Non-ST segment elevation acute coronary syndromes.

Non-ST elevation (NSTE) acute coronary syndrome (ACS) is a common cardiovascular diagnosis and includes a range of presentations with myocardial ischemia from unstable angina (UA) to NSTE acute myocardial infarction (AMI). Recent statistics give a conservative estimate of more than 1.5 million hospital discharges with a primary or secondary diagnosis of ACS components in 2003. (1) This included nearly one million patients with AMI and 650,000 patients with UA. (1) It is estimated that NSTE AMI constitutes between 55 to 70% of all diagnoses of AMI on discharge. (2)

With improved understanding of the pathogenesis of ACS, significant advances have been made in the diagnosis and management of NSTE ACS as elegantly summarized by Martinez-Rumayor and Januzzi in this issue of the Journal. (3) Adherence to evidence-based therapeutic options, guided by effective risk stratification strategies, has been shown to improve the outcome of patients with NSTE ACS. However, several problems continue to prevent widespread application of appropriate and evidence-based diagnostic and therapeutic options. Clinical assessment, electrocardiography, and measurement of the serum levels of biomarkers of myocardial injury, such as troponin, only identify 25% of patients with ACS (4). On the other hand, many patients with chest pain of a noncardiac origin are admitted to the hospital and undergo unnecessary noninvasive or invasive tests. Unfortunately, about 5% of patients with ACS are discharged inadvertently from emergency departments after evaluation. (5) These patients are at a significant risk of death after discharge.

Following the diagnosis, adequate triage of patients with NSTE ACS is not often done in practice and many high-risk individuals are not properly evaluated and treated. In a recent report of 2939 patients in the Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE), high-risk patients were frequently admitted to nonmonitored beds and received less aggressive care than recommended by available guidelines. (6-8) Such underuse of evidence-based therapies has been reported in other studies that have looked at national practices among hundreds of hospitals, (9) despite the fact that adherence to American College of Cardiology/American Heart Association (ACC/AHA) guidelines results in improved outcomes. (10) It is also important to note that the proposed guidelines are not uniformly applied to both sexes and among all racial and ethnic groups. (11) The elderly, nonwhites, women and the uninsured are the least likely to receive guideline-based therapy. (12-14)

Patients can be risk stratified by evidence-based methods such as the TIMI (thrombolysis in myocardial infarction), (15) GRACE (Global Registry of Acute Coronary Events) risk score, (16) or PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin) risk scores. (17) These scores have provided excellent means of assessing risk of in-hospital and short-term mortality. (18) Based on the type and number of variables included in these scoring systems, the GRACE and PURSUIT scores provide an overview of the myocardial injury, whereas the TIMI risk score looks more at the extent of coronary artery disease and its instability. Use of one of the standardized criteria for risk stratification is important since accurate risk stratification is crucial in determining patients' disposition, types of pharmacotherapy, as well as the need for cardiac catheterization. A combination of troponin (marker of myocardial necrosis), N-terminal pro-B-type natriuretic peptide (an indicator of left ventricular systolic impairment) and C-reactive protein (an estimate of extent of systemic inflammation) may prove useful for outcome prediction in patients with NSTE ACS in the future. (19-21) Newer biomarkers are being studied for the detection of myocardial ischemia in the absence of necrosis and may be helpful in more specific evaluation of patients with ACS.

The role of cardiac imaging in the diagnosis, management and prognostication of NSTE ACS deserves special mention. It is anticipated that inclusion of cardiac imaging in clinical decision-making would improve detection of ACS in those with nondiagnostic or normal electrocardiograms and atypical presentation at admission. Absence of segmental wall motion abnormality on echocardiogram during active chest discomfort is a highly reliable indicator of nonischemic origin of symptoms. (22) Similarly, nuclear myocardial perfusion may improve triage of patients with suspected ACS. (23) The American Heart Association/American College of Cardiology echocardiography guidelines consider the early use of echocardiography in chest pain with a Class I indication. (24) Novel imaging techniques might allow for targeted visualization of potentially unstable plaques in the coronary circulation. (25)

Recent advances in medical therapy, such as the early use of clopidogrel, glycoprotein IIb/IIIa inhibitors and intensive lipid-lowering therapy, have been shown to improve the outcome in patients with ACS. (26,27) The different medications target the various pathologic processes involved in NSTE ACS, each offering an incremental benefit. Medications on the horizon like pioglitazones and matrix metalloproteinase inhibitors hold great promise.

Finally, it is important to recognize that in some instances, NSTE ACS may be precipitated by factors other than active, obstructive coronary lesions. Examples of the latter include severe anemia, noncardiogenic shock and the increaseingly recognized entity of transient left ventricular apical ballooning often triggered by emotional stress in older women. (28) Each of these conditions demand specific approaches to evaluation and management and may be aggravated by therapies routinely used for ACS.

Methods of diagnosis, triaging and treatment of NSTE ACS are changing at an exciting pace. In the meanwhile, familiarity with and application of the current guidelines will go a long way in reducing cardiovascular mortality, particularly given that a large number of NSTE ACS patients are managed by noncardiovascular physicians.

References

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25. Kolodgie FD, Petrov A, Virmani R, et al. Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque. Circulation 2003;108 (25):3134-9.

26. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.

27. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.

28. Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 2005;111:472-479.

Arun Kalyanasundaram, MD, MPH, James C. Blankenship, MD, and Jamshid Shirani, MD

From Geisinger Medical Center, Danville, PA.

Reprint Requests to Arun Kalyanasundaram, MD, MPH, Department of Cardiology, Geisinger Medical Center, 100 N. Academy Drive, Danville, PA 17822. Email: [e-mail]

Accepted March 27, 2006.