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Layered plaque and plaque volume in patients with acute coronary syndromes

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Abstract

Background

Layered plaque is a signature of previous subclinical plaque destabilization and healing. Following plaque disruption, thrombus becomes organized, resulting in creation of a new layer, which might contribute to rapid step-wise progression of the plaque. However, the relationship between layered plaque and plaque volume has not been fully elucidated.

Methods

Patients who presented with acute coronary syndromes (ACS) and underwent pre-intervention optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of the culprit lesion were included. Layered plaque was identified by OCT, and plaque volume around the culprit lesion was measured by IVUS.

Results

Among 150 patients (52 with layered plaque; 98 non-layered plaque), total atheroma volume (183.3 mm3[114.2 mm3 to 275.0 mm3] vs. 119.3 mm3[68.9 mm3 to 185.5 mm3], p = 0.004), percent atheroma volume (PAV) (60.1%[54.7–60.1%] vs. 53.7%[46.8–60.6%], p = 0.001), and plaque burden (86.5%[81.7–85.7%] vs. 82.6%[77.9–85.4%], p = 0.001) were significantly greater in patients with layered plaques than in those with non-layered plaques. When layered plaques were divided into multi-layered or single-layered plaques, PAV was significantly greater in patients with multi-layered plaques than in those with single-layered plaques (62.1%[56.8–67.8%] vs. 57.5%[48.9–60.1%], p = 0.017). Layered plaques, compared to those with non-layered pattern, had larger lipid index (1958.0[420.9 to 2502.9] vs. 597.2[169.1 to 1624.7], p = 0.014).

Conclusion

Layered plaques, compared to non-layered plaques, had significantly greater plaque volume and lipid index. These results indicate that plaque disruption and the subsequent healing process significantly contribute to plaque progression at the culprit lesion in patients with ACS.

Clinical Trial Registration

http://www.clinicaltrials.gov, NCT01110538, NCT03479723, UMIN000041692.

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References

  1. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM (2000) Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20:1262–1275

    Article  CAS  PubMed  Google Scholar 

  2. Vergallo R, Crea F (2020) Atherosclerotic Plaque Healing. N Engl J Med 383:846–857

    Article  CAS  PubMed  Google Scholar 

  3. Burke AP, Kolodgie FD, Farb A, Weber DK, Malcom GT, Smialek J et al (2001) Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 103:934–940

    Article  CAS  PubMed  Google Scholar 

  4. Yamamoto MH, Yamashita K, Matsumura M, Fujino A, Ishida M, Ebara S et al (2017) Serial 3-Vessel Optical Coherence Tomography and Intravascular Ultrasound Analysis of changing Morphologies Associated with lesion progression in patients with stable angina Pectoris. Circ Cardiovasc Imaging. ; 10

  5. Fracassi F, Crea F, Sugiyama T, Yamamoto E, Uemura S, Vergallo R et al (2019) Healed culprit plaques in patients with Acute Coronary Syndromes. J Am Coll Cardiol 73:2253–2263

    Article  PubMed  Google Scholar 

  6. Sugiyama T, Yamamoto E, Fracassi F, Lee H, Yonetsu T, Kakuta T et al (2019) Calcified plaques in patients with Acute Coronary Syndromes. JACC Cardiovasc Interv 12:531–540

    Article  PubMed  Google Scholar 

  7. Nakajima A, Libby P, Mitomo S, Yuki H, Araki M, Seegers LM et al (2022) Biomarkers associated with coronary high-risk plaques. J Thromb Thrombolysis.

  8. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA et al (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61:e78–e140

    Article  PubMed  Google Scholar 

  9. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr et al (2014) 2014 AHA/ACC Guideline for the management of patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 64:e139–e228

    Article  PubMed  Google Scholar 

  10. Araki M, Park SJ, Dauerman HL, Uemura S, Kim JS, Di Mario C et al (2022) Optical coherence tomography in coronary atherosclerosis assessment and intervention. Nat Rev Cardiol 19:684–703

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kato K, Yonetsu T, Kim SJ, Xing L, Lee H, McNulty I et al (2012) Nonculprit plaques in patients with acute coronary syndromes have more vulnerable features compared with those with non-acute coronary syndromes: a 3-vessel optical coherence tomography study. Circ Cardiovasc Imaging 5:433–440

    Article  PubMed  Google Scholar 

  12. Vergallo R, Uemura S, Soeda T, Minami Y, Cho JM, Ong DS et al (2016) Prevalence and predictors of multiple coronary plaque ruptures: in vivo 3-Vessel Optical Coherence Tomography Imaging Study. Arterioscler Thromb Vasc Biol 36:2229–2238

    Article  CAS  PubMed  Google Scholar 

  13. Nakajima A, Araki M, Minami Y, Soeda T, Yonetsu T, McNulty I et al (2022) Layered plaque characteristics and layer burden in Acute Coronary Syndromes. Am J Cardiol 164:27–33

    Article  PubMed  Google Scholar 

  14. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ et al (2001) 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 37:1478–1492

    Article  CAS  PubMed  Google Scholar 

  15. Nissen SE, Nicholls SJ, Wolski K, Rodés-Cabau J, Cannon CP, Deanfield JE et al (2008) Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA 299:1547–1560

    Article  CAS  PubMed  Google Scholar 

  16. Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P et al (2011) Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 365:2078–2087

    Article  CAS  PubMed  Google Scholar 

  17. Davies MJ, Bland JM, Hangartner JR, Angelini A, Thomas AC (1989) Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. Eur Heart J 10:203–208

    Article  CAS  PubMed  Google Scholar 

  18. Davies MJ (1996) Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. Circulation 94:2013–2020

    Article  CAS  PubMed  Google Scholar 

  19. Mann J, Davies MJ (1999) Mechanisms of progression in native coronary artery disease: role of healed plaque disruption. Heart 82:265–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Russo M, Kim HO, Kurihara O, Araki M, Shinohara H, Thondapu V et al (2020) Characteristics of non-culprit plaques in acute coronary syndrome patients with layered culprit plaque. Eur Heart J Cardiovasc Imaging 21:1421–1430

    Article  PubMed  Google Scholar 

  21. Uemura S, Ishigami K, Soeda T, Okayama S, Sung JH, Nakagawa H et al (2012) Thin-cap fibroatheroma and microchannel findings in optical coherence tomography correlate with subsequent progression of coronary atheromatous plaques. Eur Heart J 33:78–85

    Article  PubMed  Google Scholar 

  22. Araki M, Yonetsu T, Kurihara O, Nakajima A, Lee H, Soeda T et al (2021) Predictors of Rapid Plaque Progression: an optical coherence Tomography Study. JACC Cardiovasc Imaging 14:1628–1638

    Article  PubMed  Google Scholar 

  23. Shiran A, Mintz GS, Leiboff B, Kent KM, Pichard AD, Satler LF et al (1999) Serial volumetric intravascular ultrasound assessment of arterial remodeling in left main coronary artery disease. Am J Cardiol 83:1427–1432

    Article  CAS  PubMed  Google Scholar 

  24. Yamada R, Okura H, Kume T, Saito K, Miyamoto Y, Imai K et al (2010) Relationship between arterial and fibrous cap remodeling: a serial three-vessel intravascular ultrasound and optical coherence tomography study. Circ Cardiovasc Interv 3:484–490

    Article  PubMed  Google Scholar 

  25. Von Birgelen C, Hartmann M, Mintz GS, Böse D, Eggebrecht H, Gössl M et al (2004) Spectrum of remodeling behavior observed with serial long-term (>/=12 months) follow-up intravascular ultrasound studies in left main coronary arteries. Am J Cardiol 93:1107–1113

    Article  Google Scholar 

  26. Puri R, Nissen SE, Ballantyne CM, Barter PJ, Chapman MJ, Erbel R et al (2013) Factors underlying regression of coronary atheroma with potent statin therapy. Eur Heart J 34:1818–1825

    Article  CAS  PubMed  Google Scholar 

  27. Schoenhagen P, Ziada KM, Kapadia SR, Crowe TD, Nissen SE, Tuzcu EM (2000) Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation 101:598–603

    Article  CAS  PubMed  Google Scholar 

  28. Puri R, Nicholls SJ, Ellis SG, Tuzcu EM, Kapadia SR (2014) High-risk coronary atheroma: the interplay between ischemia, plaque burden, and disease progression. J Am Coll Cardiol 63:1134–1140

    Article  PubMed  Google Scholar 

  29. Yokoya K, Takatsu H, Suzuki T, Hosokawa H, Ojio S, Matsubara T et al (1999) Process of progression of coronary artery lesions from mild or moderate stenosis to moderate or severe stenosis: a study based on four serial coronary arteriograms per year. Circulation 100:903–909

    Article  CAS  PubMed  Google Scholar 

  30. Xie Z, Hou J, Yu H, Jia H, Du H, Lee H et al (2016) Patterns of coronary plaque progression: phasic versus gradual. A combined optical coherence tomography and intravascular ultrasound study. Coron Artery Dis 27:658–666

    Article  PubMed  Google Scholar 

  31. Ross R (1999) Atherosclerosis–an inflammatory disease. N Engl J Med 340:115–126

    Article  CAS  PubMed  Google Scholar 

  32. Nakajima A, Sugiyama T, Araki M, Seegers LM, Dey D, McNulty I et al (2022) Plaque rupture, compared with plaque Erosion, is Associated with a higher level of Pancoronary inflammation. JACC Cardiovasc Imaging 15:828–839

    Article  PubMed  Google Scholar 

  33. Libby P (2013) Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 368:2004–2013

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Tsunenari Soeda (Nara Medical University), Yoshiyasu Minami (Kitasato University), Takumi Higuma (St. Marianna University), Masamichi Takano (Nippon Medical School), and Bryan P. Yan (Chinese University of Hong Kong) for their help in enrolling patients.

Funding

Dr. Jang’s research 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. The funder had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street | GRB 800 |, 02114, Boston, MA, USA

    Haruhito Yuki, Daisuke Kinoshita, Keishi Suzuki, Takayuki Niida, Lena Marie Seegers, Iris McNulty & Ik-Kyung Jang

  2. Interventional Cardiology Unit, New Tokyo Hospital, 1271 Wanagaya, Matsudo, Chiba, 270-2232, Japan

    Akihiro Nakajima & Sunao Nakamura

  3. Interventional Cardiology Unit, Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy

    Rocco Vergallo

  4. Department of Cardiology, Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS Trust, London, UK

    Francesco Fracassi

  5. Department of Cardiology, S. Maria dei Battuti Hospital, AULSS 2 Veneto, Conegliano, Italy

    Michele Russo

  6. Cardiology Unit, C. and G. Mazzoni Hospital, Via degli Iris 1, 63100, Ascoli Piceno, Italy

    Luca Di Vito

  7. Institute of Cardiology, Department of Interventional Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland

    Krzysztof Bryniarski

  8. Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Hang Lee

  9. Department of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan

    Tsunekazu Kakuta

  10. Division of Cardiology, Kyung Hee University Hospital, Seoul, South Korea

    Ik-Kyung Jang

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  1. Haruhito Yuki
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Correspondence to Sunao Nakamura or Ik-Kyung Jang.

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Dr. Jang has received educational grant support from Abbott Vascular. All other authors have no relationships relevant to the contents of this paper to disclose.

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Yuki, H., Kinoshita, D., Suzuki, K. et al. Layered plaque and plaque volume in patients with acute coronary syndromes. J Thromb Thrombolysis 55, 432–438 (2023). https://doi.org/10.1007/s11239-023-02788-9

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