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2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction

2011; Lippincott Williams & Wilkins; Volume: 123; Issue: 18 Linguagem: Inglês

10.1161/cir.0b013e318212bb8b

1524-4539

Jeffrey L. Anderson, Cynthia D. Adams, Elliott M. Antman, Charles R. Bridges, Robert M. Califf, Donald E. Casey, William E. Chavey, Francis M. Fesmire, Judith S. Hochman, Thomas N. Levin, A. Michael Lincoff, Eric D. Peterson, Pierre Théroux, Nanette K. Wenger, R. Scott Wright,

Coronary Interventions and Diagnostics

HomeCirculationVol. 123, No. 182011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUB2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial InfarctionA Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Jeffrey L. Anderson, Cynthia D. Adams, Elliott M. Antman, Charles R. Bridges, Robert M. Califf, Donald E. CaseyJr, William E. ChaveyII, Francis M. Fesmire, Judith S. Hochman, Thomas N. Levin, A. Michael Lincoff, Eric D. Peterson, Pierre Theroux, Nanette Kass Wenger and R. Scott Wright Jeffrey L. AndersonJeffrey L. Anderson , Cynthia D. AdamsCynthia D. Adams , Elliott M. AntmanElliott M. Antman , Charles R. BridgesCharles R. Bridges , Robert M. CaliffRobert M. Califf , Donald E. CaseyJrDonald E. CaseyJr , William E. ChaveyIIWilliam E. ChaveyII , Francis M. FesmireFrancis M. Fesmire , Judith S. HochmanJudith S. Hochman , Thomas N. LevinThomas N. Levin , A. Michael LincoffA. Michael Lincoff , Eric D. PetersonEric D. Peterson , Pierre TherouxPierre Theroux , Nanette Kass WengerNanette Kass Wenger and R. Scott WrightR. Scott Wright Originally published28 Mar 2011https://doi.org/10.1161/CIR.0b013e318212bb8bCirculation. 2011;123:e426–e579is corrected byCorrectionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 Smith Sidney C.Preamble (UPDATED)For new or updated text, view the 2011 Focused Update (http://circ.ahajournals.org/cgi/reprint/CIR.0b013e31820f2f3e). Text supporting unchanged recommendations has not been updated.It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The American College of Cardiology (ACC)/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop, update, or revise written recommendations for clinical practice.Experts in the subject under consideration have been selected from both organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered, as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review of data on efficacy and clinical outcomes will constitute the primary basis for preparing recommendations in these guidelines.The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid any actual, potential, or perceived conflict of interest that may arise as a result of an industry relationship or personal interest of a member of the Writing Committee. Specifically, all members of the Writing Committee, as well as peer reviewers of the document, were asked to provide disclosure statements of all such relationships that may be perceived as real or potential conflicts of interest. Writing Committee members are also strongly encouraged to declare a previous relationship with industry that may be perceived as relevant to guideline development. If a Writing Committee member develops a new relationship with industry during their tenure, they are required to notify guideline staff in writing. The continued participation of the Writing Committee member will be reviewed. These statements are reviewed by the parent task force, reported orally to all members of the Writing Committee at each meeting, and updated and reviewed by the Writing Committee as changes occur. Please refer to the methodology manual for ACC/AHA Guideline Writing Committees further description of relationships with industry policy, available on the ACC and AHA World Wide Web sites (http://www.acc.org/qualityandscience/clinical/manual/manual%/5Fi.htm and http://www.circ.ahajournals.org/manual/). See Appendix 1 for a list of Writing Committee member relationships with industry and Appendix 2 for a listing of peer reviewer relationships with industry that are pertinent to this guideline.These practice guidelines are intended to assist health care providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, and prevention of specific diseases or conditions. Clinical decision making should consider the quality and availability of expertise in the area where care is provided. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. These guideline recommendations reflect a consensus of expert opinion after a thorough review of the available, current scientific evidence and are intended to improve patient care.Patient adherence to prescribed and agreed upon medical regimens and lifestyles is an important aspect of treatment. Prescribed courses of treatment in accordance with these recommendations will only be effective if they are followed. Since lack of patient understanding and adherence may adversely affect treatment outcomes, physicians and other health care providers should make every effort to engage the patient in active participation with prescribed medical regimens and lifestyles.If these guidelines are used as the basis for regulatory/payer decisions, the ultimate goal is quality of care and serving the patients best interests. The ultimate judgment regarding care of a particular patient must be made by the health care provider and patient in light of all the circumstances presented by that patient. There are circumstances in which derivations from these guidelines are appropriate.The guidelines will be reviewed annually by the ACC/AHA Task Force on Practice Guidelines and will be considered current unless they are updated, revised, or sunsetted and withdrawn from distribution. The executive summary and recommendations are published in the August 7, 2007, issue of the Journal of the American College of Cardiology and August 7, 2007, issue of Circulation. The full-text guidelines are e-published in the same issue of the journals noted above, as well as posted on the ACC (www.acc.org) and AHA (www.americanheart.org) World Wide Web sites. Copies of the full text and the executive summary are available from both organizations.1. Introduction1.1. Organization of Committee and Evidence Review (UPDATED)For new or updated text, view the 2011 Focused Update. Text supporting unchanged recommendations has not been updated.The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease (CVD). Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition of non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease.The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 2002 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) to lowest (C). The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with UA/NSTEMI summarize both clinical evidence and expert opinion.Classification of RecommendationsThe schema for classification of recommendations and level of evidence is summarized in Table 1, which also illustrates how the grading system provides an estimate of the size of the treatment effect and an estimate of the certainty of the treatment effect.Table 1. Applying Classification of Recommendations and Level of Evidence† (UPDATED) (see the 2011 Focused Update)Table 1. Applying Classification of Recommendations and Level of Evidence† (UPDATED) (see the 2011 Focused Update)*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.†In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers' comprehension of the guidelines and will allow queries at the individual recommendation level.A complete list of the thousands of publications on various aspects of this subject is beyond the scope of these guidelines; only selected references are included. The Committee consisted of acknowledged experts in general internal medicine representing the American College of Physicians (ACP), family medicine from the American Academy of Family Physicians (AAFP), emergency medicine from the American College of Emergency Physicians (ACEP), thoracic surgery from the Society of Thoracic Surgeons (STS), interventional cardiology from the Society for Cardiovascular Angiography and Interventions (SCAI), and general and critical care cardiology, as well as individuals with recognized expertise in more specialized areas, including noninvasive testing, preventive cardiology, coronary intervention, and cardiovascular surgery. Both the academic and private practice sectors were represented. This document was reviewed by 2 outside reviewers nominated by each of the ACC and AHA and by 49 peer reviewers. These guidelines will be considered current unless the Task Force revises them or withdraws them from distribution.These guidelines overlap several previously published ACC/AHA practice guidelines, including the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction,1 the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention,2 the AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update,3 and the ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina.41.2. Purpose of These GuidelinesThese guidelines address the diagnosis and management of patients with UA and the closely related condition of NSTEMI. These life-threatening disorders are a major cause of emergency medical care and hospitalization in the United States. In 2004, the National Center for Health Statistics reported 1,565,000 hospitalizations for primary or secondary diagnosis of an acute coronary syndrome (ACS), 669,000 for UA and 896,000 for myocardial infarction (MI).5 The average age of a person having a first heart attack is 65.8 years for men and 70.4 years for women, and 43% of ACS patients of all ages are women. In 2003, there were 4,497,000 visits to US emergency departments (EDs) for primary diagnosis of CVD.5 The prevalence of this presentation of CVD ensures that many health care providers who are not cardiovascular specialists will encounter patients with UA/NSTEMI in the course of the treatment of other diseases, especially in outpatient and ED settings. These guidelines are intended to assist both cardiovascular specialists and nonspecialists in the proper evaluation and management of patients with an acute onset of symptoms suggestive of these conditions. These clinical practice guidelines also provide recommendations and supporting evidence for the continued management of patients with these conditions in both inpatient and outpatient settings. The diagnostic and therapeutic strategies that are recommended are supported by the best available evidence and expert opinion. The application of these principles with carefully reasoned clinical judgment reduces but does not eliminate the risk of cardiac damage and death in patients who present with symptoms suggestive of UA/NSTEMI.1.3. Overview of the Acute Coronary Syndromes1.3.1. Definition of TermsUnstable angina/NSTEMI constitutes a clinical syndrome subset of the ACS that is usually, but not always, caused by atherosclerotic CAD and is associated with an increased risk of cardiac death and subsequent MI. In the spectrum of ACS, UA/NSTEMI is defined by electrocardiographic (ECG) ST-segment depression or prominent T-wave inversion and/or positive biomarkers of necrosis (e.g., troponin) in the absence of ST-segment elevation and in an appropriate clinical setting (chest discomfort or anginal equivalent) (Table 2, Fig. 1). The results of angiographic and angioscopic studies suggest that UA/NSTEMI often results from the disruption or erosion of an atherosclerotic plaque and a subsequent cascade of pathological processes that decrease coronary blood flow. Most patients who die during UA/NSTEMI do so because of sudden death or the development (or recurrence) of acute MI. The efficient diagnosis and optimal management of these patients must derive from information readily available at the time of the initial clinical presentation. The clinical presentation of patients with a life-threatening ACS often overlaps that of patients subsequently found not to have CAD. Moreover, some forms of MI cannot always be differentiated from UA at the time of initial presentation.Table 2. Guidelines for the Identification of ACS Patients by ED Registration Clerks or Triage NursesRegistration/clerical staffPatients with the following chief complaints require immediate assessment by the triage nurse and should be referred for further evaluation:• Chest pain, pressure, tightness, or heaviness; pain that radiates to neck, jaw, shoulders, back, or 1 or both arms• Indigestion or "heartburn" nausea and/or vomiting associated with chest discomfort• Persistent shortness of breath• Weakness, dizziness, lightheadedness, loss of consciousnessTriage nursePatients with the following symptoms and signs require immediate assessment by the triage nurse for the initiation of the ACS protocol:• Chest pain or severe epigastric pain, nontraumatic in origin, with components typical of myocardial ischemia or MI: ∘ Central/substernal compression or crushing chest pain∘ Pressure, tightness, heaviness, cramping, burning, aching sensation∘ Unexplained indigestion, belching, epigastric pain∘ Radiating pain in neck, jaw, shoulders, back, or 1 or both arms• Associated dyspnea• Associated nausea and/or vomiting• Associated diaphoresisIf these symptoms are present, obtain stat ECG.Medical historyThe triage nurse should take a brief, targeted, initial history with an assessment of current or past history of:• CABG, PCI, CAD, angina on effort, or MI• NTG use to relieve chest discomfort• Risk factors, including smoking, hyperlipidemia, hypertension, diabetes mellitus, family history, and cocaine or methamphetamine use• Regular and recent medication useThe brief history must not delay entry into the ACS protocol.Special considerationsWomen may present more frequently than men with atypical chest pain and symptoms.Diabetic patients may have atypical presentations due to autonomic dysfunction.Elderly patients may have atypical symptoms such as generalized weakness, stroke, syncope, or a change in mental status.Adapted from National Heart Attack Alert Program. Emergency Department: rapid identification and treatment of patients with acute myocardial infarction. Bethesda, MD: US Department of Health and Human Services. US Public Health Service. National Institutes of Health. National Heart, Lung and Blood Institute, September 1993. NIH Publication No. 93-32786ACS = acute coronary syndrome; CABG = coronary artery bypass graft surgery; CAD = coronary artery disease; ECG = electrocardiogram; ED = emergency department; MI = myocardial infarction; NTG = nitroglycerin; PCI = percutaneous coronary intervention.Download figureDownload PowerPointFigure 1. Acute Coronary Syndromes. The top half of the figure illustrates the chronology of the interface between the patient and the clinician through the progression of plaque formation, onset, and complications of UA/NSTEMI, along with relevant management considerations at each stage. The longitudinal section of an artery depicts the "timeline" of atherogenesis from (1) a normal artery to (2) lesion initiation and accumulation of extracellular lipid in the intima, to (3) the evolution to the fibrofatty stage, to (4) lesion progression with procoagulant expression and weakening of the fibrous cap. An acute coronary syndrome (ACS) develops when the vulnerable or high-risk plaque undergoes disruption of the fibrous cap (5); disruption of the plaque is the stimulus for thrombogenesis. Thrombus resorption may be followed by collagen accumulation and smooth muscle cell growth (6). After disruption of a vulnerable or high-risk plaque, patients experience ischemic discomfort that results from a reduction of flow through the affected epicardial coronary artery. The flow reduction may be caused by a completely occlusive thrombus (bottom half, right side) or subtotally occlusive thrombus (bottom half, left side). Patients with ischemic discomfort may present with or without ST-segment elevation on the ECG. Among patients with ST-segment elevation, most (thick white arrow in bottom panel) ultimately develop a Q-wave MI (QwMI), although a few (thin white arrow) develop a non–Q-wave MI (NQMI). Patients who present without ST-segment elevation are suffering from either unstable angina (UA) or a non–ST-segment elevation MI (NSTEMI) (thick red arrows), a distinction that is ultimately made on the basis of the presence or absence of a serum cardiac marker such as CK-MB or a cardiac troponin detected in the blood. Most patients presenting with NSTEMI ultimately develop a NQMI on the ECG; a few may develop a QwMI. The spectrum of clinical presentations ranging from UA through NSTEMI and STEMI is referred to as the acute coronary syndromes. This UA/NSTEMI guideline, as diagrammed in the upper panel, includes sections on initial management before UA/NSTEMI, at the onset of UA/NSTEMI, and during the hospital phase. Secondary prevention and plans for long-term management begin early during the hospital phase of treatment. *Positive serum cardiac marker. Modified with permission from Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001;104:365;(7) © 2001 Lippincott, Williams & Wilkins; The Lancet, 358, Hamm CW, Bertrand M, Braunwald E. Acute coronary syndrome without ST elevation: implementation of new guidelines, 1533–8. Copyright 2001, with permission from Elsevier8; and Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000;83:361–6.9 © 2000 Lippincott, Williams & Wilkins. CK-MB = MB fraction of creatine kinase; Dx = diagnosis; ECG = electrocardiogram."Acute coronary syndrome" has evolved as a useful operational term to refer to any constellation of clinical symptoms that are compatible with acute myocardial ischemia (Fig. 1). It encompasses MI (ST-segment elevation and depression, Q wave and non-Q wave) and UA. These guidelines focus on 2 components of this syndrome: UA and NSTEMI. In practice, the term "possible ACS" is often assigned first by ancillary personnel, such as emergency medical technicians and triage nurses, early in the evaluation process. A guideline of the National Heart Attack Alert Program6 summarizes the clinical information needed to make the diagnosis of possible ACS at the earliest phase of clinical evaluation (Table 2). The implication of this early diagnosis for clinical management is that a patient who is considered to have an ACS should be placed in an environment with continuous ECG monitoring and defibrillation capability, where a 12-lead ECG can be obtained expeditiously and definitively interpreted, ideally within 10 min of arrival in the ED. The most urgent priority of early evaluation is to identify patients with ST-elevation MI (STEMI) who should be considered for immediate reperfusion therapy and to recognize other potentially catastrophic causes of patient symptoms, such as aortic dissection.Patients diagnosed as having STEMI are excluded from management according to these guidelines and should be managed as indicated according to the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction.1,10 Similarly, management of electrocardiographic true posterior MI, which can masquerade as NSTEMI, is covered in the STEMI guidelines.1 The management of patients who experience periprocedural myocardial damage, as reflected in the release of biomarkers of necrosis, such as the MB isoenzyme of creatine kinase (CK-MB) or troponin, also is not considered here.Patients with MI and with definite ischemic ECG changes for whom acute reperfusion therapy is not suitable should be diagnosed and managed as patients with UA. The residual group of patients with an initial diagnosis of ACS will include many patients who will ultimately be proven to have a noncardiac cause for the initial clinical presentation that was suggestive of ACS. Therefore, at the conclusion of the initial evaluation, which is frequently performed in the ED but sometimes occurs during the initial hours of inpatient hospitalization, each patient should have a provisional diagnosis of 1) ACS (Fig. 1), which in turn is classified as a) STEMI, a condition for which immediate reperfusion therapy (fibrinolysis or percutaneous coronary intervention [PCI]) should be considered, b) NSTEMI, or c) UA (definite, probable, or possible); 2) a non-ACS cardiovascular condition (e.g., acute pericarditis); 3) a noncardiac condition with another specific disease (e.g., chest pain secondary to esophageal spasm); or 4) a noncardiac condition that is undefined. In addition, the initial evaluation should be used to determine risk and to treat life-threatening events.In these guidelines, UA and NSTEMI are considered to be closely related conditions whose pathogenesis and clinical presentations are similar but of differing severity; that is, they differ primarily in whether the ischemia is severe enough to cause sufficient myocardial damage to release detectable quantities of a marker of myocardial injury, most commonly troponin I (TnI), troponin T (TnT), or CK-MB. Once it has been established that no biomarker of myocardial necrosis has been released (based on 2 or more samples collected at least 6 h apart, with a reference limit of the 99th percentile of the normal population),11 the patient with ACS may be considered to have experienced UA, whereas the diagnosis of NSTEMI is established if a biomarker has been released. Markers of myocardial injury can be detected in the bloodstream with a delay of up to several hours after the onset of ischemic chest pain, which then allows the differentiation between UA (i.e., no biomarkers in circulation; usually transient, if any, ECG changes of ischemia) and NSTEMI (i.e., elevated biomarkers). Thus, at the time of presentation, patients with UA and NSTEMI can be indistinguishable and therefore are considered together in these guidelines.1.3.2. Pathogenesis of UA/NSTEMIThese conditions are characterized by an imbalance between myocardial oxygen supply and demand. They are not a specific disease, such as pneumococcal pneumonia, but rather a syndrome, analogous to hypertension. A relatively few nonexclusive causes are recognized12 (Table 3).Table 3. Causes of UA/NSTEMI*Thrombus or thromboembolism, usually arising on disrupted or eroded plaque• Occlusive thrombus, usually with collateral vessels†• Subtotally occlusive thrombus on pre-existing plaque• Distal microvascular thromboembolism from plaque-associated thrombusThromboembolism from plaque erosion• Non-plaque-associated coronary thromboembolismDynamic obstruction (coronary spasm‡ or vasoconstriction) of epicardial and/or microvascular vesselsProgressive mechanical obstruction to coronary flowCoronary arterial inflammationSecondary UACoronary artery dissection§*These causes are not mutually exclusive; some patients have 2 or more causes.†DeWood MA, Stifter WF, Simpson CS, et al. Coronary arteriographic findings soon after non-Q-wave myocardial infarction. N Engl J Med 1986;315:417–23.13‡May occur on top of an atherosclerotic plaque, producing missed-etiology angina or UA/NSTEMI.§Rare. Modified with permission from Braunwald E. Unstable angina: an etiologic approach to management. Circulation 1998;98:2219–22.12UA = unstable angina; UA/NSTEMI = unstable angina/non-ST-elevation myocardial infarction.The most common mechanisms involve an imbalance that is caused primarily by a reduction in oxygen supply to the myocardium, whereas with the fifth mechanism noted below, the imbalance is principally due to increased myocardial oxygen requirements, usually in the presence of a fixed, restricted oxygen supply: The most common cause of UA/NSTEMI is reduced myocardial perfusion that results from coronary artery narrowing caused by a thrombus that developed on a disrupted atherosclerotic plaque and is usually nonocclusive. Microembolization of platelet aggregates and components of the disrupted plaque are believed to be responsible for the release of myocardial markers in many of these patients. An occlusive thrombus/plaque also can cause this syndrome in the presence of an extensive collateral blood supply.The most common underlying molecular and cellular pathophysiology of disrupted atherosclerotic plaque is arterial inflammation, caused by noninfectious (e.g., oxidized lipids) and, possibly, infectious stimuli, which can lead to plaque expansion and destabilization, rupture or erosion, and thrombogenesis. Activated macrophages and T lymphocytes located at the shoulder of a plaque increase the expression of enzymes such as metalloproteinases that cause thinning and disruption of the plaque, which in turn can lead to UA/NSTEMI.A less common cause is dynamic obstruction, which may be triggered by intense focal spasm of a segment of an epicardial coronary artery (Prinzmetals angina) (see Section 6.7). This local spasm is caused by hypercontractility of vascular smooth muscle and/or by endothelial dysfunction. Large-vessel spasm can occur on top of obstructive or destabilized plaque, resulting in angina of "mixed" origin or UA/NSTEMI. Dynamic coronary obstruction can also be caused by diffuse microvascular dysfunction; for example, due to endothelial dysfunction or the abnormal constriction of small intramural resistance vessels. Coronary spasm also is the presumed mechanism underlying cocaine-induced UA/NSTEMI.A third cause of UA/NSTEMI is severe narrowing without spasm or thrombus. This occurs in some patients with progressive atherosclerosis or with restenosis after a PCI.A fourth cause of UA/NSTEMI is coronary artery dissection (e.g., as a cause of ACS in peripartal women).The fifth mechanism is secondary UA, in which the precipitating condition is extrinsic to the coronary arterial bed. Patients with secondary UA usually, but not always, have underlying coronary atherosclerotic narrowing that limits myocardial perfusion, and they often have chronic stable angina. Secondary UA is precipitated by conditions that 1) increase myocardial oxygen requirements, such as fever, tachycardia, or thyrotoxicosis; 2) reduce coronary blood flow, such as hypotension; or 3) reduce myocardial oxygen delivery, such as anemia or hypoxemia.These causes of UA/NSTEMI are not mutually exclusive.1.3.3. Presentations of UA and NSTEMIThere are 3 principal presentations of UA: 1) rest angina (angina co