Acute coronary syndrome: Terminology and classification

INTRODUCTION — The term acute coronary syndrome (ACS) is applied to patients in whom there is a suspicion or confirmation of acute myocardial ischemia or infarction. Non-ST-elevation myocardial infarction (NSTEMI), ST-elevation MI (STEMI), and unstable angina are the three traditional types of ACS. However, the widespread use of the high-sensitivity troponin test has changed the diagnosis of unstable angina to NSTEMI in almost all patients formerly diagnosed with unstable angina. This has occurred because those patients formerly called unstable angina actually have abnormally elevated high-sensitivity troponin values. Traditionally, unstable angina was defined as clinical and electrocardiographic (ECG) findings in the absence of an elevated biomarker level. Few if any patients with clinical and ECG evidence of myocardial ischemia have normal high-sensitivity troponin levels. Indeed, they demonstrate elevated levels of this biomarker, thus confirming the presence of myocardial cell death induced by ischemia. Almost all of these patients do not show a STEMI pattern on their ECG, and so they should be diagnosed as an NSTEMI [1].

While some of the rationale to classify ACS patients as having NSTEMI or STEMI is historical, the central reason is that the clinical management for each of these differs. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department" and "Overview of the acute management of ST-elevation myocardial infarction".)

DEFINITION OF MYOCARDIAL INFARCTION — The 2018 joint task force of the European Society of Cardiology (ESC), American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the World Health Federation (WHF) defined MI, whether STEMI or NSTEMI, as the presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia [2]. The joint task force further refined the definition of MI by developing a clinical classification according to the assumed proximate cause of the myocardial ischemia. This classification system is presented in detail separately. (See "Diagnosis of acute myocardial infarction", section on 'Definitions'.)

STEMI AND NSTEMI — The terms STEMI and NSTEMI are most correctly used in patients who present with clinical characteristics compatible with myocardial ischemia and who demonstrate elevated troponin levels in the blood (see "Approach to the patient with suspected angina pectoris"). The terms are also used in patients found to have an elevated troponin level (with other evidence of ischemia such as symptoms or ECG changes) that was performed after a coronary revascularization procedure (see "Diagnosis of acute myocardial infarction", section on 'After revascularization' and "Periprocedural myonecrosis following percutaneous coronary intervention", section on 'Diagnosis').

Similarly, the terms are applied in the setting of MI after noncardiac surgery when other evidence of ischemia is present. However, management may differ slightly based on ECG changes and the clinical setting. (See "Perioperative myocardial infarction or injury after noncardiac surgery", section on 'Acute treatment'.)

STEMI and NSTEMI, which require the finding of an elevated troponin, are distinguished from each other based on ECG characteristics (see "ECG tutorial: Myocardial ischemia and infarction" and "Electrocardiogram in the diagnosis of myocardial ischemia and infarction"). The distinction is important to the extent that early management differs (see 'Introduction' above). In patients with NSTEMI, the ECG on presentation may show no significant abnormalities, ST-segment depression or elevation (usually transient), or T wave inversion. ST-segment and/or T wave changes are often dynamic and can be transient.

Since an elevation in troponin using high-sensitivity assays may not be detectable for up to three hours after presentation, an NSTEMI is frequently not diagnosed during the initial evaluation of patients who present with suspected ischemic chest pain. However, subsequent analysis of blood troponin levels at a later time is abnormal, confirming the presence of a NSTEMI.

Most medical centers are using the high-sensitivity troponin test.

UNSTABLE ANGINA — As discussed above (see 'Introduction' above), the diagnosis of unstable angina is uncommon in the era of high-sensitivity troponin.

New onset angina — The natural history of new onset angina depends in part upon the degree of exertion required to induce chest pain. Patients with new onset angina occurring only after heavy physical exertion, such as shoveling snow or lifting a 50 pound weight, have a prognosis similar to patients with chronic stable angina. In comparison, new angina occurring after minimal exercise or at rest, particularly if prolonged, carries a worse prognosis in the absence of intervention. A study evaluated short- and long-term outcomes of patients with acute coronary syndromes in clinical trials [3]. While one large trial of 8859 patients showed no difference in short- and long-term mortality in patients with STEMI versus NSTEMI (the latter population includes unstable angina patients), other trials showed a significant increase in mortality in STEMI patients.

Rest angina — Rest angina, particularly if prolonged and/or associated with transient ST-segment changes >0.05 mV, identifies patients at increased risk (table 1).

Early post-MI angina — Early postinfarction angina (defined as chest pain occurring within 48 hours after an acute MI) is typically associated with complex lesions and/or persistent intracoronary thrombus and with more severe coronary disease [4,5]. The recurrent chest pain may signify either remaining viable myocardium in the infarct zone or a different area of myocardium at risk [6].

Angina occurring soon after an acute MI is associated with high risk in the absence of intervention [5,7-9]. This was illustrated in a report from the GUSTO-IIb trial [8]. Among 3513 patients with NSTEMI (using the old definition that did not include serum troponins), 36 percent had recurrent ischemia that was responsive to medical therapy in 79 percent. Patients with recurrent ischemia that was refractory or responsive to medical therapy had a higher rate of reinfarction at 30 days (22 and 7.2 versus 2.3 percent in those without recurrent ischemia) and six months. In addition, the occurrence of refractory ischemia was associated with a higher mortality compared with responsive ischemia or no ischemia at 30 days (16 versus 6 and 4.3 percent) and one year. Similar findings were noted among 4125 patients with an STEMI and in over 40,000 patients with an STEMI in GUSTO-I [9].

Postrevascularization angina — Angina after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) can reflect a procedural event or, over the long-term, restenosis after PCI, stenosis in a graft (usually with saphenous vein grafts), or progression of native disease. (See "Periprocedural complications of percutaneous coronary intervention" and "Percutaneous coronary intervention with intracoronary stents: Overview" and "Early noncardiac complications of coronary artery bypass graft surgery" and "Coronary artery bypass graft surgery: Prevention and management of vein graft stenosis", section on 'Clinical presentation'.)

Periprocedural angina — A periprocedural ischemic event may occur with or without symptoms, with or without troponin elevation, and either at the site of PCI or remotely. (See "Periprocedural complications of percutaneous coronary intervention".)

●Ischemic chest pain (with or without troponin elevation) within 48 hours after stenting usually results from procedural events such as abrupt vessel closure (usually due to stent thrombosis or progression of an untreated dissection), transient coronary spasm, side branch occlusion, or distal embolization of atherosclerotic or thrombotic debris.

●Other patients have asymptomatic enzyme elevations indicative of procedural-related myocardial injury of a type 4 MI if the troponin level is above five times the upper reference limit, and there is clinical evidence of ischemia on the electrocardiogram or an event during or after PCI such as stent thrombosis.

●On occasion, periprocedural ischemia early after PCI may occur at the site of stenotic lesions not addressed at the time of the procedure.

Electrocardiographic changes are associated with a worse prognosis [10].

An important diagnostic consideration soon after PCI is the distinction between ischemic and nonischemic chest pain. Nonischemic chest pain is typically manifested at rest, without ECG changes or elevation of cardiac enzymes [11,12]. Most patients describe pain characteristics different from their typical angina (more localized and frequently pleuritic). This discomfort lasts for less than 72 hours in about 80 percent of patients, and less than two weeks in the remainder [11]. Overexpansion of the stent is thought to be responsible in most cases. (See "Periprocedural complications of percutaneous coronary intervention".)

Recurrent angina during the postoperative period after CABG is usually due to a technical problem with a graft or with early graft closure. It is therefore an indication for prompt catheterization with revascularization by PCI, if feasible. The diagnosis of recurrent ischemia may be difficult to make after CABG, since cardiac enzyme elevations occur as a result of the surgical procedure and since ECG changes may reflect postoperative pericardial inflammation. (See "Early noncardiac complications of coronary artery bypass graft surgery".)

Late angina — The delayed onset of angina (30 days or more after PCI) can reflect restenosis after PCI, graft stenosis after CABG, or progression of native disease. Affected patients typically present with the gradual and progressive return of effort angina. Prompt stress testing should be performed, since these patients are at increased risk. Stress radionuclide myocardial perfusion imaging or echocardiography is preferred over exercise ECG testing, since these modalities can document both the site and extent of ischemia. (See "Role of stress testing after coronary artery revascularization".)

While less common, some patients with recurrent ischemia present with unstable angina. Such patients should be evaluated with cardiac catheterization after adequate medical stabilization.

NSTEMI can also occur in patients with prior CABG; such patients have an increased rate of significant coronary events [13,14]. This issue was best illustrated in the PURSUIT trial of almost 11,000 patients with a non-ST-ACS, 12 percent (1134 patients) of whom had a prior CABG [13]. Patients with a prior CABG had a significantly higher mortality at 30 days (5.2 versus 3.4 percent without a prior CABG, adjusted hazard ratio 1.45) and six months (8 versus 6.6 percent, adjusted hazard ratio 1.32). This difference may reflect a greater degree of cardiac disease.

The older the saphenous vein graft, the higher the likelihood that unstable angina is due to a culprit lesion within the graft (figure 1) [15]. Grafts are more likely than native vessels to show total occlusion or thrombus, complications that are more refractory to medical therapy. Among patients who undergo PCI for saphenous vein graft disease, the development of restenosis is manifested by unstable angina presentation in as many as 25 percent of patients [16]. (See "Coronary artery bypass graft surgery: Prevention and management of vein graft stenosis".)

Absence of significant coronary disease — In different clinical trials and the CRUSADE registry, 9 to 14 percent of patients with a non-ST-elevation ACS have either normal vessels or no vessel with ≥50 to 60 percent stenosis on coronary angiography [17-23].

Possible mechanisms for the absence of significant coronary disease in these patients include coronary thrombosis with rapid clot lysis, vasospasm, macro- and microemboli, coagulopathy, vasculitis, small vessel disease, coronary microvascular dysfunction, and myocarditis. The absence of significant coronary disease has also been described in patients with stable angina (see "Microvascular angina: Angina pectoris with normal coronary arteries").

The characteristics of patients with ACS who have mild or no coronary disease was further examined in a study of 5767 patients with a non-ST-segment elevation ACS who were enrolled in the PURSUIT trial and who underwent angiography: 6 percent had mild coronary disease (>0 to ≤50 percent stenosis) and 6 percent had no disease [19]. The strongest independent predictors of insignificant coronary disease were:

●Younger age.

●Female sex; a greater prevalence of mild or no coronary disease in women was also noted in the TACTICS-TIMI 18 trial (17 versus 9 percent in men) [22].

●Absence of enrollment MI, prior angina, diabetes, or ST-segment depression.

Similar predictors of insignificant coronary disease, as well as lack of current/recent smoking, were found in the CRUSADE registry [23].

Patients with a non-ST-elevation ACS who do not have significant coronary disease have a better outcome than those with a culprit coronary lesion. (See "Risk stratification after non-ST elevation acute coronary syndrome", section on 'Absence of significant coronary disease'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Heart attack (Beyond the Basics)")

SUMMARY

●Acute coronary syndromes – Non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation MI (STEMI) are the two types of acute coronary syndromes (ACS). (See 'STEMI and NSTEMI' above.)

●Unstable angina – Unstable angina is further categorized based on patient characteristics at the time of presentation. New onset, rest, and early post-MI are examples. (See 'Unstable angina' above.)

●Myocardial infarction related to procedures – While these terms are most commonly applied to patients who develop symptoms during the course of their daily lives, they can also be used for patients who have undergone myocardial revascularization or noncardiac surgery. (See 'STEMI and NSTEMI' above and 'Postrevascularization angina' above.)