Abstract
While exercise treadmill test (ETT) is a useful initial test for patients with suspected cardiovascular disease, there is concern regarding the use of downstream imaging tests especially in the setting of equivocal or positive ETTs. Patients with no prior history of coronary artery disease (CAD) who underwent ETT between 2009 and 2010 were prospectively included. Referring physicians were categorized as cardiologists and non-cardiologists. Downstream tests included nuclear perfusion imaging, coronary computed tomography (CT) angiography, stress echocardiography, stress magnetic resonance, and invasive coronary angiography performed up to 6 months after the ETT. Patients were followed for cardiovascular death, myocardial infarction, and coronary revascularization for a median of 2.7 years. Among 3,656 patients, the ETT were negative in 2876 (79%), positive in 132 (3.6%) and inconclusive in 643 (18%). Cardiologists ordered less downstream tests than non-cardiologists (9.5% vs. 12.2%, p=0.02), with less non-invasive tests (5.9% vs. 10.4%, p<0.0001) and more invasive angiography (3.6% vs. 1.8%, p<0.0001). After adjustment for confounding, patients evaluated by cardiologists were less likely to undergo additional testing after equivocal (odds ratio: 0.65, p=0.02) or positive ETT results (odds ratio: 0.39, p=0.02), while after negative ETT the odds ratio was 1.7 (p=0.06). There was no difference in the rate of adverse cardiovascular events between patients referred by cardiologists versus non-cardiologists. In conclusion, patients referred for ETT by cardiologists are less likely to undergo additional testing, particularly non-invasive tests, than those referred by non-cardiologists. The lower rate of tests is driven by a lower rate of tests following positive or inconclusive ETT.
Keywords: exercise treadmill testing, downstream utilization, physician specialty, outcomes/ coronary artery disease
Introduction
Exercise treadmill testing (ETT) is commonly performed to evaluate patients with chest pain who are able to exercise and have a normal baseline electrocardiogram (ECG).1 Due to its widespread availability, ETT is routinely ordered by both cardiologists and non-cardiologists for a wide range of clinical indications. However, appropriate interpretation of ETT results is not always simple2 and prior experience and training may impact how the test results are integrated with other clinical information into a management plan. The expanded use of advanced non-invasive imaging tests has led to growing concerns about the increased use of CV testing.3 Although medical societies have developed appropriate use criteria to address these concerns,4–7 preliminary data shows that they do not reduce the utilization of inappropriate tests.8 Recognizing the need for other methods to reduce overutilization of testing, some studies have evaluated the impact of patient characteristics on the use of CV imaging tests.9,10 However, there is limited data evaluating the contribution of physician specialty as a source of variability in the use of CV imaging tests. Therefore, we sought to evaluate the impact of physician specialty on the use of additional cardiac testing following ETT.
Methods
We prospectively collected data on all consecutive patients above the age of 18 years who underwent clinically indicated ETT between January 1, 2009 and December 31, 2010 at Brigham and Women’s Hospital, in Boston, Massachusetts. The study excluded patients with prior diagnoses of CAD, (defined as prior coronary artery bypass grafting, percutaneous coronary intervention, and myocardial infarction (MI)) and patients with non-clinical indications for testing such as exercise prescription, participation in a research protocol, and post-heart transplant evaluation. The Partners Healthcare Institutional Review Board approved this study.
Information on demographics, clinical history, risk factors, medications and indications for testing was collected using a standardized patient interview and confirmed by review of each patient’s longitudinal electronic medical record. We estimated the pretest probability of CAD using the Morise score11. Each physician initiating the referral for an ETT was then categorized as a cardiologist or non-cardiologist. Non-cardiologists included primary care / internal medicine physicians as well as other specialists.
ETTs were performed using a symptom-limiting Bruce protocol according to established guidelines 12 as part of routine clinical care. The target heart rate was determined as 85% of the maximum predicted heart rate, which equals 220 – age. All ST segment deviations were assessed 80ms after the J point. The Duke treadmill score was calculated for each patient as: exercise time (minutes) – (5 × maximal ST-segment depression in millimeter) – (4 × angina index; 0, no angina; 1, angina; 2, angina as reason for stopping test)13.
We categorized each test results as positive, negative, or inconclusive. Positive tests were defined as upsloping ST depressions ≥ 1.5mm, or downsloping or horizontal depressions ≥ 1.0mm in at least two contiguous ECG leads. Inconclusive tests included any result that may be interpreted as indeterminate, and comprised the following categories: (1) negative ECG with reduced sensitivity due to submaximal exercise (<85% maximum predicted heart rate and rate pressure product < 25,000); (2) positive ECG with reduced specificity due to baseline ECG abnormalities; (3) positive ECG with reduced specificity due to rapid recovery of ECG changes; (4) typical anginal symptoms or (5) inappropriate dyspnea despite a negative ECG findings, and (6) clinically significant rhythm disturbances (any sustained arrhythmia or >3 beats of ventricular tachycardia).
For each patient, we identified the use of all non-invasive imaging and invasive angiography tests performed within 6 months following ETT through review of the electronic medical record. We chose the 6-month cutoff to capture any downstream testing that was likely triggered by the ETT results.
We included all possible subsequent non-invasive imaging tests available at our institution: nuclear stress tests, stress echocardiograms, coronary computed tomography angiography, and stress magnetic resonance imaging. All tests were performed and reported according to institutional protocols. We categorized all nuclear stress tests (positron emission tomography and single photon emission computed tomography) results as follows: negative, for normal test results; equivocal for ‘inconclusive’ or ‘negative with reduced exercise capacity’; and positive for ‘abnormal’ or ‘probably abnormal’ results14 15. We categorized the coronary computed tomography angiography results as negative for reports of no plaque or stenosis ≤50%; and positive for stenosis >70% (or >50% in the left main coronary). We defined as inconclusive for the evaluation of ischemia any studies that were uninterpretable or had moderate (51–70%) stenosis, given that such lesions may not be associated with ischemia and have uncertain hemodynamic significance16. We categorized cardiac magnetic resonance results as negative if no ischemia was detected; equivocal if image quality precluded interpretation and positive if ischemia was identified. We categorized results of echocardiograms as positive, negative, or equivocal based on the presence or absence of stress-induced wall motion abnormalities. Equivocal tests were defined as ones in which reduced image quality limited the evaluation, or if patients failed to achieve 85% of the maximum predicted heart rate.
We defined obstructive CAD as a stenosis greater than or equal to 50% in the left main coronary artery or greater than or equal to 70% in any other coronary vessel.
We reviewed all patient charts to identify incident non-fatal myocardial infarction and coronary revascularizations, which comprised all percutaneous coronary interventions and coronary artery bypass graft procedures. MI was defined using universal criteria17.
We determined patients’ vital status using the Social Security Death Index, and the cause of death using chart review, autopsy findings, and hospice notes where available. If the chart lacked information to determine the cause of death, we used death certificates obtained from the Massachusetts Registry of Vital Records & Statistics. Two cardiologists blinded to all clinical information and test results adjudicated the cause of death for each patient. CV death was defined as acute MI, atherosclerotic coronary vascular disease, congestive heart failure, valvular heart disease, arrhythmic heart disease, or stroke. Major adverse CV events were the combined outcome of CV death, non-fatal MI and coronary revascularization.
Continuous variables are expressed as the mean ± standard deviation or median and interquartile range, as appropriate. Categorical variables are presented as frequencies. Differences between groups were tested using chi-square or Fisher’s exact tests for discrete variables and one-way analysis of variance (ANOVA) for continuous variables. The analysis of the rate of second testing was performed with the estimation of univariable and multivariable logistic regressions. To adjust for confounding on variables that may influence the use of downstream testing, we built multivariable logistic regression models including age, gender, number of risk factors, symptoms and ETT results. Separate models were developed for: (a) all downstream testing, (b) non-invasive testing, and (c) invasive testing. In order to evaluate for effect modification of ETT results between cardiologists and non-cardiologists, interaction terms were included in the models and reported when significant. To compare cardiovascular outcomes, we calculated the annualized rate of CV death, myocardial infarction, and coronary revascularization as well as the combined outcome which includes any of these three events. All tests were two-sided, and p <0.05 was considered statistically significant. Statistical analysis was performed using Stata version 12 (Statacorp, EUA). This study had no external funding source.
Results
Among 4,262 consecutive patients referred for ETT during the study period, we excluded 509 patients with prior CAD, 9 patients with age under 18, and 88 patients who underwent ETT for indications other than evaluation of CAD, such as a research protocol or post-heart transplantation. The final study population included 3,656 patients, all of which had complete follow-up for cardiovascular death. Follow-up data for incident MI or coronary revascularization was available for 3,345 (91.4%) patients. Patients with incomplete follow-up for incident MI or coronary revascularization achieved higher MET, had a higher Duke Treadmill score, and were less likely to have typical angina symptoms.
The baseline characteristics of the patient population (age 54 (13) years, 46% male) stratified by specialty of the physician initiating the referral to ETT are presented in Table 1. Among all patients referred for ETT, 1058 (29%) were referred by cardiologists, whereas 2598 (71%) were referred by non-cardiologists. Although patients referred by cardiologists were older and more likely to be male, they had a lower prevalence of diabetes and hypertension as well as lower BMI. Accordingly, patients referred by cardiologists had a lower probability of CAD by the Morise score [29.8% (22.0%) vs. 36.5% (21.1%), p<0.0001].
Table 1.
Baseline characteristics stratified by physician specialty.
| Variable | All | Cardiologists | Non-Cardiologists | p-value |
|---|---|---|---|---|
| n = 3656 | n = 1058 (29%) | n = 2598 (71%) | ||
| Men | 1681 (46%) | 552 (52%) | 1129 (43%) | <0.0001 |
| Age (years) | 53.6±13.2 | 54.7±11.9 | 51.1±15.9 | <0.0001 |
| Hypertension* | 1681 (46%) | 450 (43%) | 1231 (47%) | 0.008 |
| Diabetes mellitus | 470 (13%) | 96 (9%) | 374 (14%) | <0.0001 |
| Hyperlipidemia† | 1537 (42%) | 461 (44%) | 1076 (41%) | 0.23 |
| Smoker | 468 (13%) | 120 (11%) | 348 (13%) | 0.09 |
| Body Mass Index (kg/m2) | 28.2 (6.5) | 26.9 (5.9) | 28.7 (6.6) | <0.0001 |
| Morise score | 10.4 (4.5) | 9.3 (4.8) | 10.9 (4.3) | <0.0001 |
| Symptoms | <0.0001 | |||
| Asymptomatic | 214 (6%) | 89 (8%) | 125 (5%) | |
| Non-anginal chest pain | 1676 (46%) | 275 (26%) | 1401 (54%) | |
| Atypical chest pain | 297 (8%) | 39 (4%) | 258 (10%) | |
| Typical chest pain | 241 (7%) | 53 (5%) | 188 (7%) | |
| Dyspnea or other symptoms | 1228 (34%) | 602 (56%) | 626 (24%) | |
| Medications at baseline | ||||
| Statins | 1045 (29%) | 314 (29%) | 731 (28%) | 0.34 |
| Aspirin | 1103 (30%) | 289 (27%) | 814 (31%) | 0.01 |
| β blocker | 746 (20%) | 285 (27%) | 461 (18%) | <0.0001 |
| Exercise test results | 0.44 | |||
| Negative | 2478 (68%) | 701 (66%) | 1777 (68%) | |
| Equivocal | 1043 (28%) | 317 (30%) | 726 (28%) | |
| Positive | 135 (4%) | 40 (4%) | 95 (4%) | |
| MET | 10.8 (4.3) | 11.8 (4.1) | 10.4 (4.3) | <0.0001 |
| Duke Score | 8.6 (5.2) | 9.5 (4.9) | 8.3 (5.3) | <0.0001 |
| Symptoms during ETT | <0.0001 | |||
| None | 2420 (66%) | 757 (72%) | 1663 (64%) | |
| Typical angina pectoris | 150 (4%) | 38 (4%) | 112 (4%) | |
| Atypical angina pectoris | 184 (5%) | 26 (3%) | 158 (6%) | |
| Dyspnea | 459 (13%) | 108 (10%) | 351 (14%) | |
| Other symptoms | 443 (12%) | 129 (12%) | 314 (2%) | |
Hypertension was defined as a systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg, or diagnosis/treatment of hypertension.
Hyperlipidemia was defined as total cholesterol > 240 mg/dL or high density lipoprotein cholesterol (HDL) <40 mg/dL (male) or < 50 mg/dL (women) or diagnosis/treatment of dyslipidemia.
There was no significant difference in ETT results when ordered by cardiologists versus non-cardiologists (Figure 1). However, patients referred by cardiologists achieved higher MET (11.8 (4.1) vs. 10.4 (4.3), p<0.0001 and had a higher Duke Treadmill score [9.5 (4.9) vs. 8.3 (5.3), p<0.0001] (Table 1).
Figure 1.
Results of ETTs according to the specialty of the physician ordering the initial test. p=0.01
Patients who had the ETT ordered by a cardiologist underwent less downstream testing (9.5% vs. 12.2%, p=0.02) (Figure 2A.). This difference was driven by a lower rate of non-invasive imaging (5.9% vs. 10.4%, p<0.001). However, the rate of downstream invasive angiography was higher among patients initially evaluated by cardiologists (3.6% vs. 1.8%, p=0.001).
Figure 2.
A: Proportion of all patients undergoing additional testing after ETT according to physician specialty. B: Proportion of patients undergoing additional testing after negative ETT. C: Proportion of patients undergoing additional testing after equivocal ETT. D: Proportion of patients undergoing additional testing after positive ETT.
As expected, downstream utilization of all tests was lowest after a negative ETT and highest after a positive ETT irrespective of physician specialty (figure 2A). However, the relative frequency of downstream testing was different between cardiologists and non-cardiologists. In the setting of a negative ETT result, there was no significant difference in downstream testing between cardiologists and non-cardiologists (3.0% vs. 2.3%, respectively, p=0.21; figure 2B). Following an equivocal ETT, however, cardiologists ordered significantly less additional testing (18.0% vs. 28.0%, p=0.001; figure 2C). Similarly, the rate of downstream testing after a positive ETT was lower in patients referred by cardiologists (76.9% vs. 52.5%, p=0.005; figure 2D).
When specifically evaluating the rate of downstream non-invasive imaging tests, there was a lower rate for those initially evaluated by cardiologists when the ETT results were equivocal (10.7% vs. 26.5%, p<0.0001) or positive (25.0% vs. 45.3%, p=0.004), but not significantly different when the ETT results were negative (2.6% vs. 2.0%, p=0.35).
When specifically examining the use of downstream invasive angiography, there was a similar proportion between cardiologists and non-cardiologists following a negative (0.3% vs. 0.4%, p=0.55) as well as a positive ETT (27.5% vs. 31.6%, p=0.63). However, patients whose ETT was ordered by a cardiologist were more likely to undergo invasive angiography after an equivocal ETT (7.3% vs. 1.5%, p<0.0001).
In the setting of a negative test, and after adjusting for risk factors, age, gender, and indication for the ETT, the likelihood of additional testing was overall low and not significantly different between cardiologists and non-cardiologists (Figure 3).
Figure 3.
Multivariable analysis: Odds of downstream testing if ETT was ordered by cardiologists versus non-cardiologists. The values below 1 indicate groups in which non-cardiologists were more likely to order additional testing. Values above 1 indicate situations when a cardiologist was more likely to order additional testing. The black dots indicate the overall rate according to ETT result (negative on top, equivocal in the middle and positive in the bottom). The Red dots indicated the odds of additional NICVI be ordered in each subgroup, while the blue indicates the odds of downstream invasive angiography in each subgroup.
However, in the setting of equivocal (OR: 0.65; 95%CI: 0.46 – 0.93) or positive ETT (OR: 0.39; 95%CI: 0.17 – 0.86) results, those initially evaluated by cardiologists were less likely to undergo additional testing. These results were mainly driven by a reduction in the rate of non-invasive tests after equivocal (OR: 0. 41; 95%CI: 0.27 – 0.62) or a positive ETT (OR: 0.31; 0.12 – 0.81). However, those evaluated by cardiologists were more likely to undergo invasive angiography after an equivocal ETT exam (OR: 5.86; 95%CI: 2.71 – 12.63). The odds of downstream invasive angiography after positive ETT were similar between the two groups (OR: 0.93; 95%CI: 0.38 – 2.24). (Figure 3)
Overall, 73% of all additional tests following ETT were normal irrespective of who initiated the referral. However, there was a slightly higher frequency of abnormal tests if the initial evaluation was performed by a cardiologist compared to a non-cardiologist (25% vs. 18%, respectively, p=0.04). (Figure 4)
Figure 4.
Downstream test results, including both invasive and non-invasive testing, according to physician specialty.
Cardiovascular events
During a median follow up of 2.7 years (interquartile range 2.1 to 3.3 years), 47 (1.3%) patients died, including 9 (0.25%) from a CV cause; 11 (0.3%) patients had a MI, and 69 (2%) underwent coronary revascularization. The overall combined outcome of CV death, MI or revascularization occurred in 76 (2.2%) patients.
There was no difference in the annualized rate for the combined outcome of CV death, MI, or coronary revascularization for those initially evaluated by cardiologists versus non-cardiologists (1.27% vs. 0.85%, p=0.23). While there was no difference in the annualized event rate between cardiologists and non-cardiologists following a positive (p=0.65) or equivocal ETT (p=0.54), there was a significantly higher event rate following a negative ETT ordered by cardiologists (p=0.01, Figure 5). These differences in the rate of events after a negative ETT were mainly driven by coronary revascularizations, which represented 8 out of the 12 events observed among patients with a negative ETT.
Figure 5.
Overall incidence rate of events after ETT according physician specialty and ETT results.
Discussion
In the present study we compared downstream cardiovascular testing and outcomes following exercise treadmill tests between cardiologists and non-cardiologists. We found that patients initially evaluated by non-cardiologists underwent significantly more additional testing than those evaluated by cardiologists (12.1% versus 9.6%). This difference was driven mainly by an increase in the rate of noninvasive imaging tests (10.3% versus 6.0%), while the rate of invasive evaluation was increased in the group initially evaluated by cardiologists (3.6% vs. 1.8%). Interestingly, those trends remained essentially unchanged after adjustment for confounding patient characteristics, a finding which was not unexpected given the similar risk profiles of patients without CAD who are referred for ETT by the two groups. Additionally, we have demonstrated that even though the rate of testing was lower, the group evaluated by cardiologists had a higher yield (i.e. prevalence of positive results) when additional downstream testing was performed. Finally, we have demonstrated that despite these differences in use of testing, there was no significant difference in the overall event rate between these two groups.
Differences in the practice of medicine between generalists and specialists have been observed in many fields.18–22 In cardiology, prior studies demonstrated differences in prescription patterns, and outcomes among patients with heart failure and myocardial infarction. Prior studies have also demonstrated that non-cardiologists are less likely to order appropriately indicated nuclear stress tests23 or invasive angiograms.24 However, the use of downstream testing between cardiologists and non-cardiologists has not been reported previously.
Various factors may explain the differences in the use of downstream testing between cardiologists and non-cardiologists. First, non-cardiologists may have less expertise on how to interpret test results. Thus, an unexpected finding (equivocal or positive) may be more likely to be further investigated. On the other hand, cardiologists may have increased comfort in avoiding further testing in patients with abnormal results, when an overall favorable prognosis can be established based on patient characteristics and/or test result findings. Second, non-cardiologists in our center (and many others) are unable to directly order invasive angiography. Therefore, they may choose to first investigate patients with a non-invasive test instead of referring them to a cardiologist. Cardiologists, on the other hand, have easier access to invasive angiography, and are more likely to order them.
Even after a negative ETT, eight individuals were referred directly to invasive angiography without undergoing any non-invasive studies. Among those, one patient presented with an acute myocardial infarction within six months following ETT, two underwent invasive angiography as part of pre-operative evaluation, and five were referred to invasive angiography because of persistent chest pain despite negative ETT. Among these five patients, none were found to have obstructive CAD on invasive angiography.
This study has several limitations. First, this is a single center study and, thus, our results may be less reproducible in other health care systems in which the practice of cardiologists and non-cardiologists may be different. Second, although statistical methods were used to adjust for confounding, residual confounding of unmeasured patient characteristics may persist. Third, due to the low event rate observed in our study, our ability to detect differences in outcomes between different sub-groups of patients was limited.
Our results suggest the need for minimizing variability in downstream testing following ETT. Accomplishing this may require education of referring physicians regarding when to obtain (or defer) downstream testing. In addition, consultation with cardiologists (and possibly, cardiovascular imaging specialists), may be useful for deciding whether additional testing will be helpful. Further studies will be required to show whether such measures may decrease the rate of non-invasive testing, without affecting patient outcomes.
Table 2.
Baseline characteristics according to the use of downstream tests.
| Downstream testing | ||||
|---|---|---|---|---|
| All | No | Yes | p-value | |
| n = 3656 | n = 3240 (89%) | n = 416 (11%) | ||
| Men | 1681 (46%) | 1488 (46%) | 193 (46%) | 0.86 |
| Age (years) | 53.6±13.0 | 53.0±13.3 | 59.0±11.6 | <0.0001 |
| Hypertension* | 1681 (46%) | 1460 (45%) | 221 (53%) | 0.002 |
| Diabetes | 470 (13%) | 395 (12%) | 75 (18%) | 0.001 |
| Hyperlipidemia† | 1537 (42%) | 1330 (41%) | 207 (50%) | 0.001 |
| Smoker | 468 (13%) | 408 (13%) | 60 (14%) | 0.29 |
| Body Mass Index (kg/m2) | 28.2 (6.5) | 28.2 (6.5) | 27.7 (6.8) | 0.14 |
| Morise score | 10.4 (4.5) | 10.2 (4.5) | 12.1 (4.3) | <0.0001 |
| Symptoms | <0.0001 | |||
| Asymptomatic | 214 (6%) | 196 (6%) | 18 (4%) | |
| Non-anginal pain | 1676 (46%) | 1505 (46%) | 171 (42%) | |
| Atypical chest pain | 297 (8%) | 259 (8%) | 38 (9%) | |
| Typical chest pain | 241 (7%) | 185 (6%) | 56 (13%) | |
| Dyspnea or other symptoms | 1228 (33%) | 1095 (34%) | 133(32%) | |
| Medications at baseline | ||||
| Statins | 1045 (29%) | 887 (27%) | 158 (38%) | <0.0001 |
| Aspirin | 1103 (30%) | 939 (29%) | 164 (39%) | <0.0001 |
| β blocker | 746 (20%) | 648 (20%) | 98 (24%) | 0.09 |
| Exercise test results | <0.0001 | |||
| Negative | 2478 (68%) | 2416 (75 %%) | 62 (15%) | |
| Equivocal | 1043 (28%) | 785 (24%) | 258 (62%) | |
| Positive | 135 (4%) | 41 (1%) | 94 (23% | |
| METs | 10.8 (4.3) | 11.0 (4.4) | 9.3 (3.3) | <0.0001 |
| Duke Score | 8.6 (5.2) | 9.2 (4.3) | 3.7 (8.5) | <0.0001 |
| Symptoms during ETT | <0.0001 | |||
| None | 2420 (66%) | 2218 (68%) | 202 (48%) | |
| Typical angina | 150 (4%) | 69 (2%) | 81 (19%) | |
| Atypical angina | 184 (5%) | 171 (5%) | 13 (3%) | |
| Dyspnea | 459 (13%) | 366 (11%) | 93 (22%) | |
| Other symptoms | 443 (12%) | 416 (13%) | 27 (6%) | |
Hypertension was defined as a systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg, or diagnosis/treatment of hypertension.
Hyperlipidemia was defined as total cholesterol > 240 mg/dL or high density lipoprotein cholesterol (HDL) <40 mg/dL (male) or < 50 mg/dL (women) or diagnosis/treatment of dyslipidemia.
Footnotes
All authors report no conflict of interest.
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