Sunday, August 10, 2008

Unstable Angina

Unstable Angina and Non-ST-Elevation Myocardial Infarction
Harrison's Principle of Internal Medicine 17th Ed.2008

Patients with ischemic heart disease fall into two large groups: patients with chronic coronary artery disease (CAD) who most commonly present with stable angina and patients with acute coronary syndromes (ACSs). The latter group, in turn, is composed of patients with acute myocardial infarction (MI) with ST-segment elevation on their presenting electrocardiogram and those with unstable angina and non-ST-segment elevation MI (UA/NSTEMI). Every year in the United States, ~1.3 million patients are admitted to hospitals with UA/NSTEMI as compared with ~300,000 patients with acute STEMI. The relative incidence of UA/NSTEMI compared to STEMI appears to be increasing. Almost one-half of patients with UA/NSTEMI are women, while more than three-fourths of patients with STEMI are men.


The diagnosis of UA is based largely on the clinical presentation. Stable angina pectoris is characterized by chest or arm discomfort that may not be described as pain but is reproducibly associated with physical exertion or stress and is relieved within 5–10 min by rest and/or sublingual nitroglycerin. UA is defined as angina pectoris or equivalent ischemic discomfort with at least one of three features: (1) it occurs at rest (or with minimal exertion), usually lasting >10 min; (2) it is severe and of new onset (i.e., within the prior 4–6 weeks); and/or (3) it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than previously). The diagnosis of NSTEMI is established if a patient with the clinical features of UA develops evidence of myocardial necrosis, as reflected in elevated cardiac biomarkers.


UA/NSTEMI is most commonly caused by a reduction in oxygen supply and/or by an increase in myocardial oxygen demand superimposed on an atherosclerotic coronary plaque, with varying degrees of obstruction. Four pathophysiologic processes that may contribute to the development of UA/NSTEMI have been identified: (1) plaque rupture or erosion with superimposed nonocclusive thrombus, believed to be the most common cause—NSTEMI may occur with downstream embolization of platelet aggregates and/or atherosclerotic debris; (2) dynamic obstruction [e.g., coronary spasm, as in Prinzmetal's variant angina (p. 4)]; (3) progressive mechanical obstruction [e.g., rapidly advancing coronary atherosclerosis or restenosis following percutaneous coronary intervention (PCI)]; and (4) secondary UA related to increased myocardial oxygen demand and/or decreased supply (e.g., tachycardia, anemia). More than one of these processes may be involved.

Among patients with UA/NSTEMI studied at angiography, approximately 5% have left main stenosis, 15% have three-vessel CAD, 30% have two-vessel disease, 40% have single-vessel disease, and 10% have no critical coronary stenosis; some of the latter have Prinzmetal's variant angina (see below). The "culprit lesion" on angiography may show an eccentric stenosis with scalloped or overhanging edges and a narrow neck. Angioscopy may reveal "white" (platelet-rich) thrombi, as opposed to "red" thrombi, more often seen in patients with acute STEMI. Patients with UA/NSTEMI often have multiple plaques vulnerable to disruption.

Clinical Presentation

History and Physical Examination

The clinical hallmark of UA/NSTEMI is chest pain, typically located in the substernal region or sometimes in the epigastrium, that radiates to the neck, left shoulder, and left arm. This discomfort is usually severe enough to be considered painful. Anginal "equivalents" such as dyspnea and epigastric discomfort may also occur, and these appear to occur more often in women. The examination resembles that in patients with stable angina and may be unremarkable. If the patient has a large area of myocardial ischemia or a large NSTEMI, the physical findings can include diaphoresis, pale cool skin, sinus tachycardia, a third and/or fourth heart sound, basilar rales, and sometimes hypotension, resembling the findings of large STEMI.


In UA, ST-segment depression, transient ST-segment elevation, and/or T-wave inversion occur in 30–50% of patients, depending on the severity of the clinical presentation. In patients with the clinical features of UA, the presence of new ST-segment deviation, even of only 0.05 mV, is an important predictor of adverse outcome. T-wave changes are sensitive for ischemia but less specific, unless they are new, deep T-wave inversions (>0.3 mV).

Cardiac Biomarkers

Patients with UA who have elevated biomarkers of necrosis, such as CK-MB and troponin (a much more specific and sensitive marker of myocardial necrosis), are at increased risk for death or recurrent MI. Elevated levels of these markers distinguish patients with NSTEMI from those with UA. There is a direct relationship between the degree of troponin elevation and mortality. However, in patients without a clear clinical history of myocardial ischemia, minor troponin elevations have been reported and can be caused by congestive heart failure, myocarditis, or pulmonary embolism, or they may be false-positive readings. Thus, in patients with an unclear history, small troponin elevations may not be diagnostic of an ACS.

Diagnostic Evaluation

Approximately 6–7 million persons per year in the United States present to hospital emergency departments (EDs) with a complaint of chest pain or other symptoms suggestive of ACS. A diagnosis of an ACS is established in 20–25% of such patients. The first step in evaluating patients with possible UA/NSTEMI is to determine the likelihood that CAD is the cause of the presenting symptoms. The American College of Cardiology/American Heart Association (ACC/AHA) Guidelines include, among the factors associated with a high likelihood of ACS, a clinical history typical of ischemic discomfort, a history of established CAD by angiography, prior MI, congestive heart failure, new electrocardiographic (ECG) changes, or elevated cardiac biomarkers. Factors associated with an intermediate likelihood of ACS in patients with the clinical features of this condition but without the above high-risk factors are: age >70 years, male gender, diabetes mellitus, known peripheral arterial or cerebrovascular disease, and old ECG abnormalities.

Diagnostic Pathways

Four major diagnostic tools are used in the diagnosis of UA/NSTEMI in the ED: the clinical history, the ECG, cardiac markers, and stress testing. The goals are to (1) recognize or exclude MI (using cardiac markers), (2) evaluate for rest ischemia (chest pain at rest, serial or continuous ECGs), and (3) evaluate for significant CAD (using provocative stress testing). Typical pathways begin with assessment of the likelihood that the presenting symptoms are due to ischemia. Patients with a low likelihood of ischemia are usually managed with an ED-based critical pathway (which in some institutions is carried out in a "chest pain unit" (Fig. 1). Evaluation of such patients includes clinical monitoring for recurrent ischemic discomfort, serial ECGs, and cardiac markers, typically performed at baseline and at 4–6 h and 12 h after presentation. If new elevations in cardiac markers (CK-MB and/or troponin) or ECG changes are noted, the patient is admitted to the hospital. If the patient remains pain-free and the markers are negative, the patient may go on to stress testing. This may be performed as early as 6 h after presentation in the ED or chest pain center, or on an outpatient basis within 72 h. For most patients, standard treadmill ECG stress testing is used, but for patients with fixed abnormalities on the ECG (e.g., left bundle branch block), perfusion or echocardiographic imaging is used. For patients who cannot walk, pharmacologic stress is used. By demonstrating normal myocardial perfusion, sestamibi or thallium imaging can reduce unnecessary hospitalizations by excluding acute ischemia. CT angiography is used with increasing frequency to exclude obstructive CAD.

Figure 1. Diagnostic evaluation of patients presenting with suspected UA/NSTEMI. The first step is to assess the likelihood of coronary artery disease (CAD). Patients at high or intermediate likelihood are admitted to the hospital. Those with clearly atypical chest pain are sent home. Patients with a low likelihood of ischemia enter the pathway and are observed in a monitored bed in the emergency department (ED) or observation unit over a period of 6 h, and 12-lead electrocardiograms are performed if the patient has recurrent chest discomfort. A panel of cardiac markers (e.g., troponin and CK-MB) is drawn at baseline and 6 h later. If the patient develops recurrent pain, has ST-segment or T-wave changes, or has positive cardiac markers, he/she is admitted to the hospital and treated for UA/NSTEMI. If the patient has negative markers and no recurrence of pain, he/she is sent for exercise treadmill testing, with imaging reserved for patients with abnormal baseline electrocardiograms (e.g., left bundle branch block or left ventricular hypertrophy). If positive, the patient is admitted; if negative, the patient is discharged, with follow-up to his/her primary physician. ETT, exercise tolerance test; MI, myocardial infarction. [Adapted from CP Cannon, E Braunwald, in Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed, E Braunwald et al (eds). Philadelphia, Saunders, 2001.]

Risk Stratification and Prognosis

Patients with documented UA/NSTEMI exhibit a wide spectrum of early (30 days) risk of death, ranging from 1 to 10%, and of new or recurrent infarction of 3–10%. Assessment of "global risk" can be accomplished by clinical risk scoring systems such as that developed from in the Thrombolysis in Myocardial Infarction (TIMI) Trials, which includes seven independent risk factors: age >65 years, three or more risk factors for CAD, documented CAD at catheterization, development of UA/NSTEMI while on aspirin, more than two episodes of angina within the preceding 24 h, ST deviation >0.5 mm, and an elevated cardiac marker (Fig. 2). Other risk factors include diabetes mellitus, left ventricular dysfunction, and elevated levels of creatinine, atrial natriuretic peptides, and C-reactive protein.

Figure 2. The TIMI Risk Score for UA/NSTEMI, a simple but comprehensive clinical risk stratification score to identify increasing risk of death, myocardial infarction, or urgent revascularization to day 14. CAD, coronary artery disease; ASA, aspirin. (Adapted from Antman et al.)

Early risk assessment (especially using troponin, ST-segment changes, and/or a global risk scoring system) is useful both in predicting the risk of recurrent cardiac events and in identifying those patients who would derive the greatest benefit from antithrombotic therapies more potent than unfractionated heparin, such as low-molecular-weight heparin (LMWH) and glycoprotein (GP)IIb/IIIa inhibitors, and from an early invasive strategy. For example, in the TACTICS-TIMI 18 Trial, an early invasive strategy conferred a 40% reduction in recurrent cardiac events in patients with a positive troponin level, whereas no benefit was observed in those with a negative troponin level.

C-reactive protein, a marker of vascular inflammation, and B-type natriuretic peptide, a marker of increased myocardial wall tension, correlate independently with increased mortality (and, in some studies, recurrent cardiac events) in patients presenting with UA/NSTEMI. Multimarker strategies are now gaining favor both to define the pathophysiologic mechanisms underlying a given patient's presentation more fully and to stratify the patient's risk further.


Medical Treatment

Patients with UA/NSTEMI should be placed at bed rest with continuous ECG monitoring for ST-segment deviation and cardiac rhythm. Ambulation is permitted if the patient shows no recurrence of ischemia (discomfort or ECG changes) and does not develop a biomarker of necrosis for 12–24 h. Medical therapy involves simultaneous anti-ischemic treatment and antithrombotic treatment.

Anti-Ischemic Treatment

(Table 1) In order to provide relief and prevention of recurrence of chest pain, initial treatment should include bed rest, nitrates, and beta blockers.

Table 1 Drugs Commonly Used in Intensive Medical Management of Patients with Unstable Angina and Non-ST Elevation MI

Drug Category

Clinical Condition

When to Avoida



Administer intravenously when symptoms are not fully relieved with three sublingual nitroglycerin tablets and initiation of beta-blocker therapy


Patient receiving sildenafil or other PDE-5 inhibitor

5–10 µg/min by continuous infusion

Titrated up to 75–100 µg/min until relief of symptoms or limiting side effects (headache or hypotension with a systolic blood pressure <90>

Topical, oral, or buccal nitrates are acceptable alternatives for patients without ongoing or refractory symptoms

Beta blockersb

Unstable angina

PR interval (ECG) >0.24 s

2° or 3° atrioventricular block

Heart rate <60>

Blood pressure <90>


Left ventricular failure with congestive heart failure

Severe reactive airway disease


5-mg increments by slow (over 1–2 min IV administration)

Repeated every 5 min for a total initial dose of 15 mg

Followed in 1–2 h by 25–50 mg by mouth every 6 h

If a very conservative regimen is desired, initial doses can be reduced to 1–2 mg


Starting maintenance dose of 0.1 mg/kg per min IV

Titration in increments of 0.05 mg/kg per min every 10–15 min as tolerated by blood pressure until the desired therapeutic response has been obtained, limiting symptoms develop, or a dose of 0.20 mg/kg per min is reached

Optional loading dose of 0.5 mg/kg may be given by slow IV administration (2–5 min) for more rapid onset of action

Calcium channel blockers

Patients whose symptoms are not relieved by adequate doses of nitrates and beta blockers or in patients unable to tolerate adequate doses of one or both of these agents or in patients with variant angina

Pulmonary edema

Evidence of left ventricular dysfunction (for diltiazem or verapamil)

Dependent on specific agent

Morphine sulfate

Patients whose symptoms are not relieved after three serial sublingual nitroglycerin tablets or whose symptoms recur with adequate anti-ischemic therapy


Respiratory depression



2–5 mg IV dose

May be repeated every 5–30 min as needed to relieve symptoms and maintain patient comfort

aAllergy or prior intolerance is a contraindication for all categories of drugs listed in this chart.

bChoice of the specific agent is not as important as ensuring that appropriate candidates receive this therapy. If there are concerns about patient intolerance owing to existing pulmonary disease, especially asthma, left ventricular dysfunction, risk of hypotension or severe bradycardia, initial selection should favor a short-acting agent, such as propranolol or metoprolol or the ultra-short-acting agent esmolol. Mild wheezing or a history of chronic obstructive pulmonary disease should prompt a trial of a short-acting agent at a reduced dose (e.g., 2.5 mg IV metoprolol, 12.5 mg oral metoprolol, or 25 µg/kg per min esmolol as initial doses) rather than complete avoidance of beta-blocker therapy.

cMetoprolol and esmolol are two of several beta blockers that may be employed.

Note: Some of the recommendations in this guide suggest the use of agents for purposes or in doses other than those specified by the U.S. Food and Drug Adminstration. Such recommendations are made after consideration of concerns regarding nonapproved indications. Where made such recommendations are based on more recent clinical trials or expert consensus.

IV, intravenous; aPTT, activated partial thromboplastin time; ECG, electrocardiogram; 2°, second-degree; 3°, third-degree.

Source: Modified from E Braunwald et al: Circulation 1994;90:613–622.


Nitrates should first be given sublingually or by buccal spray (0.3–0.6 mg) if the patient is experiencing ischemic pain. If pain persists after three doses given 5 min apart, intravenous nitroglycerin (5–10 µg/min using nonabsorbing tubing) is recommended. The rate of the infusion may be increased by 10 µg/min every 3–5 min until symptoms are relieved or systolic arterial pressure falls to <100 style=""> can be used once the pain has resolved, or they may replace intravenous nitroglycerin when the patient has been pain-free for 12–24 h. The only absolute contraindications to the use of nitrates are hypotension or the use of sildenafil (Viagra) or other drugs in that class within the previous 24 h.

β-Adrenergic Blockade

These agents are the other mainstay of anti-ischemic treatment. Intravenous beta blockade followed by oral beta blockade targeted to a heart rate of 50–60 beats/min is recommended. Heart rate–slowing calcium channel blockers, e.g., verapamil or diltiazem, are recommended in patients who have persistent or recurrent symptoms after treatment with full-dose nitrates and beta blockers and in patients with contraindications to beta blockade. Additional medical therapy includes angiotensin-converting enzyme (ACE) inhibition and HMG-CoA reductase inhibitors (statins) for long-term secondary prevention.

If pain persists despite intravenous nitroglycerin and beta blockade, morphine sulfate, 1–5 mg intravenously, can be administered every 5–30 min as needed.

Antithrombotic Therapy

(Table 2) This is the other main component of treatment for UA/NSTEMI. Initial treatment should begin with the platelet cyclooxygenase inhibitor aspirin (Fig. 3). The typical initial dose is 325 mg daily, with lower doses (75–162 mg daily) recommended for long-term therapy. "Aspirin resistance" has been noted in research studies in 5–10% of patients and more frequently in patients treated with lower doses of aspirin. No clear guidelines are available regarding evaluation or treatment, but the use of higher doses of aspirin and/or a thienopyridine (clopidogrel) appears to be logical in this situation.

Table 2 Clinical Use of Antithrombotic Therapy

Oral Antiplatelet Therapy


Initial dose of 162–325 mg nonenteric formulation followed by 75–162 mg/d of an enteric or a nonenteric formulation

Clopidogrel (Plavix)

Loading dose of 300 mg followed by 75 mg/d

Intravenous Antiplatelet Therapy

Abciximab (ReoPro)

0.25 mg/kg bolus followed by infusion of 0.125 µg/kg per min (maximum 10 µg/min) for 12 to 24 h

Eptifibatide (Integrilin)

180 µg/kg bolus followed by infusion of 2.0 µg/kg per min for 72 to 96 h

Tirofiban (Aggrastat)

0.4 µg/kg per min for 30 min followed by infusion of 0.1 µg/kg per min for 48 to 96 h


Heparin (UFH)

Bolus 60–70 U/kg (maximum 5000 U) IV followed by infusion of 12–15 U/kg per h (initial maximum 1000 U/h) titrated to a PTT 50–70 s

Enoxaparin (Lovenox)

1 mg/kg SC every 12 h; the first dose may be preceded by a 30-mg IV bolus; renal adjustment to 1 mg/kg once daily if creatine Cl <>


2.5 mg SQ qd


Initial bolus intravenous bolus of 0.1 mg/kg and an infusion of 0.25 mg/kg per hour. Before PCI, an additional intravenous bolus of 0.5 mg/kg was administered, and the infusion was increased to 1.75 mg/kg per hour.

aOther LMWH exist beyond those listed.

Note: IV, intravenous; SC, subcutaneously; UFH, unfractionated heparin.

Source: Modified from E Braunwald et al: J Am Coll Cardiol 2000;36:970–1056.

Figure 3. Platelets initiate thrombosis at the site of a ruptured plaque with denuded endothelium: platelet adhesion occurs via (1) the GP 1b receptor in conjunction with von Willebrand factor. This is followed by platelet activation (2), which leads to a shape change in the platelet, degranulation of the alpha and dense granules, and expression of glycoprotein IIb/IIIa receptors on the platelet surface with activation of the receptor, such that it can bind fibrinogen. The final step is platelet aggregation (3), in which fibrinogen (or von Willebrand factor) binds to the activated GP IIb/IIIa receptors. Aspirin (ASA) and clopidogrel act to decrease platelet activation, whereas the GP IIb/IIIa inhibitors inhibit the final step of platelet aggregation. GP, glycoprotein. [Modified from CP Cannon, E Braunwald, in Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed, P Libby et al (eds). Philadelphia, Saunders, 2008.]

The thienopyridine clopidogrel, which blocks the platelet P2Y12 (adenosine) receptor (in combination with aspirin), was shown in the CURE trial to confer a 20% relative reduction in cardiovascular death, MI, or stroke, compared with aspirin alone in both low- and high-risk patients with UA/NSTEMI, but to be associated with a moderate (absolute 1%) increase in major bleeding, which is more common in patients who undergo coronary artery bypass grafting. Pretreatment with clopidogrel (a 300 or 600 mg loading dose, followed by 75 mg qd) has also been shown in three studies to reduce adverse outcomes associated with and following PCI and has a Class I, Grade A evidence recommendation in the PCI Guidelines. Continued benefit of long-term (~1 year) treatment with the combination of clopidogrel and aspirin has been observed both in patients treated conservatively and in those who underwent a PCI. This combination is recommended for all patients with UA/NSTEMI who are not at excessive risk for bleeding.

Four options are available for anticoagulation therapy to be added to aspirin and clopidogrel. Unfractionated heparin (UFH) is the mainstay of therapy. The LMWH enoxaparin has been shown in several studies to be superior to UFH in reducing recurrent cardiac events, especially in conservatively managed patients. The Factor Xa inhibitor fondaparinux is equivalent for early efficacy compared with enoxaparin but appears to have a lower risk of major bleeding and thus may have the best benefit risk ratio. However, UFH, LMWH, or a direct thrombin inhibitor such as bivalirudin should be used during cardiac catheterization or PCI. Preliminary data indicate that bivalirudin is equivalent (for both efficacy and safety) to either UFH or enoxaparin among patients treated with a GP IIb/IIIa inhibitor, but use of bivalirudin alone had less bleeding than the combination of a heparin and GP IIb/IIIa inhibitor in patients with UA/NSTEMI undergoing PCI.

Intravenous GP IIb/IIIa inhibitors have also been shown to be beneficial in treating UA/NSTEMI. For "upstream" management of high-risk patients in whom an invasive management is intended (i.e., initiating therapy when the patient first presents to the hospital), the small molecule inhibitors eptifibatide and tirofiban show benefit, while the monoclonal antibody abciximab appears not to be effective in patients treated conservatively, (i.e., in those not undergoing coronary angiography or PCI). However, abciximab has been shown to be beneficial in patients with UA/NSTEMI undergoing PCI, even among troponin positive patients pretreated with clopidogrel. The ACC/AHA Guidelines note that these agents can be started either in the ED or during PCI. As with all antithrombotic agents, bleeding is the most important adverse effect of antiplatelet drugs, especially their combination. Thus, patients with a history of bleeding must be screened carefully and given fewer antithrombotic agents.

Invasive versus Conservative Strategy

Multiple clinical trials have shown the benefit of an early invasive strategy in high-risk patients, i.e., patients with multiple clinical risk factors, ST-segment deviation, and/or positive biomarkers (Table 3). In this strategy, following treatment with anti-ischemic and antithrombotic agents, coronary arteriography is carried out within ~48 h of admission, followed by coronary revascularization (PCI or coronary artery bypass grafting), depending on the coronary anatomy.

Table 3 Class I Recommendations for Use of an Early Invasive Strategya

Class I (level of evidence: A) indications

Recurrent angina at rest/low-level activity despite Rx

Elevated TnT or TnI

New ST-segment depression

Rec. angina/ischemia with CHF symptoms, rales, MR

Positive stress test

EF <>

Decreased BP

Sustained VT

PCI <>

aAny one of the high-risk indicators.

Abbreviations: TnT, troponin T; TnI, troponin I; Rec, recurrent; CHF, congestive heart failure; MR, mitral regurgitation; EF, ejection fraction; BP, blood pressure; VT, ventricular tachycardia; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.

Source: E Braunwald et al: Circulation 106:1893, 2002.

In low-risk patients, the outcomes from an invasive strategy are similar to those obtained from a conservative strategy, which consists of anti-ischemic and antithrombotic therapy followed by "watchful waiting," in which coronary arteriography is carried out only if rest pain or ST-segment changes recur or there is evidence of ischemia on a stress test.

Long-Term Management

The time of hospital discharge is a "teachable moment" for the patient with UA/NSTEMI, when the physician can review and optimize the medical regimen. Risk factor modification is key, and the physician should discuss with the patient the importance of smoking cessation, achieving optimal weight, daily exercise following an appropriate diet, blood pressure control, tight control of hyperglycemia (for diabetic patients), and lipid management, as recommended for patients with chronic stable angina.

There is evidence of benefit with long-term therapy with five classes of drugs that are directed at different components of the atherothrombotic process. Beta blockers are appropriate anti-ischemic therapy and may help decrease triggers for MI. Statins (at a high dose, e.g., atorvastatin 80 mg/d) and ACE inhibitors are recommended for long-term plaque stabilization. Antiplatelet therapy, now recommended to be the combination of aspirin and clopidogrel for at least 9–12 months, with aspirin continued thereafter, prevents or reduces the severity of any thrombosis that would occur if a plaque does rupture. Thus, a multifactorial approach to long-term medical therapy is directed at preventing the various components of atherothrombosis. This therapy should be begun early, i.e. within a week of the event, whenever possible.

Observational registries have shown that patients with UA/NSTEMI at high risk, including women and the elderly as well as racial minorities, are less likely to receive evidence-based pharmacologic and interventional therapies with resultant poorer clinical outcomes and quality of life.


In 1959 Prinzmetal et al. described a syndrome of ischemic pain that occurs at rest but not usually with exertion and is associated with transient ST-segment elevation. This syndrome is due to focal spasm of an epicardial coronary artery, leading to severe myocardial ischemia. The exact cause of the spasm is not well defined, but it may be related to hypercontractility of vascular smooth muscle due to vasoconstrictor mitogens, leukotrienes, or serotonin. In some patients it is a manifestation of a vasospastic disorder and is associated with migraine, Raynaud's phenomenon, or aspirin-induced asthma.

Clinical and Angiographic Manifestations

Patients with variant angina are generally younger and have fewer coronary risk factors (with the exception of cigarette smoking) than patients with UA secondary to coronary atherosclerosis. The anginal discomfort is often extremely severe and has usually not progressed from a period of chronic stable angina. Cardiac examination is usually normal in the absence of ischemia.

The clinical diagnosis of variant angina is made with the detection of transient ST-segment elevation with rest pain. Many patients also exhibit multiple episodes of asymptomatic ST-segment elevation (silent ischemia). Small elevations of CK-MB and troponin may occur in patients with prolonged attacks of variant angina. Exercise testing in patients with variant angina is of limited value because the patients can demonstrate ST elevation, depression, or no ST changes.

Coronary angiography demonstrates transient coronary spasm as the diagnostic hallmark of Prinzmetal's angina. Atherosclerotic plaques, which do not usually cause critical obstruction, in at least one proximal coronary artery occur in the majority of patients, and in them spasm usually occurs within 1 cm of the plaque. Focal spasm is most common in the right coronary artery, and it may occur at one or more sites in one artery or in multiple arteries simultaneously. Ergonovine, acetylcholine, other vasoconstrictor medications, and hyperventilation have been used to provoke and demonstrate focal coronary stenosis to establish the diagnosis. Hyperventilation has also been used to provoke rest angina, ST-segment elevation, and spasm on coronary arteriography.

Prinzmetal's Variant Angina: Treatment

Nitrates and calcium channel blockers are the main treatments for patients with variant angina. Sublingual or intravenous nitroglycerin often abolishes episodes of variant angina promptly, and long-acting nitrates are useful in preventing recurrences. Calcium antagonists are extremely effective in preventing the coronary artery spasm of variant angina, and they should be prescribed in maximally tolerated doses. Similar efficacy rates have been noted among the various types of calcium antagonists. Prazosin, a selective α-adrenoreceptor blocker, has also been found to be of value in some patients, while aspirin may actually increase the severity of ischemic episodes. The response to beta blockers is variable. Coronary revascularization may be helpful in patients with variant angina who also have discrete, proximal fixed obstructive lesions.


Many patients with Prinzmetal's angina pass through an acute, active phase, with frequent episodes of angina and cardiac events during the first 6 months after presentation. Long-term survival at 5 years is excellent (~90–95%). Patients with no or mild fixed coronary obstruction tend to experience a more benign course than do patients with associated severe obstructive lesions. Nonfatal MI occurs in up to 20% of patients by 5 years. Patients with variant angina who develop serious arrhythmias during spontaneous episodes of pain are at a higher risk for sudden death. In most patients who survive an infarction or the initial 3–6-month period of frequent episodes, the condition stabilizes, and there is a tendency for symptoms and cardiac events to diminish with time.


Suhana Ansari said...

Chest pain is considered a chief symptom of heart related problems.
It can occur due to various causes such as heart attack, pulmonary embolism,
thoracic aortic dissection, oesophageal rupture, tension pneumothorax and cardiac tamponade.

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Darius said...

I am a medical resident on cardiology and I also wrote a few words about unstable angina.