Editor's Note: Based on Rozanski A, Gransar H, Hayes SW et al. Temporal trends in the frequency of inducible myocardial ischemia during cardiac stress testing: 1991 to 2009. J Am Coll Cardiol 2013;61:1054-65.

Background

The last two decades have fostered many advances in the field of cardiology with the evolution of non-invasive diagnostic strategies for coronary artery disease (CAD) as well as widespread use of pharmacological therapies for primary and secondary prevention of CAD. Over this time frame, there has been a dramatic decline in the rates of cardiac death, myocardial infarction (MI), and stroke, despite increases in the prevalence of common risk factors for CAD.¹ Rozanski and colleagues report the first study that investigates the temporal trends in frequency of abnormal myocardial perfusion imaging (MPI) in a large group of patients at a single center undergoing stress-rest single-photon emission computed tomography (SPECT) in the midst of these population-level changes in mortality and morbidity of cardiovascular disease.²

Methods

The study population was composed of a consecutive cohort of patients enrolled in the Cedars-Sinai Medical Center registry of SPECT-MPI between January 1991 and December 2009. Of the 51,689 patients, 12,174 were excluded for a history of known cardiovascular disease described as prior MI, percutaneous coronary intervention (PCI), coronary bypass surgery (CABG), cardiomyopathy, or valvular heart disease. The remaining 39,515 were divided into groups based on four-year intervals from 1991 to 2009. Patients who had repeat SPECT-MPI studies only had their first one included in the analysis.

Patients underwent treadmill exercise testing using the symptom-limited Bruce protocol or pharmacological stress testing using adenosine, dipyridamole or dobutamine. Patients who could not attain 85% of their maximal predicted heart rate with exercise were converted to pharmacological stress testing. The interpretation of myocardial perfusion abnormalities was performed by using a 5-point score for each of the 20 segments prior to February 2005 and for 17 segments after February 2005. The summed scores were converted to a percentage of the left ventricle. Ischemic myocardium was then defined as normal, mild, moderate and severe based on scores of <5%, 5% to 9%, 10% to 14%, and >15% of the left ventricle, respectively. The mean follow-up for patients was 9.3 +/- 4.7 years (median 9.0 years).

Results

The baseline clinical characteristics demonstrated important trends with patients being younger in the later time periods as well as a higher proportion of women, non-whites, and inpatients. In addition, the symptom profile changed with a reduction in the proportion of patients referred with typical angina. Prevalence of CAD risk factors increased over time, which correlated with a slight increase of the mean pre-test Bayesian likelihood for CAD to 42.9% from 40.1%. There was an increased use of aspirin, lipid-lowering, and anti-hypertensive medications. The method of testing also changed with a decrease in the percentage of patients referred for exercise-stress testing from 1991 to 2009 (47.5% from 70.4%).

The prevalence of abnormal stress SPECT-MPI studies declined from 40.9% in 1991 to 8.7% in 2009 (p<0.00001). This was paralleled by a decline in ischemic SPECT-MPI studies as well as moderately to severely abnormal SPECT-MPI from 29.6% in 1991 to 5.0% in 2009 (p<0.0001) and 20.6% in 1991 to 4.6% in 2009 (p<0.00001), respectively. In addition, the subset of patients who underwent exercise stress testing with MPI had the lowest rate of abnormal tests with a prevalence of only 2.9%. This decline was seen among all age groups, both genders, all ethnicities, and regardless of referral from an outpatient or inpatient center.

The following risk factors were identified as predictors of abnormal and ischemic SPECT-MPI for each of the four temporal groups: age, male sex, inpatient status, typical angina, dyspnea, hypertension, smoking, diabetes, higher body mass index, abnormal rest electrocardiogram, the use of cardioprotective medications, and the performance of pharmacological stress testing.

Conclusions

From 1991 to 2009 there has been a marked progressive decline in the frequency of both abnormal SPECT-MPI studies as well as ischemic studies with the absolute prevalence of abnormal or ischemic tests accounting for <10% of all studies performed at a single academic center. These findings suggest that clinicians may need to reconsider whom they send for SPECT-MPI (and other methods of stress testing), and new approaches are needed to evaluate these low-risk patients.

Perspective

This study by Rozanski et al. highlights the low rates of abnormal SPECT MPI studies in a large cohort of patients being evaluated at a single tertiary academic center in the modern era.The cause of these low rates is clearly multifactorial including the patient population, referral biases, and increases in widespread use of aggressive medical therapy for primary prevention of coronary artery disease. In a contemporary group of outpatients referred for stress testing Mudrick and colleagues found that within 60 days of stress testing only 8.8% of these patients underwent coronary angiography and only 2.7% required revascularization. These patients also had a very low rate of cardiovascular events at one year. This study also highlighted that SPECT-MPI was the most frequent type of stress test ordered, accounting for 54% of referrals of 80,676 studies performed.³ Bourque et al. demonstrated similar low rates of significant ischemia in diabetic patients at intermediate risk for coronary artery disease with 5% and only 2.1% subsequently undergoing cardiac catheterization.⁴ One explanation for the low rate of abnormal studies was the substantial proportion of patients that were asymptomatic ranging from 23% to 32% in the Cedars-Sinai cohort. In addition, those patients who were able to exercise with good functional capacity had the lowest rates of inducible ischemia. Bourque and coworkers further explored this cohort and demonstrated that patients who achieved ≥ 10 METS with an intermediate risk profile had an exceedingly low rate of ischemia on MPI at less than 1%.⁵ This emphasizes the need to reassess whether the addition of MPI to standard exercise treadmill testing offers any incremental benefit in the prediction of cardiac events in the low to intermediate risk patient that may be referred for SPECT-MPI. This topic is highlighted in the accompanying case.

In addition to the low rates of inducible ischemia, the fact that these rates have progressively declined over the past two decades warrants a review of overall ordering trends. This is the only large retrospective study in the literature that compares rates of ischemia over the past 20 years. It is important to note that the volume of studies performed and included in this analysis also varied over time with the lowest volume at 6,335 studies in the earliest group from 1991 to 1995 and the peak at 14,089 studies in the third group from 2001-2005. The number of studies subsequently decreased in the 2005-2009 group to 8,827. These numbers are after the exclusion of 12,174 patients with known prior cardiovascular disease (which accounted for 25% of the population) and repeat studies for patients during this time period (unknown number). When we compare the volume of SPECT MPI studies at our nuclear cardiology laboratory at Northwestern Memorial Hospital, we see similar trends. It appears that our percentage of normal studies has increased as well. A recent abstract from our lab indicated that 73% of the studies were read as normal although this analysis didn't exclude all patients with prior CAD, just those with prior CABG.⁶

It is important to note that the ACCF/ASNC Appropriate Use Criteria for SPECT MPI were first released in 2005,⁷ and adherence to these recommendations may have contributed to this reduction in overall volume. Other national organizations such as the American Board of Internal Medicine have continued to place escalating pressure to limit over-utilization and transition towards high-value cost-conscious care strategies highlighting stress testing with cardiac imaging as an over-utilized diagnostic strategy.^{8, 9} In this modern era of health care reform, there will continue to be increasing emphasis on minimizing cost while maximizing value, and this study by Rozanski et al. offers critical insight into the low rates of inducible myocardial ischemia with SPECT-MPI in a contemporary referral base of patients at a major academic center, which supports the need to revise referral strategies for SPECT-MPI to limit detrimental downstream economic and health effects.

However, despite the introduction of the Appropriate Use Criteria, widespread acceptance has not yet been accomplished and there remains substantial variation in referral patterns among providers. Hendel et al. undertook a prospective study to assess for rates of "inappropriate" studies among large academic centers and enrolled 6,351 patients at six diverse clinical sites and demonstrated that 14% of studies were deemed inappropriate of which low-risk asymptomatic patients accounted for 45% of ordered studies. In addition, they suggested that live tracking with feedback to providers may promote quality initiatives to reduce inappropriate referrals.¹⁰ One particular subset of patients that may account for asymptomatic referrals are patients who are referred prior to non-cardiac surgery for risk stratification. Koh et al. demonstrated that these asymptomatic patients who are referred for SPECT-MPI prior to non-cardiac surgery account for the majority of inappropriate referrals and further demonstrated that MPI results did not predict outcomes in these inappropriately referred patients as the overall incidence of events was exceedingly low.^{11, 12}

Emerging diagnostic modalities will also play a role in the value equation for SPECT-MPI. Min et al. demonstrated that use of coronary CTA evaluation compared with SPECT-MPI in patients with stable CAD resulted in increased rates of medical therapy and coronary revascularization but with lower total costs and lower effective radiation dose.¹³ Ultimately, our role on an individual and national level will be to determine how to utilize each diagnostic modality in the appropriate patient to garner the greatest benefit, limit harm, and provide high value cost-conscious care.

---

References

1. Roger VL, Go AS, Lloyd-Jones DM et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 2012;125:e2-e220.
2. Rozanski A, Gransar H, Hayes SW et al. Temporal trends in the frequency of inducible myocardial ischemia during cardiac stress testing: 1991 to 2009. Journal of the American College of Cardiology 2013;61:1054-65.
3. Mudrick DW, Cowper PA, Shah BR et al. Downstream procedures and outcomes after stress testing for chest pain without known coronary artery disease in the United States. American Heart Journal 2012;163:454-61.
4. Bourque JM, Patel CA, Ali MM, Perez M, Watson DD, Beller GA. Prevalence and Predictors of Ischemia and Outcomes in Outpatient Diabetic Patients Referred for SPECT Myocardial Perfusion Imaging. Circulation Cardiovascular Imaging 2013.
5. Bourque JM, Charlton GT, Holland BH, Belyea CM, Watson DD, Beller GA. Prognosis in patients achieving >/=10 METS on exercise stress testing: was SPECT imaging useful? Journal of Nuclear Cardiology 2011;18:230-7.
6. Trivedi A LE, Lee D, Holly TA. . Adding Routine Prone Imaging to Supine Single Photon Emission Computed Tomography Myocardial Perfusion Imaging Safely Improves CAD Evaluation. . J Nucl Cardiol (in press) 2013.
7. Hendel RC, Berman DS, Di Carli MF et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 appropriate use criteria for cardiac radionuclide imaging: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. Circulation 2009;119:e561-87.
8. Qaseem A, Alguire P, Dallas P et al. Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care. Annals of Internal Medicine 2012;156:147-9.
9. Ferguson T. Improving health outcomes and promoting stewardship of resources: ABIM Foundation's Choosing Wisely campaign. The virtual mentor : VM 2012;14:880-4.
10. Hendel RC, Cerqueira M, Douglas PS et al. A multicenter assessment of the use of single-photon emission computed tomography myocardial perfusion imaging with appropriateness criteria. Journal of the American College of Cardiology 2010;55:156-62.
11. Koh AS, Flores JL, Keng FY, Tan RS, Chua TS. Evaluation of the American College of Cardiology Foundation/American Society of Nuclear Cardiology appropriateness criteria for SPECT myocardial perfusion imaging in an Asian tertiary cardiac center. Journal of Nuclear Cardiology 2011;18:324-30.
12. Koh AS, Flores JL, Keng FY, Tan RS, Chua TS. Correlation between clinical outcomes and appropriateness grading for referral to myocardial perfusion imaging for preoperative evaluation prior to non-cardiac surgery. Journal of Nuclear Cardiology 2012;19:277-84.
13. Min JK, Koduru S, Dunning AM et al. Coronary CT angiography versus myocardial perfusion imaging for near-term quality of life, cost and radiation exposure: a prospective multicenter randomized pilot trial. Journal of Cardiovascular Computed Tomography 2012;6:274-83.

Keywords: Coronary Artery Disease, Coronary Disease, Myocardial Infarction, Myocardial Perfusion Imaging, Secondary Prevention, Stroke, Tomography, Emission-Computed, Single-Photon

< Back to Listings