Non ST elevation myocardial infarction pathophysiology & etiology


 * Associate Editors-In-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

NSTEMI Background
As alluded to in prior sections, Unstable Angina and NSTEMI are at different ends of the spectrum of the same disease. While there is no way to determine which patients presenting with Unstable Angina will ultimately progress to NSTEMI, the distinction between the two entities is clear. Often, for patients presenting prior to the four hour window before cardiac biomarkers are positive (namely CK-MB), the EKG in context of the patient's chest pain will be marker for whether patient has STEMI versus UA/NSTEMI and needs to urgently undergo percutaneous revascularization.

Complete List of (known) Underlying Mechanisms of NSTEMI

 * Coronary artery vasoconstriction
 * Culprit lesion morphology
 * Embolism / microembolism
 * Infection
 * Chlamydia pneumoniae
 * Cytomegalovirus
 * Helicobacter pylori


 * Inflammation
 * Leukocytes, platelets
 * Plaque disruption or plaque erosion
 * Thrombosis

Plaque rupture, thrombus formation, and embolization underly the pathophysiology of NSTEMI


This video shows plaque rupture or disruption of the atherosclerotic plaque in the mid LAD. As is often the case, the plaque has torn at its edge, a location where the fibrous cap covering the atherosclerotic plaque is the thinnest. Clot has formed and it is embolizing downstream. The most common preceding pathophysiologic event in NSTEMI is the disruption of an atherosclerotic plaque in an epicardial coronary artery such as that shown here. Exposure of the atherosclerotic plaque contents to the blood stream leads to activation of the clotting cascade, local thrombus formation, and incomplete occlusion of the epicardial artery in NSTEMI. This artery is open, in NSTEMI unlike STEMI where the artery is closed. The downstream microvasculature is occluded by the clot that has embolized, and this accounts for the troponin elevation in this patient.

As opposed to the original hypothesis that acute coronary syndrome (ACS) is caused by gradual progression of coronary atherosclerosis to the point of a severe, fixed lesion, it has become clear that, in fact, ACS is usually caused by atherosclerotic plaque rupture at a site that previously had only mild to moderate stenosis. This plaque rupture exposes ligands (including collagen) for platelet adhesion which causes platelet aggregation and subsequent platelet activation. Platelets are activated by thrombin (found in blood clots), adenosine diphosphate (found in platelet granules), serotonin (also found in platelet granules) and thromboxane-A2. Upon activation, the glycoprotein IIb/IIIa receptor that in a non-active state is found in the cytosol is exteriorized and modified which enables additional platelet aggregation and cross-linking. The prothrombinase complex then binds to the activated platelet and starts to coagulation cascade. This entire process results in a thrombus which coalesces over the ruptured plaque.

Below is the animation showing clot formation which breaks off to embolize artery downstream: 

Although less common, ACS may also occur by other mechanisms. These include:


 * coronary artery spasm as in Prinzmetal's angina,
 * severe narrowing alone without plaque rupture, as in the case of restenosis after percutaneous coronary intervention (PCI) or as with progressive atherosclerosis,
 * coronary artery dissection,
 * secondary ischemia in cases in which there is either increased myocardial oxygen demand as in tachycardia from fever, anemia, hypoxemia, thyrotoxicosis, or in cases of decreased supply such as in hypotension or anemia from hemorrhage.

Genetics
To date, there does not appear to be any single genetic marker predictive acute coronary syndrome (ACS). In a recent validation study of genetic variants associated with (which includes STEMI, NSTEMI and UA) none of the 85 genetic variants tested were shown to be correlated with ACS. The study chose the polymorphic genetic variants based on statistically significant findings of prior studies. Nonetheless, although no individual marker is likely to be predictive, in the future it is possible that a panel of markers may be used to assess risk.