Síndrome coronario agudo

Acute Coronary Syndromes:Unstable Angina/Non-ST ElevationMyocardial Infarction

Rohit Bhatheja, MD

,Debabrata Mukherjee, MD, MS

a,b,

a

Gill Heart Institute, Division of Cardiovascular Medicine, University of Kentucky,900 South Limestone Street, 326 Wethington Building, Lexington, KY 40536-0200, USA

b

Department of Medicine, Division of Cardiovascular Medicine, University of Kentucky,900 South Limestone Street, 326 Wethington Building, Lexington, KY 40536-0200, USA

Coronary artery disease (CAD) affects 13.2 million Americans, including7.2 million individuals who have had a prior myocardial infarction (MI). In2003, the estimated direct and indirect health care cost of CAD was anastounding $142.5 billion[1]. The data are sobering, in that every 26 secondsan American suffers a coronary event; or every minute, someone dies fromCAD. More than 80% of those who die from CAD are more than 65 yearsof age[1]. Among patients who have CAD, acute coronary syndrome (ACS)is a major health problem affecting approximately 1.5 million individualsa year[1].Patients who have CAD may present as having stable angina or ACS.The spectrum of ACS includes ST-segment elevation MI, unstable angina(UA), and non–ST-segment elevation MI (NSTEMI). UA is characterizedby the clinical presentation of angina with or without ischemic ECG changes(ST segment depression or new T-wave inversion). NSTEMI is similar toUA but is characterized by positive biomarkers (troponin or creatinekinase-MB [CK-MB]) in the setting of angina or ECG changes. The presenceof myonecrosis as evident by positive cardiac markers portends a higher riskthan those presenting with just UA. UA and NSTEMI pathophysiologicallyandclinicallyarerelatedandinitiallymaybeindistinguishable,asbiomarkersmay not be elevated at presentation.

* Corresponding author. Gill Heart Institute, Division of Cardiovascular Medicine,University of Kentucky, 900 South Limestone Street, 326 Wethington Building, Lexington,KY 40536-0200.

E-mail address:

mukherjee@uky.edu(D. Mukherjee).0749-0704/07/$ - see front matter

Ó

criticalcare.theclinics.com

Crit Care Clin 23 (2007) 709–735

Pathogenesis of unstable angina/non–ST-segmentelevation myocardial infarction

Myocardial ischemia is the result of a mismatch between oxygen supplyand demand and, when prolonged, may lead to myocardial necrosis andinfarction. Patients who have UA/NSTEMI typically have obstructivecoronary disease; however, ACS may occur in the absence of signiﬁcantcoronary obstruction due to rupture of a nonobstructive plaque, coronaryvasospasm, or increased myocardial oxygen demand. Rupture of an athero-sclerotic plaque and subsequent formation of a thrombus usually is thetriggering event in the pathogenesis of most cases of ACS. Some othercauses may lead to coronary ischemia but are relatively rare (Table 1).Plaque rupture is precipitated by two main mechanisms

d

physical shearstress to the plaque or inflammatory mediators. Plaques that are prone torupture have a large lipid core, high macrophage and activatedT-lymphocyte density, low smooth muscle cell density, and a thin fibrouscap characterized by disorganized collagen. Rupture of the plaque shoulder,at its junction with the arterial wall, which is mechanically the weakestpoint, exposes the highly thrombogenic necrotic lipid core to platelets andcirculating inflammatory cells, stimulating the formation of acute thrombi[2,3].With the breakdown of the atherosclerotic plaque, the local milieubecomes prothrombotic because of the exposure of subendothelial matrixto the circulating blood. Platelet surface receptors recognize the vascularmatrix components (collagen, von Willebrand factor [vWF], vitronectin,and fibronectin), stimulating platelet adhesion via the glycoprotein (GP)Ib receptor and vWF. After this, there is platelet activation leading toa change in platelet morphology and degranulation of the alpha and densegranules, which release substrates, thromboxane A2[4], platelet factor 4,factor V[5], P-selectin, vWF, plasminogen activator inhibitor-1, fibrinogen,serotonin, and ADP[6]. These chemotactic and vasoactive substances leadto the recruitment and activation of GP IIb/IIIa receptors on the plateletsurface. The activated GP IIb/IIIa receptors are cross-linked by fibrinogen(or vWF), leading to platelet aggregation and formation of the white

Table 1Causes of unstable angina and non–ST-segment elevation myocardial infarction

a

1. Nonocclusive thrombus on pre-existing plaque2. Dynamic obstruction (coronary artery spasm or vasoconstriction)3. Progressive mechanical obstruction4. Inﬂammation or infection5. Secondary UA

a

These causes are not mutually exclusive; some patients have

R

2 causes.

From

Braunwald E. Unstable angina: an etiologic approach to management. Circulation1998;98:2220; with permission.710

BHATHEJA & MUKHERJEE

thrombus on the surface of the plaque[7]. Myocardial ischemia ensues, asthere is transient reduction in coronary blood flow. Further, temporaryarterial occlusion or microembolization of platelet-thrombus aggregatesand plaque material into the microcirculation leads to myocardial necrosis.Less common causes of an ACS include dynamic obstruction, progressiveatherosclerosis or restenosis, and inflammation. Noncardiac surgery orstressful events can cause a mismatch in myocardial oxygen demand andsupply, resulting in UA/NSTEMI. This may be caused by (1) increasedmyocardial oxygen demand (fever or thyrotoxicosis), (2) reduced myocar-dial oxygen delivery (anemia or hypoxemia), or (3) reduced coronary bloodflow (arrhythmia or hypotension). Although there may be coexisting CAD,it usually is stable and management should focus on the precipitatingcondition.

Presenting symptoms and signs

Typical angina is deﬁned as a deep, poorly localized chest or arm discom-fort that is reproducible with physical exertion or emotional stress and isrelieved within 5 minutes with rest or use of sublingual nitroglycerine.This characteristic association may be lacking in UA/NSTEMI. Thediscomfort usually is more severe and longer lasting, may occur at rest orat a lower level of physical exertion[8], and classically presents in one of the three ways (Table 2)[9]. Associated with the chest pain, in varying frequencies, are the symptomsof diaphoresis, dyspnea, nausea, and vomiting. Occasionally, patients(especially elderly and female) may have no discernable chest pain butmay present solely with varying components of jaw, arm or neck pain,and epigastric discomfort. Fatigue or, more commonly, a decrease inexercise threshold with worsening dyspnea on exertion, also may be thepresenting feature. When these nonchest pain symptoms clearly are relatedto physical or emotional stress and are relieved by nitroglycerin, they areconsidered anginal equivalents. Progression in frequency and intensity

Table 2Three types of presentations of unstable anginaRest angina Angina occurring at rest and prolonged,usually

O

20 minutesNew-onset angina New-onset angina of at least CCS

a

class III severityIncreasing angina Previously diagnosed angina that has becomedistinctly more frequent, longer in duration,or lower in threshold (ie, increased by

R

1CCS class to at least CCS class III severity)

a

Canadian Cardiac Society classiﬁcation.

Data from

Savonitto S, Cohen MG, Politi A, et al. Extent of ST-segment depression andcardiac events in non-ST-segment elevation acute coronary syndromes. Eur Heart J2005;26:2106–13.711

ACUTE CORONARY SYNDROMES

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