Skip to main content

Advertisement

SpringerLink
Log in

Systemic and local factors associated with reduced thrombolysis in myocardial infarction flow in ST-segment elevation myocardial infarction patients with plaque erosion detected by intravascular optical coherence tomography

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Local factors of plaque rupture (e.g. lipid burden) are related to preprocedural thrombolysis in myocardial infarction (TIMI) flow grade during primary percutaneous coronary intervention (PCI). However, the pathological mechanism differs between plaque erosion and rupture. We aimed to identify the factors associated with reduced TIMI flow in plaque erosion. A total of 329 ST-segment elevation myocardial infarction (STEMI) patients with optical coherence tomography (OCT) identified plaque erosion were divided into 2 groups by preprocedural TIMI flow grade [TIMI 0–1 group (n = 219) and TIMI 2–3 group (n = 110)]. Patients in TIMI 0–1 group were older (age > 50 years, 68.5% vs. 51.8%, P = 0.003), and had more diabetes mellitus (18.3% vs. 8.2%, P = 0.015). Plaque erosion with TIMI flow 0–1 was less frequently located in the left anterior descending artery (LAD, 58.4% vs. 72.7%, P = 0.011), but more frequently located in the right coronary artery (RCA, 34.2% vs. 7.3%, P = 0.001) than those with TIMI flow 2–3. TIMI 0–1 group had more lipid plaques (53.9% vs. 41.8%, P = 0.039), macrophage accumulation (59.8% vs. 41.8%, P = 0.002), and calcification (34.2% vs. 21.8%, P = 0.020). In the multivariable analysis, age > 50 years, diabetes mellitus, RCA location, and macrophage accumulation were the independent predictors of reduced TIMI flow grade in STEMI patients with plaque erosion. Systemic factors (older age and diabetes mellitus) and local factors (RCA location and macrophage accumulation) were independently associated with reduced coronary flow in STEMI patients with plaque erosion.

Clinical trial registration

ClinicalTrials.gov NCT03084991 May 17, 2017 (retrospectively registered).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

All data generated or analysed during this study are included in this published article.

References

  1. Stone GW, Cox D, Garcia E, Brodie BR, Morice M-C, Griffin J, Mattos L, Lansky AJ, O’Neill WW, Grines CL (2001) Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction. Circulation 104:636–641. https://doi.org/10.1161/hc3101.093701

    Article  CAS  PubMed  Google Scholar 

  2. De Luca G, Ernst N, Zijlstra F, Van’t Hof AWJ, Hoorntje JCA, Dambrink JHE, Gosslink ATM, De Boer MJ, Suryapranata H (2004) Preprocedural TIMI flow and mortality in patients with acute myocardial infarction treated by primary angioplasty. J Am Coll Cardiol 43:1363–1367. https://doi.org/10.1016/j.jacc.2003.11.042

    Article  PubMed  Google Scholar 

  3. Cura FA, L’Allier PL, Kapadia SR, Houghtaling PL, Dipaola LM, Ellis SG, Topol EJ, Brener SJ (2001) Predictors and prognosis of suboptimal coronary blood flow after primary coronary angioplasty in patients with acute myocardial infarction. Am J Cardiol 88:124–128. https://doi.org/10.1016/S0002-9149(01)01605-8

    Article  CAS  PubMed  Google Scholar 

  4. Dai J, Xing L, Jia H, Zhu Y, Zhang S, Hu S, Lin L, Ma L, Liu H, Xu M, Ren X, Yu H, Li L, Zou Y, Zhang S, Mintz GS, Hou J, Yu B (2018) In vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction: a clinical, angiographical, and intravascular optical coherence tomography study. Eur Heart J 39:2077–2085. https://doi.org/10.1093/eurheartj/ehy101

    Article  PubMed  Google Scholar 

  5. Farb A, Burke AP, Tang AL, Liang Y, Mannan P, Smialek J, Virmani R (1996) Coronary plaque erosion without rupture into a lipid core. Circulation 93:1354–1363. https://doi.org/10.1161/01.CIR.93.7.1354

    Article  CAS  PubMed  Google Scholar 

  6. Kramer MCA, Rittersma SZH, de Winter RJ, Ladich ER, Fowler DR, Liang YH, Kutys R, Carter-Monroe N, Kolodgie FD, van der Wal AC, Virmani R (2010) Relationship of thrombus healing to underlying plaque morphology in sudden coronary death. J Am Coll Cardiol 55:122–132. https://doi.org/10.1016/j.jacc.2009.09.007

    Article  PubMed  Google Scholar 

  7. Kolodgie FD, Burke AP, Wight TN, Virmani R (2004) The accumulation of specific types of proteoglycans in eroded plaques: a role in coronary thrombosis in the absence of rupture. Curr Opin Lipidol 15:575–582. https://doi.org/10.1097/00041433-200410000-00012

    Article  CAS  PubMed  Google Scholar 

  8. Kolodgie FD, Burke AP, Farb A, Weber DK, Kutys R, Wight TN, Virmani R (2002) Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion. Arterioscler Thromb Vasc Biol 22:1642–1648. https://doi.org/10.1161/01.ATV.0000034021.92658.4C

    Article  CAS  PubMed  Google Scholar 

  9. Schwartz RS, Burke A, Farb A, Kaye D, Lesser JR, Henry TD, Virmani R (2009) Microemboli and microvascular obstruction in acute coronary thrombosis and sudden coronary death. Relation to. J Am Coll Cardiol 54:2167–2173. https://doi.org/10.1016/j.jacc.2009.07.042

    Article  PubMed  Google Scholar 

  10. Ferrante G, Nakano M, Prati F, Niccoli G, Mallus MT, Ramazzotti V, Montone RA, Kolodgie FD, Virmani R, Crea F (2010) High levels of systemic myeloperoxidase are associated with coronary plaque erosion in patients with acute coronary syndromes: a clinicopathological study. Circulation 122:2505–2513. https://doi.org/10.1161/CIRCULATIONAHA.110.955302

    Article  CAS  PubMed  Google Scholar 

  11. Ino Y, Kubo T, Tanaka A, Kuroi A, Tsujioka H, Ikejima H, Okouchi K, Kashiwagi M, Takarada S, Kitabata H, Tanimoto T, Komukai K, Ishibashi K, Kimura K, Hirata K, Mizukoshi M, Imanishi T, Akasaka T (2011) Difference of culprit lesion morphologies between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome. JACC Cardiovasc Interv 4:76–82. https://doi.org/10.1016/j.jcin.2010.09.022

    Article  PubMed  Google Scholar 

  12. Toutouzas K, Tsiamis E, Karanasos A, Drakopoulou M, Synetos A, Tsioufis C, Tousoulis D, Davlouros P, Alexopoulos D, Bouki K, Apostolou T, Stefanadis C (2010) Morphological characteristics of culprit atheromatic plaque are associated with coronary flow after thrombolytic therapy. JACC Cardiovasc Interv 3:507–514. https://doi.org/10.1016/j.jcin.2010.02.010

    Article  PubMed  Google Scholar 

  13. Higuma T, Soeda T, Yamada M, Yokota T, Yokoyama H, Nishizaki F, Xing L, Yamamoto E, Bryniarski K, Dai J, Lee H, Okumura K, Jang I-K (2016) Coronary plaque characteristics associated with reduced TIMI (thrombolysis in myocardial infarction) flow grade in patients with ST-segment–elevation myocardial infarction. Circ Cardiovasc Interv 1:1. https://doi.org/10.1161/circinterventions.116.003913

    Article  Google Scholar 

  14. Nakamura M, Yamagishi M, Ueno T, Hara K, Ishiwata S, Itoh T, Hamanaka I, Wakatsuki T, Sugano T, Kawai K, Kimura T (2013) Current treatment of ST elevation acute myocardial infarction in Japan: door-to-balloon time and total ischemic time from the J-AMI registry. Cardiovasc Interv Ther 28:30–36. https://doi.org/10.1007/s12928-012-0128-x

    Article  PubMed  Google Scholar 

  15. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P (1987) Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 76:142–154. https://doi.org/10.1161/01.CIR.76.1.142

    Article  CAS  PubMed  Google Scholar 

  16. Jia H, Abtahian F, Aguirre AD, Lee S, Chia S, Lowe H, Kato K, Yonetsu T, Vergallo R, Hu S, Tian J, Lee H, Park SJ, Jang YS, Raffel OC, Mizuno K, Uemura S, Itoh T, Kakuta T, Choi SY, Dauerman HL, Prasad A, Toma C, McNulty I, Zhang S, Yu B, Fuster V, Narula J, Virmani R, Jang IK (2013) In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. J Am Coll Cardiol 62:1748–1758. https://doi.org/10.1016/j.jacc.2013.05.071

    Article  PubMed  Google Scholar 

  17. Kajander OA, Pinilla-Echeverri N, Jolly SS, Bhindi R, Huhtala H, Niemelä K, Fung A, Vijayaraghavan R, Alexopoulos D, Sheth T (2016) Culprit plaque morphology in STEMI-an optical coherence tomography study: insights from the TOTAL-OCT substudy. EuroIntervention 12:716–723. https://doi.org/10.4244/EIJV12I6A116

    Article  PubMed  Google Scholar 

  18. Prati F, Regar E, Mintz GS, Arbustini E, Di Mario C, Jang IK, Akasaka T, Costa M, Guagliumi G, Grube E, Ozaki Y, Pinto F, Serruys PWJ (2010) Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur Heart J 31:401–415. https://doi.org/10.1093/eurheartj/ehp433

    Article  PubMed  Google Scholar 

  19. Sato Y, Hatakeyama K, Yamashita A, Marutsuka K, Sumiyoshi A, Asada Y (2005) Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans. Heart 91:526–530. https://doi.org/10.1136/hrt.2004.034058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Burke AP, Farb A, Malcom GT, Liang Y, Smialek J, Virmani R (1998) Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation 97:2110–2116. https://doi.org/10.1161/01.cir.97.21.2110

    Article  CAS  PubMed  Google Scholar 

  21. Santilli F, Simeone P, Liani R, Davì G (2015) Platelets and diabetes mellitus. Prostaglandins Other Lipid Mediat 120:28–39. https://doi.org/10.1016/j.prostaglandins.2015.05.002

    Article  CAS  PubMed  Google Scholar 

  22. Zaccardi F, Rocca B, Pitocco D, Tanese L, Rizzi A, Ghirlanda G (2015) Platelet mean volume, distribution width, and count in type 2 diabetes, impaired fasting glucose, and metabolic syndrome: a meta-analysis. Diabetes Metab Res Rev 31:402–410. https://doi.org/10.1002/dmrr.2625

    Article  CAS  PubMed  Google Scholar 

  23. Bainey KR, Fu Y, Granger CB, Hamm CW, Holmes DR, O’Neill WW, Seabra-Gomes R, Pfisterer ME, Van De Werf F, Armstrong PW (2009) Benefit of angiographic spontaneous reperfusion in STEMI: Does it extend to diabetic patients? Heart 95:1331–1336. https://doi.org/10.1136/hrt.2008.160390

    Article  CAS  PubMed  Google Scholar 

  24. Ferreiro JL, Gómez-Hospital JA, Angiolillo DJ (2010) Review article: platelet abnormalities in diabetes mellitus. Diabetes Vasc Dis Res 7:251–259. https://doi.org/10.1177/1479164110383994

    Article  Google Scholar 

  25. Gray RP, Patterson DLH, Yudkin JS (1993) Plasminogen activator inhibitor activity in diabetic and nondiabetic survivors of myocardial infarction. Arterioscler Thromb 13:415–420. https://doi.org/10.1161/01.atv.13.3.415

    Article  CAS  PubMed  Google Scholar 

  26. Nordt TK, Bode C (2000) Impaired endogenous fibrinolysis in diabetes mellitus: mechanisms and therapeutic approaches. Semin Thromb Hemost 26:495–501. https://doi.org/10.1055/s-2000-13205

    Article  CAS  PubMed  Google Scholar 

  27. Hsueh WA, Lyon CJ, Quiñones MJ (2004) Insulin resistance and the endothelium. Am J Med 117:109–117. https://doi.org/10.1016/j.amjmed.2004.02.042

    Article  CAS  PubMed  Google Scholar 

  28. Jones CI (2016) Platelet function and ageing. Mamm Genome 27:358–366. https://doi.org/10.1007/s00335-016-9629-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Meade TW, Vickers MV, Thompson SG, Stirling Y, Haines AP, Miller GJ (1985) Epidemiological characteristics of platelet aggregability. Br Med J (Clin Res Ed) 290:428–432. https://doi.org/10.1136/bmj.290.6466.428

    Article  CAS  Google Scholar 

  30. Cowman J, Dunne E, Oglesby I, Byrne B, Ralph A, Voisin B, Müllers S, Ricco AJ, Kenny D (2015) Age-related changes in platelet function are more profound in women than in men. Sci Rep. https://doi.org/10.1038/srep12235

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fang C, Dai J, Zhang S, Wang Y, Wang J, Li L, Wang Y, Yu H, Wei G, Zhang X, Feng N, Liu H, Xu M, Ren X, Ma L, Tu Y, Xing L, Hou J, Yu B (2019) Culprit lesion morphology in young patients with ST-segment elevated myocardial infarction: a clinical, angiographic and optical coherence tomography study. Atherosclerosis 289:94–100. https://doi.org/10.1016/j.atherosclerosis.2019.08.011

    Article  CAS  PubMed  Google Scholar 

  32. Higuma T, Soeda T, Abe N, Yamada M, Yokoyama H, Shibutani S, Vergallo R, Minami Y, Ong DS, Lee H, Okumura K, Jang I-K (2015) A combined optical coherence tomography and intravascular ultrasound study on plaque rupture, plaque erosion, and calcified nodule in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 8:1166–1176. https://doi.org/10.1016/j.jcin.2015.02.026

    Article  PubMed  Google Scholar 

  33. Katranas SA, Kelekis AL, Antoniadis AP, Ziakas AG, Giannoglou GD (2015) Differences in stress forces and geometry between left and right coronary artery: a pathophysiological aspect of atherosclerosis heterogeneity. Hell J Cardiol 56:217–223

    Google Scholar 

  34. Hathcock JJ (2006) Flow effects on coagulation and thrombosis. Arterioscler Thromb Vasc Biol 26:1729–1737. https://doi.org/10.1161/01.ATV.0000229658.76797.30

    Article  CAS  PubMed  Google Scholar 

  35. Nesbitt WS, Westein E, Tovar-Lopez FJ, Tolouei E, Mitchell A, Fu J, Carberry J, Fouras A, Jackson SP (2009) A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat Med 15:665–673. https://doi.org/10.1038/nm.1955

    Article  CAS  PubMed  Google Scholar 

  36. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126. https://doi.org/10.1056/NEJM199901143400207

    Article  CAS  PubMed  Google Scholar 

  37. Sugiyama S, Kugiyama K, Aikawa M, Nakamura S, Ogawa H, Libby P (2004) Hypochlorous acid, a macrophage product, induces endothelial apoptosis and tissue factor expression: involvement of myeloperoxidase-mediated oxidant in plaque erosion and thrombogenesis. Arterioscler Thromb Vasc Biol 24:1309–1314. https://doi.org/10.1161/01.ATV.0000131784.50633.4f

    Article  CAS  PubMed  Google Scholar 

  38. Lu Q, Rounds S (2012) Focal adhesion kinase and endothelial cell apoptosis. Microvasc Res 83:56–63. https://doi.org/10.1016/j.mvr.2011.05.003

    Article  CAS  PubMed  Google Scholar 

  39. Virmani R, Burke AP, Farb A, Kolodgie FD (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47:C13–C18. https://doi.org/10.1016/j.jacc.2005.10.065

    Article  CAS  PubMed  Google Scholar 

  40. Moreno PR, Bernardi VH, Lopez-Cuellar J, Murcia AM, Palacios IF, Gold HK, Mehran R, Sharma SK, Nemerson Y, Fuster V, Fallon JT (1996) Macrophages, smooth muscle cells, and tissue factor in unstable angina. Circulation 94:3090–3097. https://doi.org/10.1161/01.CIR.94.12.3090

    Article  CAS  PubMed  Google Scholar 

  41. MacNeill BD, Jang IK, Bouma BE, Iftimia N, Takano M, Yabushita H, Shishkov M, Kauffman CR, Houser SL, Aretz HT, Dejoseph D, Halpern EF, Tearney GJ (2004) Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease. J Am Coll Cardiol 44:972–979. https://doi.org/10.1016/j.jacc.2004.05.066

    Article  PubMed  Google Scholar 

  42. White SJ, Newby AC, Johnson TW (2016) Endothelial erosion of plaques as a substrate for coronary thrombosis. Thromb Haemost 115:509–519. https://doi.org/10.1160/TH15-09-0765

    Article  PubMed  Google Scholar 

  43. Jia H, Dai J, Hou J, Xing L, Ma L, Liu H, Xu M, Yao Y, Hu S, Yamamoto E, Lee H, Zhang S, Yu B, Jang I-K (2016) Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study). Eur Heart J. https://doi.org/10.1093/eurheartj/ehw381

    Article  Google Scholar 

Download references

Acknowledgements

The authors sincerely thank all colleagues and patients who participated in this study. All of the authors have read the manuscript and have approved this submission.

Funding

This work was supported by National Key R&D Program of China (Grant No. 2016YFC1301100 to B.Y.), National Natural Science Foundation of China (Grant No. 81801861 to J.D. and Grant No. 81827806 to B.Y.), China Postdoctoral Science Foundation (Grant No. 2018M630373 and No. 2019T120283 to J.D.), and Hei Long Jiang Postdoctoral Foundation (Grant No. LBH-TZ15 to J.D.).

Author information

Author notes

  1. Jifei Wang and Chao Fang contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, 246 Xuefu Road, Nangang District, Harbin, 150086, China

    Jifei Wang, Chao Fang, Shaotao Zhang, Lulu Li, Jia Lu, Yidan Wang, Yini Wang, Huai Yu, Guo Wei, Yanwei Yin, Senqing Jiang, Junchen Guo, Fangmeng Lei, Huimin Liu, Maoen Xu, Xuefeng Ren, Lijia Ma, Yingfeng Tu, Lei Xing, Jingbo Hou, Jiannan Dai & Bo Yu

Authors
  1. Jifei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chao Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaotao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lulu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yidan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yini Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Huai Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guo Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yanwei Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Senqing Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Junchen Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fangmeng Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Huimin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Maoen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Xuefeng Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Lijia Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yingfeng Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Lei Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Jingbo Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jiannan Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Bo Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JW: substantial contribution to the conception and design of research, data acquisition, manuscript drafting and critical manuscript revision. CF, JD: substantial contribution to the conception and design of research, data acquisition and critical manuscript revision. SZ, JL, YW, YW, YY, SJ, JG, FL: substantial contribution to data acquisition. LL: substantial contribution to statistical analysis. HY, GW, HL, MX, XR, LM: substantial contribution to patients enrollment and cardiac intervention. YT, LX: substantial contribution to data acquisition and critical manuscript revision. JH, BY: substantial contribution to the design of research and critical manuscript revision.

Corresponding authors

Correspondence to Jiannan Dai or Bo Yu.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Consent to participate

Written informed consent was obtained from all enrolled patients.

Consent for publication

All of the authors have read the manuscript and have approved this submission.

Ethical approval

This study was approved by the Ethics Committee of our institution and written informed consents were obtained from all enrolled patients.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file 1 (DOCX 3604 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Fang, C., Zhang, S. et al. Systemic and local factors associated with reduced thrombolysis in myocardial infarction flow in ST-segment elevation myocardial infarction patients with plaque erosion detected by intravascular optical coherence tomography. Int J Cardiovasc Imaging 37, 399–409 (2021). https://doi.org/10.1007/s10554-020-02021-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-020-02021-1

Keywords

Search

Navigation