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Practice Guideline
. 2025 Jun;18(6):709-740.
doi: 10.1016/j.jcmg.2024.12.004. Epub 2025 Feb 26.

Vulnerable or High-Risk Plaque: A JACC: Cardiovascular Imaging Position Statement

Rocco Vergallo  1 , Seung-Jung Park  2 , Gregg W Stone  3 , David Erlinge  4 , Italo Porto  1 , Ron Waksman  5 , Gary S Mintz  6 , Fabrizio D'Ascenzo  7 , Sara Seitun  8 , Luca Saba  9 , Rozemarijn Vliegenthart  10 , Fernando Alfonso  11 , Armin Arbab-Zadeh  12 , Peter Libby  13 , Marcelo F Di Carli  13 , James E Muller  13 , Gerald Maurer  14 , Robert J Gropler  15 , Y S Chandrashekhar  16 , Eugene Braunwald  13 , Valentin Fuster  3 , Ik-Kyung Jang  17
Affiliations
Practice Guideline

Vulnerable or High-Risk Plaque: A JACC: Cardiovascular Imaging Position Statement

Rocco Vergallo et al. JACC Cardiovasc Imaging. 2025 Jun.

Abstract

The concept of high-risk plaque emerged from pathologic and epidemiologic studies 3 decades ago that demonstrated plaque rupture with thrombosis as the predominant mechanism of acute coronary syndrome and sudden cardiac death. Thin-cap fibroatheroma, a plaque with a large lipidic core covered by a thin fibrous cap, is the prototype of the rupture-prone plaque and has been traditionally defined as "vulnerable plaque." Although knowledge on the pathophysiology of plaque instability continues to grow, the risk profile of our patients has shifted and the character of atherosclerotic disease has evolved, partly because of widespread use of lipid-lowering therapies and other preventive measures. In vivo intracoronary imaging studies indicate that superficial erosion causes up to 40% of acute coronary syndromes. This changing landscape calls for broader perspective, expanding the concept of high-risk plaque to the precursors of all major substrates of coronary thrombosis beyond plaque rupture. Other factors to take into consideration include dynamic changes in plaque composition, the importance of plaque burden, inflammatory activation (both local and systemic), healing mechanisms, regional hemodynamic pattern, properties of the fluid phase of blood, and the amount of myocardium at risk subtended by a lesion. Rather than the traditional focus limited to the thin-cap fibroatheroma, the authors advocate a more comprehensive approach that considers both morphologic features and biological activity of plaques and blood. This position paper highlights the challenges to the usual concept of high-risk plaque, proposes a broader definition, and analyzes its key morphologic features, the technological progress of plaque imaging (particularly using intracoronary imaging techniques), advances in pharmacologic therapies for plaque regression and stabilization, and the feasibility and efficacy of focal interventional treatments including preemptive plaque sealing.

Keywords: acute coronary syndrome; erosion; high-risk plaque; imaging; lipid-lowering therapies; outcome; preemptive stenting; rupture; thin-cap fibroatheroma; thrombosis; vulnerable plaque.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Vergallo has received consulting or lecturing fees from Abbott Vascular, Abiomed, Amgen, Daiichi-Sankyo, Edwards Lifesciences, Medtronic, Novartis, and Philips. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; is a consultant to Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Abiomed, Valfix, Apollo Therapeutics, Elucid Bio, Cardiac Success, TherOx, HeartFlow, Neovasc, Ancora, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, HighLife, Elixir, Remote Cardiac Enablement, and Aria; and has equity or options in Cardiac Success, Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWAVE, Orchestra Biomed, Aria, Valfix, and Xenter. Dr Stone’s employer, Mount Sinai Hospital, has received research grants from Shockwave Medical, Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense Webster, Vascular Dynamics, Pulnovo, V-Wave and the Patient-Centered Outcomes Research Institute (via Weill Cornell Medical Center). Dr Erlinge has received consulting and speaker fees from AstraZeneca, Bayer, Novartis, Amgen, Chiesi, and Sanofi. Dr Porto has received consultant or speaker fees from Medtronic, Siemens, GE, Abiomed, Philips, Sanofi, Amgen, Daiichi-Sankyo, AstraZeneca, Bayer, and PIAM. Dr Waksman is an advisory board member or a consultant for Abbott Vascular, Boston Scientific, Philips Volcano, Biotronik, Terumo, and Cordis; has received grant support from Abbott Vascular, Biotronik, Chiesi, Philips Volcano, and Medtronic; and has equity in MedAlliance/Cordis, Pi-Cardia, and Append Medical. Dr Mintz has received honoraria from Boston Scientific, Abbott, and SpectraWAVE. Dr Vliegenthart has received institutional research grants from Siemens Healthineers; and has received honoraria for lectures and moderatorships from Siemens Healthineers and Bayer Healthcare. Dr Muller is a cofounder and shareholder of SpectraWAVE. Dr Zadeh has received grant support from Canon. Dr Libby is an unpaid consultant to or is involved in clinical trials for Amgen, the Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Novo Nordisk, Novartis, and Sanofi-Regeneron; is a member of scientific advisory boards for Amgen, Caristo Diagnostics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, Polygon Therapeutics, TenSixteen Bio, Soley Thereapeutics, and XBiotech; is on the board of directors of XBiotech; has a financial interest in XBiotech (a company developing therapeutic human antibodies), TenSixteen Bio (a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases), and Soley Therapeutics (a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics) (these interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies); and receives funding support from the National Heart, Lung, and Blood Institute (grants 1R01HL134892, 1R01HL163099-01, R01AG063839, R01HL151627, R01HL157073, and R01HL166538), the RRM Charitable Fund, and the Simard Fund. Dr Libby’s laboratory has received research funding in the past 2 years from Novartis, Novo Nordisk, and Genentech. Dr Jang’s has been supported by Mrs Gillian Gray through the Allan Gray Fellowship Fund in Cardiology and by Mukesh and Priti Chatter through the Chatter Foundation; and has received an educational grant from Abbott Vascular. Dr Braunwald has received research grants through his institution from AstraZeneca, Daiichi-Sankyo, Merck, and Novartis; and is a consultant for Bristol Myers Squibb, Boehringer Ingelheim, Cardurion, Edgewise, and Verve. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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