Significance of characterization of non-culprit lesions: An underscored clinical problem


      Sudden death or acute coronary syndromes are frequently the first manifestation of plaque rupture at non-culprit lesions. Thus, identification of high-risk non-culprit plaques may have significant impact on the prognosis of patients with coronary artery disease. At present a widely accepted diagnostic method to prospectively identify such ‘high-risk’ plaques is not available. Improved identification of high-risk plaques by novel imaging coronary modalities currently available is a goal of great importance since it will result in major decreases in coronary artery disease morbidity and mortality. Potential new treatments with systemic, regional, and local approaches have been proposed. In this review article we focus on common and different morphologic characteristics between culprit and non-culprit lesions, the natural history of non-culprit lesions, and potential methods to identify the high-risk lesions for future adverse cardiovascular events.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Kahn J.K.
        • Rutherford B.D.
        • McConahay D.R.
        • et al.
        Results of primary angioplasty for acute myocardial infarction in patients with multivessel coronary artery disease.
        J Am Coll Cardiol. 1990; 16: 1089-1096
        • Muller D.W.
        • Topol E.J.
        • Ellis S.G.
        • Sigmon K.N.
        • Lee K.
        • Califf R.M.
        Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.
        Am Heart J. 1991; 121: 1042-1049
        • Cutlip D.E.
        • Chhabra A.G.
        • Baim D.S.
        • et al.
        Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials.
        Circulation. 2004; 110: 1226-1230
        • van der Wal A.C.
        • Becker A.E.
        • van der Loos C.M.
        • Das P.K.
        Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.
        Circulation. 1994; 89: 36-44
        • Arbustini E.
        • Dal Bello B.
        • Morbini P.
        • et al.
        Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction.
        Heart. 1999; 82: 269-272
        • Muller J.E.
        • Tawakol A.
        • Kathiresan S.
        • Narula J.
        New opportunities for identification and reduction of coronary risk: treatment of vulnerable patients, arteries, and plaques.
        J Am Coll Cardiol. 2006; 47: C2-C6
        • Naghavi M.
        • Libby P.
        • Falk E.
        • et al.
        From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.
        Circulation. 2003; 108: 1772-1778
        • Goldstein J.A.
        • Demetriou D.
        • Grines C.L.
        • et al.
        Multiple complex coronary plaques in patients with acute myocardial infarction.
        N Engl J Med. 2000; 343: 915-922
        • Maehara A.
        • Mintz G.S.
        • Bui A.B.
        • et al.
        Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound.
        J Am Coll Cardiol. 2002; 40: 904-910
        • Rioufol G.
        • Finet G.
        • Ginon I.
        • et al.
        Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study.
        Circulation. 2002; 106: 804-808
        • Mauriello A.
        • Sangiorgi G.
        • Fratoni S.
        • et al.
        Diffuse and active inflammation occurs in both vulnerable and stable plaques of the entire coronary tree: a histopathologic study of patients dying of acute myocardial infarction.
        J Am Coll Cardiol. 2005; 45: 1585-1593
        • Hong M.K.
        • Mintz G.S.
        • Lee C.W.
        • et al.
        Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: a three-vessel intravascular ultrasound study in 235 patients.
        Circulation. 2004; 110: 928-933
        • Kotani J.
        • Mintz G.S.
        • Castagna M.T.
        • et al.
        Intravascular ultrasound analysis of infarct-related and non-infarct-related arteries in patients who presented with an acute myocardial infarction.
        Circulation. 2003; 107: 2889-2893
        • Schoenhagen P.
        • Tuzcu E.M.
        • Ellis S.G.
        Plaque vulnerability, plaque rupture, and acute coronary syndromes: (multi)-focal manifestation of a systemic disease process.
        Circulation. 2002; 106: 760-762
        • Fujii K.
        • Kobayashi Y.
        • Mintz G.S.
        • et al.
        Intravascular ultrasound assessment of ulcerated ruptured plaques: a comparison of culprit and nonculprit lesions of patients with acute coronary syndromes and lesions in patients without acute coronary syndromes.
        Circulation. 2003; 108: 2473-2478
        • Tanaka A.
        • Shimada K.
        • Sano T.
        • et al.
        Multiple plaque rupture and C-reactive protein in acute myocardial infarction.
        J Am Coll Cardiol. 2005; 45: 1594-1599
        • Rodriguez-Granillo G.A.
        • Garcia-Garcia H.M.
        • Valgimigli M.
        • et al.
        Global characterization of coronary plaque rupture phenotype using three-vessel intravascular ultrasound radiofrequency data analysis.
        Eur Heart J. 2006; 27: 1921-1927
        • Rodriguez-Granillo G.A.
        • McFadden E.P.
        • Valgimigli M.
        • et al.
        Coronary plaque composition of nonculprit lesions, assessed by in vivo intracoronary ultrasound radio frequency data analysis, is related to clinical presentation.
        Am Heart J. 2006; 151: 1020-1024
        • Van Mieghem C.A.
        • McFadden E.P.
        • de Feyter P.J.
        • et al.
        Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS).
        J Am Coll Cardiol. 2006; 47: 1134-1142
        • MacNeill B.D.
        • Jang I.K.
        • Bouma B.E.
        • et al.
        Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease.
        J Am Coll Cardiol. 2004; 44: 972-979
        • Asakura M.
        • Ueda Y.
        • Yamaguchi O.
        • et al.
        Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study.
        J Am Coll Cardiol. 2001; 37: 1284-1288
      1. Toutouzas K, Synetos A, Stefanadi E, et al. Correlation between morphological characteristics and local temperature differences in culprit lesions of patients with symptomatic coronary artery disease. J Am Coll Cardiol, in press.

        • Toutouzas K.
        • Drakopoulou M.
        • Mitropoulos J.
        • et al.
        Elevated plaque temperature in non-culprit de novo atheromatous lesions of patients with acute coronary syndromes.
        J Am Coll Cardiol. 2006; 47: 301-306
        • Rzeszutko L.
        • Legutko J.
        • Kaluza G.L.
        • et al.
        Assessment of culprit plaque temperature by intracoronary thermography appears inconclusive in patients with acute coronary syndromes.
        Arterioscler Thromb Vasc Biol. 2006; 26: 1889-1894
        • Leborgne L.
        • Dascotte O.
        • Jarry G.
        • et al.
        Multi-vessel coronary plaque temperature heterogeneity in patients with acute coronary syndromes. First study with the Radi Medical System Wire.
        Circulation. 2005; 112: 3092
      2. Stone G. First presentation of the baseline features and plaque characteristics from the PROSPECT trial., TCT 2006.

      3. Verheye S. Iteration of the Thermocore device and the VIP studies., TCT 2006.

        • Buffon A.
        • Biasucci L.M.
        • Liuzzo G.
        • et al.
        Widespread coronary inflammation in unstable angina.
        N Engl J Med. 2002; 347: 5-12
        • Stefanadis C.
        • Tsiamis E.
        • Vaina S.
        • et al.
        Temperature of the blood in the coronary sinus and right atrium in patients with and without coronary artery disease.
        Am J Cardiol. 2004; 93: 207-210
        • Toutouzas K.
        • Drakopoulou M.
        • Markou V.
        • et al.
        Increased coronary sinus blood temperature: correlation with systemic inflammation.
        Eur J Clin Invest. 2006; 36: 218-223
        • Madjid M.
        • Awan I.
        • Willerson J.T.
        • Casscells S.W.
        Leukocyte count and coronary heart disease: implications for risk assessment.
        J Am Coll Cardiol. 2004; 44: 1945-1956
        • O’Donoghue M.
        • Morrow D.A.
        • Sabatine M.S.
        • et al.
        Lipoprotein-associated phospholipase A2 and its association with cardiovascular outcomes in patients with acute coronary syndromes in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial.
        Circulation. 2006; 113: 1745-1752
        • Kaski J.C.
        • Chester M.R.
        • Chen L.
        • Katritsis D.
        Rapid angiographic progression of coronary artery disease in patients with angina pectoris. The role of complex stenosis morphology.
        Circulation. 1995; 92: 2058-2065
        • Moise A.
        • Theroux P.
        • Taeymans Y.
        • et al.
        Clinical and angiographic factors associated with progression of coronary artery disease.
        J Am Coll Cardiol. 1984; 3: 659-667
        • Moise A.
        • Theroux P.
        • Taeymans Y.
        • Waters D.D.
        Factors associated with progression of coronary artery disease in patients with normal or minimally narrowed coronary arteries.
        Am J Cardiol. 1985; 56: 30-34
        • Lee S.G.
        • Lee C.W.
        • Hong M.K.
        • et al.
        Change of multiple complex coronary plaques in patients with acute myocardial infarction: a study with coronary angiography.
        Am Heart J. 2004; 147: 281-286
        • Casscells W.
        • Hassan K.
        • Vaseghi M.F.
        • et al.
        Plaque blush, branch location, and calcification are angiographic predictors of progression of mild to moderate coronary stenoses.
        Am Heart J. 2003; 145: 813-820
        • Rioufol G.
        • Gilard M.
        • Finet G.
        • et al.
        Evolution of spontaneous atherosclerotic plaque rupture with medical therapy: long-term follow-up with intravascular ultrasound.
        Circulation. 2004; 110: 2875-2880
        • Chen L.Y.
        • Lennon R.J.
        • Grantham J.A.
        • et al.
        In-hospital and long-term outcomes of multivessel percutaneous coronary revascularization after acute myocardial infarction.
        Am J Cardiol. 2005; 95: 349-354
        • Yamagishi M.
        • Terashima M.
        • Awano K.
        • et al.
        Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome.
        J Am Coll Cardiol. 2000; 35: 106-111
        • Leschka S.
        • Alkadhi H.
        • Plass A.
        • et al.
        Accuracy of MSCT coronary angiography with 64-slice technology: first experience.
        Eur Heart J. 2005; 26: 1482-1487
        • Gopal A.
        • Nasir K.
        • Liu S.T.
        • et al.
        Coronary calcium progression rates with a zero initial score by electron beam tomography.
        Int J Cardiol. 2006;
        • Toutouzas K.
        • Drakopoulou M.
        • Markou V.
        • et al.
        Correlation of systemic inflammation with local inflammatory activity in non-culprit lesions: Beneficial effect of statins.
        Int J Cardiol. 2007 Jan; : 25
        • Moreno P.R.
        • Purushothaman K.R.
        • Sirol M.
        • Levy A.P.
        • Fuster V.
        Neovascularization in human atherosclerosis.
        Circulation. 2006; 113: 2245-2252
        • Stefanadis C.
        • Toutouzas K.
        • Stefanadi E.
        • et al.
        Inhibition of plaque neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with bevacizumab-eluting stent: An experimental study.
        Atherosclerosis. 2007; 195: 269-276
        • Rodriguez-Granillo G.A.
        • Garcia-Garcia H.M.
        • Mc Fadden E.P.
        • et al.
        In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis.
        J Am Coll Cardiol. 2005; 46: 2038-2042