Morbidity and Use of Medical Resources in Patients With Chest Pain and Normal or Near-Normal Coronary Arteries

Morbidity and Use of Medical Resources in Patients With Chest Pain and Normal or Near-Normal Coronary Arteries Per Albertsson, MD, PhD, Ha˚kan Emanuelsson, MD, PhD, Thomas Karlsson, MSc, Carl Lamm, MD, Wanja Sande´n, RN, Gunilla Lagerberg, RN, and Johan Herlitz, MD,

PhD

To evaluate morbidity and use of medical resources in patients with chest pain and normal or near-normal coronary angiograms: 2,639 consecutive patients who underwent coronary angiograms due to chest pain were registered. Two years thereafter all patients who showed normal or near-normal coronary angiograms were approached with a questionnaire regarding hospitalization during the last 4 years (2 years before and 2 years after angiography). All medical files were also examined. Of the patients who underwent angiography, 163 (6%) had no significant stenoses, and of these, 113 showed complete normal angiograms and 50 showed mild (i.e. õ50%) stenoses. During the 2 years before diagnostic angiogram, 66% of the patients were

hospitalized compared with only 35% during 2 years after angiography (p õ0.001). The reduction in hospitalization was due to curtailed utilization of medical resources for cardiac reasons; mean days in hospital was 6.6 days before angiography versus 2.8 days after (p õ0.001). There were no significant differences in hospitalization when comparing patients with mild stenoses and completely normal angiograms. There were, furthermore, no differences between patients with positive or negative exercise tests. Thus, the need for hospitalization is significantly reduced after a diagnostic angiogram reveals normal or near-normal coronary arteries. Q 1997 by Excerpta Medica, Inc. (Am J Cardiol 1997;79:299–304)

significant proportion of patients undergoing diagnostic coronary catheterization because of A chest pain, have normal or near-normal coronary ar-

since registration data were incomplete. Patients who previously had undergone coronary artery bypass grafting (n Å 280), percutaneous transluminal coronary angioplasty (n Å 182), and patients with concomitant valvular disease (n Å 636) were also excluded, as were patients with arrhythmias, congestive heart failure, cardiac tumors, and other nonischemic heart diseases (n Å 424). There remained 2,639 patients who underwent coronary angiogram due to chest pain suspected to originate from coronary heart disease, and since previous coronary artery bypass graft or percutaneous transluminal coronary angiograms were exclusion criteria, presence of coronary artery stenoses were not known at time of registration. Coronary angiogram: Coronary angiogram was performed with standard Judkins’ technique using 5 to 8Fr catheters. The investigations were recorded on cinefilm and analyzed by at least 3 experienced investigators. The coronary tree was thoroughly examined and 3 different degrees of stenoses were used for ‘‘quantification’’ of lesion severity: group 1, completely normal angiographically; group 2, nonsignificant disease (ú0 to 50% stenosis); and group 3, significant lesion (50% to 100% stenosis). Exercise tests: Patients who underwent exercise tests in groups 1 and 2 were analyzed. All tests were performed on a bicycle and the starting workload was 30 to 50 W with a 10-W increment per minute. The ST-segment depression 60 ms from the Jpoint was measured and ú1 mm horizontal or downsloping depression was required for a positive test. Follow-up interviews: All patients approached for inclusion in the study gave informed consent, and the study was approved by the local ethics committee.

teries.1 – 5 Although the heterogeneous nature behind chest pain in this group of patients should be emphasized, the overall prognosis in terms of life expectancy and cardiac pathology is excellent, with low rates of myocardial infarction and cardiac death.4,6 – 9 There is, however, a considerable residual morbidity associated with continuous chest pain and functional limitation.10 – 14 We report an investigation of morbidity and use of medical resources 2 years before and 2 years after the findings of normal arteries on coronary angiograms, where all patients in western Sweden presenting with chest pain suspicious of coronary artery disease were eligible for inclusion in the study.

METHODS Patient population: Between May 1988 and May 1991, all patients who underwent diagnostic coronary angiography at 2 university hospitals and 1 community hospital were registered. At the time of registration these hospitals were the only centers performing coronary angiography in western Sweden, serving a population of 1.5 million. Four hundred twenty-one patients were excluded from the analysis From the Division of Cardiology and Department of Radiology, Sahlgrenska University Hospital, Go¨teborg, Sweden. This study was supported by grants from the Medical Society of Go¨teborg, the Swedish Heart and Lung Foundation, Stockholm; and Astra Ha¨ssle AB, Mo¨lndal, Sweden. Manuscript received April 1, 1996; revised manuscript received and accepted August 26, 1996. Address for reprints: Per Albertsson, MD, PhD, Division of Cardiology, Sahlgrenska University Hospital, S-41345 Go¨teborg, Sweden. Q1997 by Excerpta Medica, Inc.

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TABLE I Demographic Data and Baseline Characteristics of all Patients

Age (yrs) mean { SD Median (range) Women (%) Height (cm) mean { SD Weight (kg) mean { SD Smoking (%): Currently Previous Never Duration of angina (mo) mean { SD Median (range) Functional class (NYHA), (%) I II III IV Previous MI (%)† Congestive heart failure (%) Ejection fraction (%) Hypertension (%) mean { SD Systolic blood pressure (mm Hg) mean { SD Diastolic blood pressure (mm Hg) mean { SD Cerebrovascular disease (%) Stroke Transitoric ischemic attack Claudication (%) Diabetes mellitus (%) Insulin Oral Diet only

No Stenoses (n Å 113)

Mild Stenoses õ50% (n Å 50)

p Value

ú50% Stenoses (n Å 2,476)

55 { 11 56 (19–75) 50 170 { 9 76 { 14

58 { 8 58 (41–76) 52 169 { 8 74 { 15

— — — — —

61 { 9 63 (28–86) 20 173 { 8 78 { 12

16 37 47 50 { 58 24 (2–300)

8 47 45 56 { 57 36 (1–240)

— — — — —

17 52 32 52 { 58 30 (1–360)

5 37 53 5 19 6 71 { 13 31 142 { 22 83 { 11 0 0 0 12 3 1 0 2

4 33 58 4 22 8 73 { 11 41 143 { 22 85 { 10 4 4 0 10 12 2 6 4

— — — — — — — — — — — — — — õ0.05 — õ0.05 —

2 22 62 14 57 12 64 { 15 37 144 { 21 83 { 10 6 3 3 11 11 4 5 3

p Value*

õ0.001 —

õ0.001 õ0.001 õ0.05 —

õ0.01 õ0.001 — — õ0.001 — — — — õ0.001 õ0.05 õ0.001 — — — õ0.01 — õ0.05 — õ0.05 — — —

*Comparison between patients with significant stenoses (n Å 2,476) and nonsignificant stenoses: patients with mild stenoses plus patients with completely normal angiograms (n Å 163). † Based on anamnestic report. p Å Comparison between patient with mild stenoses (õ50%) and completely normal angiography. p values are given if õ0.05. NYHA Å New York Heart Association.

All patients were registered at the time of coronary angiography, and basal data are based on patients’ history in combination with available medical files. Two years thereafter the patients in groups 1 and 2 were supplied with a questionnaire inquiring if and where they had been hospitalized during the previous 4 years (2 years before and 2 years after the diagnostic angiogram). Furthermore, all files from hospitals in western Sweden (15 hospitals) were collected. Only the main diagnosis per hospital visit was registered. Statistical methods: The sign test was used to test for differences of proportions before and after angiography. For number of days Wilcoxon’s signed rank test was used. To test for difference at baseline as well as hospitalization before and after angiography between groups, Fisher’s exact test was used for dichotomous variables and Wilcoxon’s rank sum test for ordered/continuous variables. All p values are 2-tailed and given in the tables if ú0.05.

113 had completely normal coronary arteries (group 2) and mild disease, defined as õ50% stenoses, was found in 50 patients (group 1). Demographic data and baseline characteristics are described in Table I. Regarding medical history, patients with coronary stenoses had more often suffered from previous myocardial infarction, congestive heart failure, cerebrovascular disease, and diabetes mellitus. Fiftyseven percent of the patients in group 3 had received a diagnosis of myocardial infarction before the angiogram. The corresponding anamnestic number in patients in groups 1 and 2 was 20% (n Å 33). All these data were thoroughly examined by analyzing the medical files. Only 11 patients without significant stenoses had really been given the diagnosis of acute myocardial infarction, 4 of whom had completely normal angiograms and 7 nonsignificant stenoses. Among the 22 patients under misapprehension that they had had a myocardial infarction, 14 were men, 10 had a positive exercise test, and 17 had a completely normal angiogram. Of the patients without significant stenoses, 78 (48%) showed a positive and 84 (51%) a negative stress test, equally distributed in the groups with normal angiogram and mild stenoses. Two patients who

RESULTS Of the patients undergoing angiography 2,476 were found to have significant coronary artery disease (group 3), and 163 (6%) were found to have nonsignificant coronary artery stenoses, of whom 300

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TABLE II Medication at Time of Admission for Angiography Percent

b blockers Calcium antagonists Long-acting nitrates Diuretics for heart failure Digitalis Other treatment for heart failure Antihypertensives (other) Antiarrhythmics (other) Aspirin Dipyridamole Coumadin Psychopharmaceuticals Lipid-lowering drugs Antidiabetics Other medication

No Stenoses (n Å 133)

õ50% (n Å 50)

Mild Stenoses p Value

ú50% Stenoses (n Å 2,476)

77 58 50 12 6 6 15 3 36 0 2 7 1 1 21

72 56 60 10 10 4 20 0 43 2 10 6 6 8 31

— — — — — — — — — — õ0.05 — — õ0.05 —

83 56 69 20 5 5 10 1 62 2 3 5 6 8 32

p Value*

õ0.05 —

õ0.001 õ0.01 — — õ0.05 — õ0.001 — — — — õ0.05 õ0.05

* Comparison between patients with significant stenoses (n Å 2,476) and nonsignificant stenoses: patients with mild stenoses plus patients with completely normal angiograms (n Å 163). p Å Comparison between patient with mild stenoses (õ50%) and completely normal angiography. p values are given if õ0.05.

developed complete left bundle branch block during exercise were classified as having positive tests, and an additional 5 patients with left bundle branch block at rest and reversible perfusion defects on 201 thallium scintigraphy were also allocated to the group with positive exercise tests. Only 1 patient did not perform an exercise test. Regarding patients on-going medication, suspicion of coronary artery disease seems to have been stronger in group 3 since these patients were more often treated with aspirin, b blockers, and long acting nitrates (Table II). Nevertheless, a high proportion of the patients in groups 1 and 2 were also prescribed cardiovascular medication. There were no differences in cardiovascular medication whether the exercise test was positive or not. The use of medical resources in terms of hospitalization was analyzed in groups 1 and 2 and revealed that 66% of the patients were hospitalized during the 2 years before the diagnostic angiogram, the majority of reasons being cardiac, mainly angina pectoris. During the 2 years following the angiogram, need for hospitalization was reduced to 35% of the patients (Figure 1). There was also a significant reduction in total days in hospital, due to less need for hospitalization of cardiac causes. There were, however, significant increases in days of hospitalization due to noncardiac causes (Table III). When comparing patients with a complete normal coronary angiogram (group 1) and patients with mild stenoses (group 2), the only significant difference was more frequent hospitalization and days in hospital due to myocardial infarction 2 years before angiography in group 2 (Table IV). When comparing patients with a positive exercise test (n Å 78) to patients with a negative exercise test (n Å 84), there was a significant difference regarding hospitalization due to congestive heart failure 2 years before angiography, which was more common in patients with positive exercise tests (Table V).

During the 2-year observation time after angiography, there were 4 deaths. One patient with negative exercise test in group 1 died at age 50 due to suicide. A 69-year-old man in group 1 with a positive exercise test died of pulmonary embolism following surgery of an abdominal aortic aneurysm. A 51-yearold woman in group 2 with a positive exercise test and a mild stenosis in the right coronary artery died due to respiratory insufficiency, and finally, a male patient in group 2 with a mild stenosis in the left anterior descending artery and a nonsignificant stenosis in the right coronary artery who had a positive exercise test, died at age 46 because of a stroke.

DISCUSSION Previously, long-term follow-up studies have shown an excellent outcome regarding cardiac death and myocardial infarction in patients with chest pain and a normal coronary angiogram.3,4,8,9 Hence, there seems to be reasons to discern between patients with mild disease and patients with completely normal angiograms. Bruschke et al15 demonstrated that patients with entirely normal angiograms had an incidence of myocardial infarction and cardiac death of only 0.9% and 0.6%, respectively, during a 5-year follow-up period. In the presence of mild disease the incidence of myocardial infarction increased to 5.3% and cardiac death to 3.5%. A similar result was found by Proudfit,7 with cardiac mortality being 0.6% in patients with normal angiography, increasing to 1.9% in the presence of õ30% stenosis, and 15.9% in patients with 30% to 50% stenosis during a 10year follow-up period. In our study, myocardial infarction requiring hospitalization 2 years before the angiogram was more common in group 2. On the other hand, no significant difference in development of myocardial infarction has been demonstrated during 2 years following the angiogram. Probably the discrepancies between our study and previous studies can be explained by the relative short follow-

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FIGURE 1. Percentage of patients with normal or near-normal coronary angiogram requiring hospitalization during 2 years before and 2 years after angiography.

a rather small proportion of the 57 of 75 patients who were found to have normal coronary angiograms. Groups 1 and 2 (n Å 163) Our data show a significant reHospitalization (d) duction in need for hospitalization Before Angiography After Angiography p Value mean { SD during the 2 years after diagnostic All reasons 7.6 { 10.8 4.9 { 16.0 õ0.001 angiogram compared with the 2 Cardiac 6.6 { 10.3 2.8 { 13.0 õ0.001 years before the procedure in those Myocardial infarction 0.5 { 2.0 0.0 { 0.0 õ0.001 Angina pectoris 4.8 { 9.0 1.3 { 8.7 õ0.001 patients with normal and near-norChest pain, unspecific 0.4 { 2.3 0.5 { 4.3 — mal coronary angiography. This is Heart investigation 0.5 { 1.5 0.5 { 3.7 — entirely owing to reduction of hosCongestive heart failure 0.2 { 1.6 0.4 { 4.2 — pitalization due to cardiac causes. Arrythmias 0.2 { 1.0 0.1 { 0.5 — The explanation for less frequent Noncardiac 1.0 { 4.0 2.0 { 6.6 õ0.05 Stroke 0.0 { 0.0 0.1 { 0.9 — hospitalization could be an improvePulmonary embolism 0.0 { 0.6 0.5 { 4.1 — ment in symptoms that have been described in a frequency of 20% to p values are given if õ0.05. 80% in patients with nonsignificant coronary arteriograms.6,7,16 – 18 The large variance in these studies can be exup (2 years). Myocardial infarction being more com- plained by different populations being investimon before the diagnostic angiogram could be ex- gated. Another explanation for the reduction of plained by the fact that myocardial infarction hospitalization could be reassurance, for both the constituted an indication for performing coronary patient and the physician, that no serious coronary angiography. artery disease is present.16 The increase in hospiRequirement of hospitalization describes the mor- talization due to noncardiac causes after the angibidity since this could be an expression of severe or ogram can be explained by other diagnoses (e.g., disabling chest pain as well as other severe symp- esophagus or musculoskeletal disease was given toms. Ockene et al16 described that use of medical instead of angina pectoris). In conclusion, early facilities decreased from 1.6 to 0.16 visits per year catheterization seems to be a long-term cost effecafter the diagnostic procedure. This was nevertheless tive approach to most patients with chest pain. TABLE III Hospitalization During Two Years Before and During Two Years After Investigation Revealing Normal or Near-Normal Coronary Angiography

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TABLE IV Hospitalization During Two Years Before and Two Years After the Diagnostic Angiogram in Relation to Angiographic Finding Before Angiogram Group 2

Group 1

All reasons Cardiac Myocardial infarction Angina pectoris Chest pain (other genesis) Congestive heart failure Arrhythmia Heart investigation Noncardiac Stroke Pulmonary embolism

After Angiogram Group 2

Group 1

%

Mean

%

Mean

p Value

%

Mean

%

Mean

p Value

65 61 4 47 7 4 3 13 10 0 1

7.3 6.6 0.2 5.1 0.5 0.3 0.1 0.5 0.7 0.0 0.1

66 62 14 50 4 0 6 16 14 0 0

8.2 6.6 1.1 4.0 0.4 0.0 0.4 0.6 1.6 0.0 0.0

— — õ0.05 — — — — — — — —

33 19 0 8 4 1 1 9 20 1 2

5.2 3.5 0.0 1.6 0.6 0.5 0.0 0.8 1.8 0.1 0.5

40 24 0 14 6 2 4 4 24 4 2

4.0 1.3 0.0 0.6 0.3 0.2 0.2 0.1 2.7 0.2 0.6

— — — — — — — — — — —

p values are given if 0.05. % Å percentage of patients being hospitalized. Group 1 Å patients with normal coronary angiogram (n Å 113). Group 2 Å patients with near-normal coronary angiogram (n Å 50). Mean Å mean days in hospital. p Å difference between patients with completely normal and near-normal angiogram in mean days of hospital stay.

TABLE V Hospitalization During Two Years Before and Two Years After the Diagnostic Angiogram in Relation to Exercise Test Before Angiogram Negative ETT

All reasons Cardiac Myocardial infarction Angina pectoris Chest pain (other genesis) Congestive heart failure Arrhythmia Heart investigation Noncardiac Stroke Pulmonary embolism

After Angiogram

Positive ETT

Negative ETT

Positive ETT

%

Mean

%

Mean

p Value

%

Mean

%

Mean

p Value

70 67 7 51 10 0 4 15 11 0 0

7.6 6.8 0.5 4.9 0.8 0.0 0.2 0.5 0.8 0.0 0.0

60 55 6 44 3 5 4 13 12 0 1

7.5 6.4 0.5 4.6 0.1 0.5 0.1 0.6 1.2 0.0 0.1

— — — — — õ0.05 — — — — —

31 20 0 7 6 0 1 8 17 1 0

2.8 1.7 0.0 0.9 0.3 0.0 0.0 0.5 1.2 0.1 0.0

40 21 0 13 3 3 3 6 27 3 4

7.1 4.1 0.0 1.8 0.7 0.8 0.1 0.7 3.0 0.1 1.1

— — — — — — — — — — —

p values are given is below 0.05. % Å percentage of patients being hospitalized. Mean Å mean days in hospital. Negative ETT Å patients with negative exercise test (n Å 48). p Å difference between patients with positive and negative exercise test in mean days of hospital stay. Positive ETT Å patients with positive exercise test (n Å 78).

Study limitations: Some weaknesses in the analysis must be pointed out. Registration data were incomplete in 421 patients (12%) but few of these showed nonsignificant disease. Missing data regarding hospitalization in geographic areas other than those we examined are probably limited since in Sweden the responsible physician is routinely notified if patients are hospitalized in another area. Furthermore, this is an observational trial and within the groups a comparison is made between 2 different time periods; 1 before and 1 after the coronary angiogram. This implies that time, because patients were older at the second period, could have influenced the result; it is reasonable to believe that utilization of medical resources increases with age.

Acknowledgment: We are grateful to Maria Haglid, Margareta Sjo¨lin, and Maureen Jehler for their excellent technical assistance.

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