Abstract
BACKGROUND
A diagnosis of unstable angina pectoris (UAP) often carries with it a decision to catheterize the patient promptly. However, UAP remains a clinical diagnosis, based mostly on a patient’s clinical history and electrocardiogram (ECG) findings.
OBJECTIVE
To evaluate whether the diagnosis of UAP is overused in patients referred for coronary arteriography.
METHODS
Ninety-six patients with a diagnosis of UAP who were referred for invasive studies were re-examined clinically before catheterization. Coronarography was independently reviewed for correlation with clinical findings.
RESULTS
Based on the patient’s history and ECG changes, UAP was classified by two independent cardiologists as ‘very likely’ in 58% and 49%, ‘possible’ in 19% and 30%, and of ‘low probability’ in 23% and 21%, respectively. Patients with ‘very likely’ UAP had a high incidence of significant coronary lesions (87% and 96% for each cardiologist) and complex lesions by angiography (41% and 49%, respectively). Patients with a diagnosis of ‘low probability’ UAP had a low incidence of significant coronary lesions (55% for each cardiologist) and a very low incidence of complex angiographic lesions (5% for each cardiologist). Patients with ‘possible’ UAP had intermediate results.
CONCLUSION
Because of a presumptive diagnosis of UAP, approximately 22% of all patients referred for coronarography have no clinical and/or ECG evidence for this diagnosis. The incidence of complex coronary lesions in this group is very low.
Keywords: Catheterization, Chest pain, Clinical diagnosis, Coronary, Electrocardiogram, Unstable angina
Guidelines detailing the indications for coronary arteriography for various clinical presentations of coronary artery disease have been published (1–3). Within these guidelines, much controversy persists between physicians favouring a conservative approach and those favouring an early invasive investigation (1–4). Several risk scores have been developed for risk stratification in patients presenting with acute coronary syndrome without ST-segment elevation; the most widely used are Thrombolysis in Myocardial Infarction risk score, Global Registry of Acute Coronary Events risk score (5,6), and Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy risk model (7). However, application of these models to guide treatment decisions assumes that the diagnosis is accurate. Unstable angina pectoris (UAP) is very much a clinical diagnosis (8). Two reasonable physicians evaluating the same patient with chest pain can arrive at opposite conclusions. The purpose of the present study was to evaluate the appropriateness of the diagnosis of UAP in patients referred for coronary arteriography in a major university hospital, and to correlate the diagnosis with angiographic findings.
METHODS
Consecutive patients with a diagnosis of UAP who were referred for coronary arteriography at Rambam Medical Center (Haifa, Israel) were evaluated for enrolment in the study during an eight-month period. Subjects undergoing emergency procedures and catheterization during the evening shift were excluded. Performance of catheterization during the morning, versus the evening shift (in nonurgent patients), usually reflects the patient’s insurance plan and not the clinical presentation. All Israeli citizens, by law, have medical insurance. Hospitalization (including catheterization) is free of charge. To evaluate a relatively homogenous group, patients with secondary angina and postinfarction angina were excluded (9). Repeat examinations of cardiac troponin T levels were performed in all patients. Troponin T levels in serum were determined using an Elecsys 2010 automated immunochemistry analyzer (Roche Diagnostics, Germany). The upper normal limits were defined as the 99th percentiles of the normal population, according to Joint European Society of Cardiology/American College of Cardiology guidelines (10). The cut-off value for abnormal cardiac troponin T was 0.01 μg/L. Patients with abnormal cardiac troponin T at the time of referral for catheterization were classified as having myocardial infarction and were excluded from the study.
Rambam Medical Center is a 950-bed university hospital affiliated with the Technion Medical School (Haifa, Israel). The cardiac catheterization laboratory performs approximately 2000 diagnostic and approximately 1100 adult intervention procedures per year. The decision to perform coronary arteriography is made by the attending physician responsible for the patient. The procedure is usually performed zero to five days later, depending on the patient’s clinical status and on availability in the catheterization laboratory. UAP was the major diagnosis indicated on the patient chart at the time the request for catheterization was transmitted to the cardiac catheterization laboratory. On receiving the request for cardiac catheterization, and before the procedure, the patient was interviewed by one of two cardiac fellows (Dr Alexander Goldberg or Dr Sergey Yalonetsky). A new history was recorded, with particular attention given to the complaint prompting admission. All available electrocardiogram (ECG) and laboratory data were reviewed. For the purpose of the present study, chest pain, when present, was classified according to a 1 to 5 grading system. A typical angina pectoris pain (score 5) has typical attributes of angina pectoris in terms of character, location, radiation and duration of pain (11–13). Nearly typical angina (score 4) has all the characteristics of typical angina pectoris except for one slightly atypical feature. Fairly typical angina pectoris (score 3) has the characteristics of typical angina pectoris except for one clearly atypical feature. Atypical angina (score 2) indicates that chest pain has some attributes of anginal pain but also includes two or more atypical components. Atypical chest pain (score 1) indicates that the pain does not have the usual characteristics of anginal pain. When no chest pain was present, attention was given to shortness of breath (‘angina equivalent’). Shortness of breath that was compatible, possibly compatible or probably not compatible with myocardial ischemia was given scores of 3, 2 and 1, respectively. The chest complaint was further classified as being stable or unstable using the Braunwald classification (9).
All available ECGs were reviewed and scored as follows: 5, new ST-segment deviation 0.05 mV or greater; 4, new T-wave inversion 0.1 mV or greater, new complete left bundle branch block, presumably new ST-segment deviation 0.05 mV or greater; 3, presumably new T-wave inversion 0.1 mV or greater, presumably new complete left bundle branch block; 2, lesser ST-segment changes, new or dynamic; 1, abnormal ST segment, age unknown; and 0, normal ECG. The maximum score for ECG changes is 5. For the purpose of the present study, the ECG score was added to the clinical score to create a total score. The maximum total score is 10. The total score was devised for the purpose of the present study to provide a rough semiquantitative estimation of the likelihood that the patient complaints were related to myocardial ischemia (unstable or not), and for correlation with angiographic findings.
Two board certified cardiologists (Dr Zaher Azzam and Dr Walter Markiewicz) separately analyzed the data collected by the cardiac fellows before cardiac catheterization. UAP was classified by the two cardiologists as belonging to one of four groups: ‘very likely’, ‘possible’, ‘very unlikely’ and ‘another diagnosis’. ‘Another diagnosis’ indicated that the complaints and findings were best compatible with a disease other than angina pectoris (eg, cholelithiasis). Patients with stable complaints were classified as having ‘another diagnosis’ than UAP. Patients with ‘very unlikely’ UAP and ‘another diagnosis’ were grouped together for comparison with angiographic findings and were classified has having ‘low probability’ UAP.
A cardiologist with extensive experience in invasive cardiology (Dr Michael Kopeliovich) reviewed all coronary angiograms. He had no knowledge of the clinical findings. Coronary lesions were considered hemodynamically significant when the coronary diameter of an epicardial artery was reduced by 50% or more (by visual evaluation). Lesions were described as complex or noncomplex using the classification of Dangas et al (14).
Except for the authors, the clinical staff in the hospital was unaware of the purpose of the study. The study protocol was approved by the hospital’s Helsinki committee.
Statistical analysis
Continuous variables are expressed as mean ± SD. Differences were evaluated by ANOVA and by χ2 statistics. P<0.05 was considered statistically significant.
RESULTS
Three hundred seventy patients with a diagnosis of UAP underwent coronary arteriography during the study period. One hundred eighty-five underwent arteriography during the evening shift and were excluded. Another 89 subjects fulfilled the exclusion criteria, leaving 96 patients in the study group. Baseline demographics and clinical characteristics are presented in Table 1. Sixty-nine of 96 patients (72%) had a history of ischemic heart disease, and 32 of 96 patients (33%) had previously undergone coronary revascularization.
TABLE 1.
Baseline clinical characteristics (n=96)
| Characteristic | |
|---|---|
| Age, years, mean ± SD | 63±12 |
| Male subjects, n (%) | 61 (64) |
| Hypercholesterolemia, n (%) | 60 (63) |
| Hypertension, n (%) | 67 (70) |
| Diabetes, n (%) | 29 (30) |
| Smoking , n (%) | 40 (42) |
| Family history of IHD, n (%) | 37 (39) |
| Previous history of IHD, n (%) | 69 (72) |
| Previous PCI, n (%) | 28 (29) |
| Previous CABG, n (%) | 6 (6) |
| Any revascularization, n (%) | 32 (33) |
| Length of symptoms, days, mean ± SD | 16±25 |
| Time to catheterization, days, mean ± SD | 4±3 |
Length of symptoms is defined as the period between symptom appearance and hospital admission. Time to catheterization was the period between admission and catheterization. CABG Coronary artery bypass graft; IHD Ischemic heart disease; PCI Percutaneous coronary intervention
Ninety-five of 96 patients had chest pain. The complaint was typical for angina pectoris in 21 patients, nearly typical in 34 patients and fairly typical in 28 patients. The chest complaint suggested atypical angina in 10 patients and atypical chest pain in two patients. Irrespective of the pain characteristics, pain occurrence pattern indicated an unstable condition in 90 of 96 patients and a stable condition in six of 96 patients. The Braunwald classification was applied to the 90 patients with unstable complaints (9). All patients were class B by design (primary angina). Pain severity was class I in five patients, class II in 48 patients and class III in 37 patients.
ECG scoring was grade 5 in 17 patients, grade 4 in 11, grade 3 in 10, grade 2 in seven and grade 1 in 12. Thirty-nine of 96 patients (41%) had normal ECG tracings (grade 0). Combining the presenting symptoms and ECG findings, one senior cardiologist believed that 56 of 96 patients (58%) had ‘very likely’ UAP. The second cardiologist applied the same diagnosis to 47 of 96 patients (49%). The cardiologists believed that 18 of 96 patients (19%) and 29 of 96 patients (30%), respectively, had ‘possible’ UAP. Unstable angina was considered ‘very unlikely’ in 15 of 96 (16%) and 10 of 96 patients (10%), respectively. Both cardiologists believed that ‘another diagnosis’ best explained the complaints or findings in seven and 10 patients, respectively: this included six patients with stable complaints, and one and four patients, respectively, with complaints believed to be best explained by a noncardiac disease. Both cardiologists agreed on the diagnosis in 76 of 96 patients (79%) and disagreed in 20 of 96 (21%).
The correlation between the clinical diagnosis and the angiographic findings is presented in Table 2. Significant (greater than 50%) stenosis was seen in 75 of 96 patients (78%): single-vessel disease in 26 patients, two-vessel disease in 28, three-vessel disease in 13 and left main disease in eight. Patients with ‘very likely’ UAP were significantly more likely to have significant coronary artery disease than patients with a clinical diagnosis of ‘low probability’ UAP as defined above (88% and 96% for each cardiologist, respectively, versus 55% for each cardiologist) (P=0.01 and P<0.01 for each cardiologist). Patients with ‘very likely’ UAP had more complex lesions (by angiography) than the group with ‘low probability’ UAP (41% and 49% versus 5% and 5%, respectively; P<0.01). Patients with a ‘possible’ UAP had intermediate findings. Only one of 22 patients (first cardiologist, 5%) and one of 20 patients (second cardiologist, 5%) with ‘low probability’ UAP had angiographic evidence of plaque rupture or thrombus. A significant relationship was noted between the total score (as described in the Methods section) and the angiographic findings (Table 3) (P<0.01).
TABLE 2.
Correlation of coronary arteriography findings with clinical diagnosis
| Unstable angina pectoris
|
||||
|---|---|---|---|---|
| Findings on coronary angiography | Very likely, n (%) | Possible, n (%) | Low probability, n (%) | Total, n (%) |
| Cardiologist 1 | n=56 | n=18 | n=22 | n=96 |
| Nonsignificant CAD | 7 (13) | 4 (22) | 10 (45) | 21 (22) |
| Significant CAD* | 49 (88) | 14 (78) | 12 (55) | 75 (78) |
| Complex lesion* | 23 (41) | 5 (28) | 1 (5) | 29 (30) |
| Cardiologist 2 | n=47 | n=29 | n=20 | n=96 |
| Nonsignificant CAD | 2 (4) | 10 (34) | 9 (45) | 21 (22) |
| Significant CAD* | 45 (96) | 19 (66) | 11 (55) | 75 (78) |
| Complex lesion* | 23 (49) | 5 (17) | 1 (5) | 29 (30) |
See the Methods section for definitions of significant coronary artery disease (CAD) and complex lesion
TABLE 3.
Correlation between angiographic findings and scores
| Significant CAD
|
|||
|---|---|---|---|
| Score | Nonsignificant CAD, (n=21) | No complex plaque, (n=46) | Complex plaque, (n=29) |
| Chest pain score | 3.05±1.10 | 3.67±1.06 | 3.93±0.94 |
| ECG score | 1.00±1.34 | 1.58±1.96 | 3.18±1.79 |
| Total score | 4.55±1.32 | 5.23±2.52 | 7.11±2.13 |
P<0.01 for the three parameters (ANOVA). CAD Coronary artery disease; ECG Electrocardiogram
Following catheterization, revascularization was performed in 68 of 96 patients (percutaneous coronary intervention in 56 and coronary bypass surgery in 12). Revascularization was performed in 44 of 56 patients (79%) and in 38 of 47 patients (81%) with a diagnosis of ‘very likely’ UAP by cardiologist 1 and 2, respectively. Revascularization was also performed in six of 22 patients (cardiologist 1, 27%) and in seven of 20 (cardiologist 2, 35%) with a diagnosis of ‘low probability’ UAP.
DISCUSSION
Patients admitted to our centre with a diagnosis of UAP generally undergo catheterization during hospitalization. This policy is controversial but widely recommended and practised (1–4,8). The policy assumes that the diagnosis of UAP is accurate. Accuracy of the clinical diagnosis of UAP reflects the accuracy of the clinical evaluation of the patient by the consultant reviewing the history and evaluating the various ancillary tests performed.
Studies evaluating the value of various tests for diagnosing UAP have been hampered by the lack of a ‘gold standard’ for this syndrome. In the absence of a ‘gold standard’, investigators use end points to test the value of different clinical parameters used to diagnose UAP. End points include the presence of significant coronary artery disease or of ‘complex lesions’ on subsequent angiography, or the likelihood that the patient will develop a cardiac event during a given period of time (5–7,15–18). Accepted end points help relate specific signs or symptoms to risk stratification rather than to diagnostic accuracy. Indeed, various risk scores developed to assist risk stratification and guide treatment decisions in patients with unstable angina (5–7) may not be applicable and may even be misleading if the diagnosis of unstable angina is incorrect.
UAP remains a clinical diagnosis. Complaints related to ischemia (usually chest discomfort) and dynamic ECG changes are the basis for the diagnosis. Other easily obtained historical findings such as history of coronary artery disease, history of angina, age older than 60 years, male sex, diabetes and peripheral vascular disease are helpful in assessing the likelihood that a patient presenting with symptoms suggesting UAP has coronary artery disease. Yet, finding that a given patient has significant coronary artery narrowing does not necessarily mean that the narrowing is the cause of the complaints prompting admission. Seventy-two per cent of our patients had a history of ischemic heart disease. In this population, finding one or more coronary stenoses greater than 50% is very common and not necessarily helpful in supporting the diagnosis of UAP. Finding a complex plaque on angiography markedly increases the likelihood that an unstable coronary syndrome is present (13,19,20).
One in five patients referred for cardiac catheterization with a diagnosis of UAP had little evidence to support this diagnosis. This group included patients with very atypical chest pain, patients with complaints clearly related to another diagnosis, and patients with complaints of a stable character; most had normal ECG before catheterization. This population had a low incidence of coronary artery disease on angiography and a very low (5%) incidence of complex lesions by angiography. Our findings suggest that the complaint that sent many patients with ‘low probability’ UAP to the emergency room was probably not related to the abnormal angiographic findings.
The reasons for a diagnosis of UAP to patients subsequently believed by other physicians not to have evidence for this diagnosis are probably multiple. Patients may have changed the description of their complaints between the interviews. Interpretation of similar complaints or ECG findings by two experienced physicians may vary (21). Indeed, our two cardiologists disagreed on the clinical diagnosis in 21% of our patients, although they were given the same information. Knowledge of the patients’ medical history may have influenced the physicians examining the patients in the emergency room and regular wards; the two cardiologists deliberately concentrated on the chest pain description and on the ECG tracings. Emergency room physicians tend to overdiagnose acute myocardial ischemia (16,22). In cases when the diagnosis is uncertain, emergency room physicians tend to admit the patient rather than risk an inappropriate discharge (16). Overdiagnosis of UAP may also be related to pressure on the ward physicians to discharge the patient as quickly as possible. Competition for internal medicine or cardiology beds is intense in Israel. Performing coronary arteriography can reduce the time frame for diagnosis, therapy and discharge (1,3). Thus, even though subsequent evolution and evaluation of many patients might point to another direction, the pressure to perform coronary arteriography without delay is difficult to resist.
Economic considerations might also be involved (23,24), which are difficult to analyze (25). Writing the words ‘unstable angina pectoris’ on the chart generally means that a catheterization procedure (often followed by a revascularization procedure) will be performed. Diagnosis-related group structure in Israel is such that performing coronary angiography and a coronary intervention is more rewarding economically for the hospital than observing the patient for a few days and referring him or her back to the primary physician for further evaluation (24). Promoting a policy of frequent and prompt catheterization for patients presenting with chest pain to the emergency room may provide direct and indirect benefits to many hospital physicians.
Because most patients admitted with a diagnosis of suspected UAP have known ischemic heart disease, the likelihood of finding significant coronary artery stenosis on arteriography is high. There is also a high tendency to attribute the complaint prompting referral to the emergency room to any abnormal finding noted at catheterization. Thus, a needless interventional procedure or operation may result. Indeed, approximately 30% of our patients with a clinical diagnosis of ‘very unlikely’ UAP underwent revascularization. Given the results of a recent Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial (26), as well as a large body of previously published scientific information (27–30), revascularization is unlikely to improve prognosis in patients with stable coronary disease. Also, one should not expect the revascularization procedure to improve symptoms in patients whose complaints are not related to coronary disease. These unnecessary revascularization procedures bear a finite risk of complications and put a significant burden on the health care system. Careful reviewing of the history and ECG tracings might lead the ward physician away from the diagnosis of UAP and away from the need to perform arteriography and/or revascularization.
Our study indicates that many patients referred for catheterization with a diagnosis of UAP do not have much clinical evidence for this diagnosis. Unnecessary invasive procedures may result. Closer attention to the patient’s history and ECG may help to improve patient selection for catheterization.
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