Aetiology

The classic mechanism of ST-elevation myocardial infarction (STEMI) 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 ischaemia causing a type 1 myocardial infarction (MI).[12]

NSTEMI may also be caused by other mechanisms, such as dynamic obstruction (i.e., focal coronary artery spasm or Prinzmetal's 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).[1]

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 non-occlusive thrombus that develops in a disrupted atherosclerotic plaque, and leads to non-occlusive or near-complete thrombosis of a vessel supplying the myocardium.

Several different sequences of events may lead to an NSTEMI:

  • Plaque rupture with superimposed non-occlusive 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, hypovolaemia, 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 intra-coronary 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.[12][13] 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.[13] Approximately 25% of patients with a diagnosis of NSTEMI have a 100% occlusion of the affected artery on coronary angiography.[14] 

The severity of myocardial damage in NSTEMI depends on:

  • Duration of ischaemia 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[2][3]

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 ischaemia by any of the following possible aetiologies. MI can be broken down into five different subtypes.

  • Type 1: spontaneous MI caused by a pathological process in the wall of the coronary artery with or without underlying CAD (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 anaemia 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 (PCI).

  • Type 4b: MI associated with stent thrombosis.

  • Type 4c: MI associated with restenosis.

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

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. Some experts advocate for a separate category of 'non-ischaemic myocardial injury' to describe biomarker elevation in the setting of critical illness, although this has not been added to current European or American clinical guidelines.[4]

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