ST elevation myocardial infarction pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]


ST elevation myocardial infarction is largely influenced by the role of plaque rupture.

The Role of Plaque Rupture in ST Elevation Myocardial Infarction

Atherosclerosis, or hardening of the arteries, is the gradual buildup of cholesterol and fibrous tissue (collagen and smooth muscle cells) throughout the vascular tree. When there is localized accumulation of lipids and scar tissue, this is called a "plaque". Somewhat paradoxically, it is not the most severe plaque narrowing that leads to ST elevation MI. Pathological studies indicate that it is often mild-to-moderate, lipid-laden, inflamed plaques that are the ones most likely to rupture and cause an ST elevation MI (STEMI) or a non ST elevation MI (NSTEMI). [1] The role of plaque rupture in STEMI and NSTEMI is supported by studies demonstrating that plaque rupture is present in about 70% and superficial erosion is present in 30% of patients who die suddenly in whom there is documented coronary artery disease. [2] Exposure of the blood stream to the thrombogenic components of the plaque leads to activation of the coagulation cascade and thrombus formation. In STEMI, the clot completely occludes the epicardial artery, and there is a complete lack of blood flow to the involved territory. This causes transmural injury and ST elevation. In NSTEMI, there is partial obstruction with embolization. This causes ischemia and subendocardial injury that are manifested by ST depression.

Shown here are multiple slices of the LAD. The proximal LAD is located to the left. Plaque rupture with thrombus formation begins in the second slice of the LAD.
Shown here is a magnified view of the second slice from the left. In yellow is atherosclerotic plaque, in red is clot that has formed inside the ruptured plaque and in the lumen of the coronary artery.

Pathophysiology of and Risk Factors for Plaque Rupture

  1. Macrophage accumulation has been shown to be present to a greater degree in patients with acute coronary syndromes than in those patients with chronic stable angina [3] [4] These activated macrophages can release enzymes such as metalloproteinases, interstitial collagenase, gelatinase, and stromelysin that degrade collagen, elastin, and proteoglycans. [5] This enzymatic degradation in turn leads to breakdown of the fibrous cap. The thin shoulders or edges of the fibrous cap appear to be particularly vulnerable to erosion and breakdown.
  2. Neovascularization of the plaque Moreno et have shown that microvessel density was increased in ruptured plaques when compared with nonruptured plaques (P=0.0001). Furthermore, among lesions with severe macrophage infiltration at the fibrous cap, microvessel density was increased (P=0.0001) was well as at the edges or shoulders of the plaque (P=0.0001). Intraplaque hemorrhage was also associated with an increase in microvessel density (P=0.04) as was the presence of thin-cap fibroatheromas (P=0.038). Microvessel density at the base of the plaque was identified as an independent (P=0.003) correlate of plaque rupture. [6]
  3. High oscillatory shear stress
  4. Vasoconstriction
  5. Spontaneous coronary dissection

Pathophysiology of and Risk Factors for Thrombosis Following Plaque Rupture

There are numerous systemic risk factors associated with thrombus formation following plaque rupture:

  1. Smoking: Smoking increases platelet aggregation and plasma epinephrine levels [7]
  2. Fibrinogen: Elevated levels of fibrinogen have been associated with thrombosis including abnormal levels of fibrinogen [8]
  3. Von Willebrand factor antigen [8]
  4. Tissue plasminogen activator [8]
  5. Anticardiolipin antibodies [9]
  6. Cross-linked fibrin-degradation products [10]
  7. Polymorphisms of a platelet glycoprotein receptor [11]

Gross Pathology Findings in Plaque Rupture

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

Plaque Rupture Histopathological Findings

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

The Consequence of Plaque Rupture and Vessel Occlusion: The Time Dependent Wavefront of Necrosis

Time dependent wavefront of necrosis working its way from the subendocardium to the subepicardium
Time dependent wavefront of necrosis working its way from the subendocardium to the subepicardium

In 1940, Blumgart ligated or tied off the coronary artery in dogs and cats and for the first time demonstrated a wavefront of cell death folllowing vessel occlusion [12] [13] [14] [15] [16]

Irreversible injury of ischemic myocytes occurs first in the subendocardial zone. With more extended ischemia, a wavefront of cell death moves through the myocardium to involve progressively more of the transmural thickness of the ischemic zone. The precise location, size, and specific morphologic features of an acute myocardial infarction depend on:

  1. The location, severity, and rate of development of coronary atherosclerotic obstructions,
  2. The size of the vascular bed perfused by the obstructed vessels
  3. The duration of the coronary artery occlusion
  4. The metabolic / oxygen needs of the myocardium at risk,
  5. The extent of collateral blood vessels

Decrease of ATP levels in myocytes in reaction to ischemia starts within seconds and causes loss of contractility in first two minutes. If ischemia persists, ATP levels reduced to its half level within 10 minutes and to 1/10 within 40 minutes. Irreversible cell injury occurs between 20-40 minutes and microvascular level injury starts if ischemia lasts more than an hour.[17]

If impaired blood flow to the heart lasts long enough, it triggers a process called the ischemic cascade; the heart cells die (chiefly through necrosis) and do not grow back. A collagen scar forms in its place. Recent studies indicate that another form of cell death called apoptosis also plays a role in the process of tissue damage subsequent to myocardial infarction.[18] As a result, the patient's heart can be permanently damaged. This scar tissue also puts the patient at risk for potentially life threatening arrhythmias.

Pathophysiology of ST segment elevation on the electrocardiogram

In ST segment myocaridal infarction (STEMI), the ST segments on the ECG are by definition elevated and there is myonecrosis (death of myocytes) as reflected by elevation of biomarkers such as creatine kinase MB fraction (CK-MB) or troponin T or I (tn). The ST segments are elevated due to full thickness injury of the myocardium.

Videos of STEMI pathophysiology

The following are excellent videos demonstrating the underlying pathophysiology. {{#ev:youtube|L6EiPLli5x8}} {{#ev:youtube|cOMzh2hf_Vw}} {{#ev:youtube|a8Idk4EUYTs}}


  1. Falk E, Shah PK, Fuster V (1995). "Coronary plaque disruption". Circulation. 92 (3): 657–71. PMID 7634481. Unknown parameter |month= ignored (help)
  2. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R (1997). "Coronary risk factors and plaque morphology in men with coronary disease who died suddenly". N. Engl. J. Med. 336 (18): 1276–82. PMID 9113930. Unknown parameter |month= ignored (help)
  3. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT (1994). "Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture". Circulation. 90 (2): 775–8. PMID 8044947. Unknown parameter |month= ignored (help)
  4. van der Wal AC, Becker AE, van der Loos CM, Das PK (1994). "Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology". Circulation. 89 (1): 36–44. PMID 8281670. Unknown parameter |month= ignored (help)
  5. Shah PK, Falk E, Badimon JJ; et al. (1995). "Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture". Circulation. 92 (6): 1565–9. PMID 7664441. Unknown parameter |month= ignored (help)
  6. Moreno PR, Purushothaman KR, Fuster V; et al. (2004). "Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability". Circulation. 110 (14): 2032–8. doi:10.1161/01.CIR.0000143233.87854.23. PMID 15451780. Unknown parameter |month= ignored (help)
  7. Hung J, Lam JY, Lacoste L, Letchacovski G (1995). "Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin". Circulation. 92 (9): 2432–6. PMID 7586342. Unknown parameter |month= ignored (help)
  8. 8.0 8.1 8.2 Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC (1995). "Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group". N. Engl. J. Med. 332 (10): 635–41. PMID 7845427. Unknown parameter |month= ignored (help)
  9. Vaarala O, Mänttäri M, Manninen V; et al. (1995). "Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men". Circulation. 91 (1): 23–7. PMID 7805207. Unknown parameter |month= ignored (help)
  10. Ridker PM, Hennekens CH, Cerskus A, Stampfer MJ (1994). "Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men". Circulation. 90 (5): 2236–40. PMID 7955179. Unknown parameter |month= ignored (help)
  11. Weiss EJ, Bray PF, Tayback M; et al. (1996). "A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis". N. Engl. J. Med. 334 (17): 1090–4. PMID 8598867. Unknown parameter |month= ignored (help)
  12. Blumgart HL, Schlesinge MJ, Davis D: Studies on the relation of the clinical manifestations of angina pectoris, coronary thrombosis, and myocardial infarction to the pathologic findings, with particular reference to the significance of collateral circulation. Amer Heart J 19: 1, 1940
  13. Blumgart HL, Zoll PM, Freedberg AS, Gilligan DR: The experimental production of intercoronary arterial anastomoses and their functional significance. Circulation 1: 10, 1950 PMID 15401193
  14. Blumgart HL, Zoll PM, Kurland CS: Discussion of direct relief of coronary occlusion. Arch Intern Med (Chicago) 104: 862, 1959 PMID 13801751
  15. Blumgart HL, Zoll PM. Pathologic physiology of angina pectoris and acute myocardial infarction. Circulation. 1960 Aug;22:301-7. PMID 13801752
  16. Blumgart HL, Zoll PM, Clinical Pathologic Correlations in Coronary Artery Disease, Circulation, Volume XLVII, No 6, June 1973, 1139-43 PMID 4575525
  17. Robbins Pathologic Basis of Disease, Kumar V, 7th ed
  18. Krijnen PA, Nijmeijer R, Meijer CJ, Visser CA, Hack CE, Niessen HW. (2002). "Apoptosis in myocardial ischaemia and infarction". J Clin Pathol. 55 (11): 801–11. PMID 12401816.

Additional Resources

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