ST elevation myocardial infarction pathophysiology

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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 narrowings that lead to ST elevation MI. Pathology studies indicate that it is often mild-to-moderate, lipid-laden, inflammed plaques that are the ones most likely to rupture and cause an ST elevation MI (STEMI) or a non ST elevation MI (NSTEMI). 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. 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 below 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 below 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.''

Te following are excellent videos demonstrating the underlying pathophysiology:







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  These activated macrophages can release enzymes  such as metalloproteinases, interstitial collagenase, gelatinase, and stromelysin that degrade collagen, elastin, and proteoglycans. 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.
 * 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
 * 2) Fibrinogen: Elevated levels of fibrinogen have been associated with thrombosis including abnormal levels of fibrinogen
 * 3) von Willebrand factor antigen
 * 4) tissue plasminogen activator
 * 5) Anticardiolipin antibodies
 * 6) Cross-linked fibrin-degradation products
 * 7) Polymorphisms of a platelet glycoprotein receptor

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
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

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.

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. 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.  Other causes of ST segment elevation that are not due to vessel occlusion are discussed below.

Differential Diagnosis of Causes of ST Segment Elevation in the Absence of Myonecrosis
Acute epicardial artery occlusion by thrombus is certainly one cause of ST segment elevation, but other causes of ST segment elevation which are not associated with myonecrosis include the following: (listed in alphabetical order)


 * Aneurysm of the ventricle can result in persistent ST segment elevation that can be exacerbated with tachycardia.


 * Arrhythmogenic right ventricular cardiomyopathy


 * Balloon inflation in a coronary artery during percutaneous coronary intervention


 * Brugada syndrome


 * Transthoracic cardioversion


 * Coronary artery rupture during percutaneous coronary intervention


 * Early repolarization is a normal variant that can result in ST segment elevation. It is more common in males of younger age. The ST elevation is exacerbated by bradycardia.


 * Hyperkalemia known as the "dialyzable current of njury" hyperkalemia may cause hyperacute ECG changes due to changes in membrane polarity


 * Left bundle branch block is associated with ST segment elevation in those leads that are discordant to the QRS. Stated differently, if the QRS is predominantly of a negative deflection, it is normal to observe ST segment elevation in the same leads. The presence of ST elevation in leads where the QRS deflection is upright (concordance) may be a marker of myocardial injury.


 * Myopericarditis can cause injury to the subepicardial myocytes and ST segment elevation.


 * Myocarditis can cause injury to the subepicardial myocytes and ST segment elevation.


 * Pericardiocentesis when the needle comes into contact with the myocardium, there can be ST segment elevation reflecting local injury of the myocardium.


 * Pericarditis can cause injury to the subepicardial myocytes and ST elevation.


 * Pulmonary Embolism


 * Prinzmetal's angina is associated with ST segment elevation due to transient epicardial coronary artery spasm either in the absence or presence of atherosclerosis. If the condition persists long enough, myonecrosis can be observed.


 * Stroke Intracranial hemorrhage can in some cases cause ST segment elevation due to direct myocyte injury from a hyperadrenergic stimulation emanating from the central nervous system.

Differential Diagnosis of Causes of ST Segment Elevation in the Presence of Myonecrosis (STEMI)
While plaque rupture is the most common cause of ST segment elevation MI, other conditions can cause ST elevation and myocardial necrosis. In order to expeditiously treat an alternate underlying cause of myonecrosis, it is important to rapidly identify conditions other than plaque rupture that may also cause ST elevation and myonecrosis. Indeed, the management of some of these conditions might be differ substantially from that of plaque rupture: cocaine induced STEMI would not be treated with beta-blockers, and myocardial contusion would not be treated with an antithrombin. These conditions include the following:

Additional Resources

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