Medical Management of Acute Coronary Syndromes

Acute Coronary Syndrome

Definition

Acute coronary syndrome (ACS) refers to a constellation of clinical symptoms (usually including some type of chest discomfort) that is compatible with acute myocardial ischemia. Patients with suspected ACS may eventually prove to have a diagnosis other than ischemia. However, true ACS can be classified into the following clinical subsets:

1
ST-segment elevation myocardial infarction (STEMI).
2
Non–ST-segment elevation ACS (NSTEACS). This can be subcategorized as either unstable angina (UA) or non–ST-segment elevation MI (NSTEMI).

Typically UA presents in one of three ways: prolonged angina at rest (usually >20 minutes); new-onset Canadian Cardiovascular Society (CCS) class III angina; or increasing frequency, severity, and class of angina (increased ≥1 class from baseline and reaching CCS class III or higher). Frequently, UA is accompanied by ischemic electrocardiographic changes. NSTEMI is distinguished from UA by elevation of cardiac biomarkers suggestive of myocardial necrosis.

Epidemiology

Of 1,141,000 hospitalizations for ACS in 2010, approximately 70% were classified as myocardial infarction (MI) and 30% as UA. In the National Registry of Myocardial Infarction 4 (NRMI-4) and the Global Registry of Acute Coronary Events (GRACE), 29% of all MI patients and 27% of ACS patients were diagnosed with STEMI, respectively. Aggressive treatment of patients with NSTEMI and STEMI has yielded significant reductions in recurrent MI, cardiogenic shock, and in-hospital mortality. Nevertheless, up to 25% of opportunities to provide American College of Cardiology/American Heart Association (ACC/AHA) guideline-recommended care are still missed, and these omissions correlate with increased in-hospital mortality. The recommendations for treatment of NSTEACS in this chapter are therefore based on the 2007 American College of Cardiology Foundation (ACCF)/AHA guidelines for the management of patients with UA/NSTEMI with incorporation of the 2012 focused update. Recommended management of STEMI is based on the recently updated 2013 ACCF/AHA guidelines.

Pathophysiology

Plaque Rupture/Erosion

Advanced atherosclerotic coronary lesions are characterized by a lipid-rich necrotic core encapsulated by a fibrous cap composed of smooth muscle cells, collagen, and elastin. Mechanisms such as digestion of the fibrous cap by matrix metalloproteinases, loss of smooth muscle cells through apoptosis, and plaque hemorrhage can create a thin-cap fibroatheroma (TCFA) or “vulnerable plaque.” Rupture of a TCFA is the most common precipitant of ACS ( Fig. 57-1 ). Another mechanism of ACS involves superficial erosion of less advanced lesions, typically rich in proteoglycan matrix and smooth muscle cells. Both plaque rupture and erosion precipitate intracoronary thrombus formation via exposure of highly thrombogenic subendothelial collagen, necrotic material, and the lipid pool to von Willebrand factor (vWF) and platelets. In an autopsy study, plaque rupture or erosion with thrombus was noted in all patients who died of sudden cardiac death caused by ACS. Patients who had evidence of ruptured fibrous caps were older, were more often male, and had greater luminal area stenosis, calcification, and macrophage and T cell infiltration than patients who had plaque erosion.

FIGURE 57-1, Optical coherence tomographic images of disrupted plaque at culprit site in acute coronary syndrome. A, The thickness of ruptured fibrous cap is 40 µm, and crater formation is identified within lipid plaque in a ruptured plaque. B, Ulceration (yellow arrows) of thick fibrous cap is observed with white thrombus (green arrows) in plaque erosion.

Central Role of Platelets

Platelets are central to the pathogenesis of ACS. Platelets adhere to collagen and soluble vWF immobilized by exposed subendothelial collagen. This is followed by the release of adenosine diphosphate (ADP), thromboxane A2, and serotonin from platelet granules. Along with thrombin, collagen, and epinephrine, these factors promote platelet recruitment and “activation.” Activation involves platelet shape change, expression of pro-inflammatory ligands, and conversion of the glycoprotein (GP) IIb/IIIa receptor to its active form. Platelets then aggregate, by cross-linking with each other, via fibrinogen, which attaches to the active GP IIb/IIIa receptor. Thrombin, generated by tissue factor released from eroded plaque, results in formation of fibrin. Cross-linked platelets combine with fibrin to form an occlusive or subocclusive thrombus ( Fig. 57-2 ). Platelet activators amplify the process by promoting each other's release and induction of procoagulant activity.

FIGURE 57-2, Platelet plug formation. Vascular injury results in the exposure of collagen and von Willebrand factor (vWF) in the vessel wall. Circulating platelets adhere and form a monolayer of activated platelets on the collagen matrix, which drives the release of adenosine diphosphate (ADP) and thromboxane (Tx) A2 from the adherent platelets. Secretion of ADP and TxA2 promotes changes in platelet shape and amplification of platelet activation. Thrombin, generated by locally produced tissue factor (TF), is the most potent platelet activator. In the perpetuation phase, platelet contacts promote growth and stabilization of the platelet plug. GP, Glycoprotein.

Role of Inflammation

ACS is characterized by an acute inflammatory state. Platelets induce inflammation in endothelial cells, and inflamed intact or damaged endothelium is able to bind to platelets. Activated platelets secrete CD40 ligand, which binds to CD40 on endothelial cells. This process induces release of factors that stimulate expression of adhesion molecules, such as ICAM-1 on endothelial cells and P-selectin on platelets. The resultant platelet-monocyte-neutrophil interactions stimulate release of prothrombotic and proinflammatory factors, leukocyte attachment to the endothelium, and release of matrix metalloproteinase, leading to basement membrane degradation, thereby favoring plaque rupture.

Diagnosis

Clinical Manifestations

The most common presentation of ACS is some type of prolonged chest discomfort. One third to one half of MIs may be clinically silent. Women, older patients, patients with diabetics, and those with a history of heart failure are more likely to present without chest discomfort. The lack of typical symptoms may lead to delays in presentation to the hospital, establishment of a diagnosis, and institution of medical therapy and revascularization. Symptoms other than chest pain that may reflect ACS include unexplained dyspnea, nausea or indigestion, arrhythmias, syncope, back or arm pain, and fatigue. Unexplained dyspnea, without angina, is associated with more than twice the risk of death compared with patients with typical angina.

Electrocardiography

The earliest manifestations of myocardial ischemia on an electrocardiogram (ECG) are typically ST-segment and T-wave changes. New horizontal or down-sloping ST depression greater than 0.5 mm or T-wave inversion greater than 1 mm in two contiguous leads is suggestive of ischemia in patients with symptoms compatible with NSTEACS. ST-segment and T-wave changes can also be caused by left ventricular hypertrophy, pericarditis, early repolarization, or electrolyte imbalance. Therefore, comparison with available prior tracings and interpretation in the context of the clinical symptoms are recommended. The hallmark of STEMI is ST elevation in anatomically contiguous leads or a new left bundle branch block (LBBB). Of note, J point elevation of up to 2.5 mm can be noted in healthy men younger than 40 years.

Cardiac Biomarkers

The preferred biomarkers for diagnosis of MI are cardiac troponin (cTN) T or I. These proteins are part of the myocardial contractile apparatus and are highly sensitive and specific for the diagnosis of myocardial necrosis. However, it is now widely recognized that cTN elevation can occur in the setting of non-ischemic causes of myocardial necrosis or injury such as congestive heart failure (CHF), sepsis, renal failure, pulmonary embolism, or myocarditis. Another commonly used biomarker is CPK-MB, but this is much less specific because of its presence in skeletal muscle and other organs. It should therefore not be used as the sole test for diagnosis. The detection of a rise and/or fall of cardiac biomarkers, with at least one of the values exceeding the 99th percentile of a normal reference population (upper reference limit), in conjunction with symptoms of myocardial ischemia, ST-segment/T-wave changes, wall motion abnormalities on imaging, or presence of coronary thrombus are now required to meet the definition of MI.

Management of Non–ST-Segment Elevation Acute Coronary Syndrome

Initial Evaluation and Risk Stratification

A 12-lead ECG should be performed and evaluated by a physician within 10 minutes of patient's arrival to the emergency room. If the first tracing proves nondiagnostic in a patient with ongoing symptoms, serial ECGs should be done at 15- to 30-minute intervals for further assessment. Cardiac biomarkers, including cardiac-specific troponins T or I, CPK, and CPK-MB, should be obtained and repeated to include the time frame of 8 to 12 hours from onset of chest pain. If the initial assessment suggests a diagnosis of ACS, the next step is risk stratification. The TIMI risk score is the most commonly used risk stratification tool, assigning 1 point for each of seven variables (age 65 years or older, three or more risk factors for coronary artery disease [CAD], known coronary stenosis at least 50%, ST-segment deviation at presentation, two or more anginal events in the previous 24 hours, use of aspirin in the previous 7 days, and elevated serum cardiac biomarkers). Patients with a score of 3 or higher have an exponential increase in short-term ischemic events and benefitted from an early invasive strategy compared with a conservative strategy in the TACTICS-TIMI 18 trial. The GRACE score can also be used to predict hospital and 6-month mortality rates in patients with UA, NSTEMI, and STEMI.

Pharmacologic Management

Anti-ischemic Therapy

Table 57-1 shows selected recommendations for anti-ischemic therapy in patients with ACS.

TABLE 57-1

Selected Recommendations for Anti-ischemic Therapy

From Anderson JL, Adams CD, Antman EM, et al: ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 50:e1–e157, 2007.

Drug	Class I Recommendation	Class III Recommendation (Contraindicated)
Intravenous nitroglycerin	Administer for 48 hours for persistent ischemia, heart failure, or hypertension.	Systolic BP < 90 mm Hg HR < 50; HR > 100 in the absence of CHF Right ventricular infarction <24 hours of sildenafil <48 hours of tadalafil
Oral beta blockers	Initiate within 24 hours if no contraindications.	ANY sign of CHF Low output state Risk of cardiogenic shock * Advanced conduction disease ^† Active asthma/reactive airways
IV beta blockers (at any time)	Class IIa recommendation: May administer at any time for HTN if no contraindications.
Oral ACEIs	Administer within 24 hours for pulmonary congestion or LVEF < 40%. ARBs may be given in case of ACEI intolerance (provided no angioedema with ACEI).	Systolic BP < 100 mm Hg Do not administer IV ACEIs in the first 24 hours (risk of hypotension).
Non-dihydropyridine CCBs	Administer for ongoing/recurrent ischemia when beta blockers are contraindicated.	Do not administer immediate-release dihydropyridine CCB.
NSAIDs		Do not use because of increased risk of myocardial rupture, CHF, and reinfarction.

ACEIs, Angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; BP, blood pressure; CCBs, calcium channel blockers; CHF, congestive heart failure; HR, heart rate; HTN, hypertension; IV, intravenous; LVEF, left ventricular ejection fraction; NSAIDs, nonsteroidal anti-inflammatory drugs.

* Age > 70, sinus tachycardia > 100, systolic BP < 120 mm Hg.

† PR interval > 0.24 sec, second- or third-degree atrioventricular block.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here