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Plaque erosion and acute coronary syndromes: phenotype, molecular characteristics and future directions

Nature Reviews Cardiology volume 18, pages 724–734 (2021)Cite this article

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Abstract

Although acute coronary syndromes (ACS) remain one of the leading causes of death, the clinical presentation has changed over the past three decades with a decline in the incidence of ST-segment elevation myocardial infarction (STEMI) and an increase in non-STEMI. This epidemiological shift is at least partially explained by changes in plaque biology as a result of the widespread use of statins. Historically, atherosclerotic plaque rupture of the fibrous cap was thought to be the main culprit in ACS. However, plaque erosion with an intact fibrous cap is now responsible for about one third of ACS and up to two thirds of non-STEMI. Two major research approaches have enabled a better understanding of plaque erosion. First, advanced intravascular imaging has provided opportunities for an ‘optical biopsy’ and extensive phenotyping of coronary plaques in living patients. Second, basic science experiments have shed light on the unique molecular characteristics of plaque erosion. At present, patients with ACS are still uniformly treated with coronary stents irrespective of the underlying pathobiology. However, pilot studies indicate that patients with plaque erosion might be treated conservatively without coronary stenting. In this Review, we discuss the patient phenotype and the molecular characteristics in atherosclerotic plaque erosion and provide our vision for a potential major shift in the management of patients with plaque erosion.

Key points

  • Plaque erosion rather than plaque rupture has become the predominant mechanism of non-ST-segment elevation myocardial infarction as a result of better control of cardiovascular risk factors since the introduction of statins.

  • Plaque erosion starts with changes in endothelial shear stress gradients that activate Toll-like receptor 2 in endothelial cells, resulting in loss of basement membrane integrity and endothelial cell desquamation, with subsequent formation of neutrophil extracellular traps and thrombosis.

  • Optical coherence tomography has enabled the in vivo diagnosis of plaque erosion, providing a better understanding of the characteristics and vascular biology of plaque erosion in patients with acute coronary syndromes.

  • Plaque erosion is characterized by preserved vascular integrity, a larger vessel lumen than in plaque rupture and the presence of a platelet-rich thrombus and, overall, is associated with a better risk profile and outcomes than plaque rupture.

  • Multiple clinical, angiographic and laboratory predictors of plaque erosion can help identify patients with plaque erosion, but more specific point-of-care biomarkers and non-invasive imaging techniques are needed.

  • Early clinical studies suggest that patients with plaque erosion might be managed without percutaneous coronary intervention, ushering in a new era of precision medicine in the management of patients with acute coronary syndromes.

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Fig. 1: Optical phenotypes of atherosclerotic plaque erosion and plaque rupture.
Fig. 2: Main molecular mechanisms of atherosclerotic plaque erosion.
Fig. 3: Potential future paradigm for tailored management of acute coronary syndromes.

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Acknowledgements

A.C.F. is supported by a grant T32HL007208 from the National Heart, Lung, and Blood Institute. I.-K.J.’s research is supported by the Allan Grey Fellowship Fund in Cardiology and by Mr. and Mrs. Michael and Kathryn Park.

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Authors and Affiliations

  1. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Akl C. Fahed & Ik-Kyung Jang

  2. Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Akl C. Fahed

  3. Kyung Hee University, Seoul, South Korea

    Ik-Kyung Jang

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A.C.F. and I.-K.J. researched data for the article, discussed its content and wrote the manuscript. I.-K.J. reviewed and edited the manuscript before submission.

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Correspondence to Ik-Kyung Jang.

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A.C.F. is a consultant and holds equity in Goodpath, which was not involved in the writing of this article. I.-K.J. has received educational grants from Abbott Vascular and a consulting fee from Svelte Medical.

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Nature Reviews Cardiology thanks H. Garcia-Garcia, P. Stone and R. Virmani for their contribution to the peer review of this work.

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Glossary

Optical coherence tomography

(OCT). Intravascular diagnostic modality used during cardiac catheterization. Near-infrared light is used to create images of the coronary artery and atherosclerotic plaque from inside the vessel.

Non-ST-segment elevation myocardial infarction

(Non-STEMI). A myocardial infarction that does not have ST-segment elevation on the 12-lead electrocardiogram.

STEMI

A myocardial infarction characterized by complete occlusion of a coronary artery by a thrombus and by ST-segment elevation on the 12-lead electrocardiogram.

Endothelial shear stress

The tangential stress generated by friction caused by flowing blood on the endothelial surface of the vessel wall.

SYNTAX score

Angiographic grading tool to determine the complexity of coronary artery disease, dependent on both the number and the characteristics of stenoses in the coronary artery tree.

Gensini score

Angiographic grading tool to determine the complexity of coronary artery disease that accounts for the degree and location of arterial stenoses.

ACC/AHA lesion classification

Classifies lesion types by complexity; includes type A (simple lesions), type B (moderate lesions) and type C (complex lesions). Takes into consideration several factors such as the length of the lesion, its location (such as major branch involvement), the tortuosity of the vessel and the angulation required to access the vessel, among others.

Oscillatory shear index

The ratio between backwards and forwards shear stress; a marker of flow reversal.

Thrombolysis In Myocardial Infarction

(TIMI). The TIMI grade flow is a scoring system for the levels of coronary blood flow distal to a stenosis. TIMI grade 0 indicates no anterograde flow, grade 1 indicates faint antegrade flow and incomplete filling of the distal coronary artery, grade 2 flow indicates delayed or sluggish antegrade flow and grade 3 indicates normal flow.

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Fahed, A.C., Jang, IK. Plaque erosion and acute coronary syndromes: phenotype, molecular characteristics and future directions. Nat Rev Cardiol 18, 724–734 (2021). https://doi.org/10.1038/s41569-021-00542-3

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