria of vulnerability, but the specificity of these findings in predicting events is too low to be useful in decision-making regarding revascularisation.18 This is because other mechanisms are involved in ACS – plaque rupture is the culprit mechanism in less than half of ACS.19 It is known that haemodynamically nonsignificant stenosis (fractional flow reserve [FFR] ≥ 0.80) in the proximal left anterior descending (LAD) is associated with an excellent long-term clinical outcome.20 This has led investigators to question whether a low FFR predicts events. The Fractional flow reserve–guided PCI vs medical therapy in stable coronary disease (FAME) 2 study found that FFR >0.80 predicted the absence of events and that FFR ≤0.80 did predict events.21 High shear stress primes platelets for subsequent activation.22

Pages

References
  1. Mintz GS, Nissen SE, Anderson WD, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001;37:1478–92.
  2. Tearney GJ, Regar E, Akasaka T, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol 2012;59:1058–72.
  3. Caplan JD, Waxman S, Nesto RW, et al. Near-infrared spectroscopy for the detection of vulnerable coronary artery plaques. J Am Coll Cardiol 2006;47:C92–6.
  4. Sathyanarayana S, Schar M, Kraitchman DL, et al. Towards real-time intravascular endoscopic magnetic resonance imaging. JACC Cardiovasc Imaging 2010;3:1158–65.
  5. Marcu L, Jo JA, Fang Q, et al. Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy. Atherosclerosis 2009;204:156–64.
  6. Yin J, Yang HC, Li X, et al. Integrated intravascular optical coherence tomography ultrasound imaging system, J Biomed Opt, 2010;15:010512.
  7. Bec J, Xie H, Yankelevich DR, et al. Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound. J Biomed Opt 2012;17:106012.
  8. Sun Y, Chaudhari AJ, Lam M, et al. Multimodal characterization of compositional, structural and functional features of human atherosclerotic plaques. Biomed Opt Express 2011;2:2288–98.
  9. Yoo H, Kim JW, Shishkov M, et al. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat Med 2011;17:1680–4.
  10. Wahle A, Prause PM, DeJong SC, et al. Geometrically correct 3-D reconstruction of intravascular ultrasound images by fusion with biplane angiography--methods and validation. IEEE Trans Med Imaging 1999;18:686–99.
  11. Slager CJ, Wentzel JJ, Schuurbiers JC, et al., True 3-dimensional reconstruction of coronary arteries in patients by fusion of angiography and IVUS (ANGUS) and its quantitative validation. Circulation 2000;102:511–6.
  12. Bourantas CV, Kalatzis FG, Papafaklis MI, et al., ANGIOCARE: an automated system for fast three-dimensional coronary reconstruction by integrating angiographic and intracoronary ultrasound data. Catheter Cardiovasc Interv 2008;72:166–75.
  13. Stone PH, Saito S, Takahashi S, et al. Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study. Circulation 2012;126:172–81.
  14. Tu S, Holm NR, Christiansen EH, et al. First presentation of 3-dimensional reconstruction and centerline-guided assessment of coronary bifurcation by fusion of X-ray angiography and optical coherence tomography. JACC Cardiovasc Interv 2012;5:884–5.
  15. Voros S, Rinehart S, Qian Z, et al. Coronary atherosclerosis imaging by coronary CT angiography: current status, correlation with intravascular interrogation and metaanalysis. JACC Cardiovasc Imaging 2011;4:537–48.
  16. Rogers IS, Nasir K, Figueroa AL, et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc Imaging 2010;3:388–97.
  17. Joshi NV, Vesey AT, Williams MC, et al. 18F-fluoride positron emission tomography for identification of ruptured and highrisk coronary atherosclerotic plaques: a prospective clinical trial. Lancet 2014;383:705–13.
  18. Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011;364:226–35.
  19. Jia H, Abtahian F, Aguirre AD, et al. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography, J Am Coll Cardiol 2013;62:1748–58.
  20. Muller O, Mangiacapra F, Ntalianis A, et al. Long-term followup after fractional flow reserve-guided treatment strategy in patients with an isolated proximal left anterior descending coronary artery stenosis. JACC Cardiovasc Interv 2011;4:1175–82.
  21. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991–1001.
  22. Sheriff J, Bluestein D, Girdhar G, et al. High-shear stress sensitizes platelets to subsequent low-shear conditions. Ann Biomed Eng 2010;38:1442–50.
  23. Meier B, Ramamurthy S. Plaque sealing by coronary angioplasty. Cathet Cardiovasc Diagn 1995;36:295–7.
  24. Wykrzykowska JJ, Diletti R, Gutierrez-Chico JL, et al. Plaque sealing and passivation with a mechanical selfexpanding low outward force nitinol vShield device for the treatment of IVUS and OCT-derived thin cap fibroatheromas (TCFAs) in native coronary arteries: report of the pilot study vShield Evaluated at Cardiac hospital in Rotterdam for Investigation and Treatment of TCFA (SECRITT). EuroIntervention 2012;8:945–54.
  25. Rodes-Cabau J, Bertrand OF, Larose E, et al. Five-year follow-up of the plaque sealing with paclitaxel-eluting stents vs medical therapy for the treatment of intermediate nonobstructive saphenous vein graft lesions (VELETI) trial. Can J Cardiol 2014;30:138–45.
  26. Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193–202.
  27. Brugaletta S, Heo JH, Garcia-Garcia HM, et al. Endothelialdependent vasomotion in a coronary segment treated by ABSORB everolimus-eluting bioresorbable vascular scaffold system is related to plaque composition at the time of bioresorption of the polymer: indirect finding of vascular reparative therapy? Eur Heart J 2012;33:1325–33.
  28. Madder RD, Goldstein JA, Madden SP, et al. Detection by nearinfrared spectroscopy of large lipid core plaques at culprit sites in patients with acute ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 2013;6:838–46.
  29. Toblli JE, DiGennaro F, Giani JF, et al. Nebivolol: impact on cardiac and endothelial function and clinical utility. Vasc Health Risk Manag 2012;8:151–60.