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J Am Coll Cardiol, 1999; 33:1756-1824 © 1999 by the American College of Cardiology Foundation |
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Table of contents |
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 Top Table of contents PreambleI. IntroductionII. General considerations...III. Coronary angiography for...Appendix AAppendix BAppendix CAppendix DAppendix EReferences |
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Preamble |
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TopTable of contentsPreambleI. IntroductionII. General considerations...III. Coronary angiography for...Appendix AAppendix BAppendix CAppendix DAppendix EReferences |
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The American College of Cardiology (ACC) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. This effort is directed by the ACC/AHA Task Force on Practice Guidelines. Its charge is to develop and revise practice guidelines for important cardiovascular diseases and procedures. Experts in the subject under consideration are selected from both organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups where appropriate. Writing groups 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. 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.
The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid any actual or potential conflicts of interest that might arise as a result of an outside relationship or personal interest of a member of the writing panel. Specifically, all members of the writing panel are asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest. These statements are reviewed by the parent task force, reported orally to all members of the writing panel at the first meeting, and updated yearly and as changes occur.
These practice guidelines are intended to assist physicians in clinical decision making by describing a range of acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the physician and patient in light of all of the circumstances presented by the patient.
The executive summary and recommendations are published in the May 4, 1999, issue of Circulation. The full text is published in the Journal of the American College of Cardiology. Reprints of both the full text and the executive summary and recommendations are available from both organizations.
These guidelines have been officially endorsed by the Society for Cardiac Angiography and Interventions.
James L. Ritchie, MD, FACC, Chair, ACC/AHA Task Force on Practice Guidelines
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I. Introduction |
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TopTable of contentsPreambleI. IntroductionII. General considerations...III. Coronary angiography for...Appendix AAppendix BAppendix CAppendix DAppendix EReferences |
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The English-language medical literature was searched for the 10 years preceding development of the guidelines. The searches yielded >1,600 references that the committee reviewed for relevance. Evidence relative to the use of coronary angiography was compiled and evaluated by the committee. Whereas randomized trials are often available for reference in the development of treatment guidelines, randomized trials regarding the use of diagnostic procedures such as coronary angiography are rarely available (2). For development of these guidelines, when coronary angiography was a necessary procedure in describing a clinical subset or in choosing a course of treatment and that therapy was shown to have an advantage for the patient, especially in the context of a randomized trial, then the indication for angiography was given greater consideration than indications cited in less-rigorous evaluations of data.
This document uses the ACC/AHA classifications of Class I, II, or III. These classes summarize the indications for coronary angiography as follows:
Class I:
Conditions for which there is evidence for and/or general agreement that the procedure is useful and effective.
Class II:
Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of performing the procedure.
Class IIa:
Weight of evidence/opinion is in favor of usefulness/efficacy.
Class IIb:
Usefulness/efficacy is less well established by evidence/opinion.
Class III:
Conditions for which there is evidence and/or general agreement that the procedure is not useful/effective and in some cases may be harmful.
The weight of evidence in support of the recommendation for each listed indication is presented as follows:
Level of Evidence A:
The presence of multiple randomized clinical trials.
Level of Evidence B:
The presence of a single randomized trial or nonrandomized studies.
Level of Evidence C:
Expert consensus.
This document was reviewed by 6 outside reviewers, 3 nominated by the ACC and 3 by the AHA, as well as by reviewers nominated by the Society for Cardiac Angiography and Interventions (SCAI), the American College of Physicians (ACP), and the American Academy of Family Physicians (AAFP). The document will be reevaluated two years after the date of publication and yearly thereafter and considered current unless the task force publishes a further revision or withdrawal.
Recommendations concerning the staffing and equipment of cardiac catheterization laboratories are beyond the scope of this report and can be found elsewhere (3). Statements concerning the use and safety of ambulatory and outpatient cardiac catheterization procedures and the performance of cardiac catheterization in laboratories without on-site cardiac surgical backup are available (3).
This report is not intended to provide strict indications or contraindications for coronary angiography because, in the individual patient, multiple other considerations may be relevant, including the family setting, occupational needs, and individual lifestyle preferences. Rather, the report is intended to provide general guidelines that may be helpful to the practitioner.
For these guidelines, coronary angiography is defined as the radiographic visualization of the coronary arteries after direct opacification with contrast media. After a discussion of general considerations regarding coronary angiography, the applications of coronary angiography in specific disease states are presented and discussed in the body of this report. Recommendations are made for appropriate use of coronary angiography in these conditions. After the body of the guidelines, appendices are presented that include a discussion of special considerations regarding coronary angiography; a discussion of alternative imaging modalities, including intravascular coronary ultrasound, intracoronary Doppler ultrasound, and coronary angioscopy; definitions of angiographic coronary anatomy and the Canadian Cardiovascular Society (CCS) classification of angina; and the desired elements of a coronary angiographic report.
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II. General considerations regarding coronary angiography |
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TopTable of contentsPreambleI. IntroductionII. General considerations...III. Coronary angiography for...Appendix AAppendix BAppendix CAppendix DAppendix EReferences |
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Coronary anatomy varies, and several nomenclatures have been used to describe the anatomy and extent of disease. Currently, the most commonly used is that described in the Coronary Artery Surgery Study (CASS), recently modified by the Bypass Angioplasty Revascularization Investigation (BARI) Study Group (6,7). These schemes acknowledge three major coronary arteries: the left anterior descending (LAD), the circumflex, and the right coronary artery, with right-dominant, balanced, or left-dominant circulations. A diagram and description of the coronary anatomy are shown in Appendix A. In this nomenclature, the coronary tree is divided into 29 segments with the ability to account for anatomic variations, such as a large branching obtuse marginal of the circumflex. The extent of disease is usually defined as one-vessel, two-vessel, three-vessel, or left main disease, with significant disease taken to mean the presence of a stenosis of 
50% diameter reduction, although many angiographers define a significant stenosis as being narrowed by 70% diameter reduction. Other methods to quantify the extent of disease, such as an obstructive coronary artery score or myocardial jeopardy score, have also been used and have been shown to be predictive of long-term outcome (8–10). Although coronary lesions that reduce luminal diameter <50% are considered hemodynamically insignificant, they are not clinically benign. These lesions may progress either acutely or chronically, and patients with nonsignificant obstructions have significantly more cardiovascular events during follow-up than those with truly normal coronary angiograms (11).
B. Purpose. The purpose of coronary angiography is to define coronary anatomy and the degree of luminal obstruction of the coronary arteries (4,5). Information obtained from the procedure includes identification of the location, length, diameter, and contour of the coronary arteries; the presence and severity of coronary luminal obstruction(s); characterization of the nature of the obstruction (including the presence of atheroma, thrombus, dissection, spasm, or myocardial bridging), and an assessment of blood flow. In addition, the presence and extent of coronary collateral vessels can be assessed.
Coronary angiography remains the standard for assessment of anatomic coronary disease, because no other currently available test can accurately define the extent of coronary luminal obstruction. Because the technique can only provide information about abnormalities that narrow the lumen, it is limited in its ability to accurately define the etiology of the obstruction or detect the presence of nonobstructive atherosclerotic disease. A more detailed description of the limitations of coronary angiography and the use of alternative imaging modalities is contained in Appendices B and C. Despite these and other limitations, coronary angiography is the only method currently available for defining the details of the entire coronary endoluminal vascular anatomy, and it provides the reference standard against which other tests are compared. The procedure is associated with a small but definable risk (Table 1) and is relatively expensive. As such, the physician must make reasoned decisions on its use based on the anticipated clinical benefit versus the risks and costs of the procedure.
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C. Morbidity and mortality. Although the incidences of significant morbidity and mortality are low, coronary angiography may cause serious complications and, thus, the benefits must justify the risks. A 1990 survey by the SCAI indicated that the total risk of all major complications from coronary angiography is <2% (Table 1) (13). Although serious complications are rare, certain groups of patients are at higher risk. The stability of the patient before the procedure significantly influences outcome, with the highest risk associated with patients who undergo the procedure in an emergency setting. Patients with critical left main coronary stenosis have a >2-fold higher risk of complications from coronary angiography, and care is required when procedures are performed on patients in whom left main lesions are suspected (14). Another study from the SCAI registry database identified 12 predictors of major complications after cardiac catheterization (Table 2) (15). Patients in a moribund condition before the procedure had the highest risk (10-fold), and shock, acute myocardial infarction (MI), renal insufficiency, and cardiomyopathy increased the risk of complications. Despite the higher risk of complications in these patients, the risk-benefit ratio may still favor performance of coronary angiography, because the information obtained may be invaluable in making appropriate decisions about therapeutic interventions. Although age is not shown in Table 2, it is generally considered to be a significant factor related to cardiovascular mortality after coronary angiography. The skill and experience of the operator, the catheterization laboratory staff, and the preprocedure and postprocedure staff are also important factors in reducing complications. Operator experience is clearly related to lower complication rates. This fact has led one national organization to recommend a minimum operator volume of 150 diagnostic catheterizations per year (16). This is also true for coronary angioplasty facilities. Recent studies have suggested that laboratory volumes of >200 angioplasty cases per year and 75 cases per operator are necessary to minimize complications and maximize success (17–19). A recent ACC expert consensus document discusses the issue in more detail (19). Many catheterization laboratories are located in hospitals without on-site cardiac surgery facilities. Although there is no evidence that outcomes are worse in these laboratories, if ad hoc angioplasty is anticipated, or the patient is likely to need urgent or emergency surgery after angiography, transfer to a hospital that can provide both diagnostic and therapeutic procedures should be strongly considered.
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Major reactions to angiographic contrast medium are rare, but in patients with a known anaphylactoid reaction to contrast media, the risk of subsequent reaction may be as high as 50% (30,31). Patients with a known cardiovascular disorder who are taking a beta-blocker are at increased risk for contrast reactions (31). Observational studies suggest that pretreatment of a reaction-prone patient with a corticosteroid and/or a H1 and H2 histamine blocker can reduce this risk to an acceptable level when the indications for the procedure justify its need (30–33). However, only one randomized trial of corticosteroids has been conducted. In that study, a two-dose corticosteroid regimen (before and after angiography) significantly reduced the incidence of anaphylactoid reactions (34). In addition, the use of nonionic contrast may reduce the incidence of subsequent anaphylactic reactions (32,34).
The presence of uncompensated congestive heart failure increases the chance of major complications after coronary angiography. Although limited data are available to accurately define its risk, treatment of the heart failure before coronary angiography is advised. In addition, it is advisable to limit contrast volume and use nonionic contrast media in patients with poor left ventricular function to reduce the adverse hemodynamic effects of contrast media.
It should be recognized that most of the relative contraindications may be temporary or reversible, and therefore if the procedure can be safely delayed, risks may be lowered. In high-risk patients and patients with relative contraindications, the procedure should not be performed in an outpatient setting. The guidelines for outpatient cardiac catheterizations are described in more detail in the "ACC/AHA Guidelines for Cardiac Catheterization and Cardiac Catheterization Laboratories" (3).
E. Utilization.
In 1993, cardiac catheterization was the second most frequently performed in-hospital operative procedure in the U.S. and the most frequently performed procedure in patients older than 65 years of age (35). In that year, 
1,078,000 inpatient cardiac catheterization procedures were performed (36). It is estimated that an additional 668,000 patients received cardiac catheterization as outpatients (John Goodman and Associates, 1996, personal oral communication). There are no similar data specific for use of coronary angiography, but in adult patients, cardiac catheterization includes coronary angiography in most cases.
Approximately 48% of cardiac catheterizations are now performed in the elderly, who are defined as 65 years of age (35). Men are more likely to have cardiac catheterization than women. There are also racial differences in use of coronary angiography in the U.S. In 1993, cardiac catheterization was performed in 349 of 100,000 patients in the white population, 235 of 100,000 in the black population, and 316 of 100,000 in other races.
The use of cardiac catheterization continues to grow. According to data from Medicare (37), the combined number of inpatient left-heart catheterizations and right- and left-heart catheterizations, ie, those procedures that most often include coronary angiography, increased from 575,000 in 1991 to 793,000 in 1995, an increase of 38% over 4 years. The number of outpatient cardiac catheterizations is more difficult to determine. It is estimated that in 1986, 5% of the total volume of catheterizations in Medicare patients were performed in outpatients, whereas in 1993, that figure had risen to 23%.
Although it has been suggested by many that managed care will curtail further growth in the frequency of cardiac catheterization, that has yet to occur. Given a prediction of 40% growth in the population aged >45 years from 1995 to 2010, and the present trend of increased utilization, it is possible that by 2010, 3,000,000 cardiac catheterizations will be performed annually in the U.S.
In 1994, 10% of cardiac catheterizations were performed in patients with a Diagnosis Related Group (DRG) diagnosis of acute MI (38,39). Although this is only a small percentage of those patients studied by coronary angiography, the infarction subgroup has been well characterized. The frequency of its use is growing in this group of patients: from 1987 to 1990, the proportion of Medicare patients with infarction who had cardiac catheterization increased from 24% to 33% (40). Infarction patients admitted to hospitals with cardiac catheterization laboratories are 3 times more likely to undergo angiography than are patients admitted to hospitals without such facilities (41,42). Patients treated for MI by invasive cardiologists have a similar likelihood of undergoing angiography as patients treated by noninvasive cardiologists (68% vs. 59% at Massachusetts General Hospital), but the likelihood of having angioplasty or surgery is higher for patients treated by invasive cardiologists (43).
In the U.S., there are substantial regional differences in the use of coronary angiography (35). In the GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) study of patients with acute MI, the proportion undergoing angiography varied substantially between 7 regions evaluated (44). In New England, 52% of patients with acute MI underwent coronary angiography, whereas in the other 7 regions, the frequency of use was much higher at between 66% and 81%. The regional use of angiography was closely related to its availability in all regions, except for New England. Despite these regional variations in utilization, there was no apparent relationship between procedure rate and certain patient outcomes. The incidence of recurrent infarction or death at 30-day and one-year follow-up did not vary from region to region. In another study that evaluated Medicare patients with MI, the frequency of catheterization was 45% in patients in Texas but only 30% in patients in New York (45). In Texas, use was higher for all clinical subgroups analyzed except for those at greatest risk for reinfarction, that is, non–Q-wave infarction or patients with postinfarction angina, for whom the rates were similar to those in New York. Despite the increased use of coronary angiography in Texas, the adjusted mortality at two-year follow-up was significantly lower in New York, and patients in New York had fewer symptoms. Conversely, in an analysis of use of coronary angiography within three months of an acute MI among 6,851 patients hospitalized at 16 Kaiser Permanente hospitals from 1990 to 1992, the rates of angiography (ranging from 30% to 77%) were inversely related to the risk of death from heart disease (p = 0.03) and the risk of heart disease events (p < 0.001) over one to four years of follow-up (46). This association was strongest among patients for whom published criteria indicated that angiography was necessary.
For postinfarction patients, there is also an international difference in use of angiography. In both the GUSTO (47) and the SAVE (Survival and Ventricular Enlargement) trials (48), angiography was used more frequently after infarction in patients in the United States than in Canada. Despite this difference in utilization, there were no differences in mortality or reinfarction rates between the two countries, although for both studies there was a higher incidence of symptoms in Canadian patients at follow-up. Similar conclusions were formed in a recent study comparing elderly patients with MI in the U.S. and Canada (49).
This variation in use has led many to question the appropriateness of angiography (50,51), particularly for patients with MI. Appropriateness was evaluated for patients treated in the Myocardial Infarction Triage and Intervention Project (MITI), a study of acute MI performed in Seattle and King County, Washington (38). It was found that except for recurrent angina, clinical risk factors that predict higher mortality were associated with a lower rather than a higher use of angiography, which suggests that many patients who needed angiography did not receive it. Although these data do not determine with certainty whether angiographic procedures are overused in patients at low mortality risk or underused in patients at greater mortality risk, they suggest that the current balance between patient survival risk and procedure utilization may not be the most efficient use of this expensive resource (38).
Other studies examining the appropriateness of angiography have yielded widely varied results (Table 4). These studies generally rely on criteria established by an expert panel to determine if angiography was necessary and appropriate. How well the opinion of such expert panels actually agreed with practicing physicians had not been examined until recently, but the level of agreement was found to be quite good (58). Areas of patient management in which variation in the appropriateness of coronary angiography was greater were in older individuals and in those with uncomplicated MI. Estimates for the rate of inappropriate angiography have varied from as high as 58% in a two-hospital study in Israel (53) to as low as 2% in a Swedish report (56). The U.S. studies have included several reports from the Rand Corporation investigators (52,55,59). Using criteria for appropriateness developed through a consensus panel of both specialists and generalists, Rand investigators categorize angiography as appropriate, of "uncertain" value, or inappropriate. By their criteria, angiography in New York State was judged as appropriate in 76% of cases, of uncertain value in 20%, and inappropriate in only 4% (52). Other studies, particularly those that compare U.S. care with that in Canada, have suggested that inappropriate indications may be as high as 15% to 18% in some centers (57). Unfortunately, current studies do not allow a final estimate as to how frequently coronary angiography is performed inappropriately.
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There are no data available regarding how often coronary angiography can appropriately be performed in any one patient. It seems reasonable that a significant clinical change could warrant a repeat angiogram in a patient with known CAD, if the indication for angiography was in agreement with these guidelines. The committee considers it unreasonable to perform a repeat angiogram in a patient with recurrent chest pain who has had a previously normal coronary angiogram within the preceding five years, unless there is an intervening documented MI or significantly worsening findings on noninvasive testing. However, in patients with angiographically significant CAD, who were initially treated medically but in whom coronary revascularization later becomes clinically necessary, it is common practice to allow such a patient to proceed with revascularization without a repeat angiogram if <6 months have elapsed since the prior coronary angiogram, but to repeat angiography if >6 months have passed.
On occasion, angiographic image quality or lesion visualization is inadequate to make a judgment regarding the best route of care for a patient, especially in deciding on a revascularization procedure. In this case, a repeat angiogram may be necessary. However, if repetitive angiography becomes an ongoing problem in any laboratory, the laboratory director should critically review the equipment and staff performance and especially the practice of those physicians who undertake repetitive angiographic procedures. In the absence of clinical indications, repeat angiography is both costly and potentially dangerous.
F. Costs.
The total cost of coronary angiography includes laboratory fee, professional fee and costs related to preprocedure and postprocedure observation and laboratory testing (63). Additional costs may accrue if inadequate studies must be repeated or if complications develop (64). Charges generally are different from costs and are usually higher. Charge information is more readily available than cost information (65). There is disagreement regarding the effect that laboratory volume has on costs. Some recommend that a laboratory should perform 300 to 400 procedures per year to maximize economic efficiency, primarily to make up for capital outlay and its amortization (66,67), whereas others have found no relation between volume and costs (68,69).
The 1992 mean charge for cardiac catheterization for inpatients younger than 65 years without a diagnosis of acute MI was $10,880, varying by state from a low of $6,400 in Maryland to $17,600 in California (70). Eighty-two percent of the total charge was for hospital care. Of this amount, 62% was related to catheterization laboratory and ancillary charges and 38% for room and board. The physician charge made up 18% of the total, averaging $2,000 and varying from $1,300 in South Carolina to $2,550 in California. Costs related to physician fees are falling. Medicare payment for physician services for a typical procedure, e.g., a left-heart catheterization with a left ventriculogram or angiography of the native coronaries as well as one additional angiographic component, with supervision and interpretation, was $725 in 1994 and $700 in 1996, and further reductions are anticipated (37).
Outpatient catheterization may be lower in cost, but how much lower is unclear. A prospective study of patients who, on the basis of published guidelines, were candidates for outpatient procedures found that charges for outpatient procedures were $580 less than for inpatient procedures, but actual cost savings were only $218 per patient (71). Previous reports suggested that the nonprofessional component of charges could be reduced by 31% to 55% for an outpatient procedure (72,73).
G. Cost-effectiveness. There has been relatively little study of the cost-effectiveness of coronary angiography compared with noninvasive techniques for the diagnosis and subsequent management of CAD (74). In part, this lack of evidence exists because coronary angiography frequently leads to a revascularization procedure, and thus it is difficult to separate the cost-benefit aspects of the diagnostic test from those of the procedure that subsequently follows. However, several reports regarding the cost-effectiveness of coronary angiography have recently been published.
Patterson et al. (74) compared the cost-effectiveness of coronary angiography with that of ECG stress testing, single photon emission-computed tomography (SPECT) imaging, and stress positron emission tomography (PET) scanning as a first technique to diagnose CAD. In this Bayesian analysis, effectiveness was defined as the number of patients with diagnosed CAD and utility as the clinical outcome, i.e., the number of quality-adjusted life years (QALY) extended by therapy after the diagnosis of CAD. The authors used published values for costs, accuracy, and complication rates of the various tests. At a clinically derived pretest probability of significant CAD of <70%, noninvasive testing was more cost-effective than coronary angiography as an initial procedure. Above a threshold probability of 70% (for example, middle-aged men with typical angina), proceeding directly to angiography as the first test had the lowest cost per effect or utility.
Other studies have examined the cost-effectiveness of combined diagnostic coronary angiography and angioplasty as a single procedure rather than having patients undergo two procedures. Rozenman and colleagues (75) studied >2,000 patients over a three-year period and found no difference in success or complication rates for patients who had diagnostic angiography and angioplasty performed at the same time, compared with having them done as separate procedures. They found no difference in length of stay after angioplasty between combined and staged treatment strategies and concluded that same-setting angioplasty was likely to be more cost-effective. However, a formal analysis of true costs was not performed. In a similar manner, O’Keefe et al. (76) compared 219 patients undergoing combined procedures with a matched population of 191 patients who had separate procedures. The success and complication rates were similar, and the average total charge for a combined procedure was $11,128 compared with $13,160 in those undergoing separate procedures. The authors also estimated that significant savings would occur with respect to total contrast, fluoroscopic time and total procedure time.
Kuntz et al. (77) recently estimated the cost-effectiveness of routine coronary angiography after acute MI. Decision-tree chance node probabilities were estimated with the use of pooled data from randomized clinical trials and other relevant literature, costs were estimated with the use of the Medicare Part A database, and quality-of-life adjustments were derived from a survey of 1,051 patients with a recent MI. Routine coronary angiography increased quality-adjusted life expectancy in almost all post-MI subgroups compared with patients given initial medical therapy without angiography; however, the cost per QALY gained ranged widely, from $17,000 to >$1 million. When a threshold of <$50,000 was considered cost-effective, which compares favorably with the cost of using various medical strategies after MI, routine angiography was cost-effective for patient subgroups with severe postinfarction angina or a strongly positive exercise tolerance test, and for most subgroups with a prior MI, even with a negative stress test. Clearly, more research on the cost-effectiveness of coronary angiography is needed before the optimal use of this procedure in a wide range of clinical circumstances can be determined.
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III. Coronary angiography for specific conditions |
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TopTable of contentsPreambleI. IntroductionII. General considerations...III. Coronary angiography for...Appendix AAppendix BAppendix CAppendix DAppendix EReferences |
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Patients may develop symptoms at one point in time but may become asymptomatic thereafter as the result of a change in the disease or as the result of therapy. For instance, many patients are asymptomatic after an uncomplicated MI, as are patients with mild angina, who can be rendered asymptomatic by medications. The severity of clinical presentations and the degree of provokable ischemia on noninvasive testing are the principal factors used in determining the appropriateness of coronary angiography. Although the extent of coronary disease defined by coronary angiography does predict outcome, use of coronary angiography as a "screening tool" in unselected populations is neither prudent nor cost-effective (74). The same can be stated regarding the routine use of exercise testing (81), radionuclide imaging (82) and stress echocardiography (83) in unselected patients. With only a few exceptions, coronary angiography is not clearly indicated in asymptomatic patients with either known or suspected CAD, unless noninvasive testing (performed as recommended in the ACC/AHA noninvasive guidelines), reveals findings that suggest a high risk for adverse outcome (81,82). Coronary angiography is also frequently done during evaluation for other cardiac conditions, such as valvular heart disease, congestive heart failure, or assessment of congenital heart disease. In this setting, angiography may be performed in asymptomatic patients. The details of indications for coronary angiography in specific conditions are described below.
2. Stable angina
a. Definitions
Patients with CAD may become symptomatic in many different ways but most commonly develop angina pectoris. In this document, angina pectoris (or simply angina) means a chest discomfort due to myocardial ischemia, often described as a transient squeezing, pressure-like precordial discomfort. Angina is generally provoked by physical effort (particularly during the postprandial state), with exposure to cold environment or by emotional stress. The discomfort on effort is relieved by rest, its duration being a matter of minutes. The ease of provocation, frequency and duration of episodes may remain relatively unchanged in individuals for extended time periods, leading to the term "stable angina pectoris."
Not all stable chest pain syndromes are truly anginal. Various authors have subdivided stable chest pain syndromes in an attempt to link the quality of symptoms with the prevalence of significant CAD. Diamond and Forrester (84) found significant CAD at angiography in 89% of patients with typical angina but in only 50% with atypical angina and merely 16% of patients with nonanginal chest pain.
In CASS, 8,157 patients with chronic stable chest pain who underwent coronary angiography were characterized by type of symptoms reported. The CASS definitions of anginal type have become standards for much subsequent literature (85). "Definite angina" was defined as substernal discomfort precipitated by exertion and relieved by rest or nitroglycerin in <10 min. Most patients reported typical radiation to the shoulders, jaw or inner aspect of the arm. Patients with probable angina had most of the features of definite angina, but the features were atypical in some respects (e.g., radiation, unpredictable relief with nitroglycerin or duration up to 15 to 20 min). The third group had "nonspecific chest pain" that did not fit either of the above two groups. The prevalence of significant CAD in patients with definite angina, probable angina and nonspecific chest pain was 93%, 66% and 14% in men, and 72%, 36% and 6% in women (p < 0.001). The age and sex of the patients as well as the character of chest pain were important determinants of disease prevalence and severity. Coronary disease associated with high risk for adverse outcomes, that is, left main or three-vessel disease, occurred in >50% of middle-aged men and older women with definite angina and most men who had probable angina who were >60 years. In contrast, high-risk coronary disease was uncommon in both men and women with nonspecific chest pain, especially in patients <60 years.
The definition and diagnosis of angina is sometimes made more difficult by the predominance of other symptoms such as exertional dyspnea or fatigue, which may be "anginal equivalents." Women frequently present with symptoms that do not have the features classically described in studies of large populations of middle-aged men. Furthermore, women have a higher frequency of asymptomatic ischemia (86).
Angina is further defined according to a gradient of severity as outlined by the CCS classification (87) (Appendix D). In addition, asymptomatic patients with CAD are those with no symptoms to suggest myocardial ischemia in the previous six weeks (88). It is recognized that when tested, a subgroup of these patients will have transient abnormalities consistent with myocardial ischemia in the absence of symptoms. This is termed silent ischemia, and the abnormalities detected may consist of reversible ECG ST-segment shifts on exercise testing or ambulatory monitoring, perfusion abnormalities on radionuclide scans (i.e., stress 201Tl, sestamibi, and PET) or regional wall motion abnormalities during left ventricular imaging (i.e., stress echocardiography or radionuclide ventriculography). It is appropriate to use the term ischemia in this context and to reserve the term angina to describe the subjective symptom felt by patients during episodes of myocardial ischemia. In general, these ischemic test results relate to the functional severity of CAD and are predictors of risk for future adverse outcome, independent of the perception of, or severity of symptoms. Thus, the absence of current symptoms does not necessarily mean either the absence of ischemia or the absence of an impaired prognosis. Diabetes, older age, female gender, hypertension, polyneuropathy, and cardiac transplantation, when accompanied by significant CAD, are all associated with a high frequency of ischemia or even MI without symptoms (89–92).
Patients with known CAD can be divided into two groups based on whether or not they ever had symptoms. One group includes those who were never symptomatic but in whom CAD was documented for other reasons. For example, abnormalities on a stress test led to an angiogram; the patient was a cardiac surgical candidate (e.g., valve replacement) and therefore angiography was done as a preoperative evaluation; or other clinical findings (e.g., asymptomatic MI or abnormal ECG) led to an angiogram. The other group includes those who were previously symptomatic but are currently asymptomatic (i.e., no symptoms within six weeks). This group would include, for example, those who previously had angina but are now asymptomatic; patients after symptomatic MI with no postinfarction angina; patients after revascularization (either CABG or PTCA) who now have no angina; and those who were effectively treated (i.e., drugs or activity restriction) who now have no angina. Although this grouping is convenient because it summarizes how these patients present to the clinician, there are no data to suggest that such clinical grouping, based on whether or not patients are currently symptomatic, has prognostic significance.
b. Management approach for symptomatic patients
Patients with stable chest pain syndromes should undergo a thorough clinical evaluation, including classification of chest pain type into definite or probable angina or nonspecific chest pain, and identification of risk factors (age, tobacco use, dyslipidemia, hypertension, family history of premature coronary disease, activity profile, obesity, postmenopausal status and diabetes). The physical examination will usually detect evidence of other types of heart disease that can cause angina, e.g., aortic stenosis, hypertrophic cardiomyopathy or severe pulmonary hypertension. An assessment of contraindications for coronary angiography should be part of this clinical assessment. The CCS classification of angina provides a useful guide for the assessment of severity of definite or probable angina. Severe symptoms (CCS class III or IV) suggest severe CAD and are an indication for cardiac catheterization.
Optimal medical management may include nitrates, long-acting calcium channel blockers, and beta-adrenergic blocking agents, as well as attention to associated conditions such as hypertension, dyslipidemia and diabetes. Therapy is considered adequate if it includes two of the three antianginal agents used at or near maximum recommended doses in addition to antiplatelet therapy. For most patients, medical therapy is considered successful when angina has been eliminated or no longer adversely influences their lifestyle, and they are able to exercise beyond the end of stage II of the Bruce protocol without experiencing angina and ST-segment depression. Patients with definite or probable angina for whom optimal pharmacologic therapy has failed and those with an intolerance to these medications are candidates for coronary angiography. Patients who are treated medically but who demonstrate subsequent deterioration on noninvasive testing that suggests progression of disease are often considered for coronary angiography. Coronary angiography should also be considered for patients whose angina accelerates or intensifies despite adequate medical care, even if their symptoms do not fulfill the criteria for a diagnosis of unstable angina. Stable angina patients who have survived sudden cardiac death or sustained ventricular tachycardia are generally referred for coronary angiography to identify coronary lesions that, if treated appropriately, could relieve the ischemic substrate for lethal arrhythmias (93).
From time to time, CCS class I to II patients, whose occupation or other circumstance constitutes a risk to themselves or others, should undergo coronary angiography even in the absence of high-risk markers for adverse outcome on noninvasive testing. Such "need-to-know" circumstances may exist for airplane pilots, train operators, firefighters, school bus drivers, serious athletes and others.
c. Management approach for asymptomatic or mildly symptomatic patients with known or suspected CAD
A scheme for noninvasive evaluation of a mildly symptomatic or asymptomatic patient suspected or known to have significant CAD is shown in Figure 1. Exercise-induced ECG changes, abnormalities on radionuclide myocardial perfusion scans, and abnormalities on ventricular wall motion studies (Table 5) are established markers for high risk of adverse outcomes. Although these noninvasive stress test markers are neither 100% sensitive nor 100% specific, when properly used, they do have very acceptable predictive value for adverse outcome. Thus, they aid in the selection of appropriate candidates for coronary angiography when symptom severity alone does not support such a recommendation. A minority of patients undergoing noninvasive testing will have findings that suggest a high risk for adverse outcome, but in most of these high-risk cases, a recommendation for coronary angiography is warranted.
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Radionuclide perfusion imaging techniques generally have higher specificity for significant CAD than ECG-based tests used alone but are much more costly. The radionuclide techniques are most cost-effective in identifying severe multivessel CAD in patients with uninterpretable ECGs and in patients who have an abnormal exercise ECG that does not fulfill high-risk criteria (Table 5). These findings are summarized in the "ACC/AHA Guidelines for Clinical Use of Cardiac Radionuclide Imaging" (82,98). That committee concluded that use of exercise or pharmacologic myocardial perfusion imaging with thallium or rest and exercise radionuclide angiography was usually appropriate and considered useful for assessment of severity of ischemia and risk stratification of patients with known or suspected CAD. They thought that the use of gated sestamibi perfusion imaging was also acceptable for this purpose but that its usefulness was less well established. The most consistent predictor of cardiac death or nonfatal MI was the number of transient perfusion defects provoked by either exercise or pharmacologic stress. Patients with CAD and redistribution defects on stress thallium imaging in >1 coronary artery region or who have a combination of redistribution abnormalities and increased lung uptake are at increased risk for adverse outcome (98). Normal stress 201Tl scans are highly predictive of a good outcome, even in patients with documented CAD. An analysis of 3,595 such patients, followed up for 
29 months in 16 separate studies, revealed a 0.9% annual rate of cardiac death or MI (99), nearly as low as that seen in the general population (100).
Assessment of left ventricular function (radionuclide ventriculography or echocardiography) shows that mortality rates progressively increase as left ventricular ejection fraction at rest decreases. When ejection fraction decreases 10% with exercise or fails to exceed 0.50 during exercise, particularly in association with new or worsening regional wall motion abnormalities, prognosis is also impaired (98). Similarly, patients at increased risk for adverse outcome can be identified by a reduced ejection fraction with rest echocardiography or by stress echocardiography that shows multiple new or worsening regional wall motion abnormalities during stress (100–109).
Appropriate treatment of patients with ischemia but not severe symptoms was addressed in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study (88,110,111). Clinically stable patients with CAD (a third were asymptomatic, and the majority had multivessel disease and normal ventricular function) and ischemia on both stress testing and ambulatory ECG monitoring were randomized to either initial medical or revascularization treatment strategies. Patients randomized to a medical strategy could cross over to revascularization at any time to relieve severe symptoms. Although there were only a small number of events, the results suggested that patients randomized to initial revascularization had better outcomes (fewer deaths and nonfatal MIs as well as hospitalizations) at one and two years than did those randomized to initial medical treatment (110,112). Although these findings require confirmation in a larger trial with mortality as the outcome, they do support overviews of nonrandomized (113,114) and randomized (115) trial data that concluded that asymptomatic or mildly symptomatic patients with severe ischemia on noninvasive testing do better with initial revascularization than with initial medical therapy.
There is varying opinion as to when coronary angiography should be performed in asymptomatic patients in whom noninvasive testing indicates ischemia (i.e., a high probability of CAD), but in whom test criteria do not indicate high risk for adverse outcomes. In part, this is attributable to the observation that the development of ischemia on these tests may not in itself indicate a poor prognosis (99). In this group with ischemia, but no test abnormalities to suggest high risk, the presence of multiple clinical risk factors such as increased age, diabetes, or occupational or lifestyle risks become increasingly important considerations when determining whether coronary angiography should be performed. However, it should be recognized that there are no controlled studies that show an advantage for angiography or revascularization over a conservative medical "wait and see" approach for any of these clinical subsets.
Because transplanted hearts often develop occlusive coronary arteriopathy, and because ischemia in patients with denervated hearts is generally asymptomatic, it has become common practice to perform periodic coronary angiography (and often intravascular coronary ultrasound), usually annually, after transplantation. The prognostic benefit of this practice has not been clearly established. It has also become a common part of the screening process to perform coronary angiography in candidates for liver, lung or kidney transplantation if they are 40 years of age, even in the absence of significant clinical risk factors for coronary disease. It would seem that noninvasive testing could be substituted for coronary angiography in many of these patients.
d. Management approach for patients resuscitated from sudden cardiac death
Adult patients successfully resuscitated from cardiac arrest who do not have clinical findings that suggest other causes of the arrest generally have extensive CAD. In the absence of recognized precipitating factors, such as acute MI, these patients are at high risk for recurrent cardiac arrest, and coronary angiography is of value in determining the underlying cause and planning the most appropriate therapeutic approach. Observational data indicate that coronary bypass surgery may be associated with reduced adverse outcome in that subgroup with significant coronary disease (93). It has been reported that immediate coronary angiography in survivors of out-of-hospital cardiac arrest reveals acute coronary occlusion in 50% of patients and that successful emergency angioplasty of an acute occlusion is an independent predictor of survival (116). A recent AHA statement further addresses this issue (117).
Recommendations for Coronary Angiography in Patients With Known or Suspected CAD Who Are Currently Asymptomatic or Have Stable Angina
Class I
Class IIa
Class IIb
2 major clinical risk factors and abnormal but not high-risk criteria on noninvasive testing (performed for indications stated in the ACC/AHA noninvasive testing guidelines) without known coronary heart disease. (Level of Evidence: C) 40 years old as part of evaluation for transplantation. (Level of Evidence: C) Class III
e. Management of patients with nonspecific chest pain
Chest pain syndromes that are not characteristic of angina have previously been called noncardiac, atypical, or angiographically negative chest pain, as well as chest pain of undetermined origin (37–39). These terms are generally used to describe chest pain syndromes that are not associated with myocardial ischemia and are not of a cardiac cause. However, "atypical angina" generally means that myocardial ischemia is the cause of the symptoms, but the clinical presentation is unusual and should not be confused with nonspecific chest pain. For the purpose of this document and for consistency with previous documents, chest pain or cardiac symptoms not thought to be consistent with definite or probable angina are classified as nonspecific chest pain.
Nonspecific chest pain is very infrequently due to myocardial ischemia secondary to significant CAD, with a prevalence of 14% in men and 6% in women in one study (85). Other causes of myocardial ischemia, such as variant angina due to coronary spasm, or cocaine abuse, or syndrome X due to microvascular dysfunction, can infrequently present as nonspecific chest pain as well. Other cardiac causes include mitral valve prolapse, myocarditis, pericarditis and aortic dissection. Mitral valve prolapse is often associated with nonspecific chest pain. Although the cause is poorly understood, one postulate is that traction of the papillary muscle, induced by abnormal mitral valve motion, causes ischemia (118).
Noncardiac causes of nonspecific chest pain include costochondritis and esophageal disorders. Several disorders of the esophagus cause retrosternal chest pressure that can mimic myocardial ischemic-type chest pain. These include gastroesophageal reflux, irritable esophagus with altered gastroesophageal motility and a hypertensive lower esophageal sphincter (119). Many patients with both ischemic cardiac and esophageal pain can distinguish the symptoms, but some cannot. Exertional symptoms resulting from an esophageal source may also occur (119–121). Gastroesophageal reflux is a common, treatable cause of chest discomfort in patients with CAD who have nonspecific chest pain symptoms and remain symptomatic despite aggressive antianginal therapy (122). In one study, esophageal manometry, pH, and Holter monitoring were performed in patients with refractory nonspecific chest pain on optimal medical therapy for CAD. Of the 88% with chest pain identical to their anginal syndrome, 23% had acid reflux, 4% had cardiac ischemia, and 73% had no demonstrable cause. Up to 30% of patients with nonspecific chest pain will have an esophageal motility disorder (123). In some cases, antianginal therapy may exacerbate esophageal reflux symptoms because many of the drugs used to reduce these symptoms also lower esophageal sphincter tone (124,125).
A generalized disorder of smooth muscle function involving the esophagus, airways, musculoskeletal vasculature, central nervous system, and coronary microvasculature has been proposed (121). Some data suggest that gastroesophageal reflux and esophageal motility abnormalities may elicit myocardial ischemia and chest pain, a phenomenon termed "linked" angina. Acid stimulation caused typical angina (associated with a reduction in coronary blood flow velocity) in about half of syndrome X patients, which suggests that linked angina may indeed occur (119). However, other studies refute this concept (125,126).
If noncardiac causes are excluded or unlikely, or if the patient has significant cardiovascular risk factors that raise the suspicion of coronary disease, a noninvasive evaluation is appropriate. A number of guidelines specifically address this issue in detail (81–83,95–99). If noninvasive testing indicates a high risk for adverse outcome, then referral for coronary angiography should be made. Patients with nonspecific chest pain and evidence of myocardial ischemia but without indicators of high risk may be started on medical therapy with careful follow-up to assess their clinical response (127). Those who are intolerant of medical therapy, who fail to respond adequately to medical therapy, or in whom chest pain limits their lifestyle significantly despite taking 2 antianginal medications should be considered for coronary angiography. Patients who repeatedly present to the hospital with nonspecific chest pain, but who fail to have high-risk markers for ischemia, may also benefit from coronary angiography. The findings of a normal coronary angiogram in such patients indicate a good long-term prognosis that is reassuring to both the patient and the physician. Studies have indicated that a normal angiogram in this setting significantly reduces symptoms and subsequent hospitalizations (128).
Recommendations for Coronary Angiography in Patients With Nonspecific Chest Pain
Class I
High-risk findings on noninvasive testing. (Level of Evidence: B)
Class IIa
None.
Class IIb
Patients with recurrent hospitalizations for chest pain who have abnormal (but not high-risk) or equivocal findings on noninvasive testing. (Level of Evidence: B)
Class III
All other patients with nonspecific chest pain. (Level of Evidence: C)
3. Unstable angina
a. Definitions
The acute coronary syndromes include unstable angina, non–Q-wave MI, and acute Q-wave MI. The diagnosis of unstable angina has been complicated by a broad range of presentations that can vary between atypical chest pain and acute MI. An expert panel of clinicians attempted to clarify the definition of unstable angina in the recently published "Clinical Practice Guideline for Unstable Angina" (129,130). Three possible presentations are described:
Varia
