Myocardial Infarction

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.

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:

Decreased aortic diastolic pressure
Increased intraventricular pressure and myocardial contraction
Coronary artery stenosis, which can be further subdivided into the following etiologies:
- Fixed coronary stenosis
- Acute plaque change (rupture, hemorrhage)
- Coronary artery thrombosis
- Vasoconstriction
Aortic valve stenosis and regurgitation
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).

"Thrombolytic therapy" with agents such as streptokinase or tissue plasminogen activator (TPA) is often used 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 (less than an hour or so) in the course of events, and can at least help to reduce further damage.

Images of coronary artery disease:

Patterns of Ischemic Heart Disease (IHD)

Angina pectoris - a symptom complex of IHD characterized by paroxysmal attacks of chest pain, usually substernal or precordial, caused by myocardial ischemia that falls short of inducing infarction. There are several patterns:

Stable angina (typical) - paroxysms of pain related to exertion and relieved by rest or vasodilators.subendocardial ischemia with ST-segment depression
Variant or Prinzmetal's angina - angina that classically occurs at rest and is caused by reversible spasm in normal to severely atherosclerotic coronary arteries. ST-segment elevation or depression maybe seen during attacks.
Unstable angina - prolonged pain, pain at rest in a person with stable angina, or worsening of pain in stable angina. ST-segment depression (usually) and ST-segment elevation.
Sudden cardiac death - Unexpected death from cardiac causes usually within one hour after a cardiac event or without the onset of symptoms. Strikes 300,000 - 400,000 persons annually. Usually high-grade stenosis with acute coronary changes.

Myocardial Infarction (MI)

The pathogenesis can include:

Occlusive intracoronary thrombus - a thrombus overlying an ulcerated or fissured stenotic plaque causes 90% of transmural acute myocardial infarctions.
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.

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 Onset	Gross Morphologic Finding
18 - 24 Hours	Pallor of myocardium
24 - 72 Hours	Pallor with some hyperemia
3 - 7 Days	Hyperemic border with central yellowing
10 - 21 Days	Maximally yellow and soft with vascular margins
7 weeks	White fibrosis

Microscopic morphologic changes evolve over time as follows:

Time from Onset	Microscopic Morphologic Finding
1 - 3 Hours	Wavy myocardial fibers
2 - 3 Hours	Staining defect with tetrazolium or basic fuchsin dye
4 - 12 Hours	Coagulation necrosis with loss of cross striations, contraction bands, edema, hemorrhage, and early neutrophilic infiltrate
18 - 24 Hours	Continuing coagulation necrosis, pyknosis of nuclei, and marginal contraction bands
24 - 72 Hours	Total loss of nuclei and striations along with heavy neutrophilic infiltrate
3 - 7 Days	Macrophage and mononuclear infiltration begin, fibrovascular response begins
10 - 21 Days	Fibrovascular response with prominent granulation tissue
7 Weeks	Fibrosis

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 is defined as death occurring 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.

Thus, clinically, 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.

Images of myocardial injury:

Laboratory Diagnosis of Myocardial Infarction

A number of laboratory tests 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 tests are available as markers for acute myocardial infarction:

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.

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.

Thus, CK-MB is a very good marker for acute myocardial injury, because of its excellent specificity, and it rises in serum within 2 to 8 hours of onset of acute myocardial infarction. Serial measurements every 2 to 4 hours for a period of 9 to 12 hours after the patient is first seen will provide a pattern to determine whether the CK-MB is rising, indicative of myocardial injury. The CK-MB is also useful for diagnosis of reinfarction or extensive of an MI because it begins to fall after a day, dissipating in 1 to 3 days, so subsequent elevations are indicative of another event.

A "cardiac index" can provide a useful indicator for early MI. This is calculated as a ratio of total CK to CK-MB, and is a sensitive indicator of myocardial injury when the CK-MB is elevated.

CK-MB Isoforms:

The CK-MB fraction exists in two isoforms called 1 and 2 identified by electrophoretic methodology. The ratio of isoform 2 to 1 can provide information about myocardial injury.

An isoform ratio of 1.5 or greater is an excellent indicator for early acute myocardial infarction. CK-MB isoform 2 demonstrates elevation even before CK-MB by laboratory testing. However, the disadvantage of this method is that it is skilled labor intensive because electrophoresis is required, and large numbers of samples cannot be run simultaneously nor continuously. False positive results with congestive heart failure and other conditions can occur.

Troponins:

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 5 to 9 days for troponin I and up to 2 weeks for troponin T. 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.

Myoglobin:

Myoglobin is a protein found in skeletal and cardiac muscle which binds oxygen. It is a very sensitive indicator of muscle injury. 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. However, it is not specific for cardiac muscle, and can be elevated with any form of injury to skeletal muscle.

Lactate dehydrogenase:

The LDH has been supplanted by other tests. It begins to rise in 12 to 24 hours following MI, and peaks in 2 to 3 days, gradually dissipating in 5 to 14 days. Measurement of LDH isoenzymes is necessary for greater specificity for cardiac injury. There are 5 isoenzymes (1 through 5). Ordinarily, isoenzyme 2 is greater than 1, but with myocardial injury, this pattern is "flipped" and 1 is higher than 2. LDH-5 from liver may be increased with centrilobular necrosis from passive congestion with congestive heart failure following ischemic myocardial injury.

References

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