Myocardial Infarction

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What is Ischemic Heart Disease?

Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Anversa and Sonnenblick, 1990)

Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction.

Factors reducing coronary blood flow include:

  1. Decreased aortic diastolic pressure

  2. Increased intraventricular pressure and myocardial contraction

  3. Coronary artery stenosis, which can be further subdivided into the following etiologies:

    • Fixed coronary stenosis

    • Acute plaque change (rupture, hemorrhage)

    • Coronary artery thrombosis

    • Vasoconstriction

  4. Aortic valve stenosis and regurgitation

  5. Increased right atrial pressure

40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995)

"Thrombolytic therapy" with agents such as streptokinase or tissue plasminogen activatorS (TPA) such as atelpase is often used within the first 12 hours following onset of symptoms and with ST-segment elevation to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. (Kumar and Cannon, Part II, 2009)

Images of coronary artery disease:

  1. Normal coronary artery, microscopic.
  2. Coronary atherosclerosis, cross sections, gross.
  3. Coronary atherosclerosis, minimal, gross.
  4. Coronary atherosclerosis, severe, gross.
  5. Coronary atherosclerosis, composite, microscopic.
  6. Coronary atherosclerosis, intimal plaque, microscopic.
  7. Coronary atherosclerosis, complicated by calcification, microscopic.
  8. Coronary atherosclerosis, occlusive, microscopic.
  9. Coronary atherosclerosis, occlusive, microscopic.
  10. Coronary artery, hemorrhage into plaque, gross.
  11. Coronary artery, atheromatous plaque with disrupted fibrin cap, microscopic.
  12. Thrombosis of coronary artery, gross.
  13. Thrombosis of coronary artery, gross.
  14. Thrombosis of coronary artery, microscopic.
  15. Thrombosis of coronary artery, microscopic.

Patterns of Ischemic Heart Disease (IHD) with Acute Coronary Syndromes

Acute coronary syndromes include several patterns (Kumar and Cannon, Part I, 2009):

  1. Unstable angina: there is no ST-segment change and there is not sufficient myocardial damage for for release of a biomarker such as the troponins or CK-MB. There is one or more of the following: (1) rest angina, (2) new-onset severe angina, and (3) a crescendo pattern of occurrence.

  2. Non-ST-segment Elevation Myocardial Infarction (NSTEMI): there is no ST-segment change but there is myocardial necrosis for release of a biomarker such as the troponins or CK-MB.

  3. ST-segment Elevation Myocardial Infarction (STEMI): there is ST-segment elevation and myocardial necrosis with release of a biomarker such as the troponins or CK-MB.

Myocardial Infarction (MI)

The pathogenesis can include:

  • Occlusive intracoronary thrombus - a thrombus overlying an plaque causes 75% of myocardial infarctions, with superficial plaque erosion present in the remaining 25%.

  • Vasospasm - with or without coronary atherosclerosis and possible association with platelet aggregation.

  • Emboli - from left sided mural thrombosis, vegetative endocarditis, or paradoxic emboli from the right side of heart through a patent foramen ovale.

In 2000, the European Society of Cardiology and the American College of Cardiology Consensus group redefined myocardial infarction, with the definition being based on myocyte necrosis as determined by troponins in the clinical setting of ischaemia. (White and Chew, 2008)

The molecular events during MI relate to the initial ischemic event, reperfusion, and subsequent inflammatory response. Up to 6 hours following the initial ischemic event, most cell loss occur via apoptosis. After that, necrosis predominates. Ischemic endothelial cells express adhesion molecules that attract neutrophils that subsequently migrate into damaged myocardium.

The gross morphologic appearance of a myocardial infarction can vary. Patterns include:

  • Transmural infarct - involving the entire thickness of the left ventricular wall from endocardium to epicardium, usually the anterior free wall and posterior free wall and septum with extension into the RV wall in 15-30%. Isolated infarcts of RV and right atrium are extremely rare.

  • Subendocardial infarct - multifocal areas of necrosis confined to the inner 1/3-1/2 of the left ventricular wall. These do not show the same evolution of changes seen in a transmural MI.

Gross morphologic changes evolve over time as follows:

Time from OnsetGross Morphologic Finding
18 - 24 HoursPallor of myocardium
24 - 72 HoursPallor with some hyperemia
3 - 7 DaysHyperemic border with central yellowing
10 - 21 DaysMaximally yellow and soft with vascular margins
7 weeksWhite fibrosis

Microscopic morphologic changes evolve over time as follows:

Time from OnsetMicroscopic Morphologic Finding
1 - 3 HoursWavy myocardial fibers but no inflammatory cells
2 - 3 HoursStaining defect in myocardial fiber cytoplasm with tetrazolium or basic fuchsin dye
4 - 12 HoursCoagulation necrosis with loss of cross striations, contraction bands, edema, hemorrhage, and early neutrophilic infiltrate
18 - 24 HoursContinuing coagulation necrosis, pyknosis of nuclei, and marginal contraction bands
24 - 72 HoursTotal loss of nuclei and cross striations along with heavy neutrophilic infiltrate
3 - 7 DaysMacrophage and mononuclear infiltration begins, fibrovascular response begins
10 - 21 DaysFibrovascular response with prominent granulation tissue containing capillaries and fibroblasts
7 WeeksFibrosis with dense collagenous connective tissue and no inflammation

The above gross and microscopic changes over time can vary. In general, a larger infarct will evolve through these changes more slowly than a small infarct. Clinical complications of myocardial infarction will depend upon the size and location of the infarction, as well as pre-existing myocardial damage. Complications can include:

  • Arrhythmias and conduction defects, with possible "sudden death"

  • Extension of infarction, or re-infarction

  • Congestive heart failure (pulmonary edema)

  • Cardiogenic shock

  • Pericarditis

  • Mural thrombosis, with possible embolization

  • Myocardial wall rupture, with possible tamponade

  • Papillary muscle rupture, with possible valvular insufficiency

  • Ventricular aneurysm formation

Sudden death occurs within an hour of onset of symptoms. Such an occurrence often complicates ischemic heart disease. Such patients tend to have severe coronary atherosclerosis (>75% lumenal narrowing). Often, a complication such as coronary thrombosis or plaque hemorrhage or rupture has occurred. The mechanism of death is usually an arrhythmia.

Ischemic Cardiomyopathy

In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)

Images of myocardial injury:

  1. Normal myocardium, microscopic.
  2. Early acute myocardial infarction (<12 hours) with loss of cross striations, microscopic.
  3. Early acute myocardial infarction (<1 day) with contraction band necrosis, microscopic.
  4. Acute myocardial infarction (1 - 2 days) with early neutrophilic infiltrate, microscopic.
  5. Acute myocardial infarction (1 - 2 days), hyperemic border, microscopic.
  6. Acute myocardial infarction (3 - 4 days), extensive neutrophilic infiltrate, microscopic.
  7. Acute myocardial infarction, gross.
  8. Acute myocardial infarction, gross.
  9. Acute myocardial infarction with rupture, gross.
  10. Acute myocardial infarction with rupture and tamponade, gross.
  11. Intermediate (healing) myocardial infarction (1 - 2 weeks), microscopic.
  12. Remote myocardial infarction (3 to 4 weeks), microscopic.
  13. Remote myocardial infarction (>2 months), microscopic.
  14. Remote myocardial infarction (weeks to years), gross.
  15. Left ventricular aneurysm, gross.
  16. Left ventricular aneurysm containing mural thrombus, gross.
  17. Ischemic cardiomyopathy, microscopic.

Laboratory Diagnosis of Myocardial Infarction

A number of laboratory biomarkers for myocardial injury are available. None is completely sensitive and specific for myocardial infarction, particularly in the hours following onset of symptoms. Timing is important, as are correlation with patient symptoms, electrocardiograms, and angiographic studies.

The following biomarkers have been described in association with acute myocardial infarction:


Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB.

Troponins will remain elevated longer than CK--up to 14 days. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or extension of infarction in a patient who has already suffered an initial MI. Troponin T lacks some specificity because elevations can appear with skeletal myopathies and with renal failure. (Kost et al, 1998) (Kumar and Cannon, Part I, 2009)

Creatine Kinase - Total:

The total CK is a simple and inexpensive test that is readily available using many laboratory instruments. However, an elevation in total CK is not specific for myocardial injury, because most CK is located in skeletal muscle, and elevations are possible from a variety of non-cardiac conditions. (Chattington et al, 1994)

Creatine Kinase - MB Fraction:

Creatine kinase can be further subdivided into three isoenzymes: MM, MB, and BB. The MM fraction is present in both cardiac and skeletal muscle, but the MB fraction is much more specific for cardiac muscle: about 15 to 40% of CK in cardiac muscle is MB, while less than 2% in skeletal muscle is MB. The BB fraction (found in brain, bowel, and bladder) is not routinely measured.

The creatine kinase-MB fraction (CK-MB) is part of total CK and more specific for cardiac muscle that other striated muscle. It tends to increase within 3 to 4 hours of myocardial necrosis, then peak in a day and return to normal within 36 hours. It is less sensitive than troponins. (Saenger and Jaffe, 2007) (Kumar and Cannon, Part I, 2009)

The CK-MB is also useful for diagnosis of reinfarction or extensive of an MI because it begins to fall after a day, so subsequent elevations are indicative of another event. (Chattington et al, 1994)


Myoglobin is a protein found in skeletal and cardiac muscle which binds oxygen. It is a very sensitive indicator of muscle injury. However, it is not specific for cardiac muscle, and can be elevated with any form of injury to skeletal muscle. The rise in myoglobin can help to determine the size of an infarction. A negative myoglobin can help to rule out myocardial infarction. It is elevated even before CK-MB. (Kumar and Cannon, Part I, 2009)


B-type natriuretic peptide (BNP) is released from ventricular myocardium. BNP release can be stimulated by systolic and diastolic left ventricular dysfunction, acute coronary syndromes, stable coronary heart disease, valvular heart disease, acute and chronic right ventricular failure, and left and right ventricular hypertrophy secondary to arterial or pulmonary hypertension. BNP is a marker for heart failure. (Saenger and Jaffe, 2007)


C-reactive protein (CRP) is an acute phase protein elevated when inflammation is present. Since inflammation is part of atheroma formation, then CRP may reflect the extent of atheromatous plaque formation and predict risk for acute coronary events. However, CRP lacks specificity for vascular events. (Saenger and Jaffe, 2007)


Arginine vasopressin (AVP) is secreted as a prohormone from the posterior pituitary and then cleaved to form a C-terminal part called copeptin. A rapid increase in copeptin can be associated with stroke, sepsis, or acute myocardial injury. In conjunction with troponin, copeptin has high negative predictive value to rule out myocardial injury.


Anversa P, Sonnenblick EH. Ischemic cardiomyopathy: pathophysiologic mechanisms. Prog Cardiovasc Dis. 1990;33:49-70.

Anversa P, Kajstura J, Reiss K, et al. Ischmic cardiomyopathy: myocyte cell loss, myocyte hypertrophy, and myocyte cellular hyperplasia. Ann N Y Acad Sci. 1995;752:47-64.

Chattington P, Clarke D, Neithercut WD. Timed sequential analysis of creatine kinase in the diagnosis of myocardial infarction in patients over 65 years of age. J Clin Pathol. 1994;47:995-998.

Kumar A, Cannon CP. Acute coronary syndromes: diagnosis and management, part I. Mayo Clin Proc. 2009;84:917-938.

Kumar A, Cannon CP. Acute coronary syndromes: Diagnosis and management, part II. Mayo Clin Proc. 2009;84:1021-1036.

Kost GJ, Kirk D, Omand K. A strategy for the use of cardiac injury markers in the diagnosis of acute myocardial infarction. Arch Pathol Lab Med. 1998;122:245-251.

Mueller C. Biomarkers and acute coronary syndromes: an update. Eur Heart J. 2014;35(9):552-556.

Otsuka F, Yasuda S, Noguchi T, Ishibashi-Ueda H. Pathology of coronary atherosclerosis and thrombosis. Cardiovasc Diagn Ther. 2016;6(4):396-408.

Saenger AK, Jaffe AS. The use of biomarkers for the evaluation and treatment of patients with acute coronary syndromes. Med Clin North Am. 2007;91:657-681.

White HD, Chew DP. Acute myocardial infarction. Lancet. 2008;372:570-584.

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