EXPEDITED REVIEW
Clinical Outcomes After Both Coronary Calcium Scanning and Exercise Myocardial Perfusion Scintigraphy
Alan Rozanski, MD, FACC*,
Heidi Gransar, MS ,
Nathan D. Wong, PhD, FACC ,
Leslee J. Shaw, PhD,
Romalisa Miranda-Peats, MPH,
Donna Polk, MD,
Sean W. Hayes, MD,
John D. Friedman, MD, MPH, FACC and
Daniel S. Berman, MD, FACC,*
* Department of Medicine, St. Luke’s Roosevelt Hospital, New York, New York
Departments of Imaging and Medicine and the Burns and Allen Research Institute, Cedars-Sinai Medical Center, and the Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
Heart Disease Prevention Program, University of California, Irvine, California.
Manuscript received August 22, 2006;
revised manuscript received November 22, 2006,
accepted December 8, 2006.
* Reprint requests and correspondence: Dr. Daniel S. Berman, Director of Cardiac Imaging, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 1258, Los Angeles, California 90048. (Email: bermand{at}cshs.org).
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Abstract
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Objectives: The purpose of this work was to assess the prognosis in patients undergoing both coronary artery calcium (CAC) scanning and exercise myocardial perfusion scintigraphy (MPS).
Background: Whereas the prognostic effectiveness of MPS is well established, recent studies indicate that quantification of CAC also predicts cardiac outcomes. However, prognostic information is not yet available upon which to guide the management of patients who have had both tests.
Methods: We assessed the frequency of cardiac death and myocardial infarction over a mean follow-up of 32 ± 16 months in 1,153 patients undergoing both CAC scanning and MPS. Results were compared with those from a referent cohort of 9,308 patients who had earlier undergone MPS only.
Results: The frequency of myocardial ischemia rose with increasing CAC scores (p < 0.001), but ischemia was present in only 64 patients. Among the 1,089 nonischemic patients, of which only 3 (0.3%) underwent early revascularization, the annualized cardiac event rate was <1% in all CAC subgroups, including those with CAC scores >1,000. Kaplan-Meier analysis revealed similarly low cardiac event rates among nonischemic patients with CAC scores >1,000 and nonischemic patients with Bayesian coronary artery disease likelihood  85%. Late myocardial revascularization rates were also similar in these 2 groups.
Conclusions: Among patients with nonischemic MPS studies, high CAC scores do not confer an increased risk for cardiac events. Thus, although patients with high CAC scores may be considered for intensive medical therapy to prevent future coronary artery disease events, a normal MPS study in such patients suggests no need for more aggressive interventions.
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Abbreviations and Acronyms
| | ASCAD = angiographically significant coronary artery disease | | CAC = coronary artery calcium | | CAD = coronary artery disease | | CSMC = Cedars-Sinai Medical Center | | EBT = electron beam computed tomography | | MPS = myocardial perfusion scintigraphy | | MSCT = multislice computed tomography |
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The clinical management of patients suspected of having angiographically significant coronary artery disease (ASCAD) is often aided by the performance of stress tests, such as myocardial perfusion scintigraphy (MPS). For instance, because a normal exercise MPS study reliably signifies a low annualized risk of major cardiac events among patients with even a high Bayesian pre-MPS likelihood of ASCAD (1), it is generally reasonable to employ conservative medical management when such patients are nonischemic. By contrast, because the likelihood of cardiac events increases exponentially according to the magnitude of ischemia (2), patients with moderate-to-severe ischemia generally deserve aggressive interventions. These robust prognostic associations help account for the current ubiquitous use of cardiac stress testing in clinical practice.
Recently, coronary artery calcium (CAC) scanning has been advocated as a new method for risk stratifying patients at intermediate risk for ASCAD. Atherosclerotic lesions are frequently associated with the presence of calcium (3,4), which can be accurately detected using computed tomography and quantified according to calcium (5), volume (6), and percentile calcium scores (7). Measurements of CAC have been shown to predict the underlying magnitude of atherosclerotic burden (8–10), the frequency of stress-induced myocardial ischemia (11,12), and the likelihood of future cardiac events in longitudinal studies (13–18). To date, however, this newer method of risk stratification has not been compared directly to cardiac stress testing for prognostic purposes. Thus, there is as yet no information to guide physicians in their clinical assessment and subsequent management of patients who have undergone both forms of testing. Perhaps most puzzling may be the following question: do high CAC scores, an indicator of increased long-term risk, still confirm an increased likelihood of future cardiac events in patients with nonischemic MPS studies, an indicator of low risk? To address this issue, we undertook a study that compares 3-year outcomes among patients undergoing both exercise MPS and CAC scanning.
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Methods
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Study population.
Two patients groups at Cedars-Sinai Medical Center (CSMC) were evaluated. The first group (the "CAC" group) consisted of 1,153 patients followed for 1 year after undergoing dual isotope exercise MPS and CAC scanning within 6 months of each other (mean of 24 ± 38 days), between April 1998 and January 2005. This CAC group included a mixed sample of 702 patients (61%) who were physician-referred for CAC scanning, 92 (8%) who were self-referred, and 359 (31%) who underwent scanning as part of an ongoing research protocol (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research Study). Coronary artery calcium scanning was performed before MPS in 517 (55%) patients and on the same day or after MPS in 636 (55%) patients. The second group (hereafter referred to as the "MPS" group) consisted of 9,308 patients followed for 1 year after undergoing MPS on a clinical basis between March 1991 and September 1999. Patients with known coronary artery disease (CAD), valvular disease, or known cardiomyopathy were excluded. This MPS referent group allowed us to investigate whether there is a parallel between the prognostic relationship between CAD likelihood values and MPS results and CAC values and MPS results, in light of data indicating that CAC increases patients’ Bayesian likelihood for CAD (19). This research was approved by the CSMC Institutional Review Board, and all patients signed informed consent.
Stress testing and imaging protocol.
Patients were injected intravenously at rest with thallium-201 (3 mCi to 4 mCi). After rest MPS, patients underwent symptom-limited Bruce protocol treadmill exercise testing, with a 20 mCi to 30 mCi dose of technetium-99m sestamibi injected at near maximal exercise, and MPS imaging was then repeated. The MPS studies were acquired using elliptical 180° orbits and standard energy windows (19). Scintigrams were assessed semiquantitatively by visual interpretation of 20 myocardial segments according to a 5-point score, and summed scores were compared at stress and rest (20). A summed difference score 4, corresponding to 5% of the myocardial segments with reversible defect (21), defined the presence of ischemia.
Calcium scanning.
Scanning was performed using either electron beam (EBT) (Imatron C-150 or GE eSpeed, General Electric, Milwaukee, Wisconsin) (n = 934 patients) or multislice computed tomography (MSCT) (n = 219 patients), with acquisitions consisting of approximately 30 to 40 3-mm or 2.5-mm slices for the 2 tomographic systems, respectively (12). Foci of coronary artery calcification were identified and scored by an experienced technician, blinded to both patient characteristics and the MPS results, using semiautomatic commercial software on a NetraMD workstation (ScImage, Los Altos, California) by detection of at least 3 contiguous pixels (voxel size = 1.03 mm3) of peak density 130 HU within a coronary artery, with scoring verified by an experienced imaging cardiologist. Coronary artery calcium scores were calculated according to the method of Agatston et al. (5), and age- and gender-adjusted CAC percentile scores were determined according to the database of Raggi et al. (7).
Likelihood of CAD.
The likelihood of ASCAD, exclusive of the MPS results, was calculated for each patient based on the Bayesian analysis of patients’ age, gender, risk factors, chest pain symptoms, and results of exercise electrocardiography according to a previously validated commercial software program (CADENZA, Advanced Heuistics, Bainbridge Island, Washington) (22).
Follow-up.
Patients were followed for the occurrence of hard cardiac events, which included either the occurrence of cardiac death, as noted and confirmed by a review of death certificate and hospital chart or physician’s record, or myocardial infarction, as evidenced by the appropriate combination of patients’ signs and symptoms and enzyme elevations (23). In addition, we identified if patients underwent cardiac catheterization or coronary revascularization procedures (coronary bypass or percutaneous coronary interventions), and defined these as "early" if they occurred  60 days of noninvasive testing and "late" if they occurred >60 days after testing. The performance of late myocardial revascularization was a secondary end point in this study based on its use as a proxy variable for worsening clinical status (24). As previously described (25), initial patient follow-up was obtained by searching our hospital-based information system (WebVS) as well as the Social Security Death Index. Follow-up in the remaining patients was sought through a mailed questionnaire or a scripted telephone interview. To ascertain the cause of death, the information provided by WebVS and the death certificates obtained for all those who died in Los Angeles County were reviewed by 2 cardiologists blinded to subjects’ clinical information. Death from cardiac causes was defined as death from any cardiac cause (e.g., lethal arrhythmia, myocardial infarction, or pump failure).
Statistical analysis.
Continuous variables were compared using t tests or nonparametric Wilcoxon rank sum tests, depending on whether or not the assumptions for the test were met, whereas categorical variables were compared using the chi-square test. Chi-square test for trend was used when appropriate. Time to follow-up or events was calculated from the date of the second test to either the follow-up time or time of the first event. Early revascularizations <60 days were censored, except as noted. Kaplan-Meier survival curves were generated, and compared using the log-rank test. Cox proportional hazards survival models, risk adjusted for mean age, gender, dyspnea, and various coronary risk factors, were also generated. The Kaplan-Meier survival curves were compared using the log-rank test. The CAC group was divided for this purpose into 3 subgroups: those with CAC scores <400, 400 to 999, and 1,000. Similarly, the MPS group was also divided into 3 groups based on CAD likelihood values, according to a commonly used division: those with "low" (<15%), "intermediate" (15% to 84%), and "high" (>85%) CAD likelihood values (1). Because of clinical differences in the CAC cohort and MPS cohorts, subgroups were selected using patient matching techniques based on propensity scores that matched patients from the CAC cohort to patients from the MPS cohort on age, gender, absence of chest pain symptoms, shortness of breath, pre-MPS likelihood of ASCAD, and exercise duration (26). The propensity-matched groups were compared using either the paired t test in the case of exercise duration or the nonparametric Wilcoxon signed rank test for all continuous variables, whereas the McNemar test was used to compare the categorical variables.
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Results
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For the CAC group, a total of 1,190 patients met inclusion criteria for our study. Of these, 37 patients (3%) were lost to follow-up, resulting in a study population of 1,153 patients. The mean (±SD) duration of follow-up in this group was 32 ± 16 months (range 12 to 76 months). For the MPS group, a total of 9,757 patients met inclusion criteria for this study. Of these, 449 patients (5%) were also lost to follow-up, resulting in a study population of 9,308 patients. The mean (±SD) duration of follow-up in this group was 35 ± 25 months (range 12 to 152 months). The clinical characteristics in our CAC and MPS groups are listed in Table 1. Patients in the CAC group were younger and contained more asymptomatic patients than those in the MPS group, but the 2 groups only differed modestly in terms of mean ASCAD likelihood and the mean number of CAD risk factors. Various exercise parameters, such as exercise duration, also differed between the 2 groups, and there was a substantially greater frequency of detected ischemia in the MPS group.
Frequencies of ischemia, revascularization rates, and cardiac events according to CAC score.
As indicated in Table 2, the frequency of inducible ischemia rose progressively with increasing CAC scores in the CAC group. Within this group, a high percentage of those patients having inducible ischemia underwent early coronary revascularization compared with the patients without inducible ischemia (42.2% vs. 0.3%, p < 0.0001). Accordingly, follow-up results for patients grouped according to level of CAC score in Table 2 are presented separately for the ischemic and nonischemic patients. Overall, only 64 (5.6%) patients had inducible ischemia, precluding any significant prognostic assessments in this patient subgroup. Among these ischemic patients, 38 (59%) had mild ischemia (i.e., summed reversibility score of 4 to 8, or involving 5% to 10% of the myocardium), whereas 26 (41%) patients had more moderate-to-severe ischemia (i.e., summed reversibility scores >8, involving >10% of the myocardium). The mean percentage of ischemic myocardium was significantly greater among the 27 patients who underwent early myocardial revascularization compared with the 37 who did not (13.9 ± 8.7% vs. 9.0 ± 4.5%, p = 0.01).
Among the nonischemic CAC patients, the frequency of referral to cardiac catheterization, early and late revascularizations, and cardiac events rose with increasing CAC scores, but the annualized frequency of cardiac events were quite modest, even among those with high CAC scores. We performed Kaplan-Meier survival curve analysis in these nonischemic CAC patients, after dividing them according to their magnitude of CAC (Fig. 1). Excluding early revascularizations, the event-free survival was >95% over the first 4 years of follow-up for each of these nonischemic CAC subgroups, and only small, but statistically significant, differences were observed in event-free survival according to the level of CAC. After adjusting for clinical factors, the differences in outcome among the 3 CAC subgroups were no longer significant. Thus, in the absence of inducible ischemia, the presence of higher CAC scores was still associated with a low risk of cardiac events during our 4-year follow-up.
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Figure 1 Cardiac Events According to CAC Scores
Survival curves for freedom from cardiac death or nonfatal myocardial infarction (MI) (y-axis) among the coronary artery calcium (CAC) patients who had nonischemic exercise myocardial perfusion scintigraphy studies. (Left) Kaplan-Meier survival curve analysis as a function of CAC scores before adjustment for covariates of outcome. The p value is derived using the log-rank test. (Right) Cox proportional hazards model for freedom from cardiac death or MI risk adjusted for age, dyspnea, and coronary risk factors. The p value is that of CAC in the Cox risk-adjusted model. Patients with early myocardial revascularization were censored from the analysis. DM = diabetes mellitus; SOB = shortness of breath.
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There was no difference in cardiac event rates among patients who were referred for CAC scanning for clinical versus research purposes or for those who were scanned using EBT versus MSCT.
Frequencies of ischemia, revascularization rates, and cardiac events in the MPS referral cohort.
As ASCAD likelihood increased, so did the frequency of inducible myocardial ischemia (Table 3). Among the MPS patients manifesting inducible ischemia, 27.7% underwent myocardial revascularization procedures, compared with only 0.4% among the patients with nonischemic MPS studies (p < 0.0001). Among the ischemic MPS patients, the frequency of revascularization procedures rose with increasing ASCAD likelihood, but the frequency of cardiac events did not. Among these patients, the percent ischemic myocardium was significantly greater in the 489 patients who underwent early myocardial revascularization compared with the 1,276 patients who did not (19.4 ± 10.0% vs. 11.6 ± 7.4%, p < 0.0001).
In the nonischemic MPS patients, the frequency of cardiac catheterization referral, early and late revascularizations, and cardiac events also rose with increasing ASCAD likelihood, but the differences among the ASCAD likelihood subgroups were modest. As seen for the nonischemic CAC patients grouped according to their CAC scores, the event-free survival was >95% over the first 4 years of follow-up for each of the ASCAD likelihood subgroups among the nonischemic MPS patients (Fig. 2). Before adjustment for significant covariates, there was a small but statistically greater cardiac event rate among the nonischemic MPS patients with ASCAD likelihood >85%, but this ASCAD subgroup no longer had a lower cardiac event rate than the other ASCAD likelihood subgroups after risk adjustment.
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Figure 2 Cardiac Events According to ASCAD LL
Survival curves for freedom from cardiac death or nonfatal myocardial infarction (MI) among the myocardial perfusion scintigraphy (MPS) referral subgroup who had nonischemic exercise MPS studies. (Left) Kaplan-Meier survival curve analysis as a function of the likelihood (LL) of angiographically significant coronary artery disease (CAD). (Right) Cox risk-adjusted model for freedom of cardiac death or MI risk adjusted for age, dyspnea, and coronary risk factors. Other abbreviations as in Figure 1.
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Comparison of cardiac event rates among matched nonischemic CAC and MPS patients.
In order to compare the relative frequency of cardiac event rates among the nonischemic CAC and MPS patients, we performed a 1:1 propensity matching, based on patient’s age, gender, distribution of type of chest pain symptoms, mean ASCAD likelihood values, and exercise duration. Both groups included 1,025 patients (Table 4), who differed statistically only in terms of dyspnea, diastolic blood pressure measurements, certain CAD risk factors, and frequency of ischemic exercise electrocardiogram responses. Figure 3
demonstrates that the overall frequency of cardiac events was very similar in the propensity-matched nonischemic CAC and MPS patients. When those with the highest CAC scores (>1,000) were compared with each of the ASCAD likelihood subgroups within the propensity-matched MPS cohort, there was no statistical difference in the frequency of cardiac events.
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Figure 3 Comparison of Outcomes Among Patient Groups
(Left) Kaplan-Meier survival curves for freedom from cardiac death or myocardial infarction in the propensity-matched coronary artery calcium (CAC) and myocardial perfusion scintigraphy (MPS) cohorts who had no ischemia during stress MPS testing. (Right) Kaplan-Meier survival curves for the propensity-matched MPS patients with coronary artery disease likelihood (LL) values <15%, 15% to 85%, and 85% and for the patients with CAC scores 1,000. There were no statistical differences among the subgroups.
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Frequency of late myocardial revascularizations.
As shown in Figure 4, event-free survival according to the secondary end point of late myocardial revascularization decreased with both increasing CAC scores in the nonischemic CAC subgroup and with increasing ASCAD likelihood in the nonischemic MPS subgroup. Comparison of the Kaplan-Meier event-free survival curves in the patients with high ASCAD likelihood to those with CAC scores >1,000 revealed no statistical difference in the frequency of late coronary revascularizations over time.
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Figure 4 Comparison of Rates for Late Revascularization
(Left) Kaplan-Meier curves for freedom from late myocardial revascularization among the coronary artery calcium (CAC) patients having nonischemic myocardial perfusion scintigraphy (MPS). (Right) Kaplan-Meier curves for freedom from late myocardial revascularization among the nonischemic MPS patients. CAD = coronary artery disease; LL = low likelihood.
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Discussion
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Recent follow-up studies demonstrate a proportional relationship between CAC scores and the frequency of adverse cardiac events (13–18). In our study, as CAC scores increased, so too did the frequency of inducible myocardial ischemia. Since myocardial ischemia is a potent predictor of future cardiac events (1,2), our results would appear to be concordant with follow-up studies concerning CAC scanning.
Prior epidemiologic studies have largely assessed the role of CAC scanning in screening populations but not the typical diagnostic patients that are referred for cardiac stress testing. However, because high CAC scores have now become a potential reason for referring patients for cardiac stress testing (11,12), there is an increasing need to understand the prognostic interrelationship between CAC scores and measurement of inducible myocardial ischemia. Accordingly, in this study, we evaluated cardiovascular outcomes among patients who underwent both CAC testing and exercise MPS in close temporal proximity. In our population, revascularization was driven by the presence of myocardial ischemia on MPS imaging, but very few patients with normal MPS underwent revascularization, even when the CAC score was very high. This practice, which probably reflected our physicians’ confidence in the prognostic significance of a normal MPS study, resulted in a unique opportunity for us to examine the interrelationship between "anatomic" evidence of CAD and physiology, namely how clinical outcomes vary according to a wide spectrum of CAC scores among patients without evidence of inducible ischemia, as measured during MPS. Our findings indicate that the magnitude of CAC exerted little influence upon outcomes among the patients who did not have inducible ischemia during MPS. Most notably, among the nonischemic patients with CAC scores >1,000, the frequency of cardiac death or myocardial infarction over  3 years of mean follow-up was <2%, thus yielding an annualized cardiac event rate of <1%.
Among patients with inducible myocardial ischemia, subsequent referral to cardiac catheterization is commonplace. In our study, 42% of CAC patients with inducible myocardial ischemia underwent early myocardial revascularization, with larger perfusion defects in these patients than those observed among ischemic patients who did not undergo myocardial revascularization. This "interventional referral bias" is the likely explanation for why cardiac event rates did not increase among our ischemic MPS subgroup as the likelihood of ASCAD increased. Similarly, because of this referral bias, we could not assess whether CAC scores added incremental information for predicting patient outcomes among patients with inducible myocardial ischemia.
Previous work by Budoff et al. (19) has suggested that progressively higher CAC scores increase the Bayesian likelihood of ASCAD, but complementary observations indicate that the likelihood of cardiac events still remains <1% for nonischemic MPS patients with a high Bayesian likelihood of CAD (1,23). Accordingly, we reasoned that there may be a parallel between outcomes observed in nonischemic patients who are stratified on the basis of ASCAD likelihood and those who are stratified on the basis of CAC scores. To assess this possibility, we also evaluated cardiac outcomes in a large series of patients who underwent exercise MPS studies in our laboratory, but from an earlier nonoverlapping period relative to the current recruitment of MPS patients for CAC scanning. Among the MPS patients without inducible ischemia, only a small increase in cardiac events occurred as the likelihood of ASCAD increased from small to high likelihood estimates, paralleling the pattern noted for CAC scores. Moreover, the frequency of cardiac events remained similarly low in the propensity-matched CAC and MPS subgroups that did not have inducible ischemia during exercise testing, including the subgroup of patients with CAC scores >1,000.
Pathophysiological considerations.
The induction of myocardial ischemia is the end result of not only angiographic stenoses but also pathophysiological factors, such as the degree of endothelial dysfunction, which can influence the adequacy of myocardial perfusion during physiological stimulation (27,28) and contribute to the magnitude of perfusion defects observed during exercise MPS (29,30). For this reason, the assessment of myocardial perfusion during stress MPS complements both angiographic measurements (31,32) and Bayesian estimations of ASCAD likelihood in the prediction of cardiac events (1,23). The presence of higher levels of CAC is a marker of greater atherosclerotic burden (8,9), but whether CAC scores also reflect greater functional abnormalities known to be associated with adverse cardiac events is not presently clear. A recent study (33) suggests that higher CAC scores signify a greater magnitude of endothelial dysfunction, but CAC measurements correlate relatively poorly, for example, with C-reactive protein levels, a measure of systemic inflammation (18,34). Although we observed a progressively higher frequency of inducible perfusion defects as CAC scores increased, our study did not assess pathophysiological abnormalities that may govern this association. However, our follow-up results suggest that the inherently greater risk that may be associated with higher CAC scores may be identified by evaluating such patients for inducible myocardial ischemia.
Various cohorts of patients have been identified who appear to have a heightened risk of cardiac events in the presence of a normal MPS study. These include diabetic patients (35), patients with atrial fibrillation (36), and patients complaining of dyspnea (24). Our data, however, suggests that a high CAC score is not an additional factor that heightens short-term risk in the presence of a normal MPS study.
Study limitations.
A number of limitations should be considered. First, because our CAC group had a low event rate with only 11 hard cardiac events, the small but statistically significant increase in hard cardiac events among nonischemic patients with high CAC scores would need additional study in larger samples to further assess the robustness of our findings. Second, a recent study (37) has suggested that diabetes and metabolic syndrome may modify the relationship between CAC scores and myocardial ischemia, but these and other potential modifying factors were not assessed in this study. One recent study (38) examined the prognostic relationship between CAC scores and MPS in type II diabetics, but the smaller sample size and event rate in that study, as well as its lack of a nondiabetic control group, precluded comparisons to our study. Third, comparison of our CAC to MPS cohorts was limited by differences in the clinical characteristics of these 2 groups, and also by differences in temporal recruitment. We overcome this issue, in part, by limiting our comparisons to propensity-matched cohorts, but this matching did not take into account important advances in the therapeutic management of nonischemic patients over the last decade. Nevertheless, this limitation does not detract from the general principle that we demonstrated in this study: neither high ASCAD likelihood values nor high CAC scores appear to constitute a pattern of increased prognostic risk in the presence of a nonischemic exercise MPS study. Finally, our study does not exclude the possibility of higher CAC scores reducing the "warranty period" associated with a normal MPS as patients are followed over longer time intervals.
Clinical relevance.
Although CAC scanning has shown promise as a means for risk stratifying patients with relatively low likelihood of ASCAD (13–18), the cost of such scanning is not widely covered by third-party insurers. A variety of factors may govern the current limited acceptance of this technology, including concern that it may lead to a substantial increase in further diagnostic tests and related healthcare costs. On the other hand, it is also possible that the judicious use of this technology could improve the risk assessment and management of patients in certain clinical subgroups in a cost-effective manner. For example, whereas a persistent trend to refer many patients with only a low likelihood of ASCAD for stress MPS studies has been documented (39), application of CAC scanning in such patients could potentially reduce the number of such patients who are then referred for MPS studies by preferentially limiting MPS referral to those patients with relatively higher CAC scores (12). However, support for such potential practice requires determination of the appropriate management for patients identified as having high CAC scores but nonischemic MPS studies. Our findings suggest that patients with this combination of findings are unlikely to benefit from myocardial revascularization procedures. Prospective study is required to determine whether a strategy of applying CAC scanning to patients with a low-to-intermediate likelihood of ASCAD, followed by the performance of MPS in those with a sufficiently elevated CAC score and reserving coronary angiography referrals for patients with inducible myocardial ischemia, represents a cost-effective strategy for managing patients.
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Footnotes
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This study was supported by a grant from The Eisner Foundation, Los Angeles, California.
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References
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