Etiology

The classic mechanism of ST-elevation myocardial infarction (MI) is complete occlusion (typically thrombosis or embolism) of a coronary artery. In contrast, NSTEMI is usually a result of a transient or near-complete occlusion of a coronary artery or acute factor that deprives myocardium of oxygen.

Unstable plaques have soft, lipid-laden contents, with thin, often sclerotic fibrous caps infiltrated by macrophages (foam cells). Release of the lipid-rich atherogenic core causes adhesion, activation, and aggregation of platelets. This initiates the coagulation cascade. A superimposed thrombus forms, occluding the coronary blood flow and resulting in myocardial ischemia causing a type 1 MI.[15]

NSTEMI may also be caused by other mechanisms, such as dynamic obstruction (i.e., focal coronary artery spasm or Prinzmetal angina), severe progressive atherosclerosis, restenosis following percutaneous coronary intervention (PCI), recreational drug use (e.g., cocaine or other stimulants), arterial inflammation, or extrinsic causes leading to myocardial supply-demand mismatch (i.e., type 2 MI precipitated by acute blood loss in a patient with underlying coronary artery disease).[2]

Pathophysiology

NSTEMI is a result of an acute imbalance between myocardial oxygen demand and supply, most commonly due to a reduction in myocardial perfusion. Type 1 myocardial infarction (MI) is most commonly caused by a nonocclusive thrombus that develops in a disrupted atherosclerotic plaque, and leads to nonocclusive or near-complete thrombosis of a vessel supplying the myocardium.

Several different sequences of events may lead to an NSTEMI:

  • Plaque rupture with superimposed nonocclusive thrombus or embolic events leading to coronary vascular obstruction

  • Dynamic obstruction, such as in vasospasm

  • Progressive luminal narrowing (i.e., chronic arterial narrowing from restenosis)

  • Inflammatory mechanisms (i.e., vasculitis)

  • Extrinsic factors leading to poor coronary perfusion (such as hypotension, hypovolemia, or hypoxia).

The most common cause is plaque rupture or obstructive atherosclerotic disease. In this setting, the release of myocardial biomarkers in type 1 MI is thought to be due to atherosclerotic plaque fissuring or rupture with resulting intracoronary thrombus or platelet emboli leading to diminished myocardial blood flow.

Plaque rupture usually occurs at the weakest and thinnest part of the atherosclerotic cap (often at the shoulder region). Ruptured plaques contain large numbers of inflammatory cells including monocytes, macrophages, and T lymphocytes.[15][16] Although one third of occlusions occur at a site with the greatest stenosis, most (66% to 78%) arise from lesions with <50% stenosis, and <5% arise from lesions exhibiting >70% stenosis.[16] Approximately 25% of patients with a diagnosis of NSTEMI have a 100% occlusion of the affected artery on coronary angiography.[17] 

The severity of myocardial damage in NSTEMI depends on:

  • Duration of ischemia and time to reperfusion

  • Extent of underlying atherosclerosis

  • Presence of collateral blood flow to the affected region (reserve blood flow)

  • Diameter of affected coronary vessel

  • Degree of occlusion

  • Presence of other comorbidities (i.e., diabetes, renal failure, or hypertension).

Classification

Myocardial infarction redefined[3][4][5]

The development of myocardial tissue-specific biomarkers and sensitive cardiac imaging techniques allows for early detection of very small amounts of myocardial injury or necrosis. Consequently, myocardial infarction (MI) has been redefined to encompass any necrosis in the setting of myocardial ischemia by any of the following possible etiologies. MI can be broken down into five different subtypes.

  • Type 1: spontaneous MI caused by a pathologic process in the wall of the coronary artery with or without underlying coronary artery disease (e.g., plaque rupture). Presentations are consistent with acute coronary syndrome-type symptoms.

  • Type 2: MI secondary to an increase in oxygen demand or decrease in supply (i.e., imbalance caused by severe anemia or hypotension; also includes dynamic coronary artery spasm).

  • Type 3: sudden unexpected cardiac death before cardiac biomarkers obtained.

  • Type 4a: MI associated with percutaneous coronary intervention.

  • Type 4b: MI associated with stent thrombosis.

  • Type 4c: MI associated with restenosis.

  • Type 5: MI associated with coronary bypass graft surgery.

Criteria required to meet the definition for acute MI (types 1, 2, and 3) include:[4]

  1. Acute myocardial injury with clinical evidence of acute myocardial ischemia and with detection of a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit (URL) and at least one of the following:

    • Ischemic symptoms

    • New, or presumed new, ECG changes indicative of ischemia (left bundle branch block, ST elevation or depression)

    • Development of pathologic Q waves on the ECG

    • Myocardial necrosis or regional wall motion abnormality evidenced by cardiac imaging

    • Intracoronary thrombus detected on angiography or autopsy.

  2. Pathologic findings of an acute MI.

The term "myocardial injury" is used when there is evidence of elevated cardiac troponin values with at least one value above the 99th percentile URL. The myocardial injury is considered acute if there is a rise and/or fall of cardiac troponin values.[4]

There has been ongoing controversy in the literature and in clinical practice about distinguishing between type 1 and type 2 MI. Type 1 MI occur spontaneously and are associated with symptoms of acute coronary syndrome, typically have more significant elevations in troponin levels than type 2 MI, and are associated with acute coronary arterial processes such as plaque rupture/ulceration/dissection noted at coronary angiography. Type 2 MI are usually associated with elevated myocardial oxygen demand or decreased myocardial blood flow such as occurs with tachycardia or hypotension. Troponin is elevated in type 2 MI, although not as elevated as in type 1 injuries. Although coronary artery disease may be present on angiogram, there is absence of acute pathology. Cardiomyocyte injury with elevated cardiac troponins may also occur with conditions other than MI.[5]

Acute coronary syndrome (ACS)[2]

ACS is a term used to describe a range of conditions resulting from sudden reduction in coronary blood flow. Symptoms should be present suggestive of angina or anginal equivalent presentation. The presence or absence of ST-segment elevation on presenting ECG indicates ST-elevation MI or non-ST-elevation acute coronary syndrome (NSTE-ACS). NSTE-ACS is further sub-divided into NSTEMI or unstable angina, depending on elevation of troponin.

  1. ST-elevation MI (STEMI): ECG demonstrates ST elevation of >1 mm in ≥2 anatomically contiguous leads, usually associated by location. Repolarization abnormalities often evolve over time from hyperacute T waves to ST elevation to T-wave inversion to the development of Q waves. STEMI patients typically have a rise and fall of serum cardiac biomarkers. While biomarkers are useful for confirmatory and prognostic purposes, they are not required for the diagnosis of STEMI and should not delay treatment. Clinicians must be careful to recognize other causes of ST elevation that mimic a STEMI. These include left ventricular hypertrophy, left bundle-branch block, paced rhythm, benign early repolarization, pericarditis, and hyperkalemia.

  2. NSTEMI: ECG does not show persistent ST elevation, but may show ischemic changes such as ST depression or T-wave inversion. The ECG may also be normal. Serum levels of cardiac biomarkers are elevated.

  3. Unstable angina pectoris: cardiac biomarkers are normal.

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