Chapter 20: Cost-Effectiveness of Nuclear Cardiology

Nuclear cardiology in its over 40 years of use has grown to one of the most utilized and performed medical procedures in the United States, with cardiovascular imaging tests frequently being listed among the top 200 Medicare expenditures.^1–3 As nuclear cardiology has blossomed into an over $1 billion per year industry, increased attention and scrutiny have been given to this testing approach, particularly with cost-effectiveness playing a more central role. This has been seen in several different ways. Appropriate use criteria (AUC) have become mainstream tools in providing decision-making support as to whether or not a test or procedure is indicated based on evidence combined with expert consensus opinion.^4–6 This has contributed to a downtrend in the number of nuclear stress tests performed annually over the last decade (Fig. 20-1).⁷ In addition, in an era with continued technological advancements in each of the cardiac imaging modalities, clinicians often have multiple testing options that can be performed for a particular patient prompting a decision process that necessitates the evaluation of cost-effectiveness.^6,8

Since 2005, which reflected the peak years of nuclear cardiology reimbursement, there have been increased restrictions on referrals for diagnostic testing including preauthorization and test substitution, as well as reductions in reimbursement for location of testing performed (outpatient vs. hospital based). In addition, the Institute of Medicine in 2009 suggested that 30% or $750 billion per year was spent on unnecessary medical services,⁹ which puts all procedures under scrutiny. As the value of an imaging study becomes a pivotal issue, every diagnostic test must now pass individually defined quality and efficiency criteria. The value of the imaging study must balance the cost of the procedure with its impact on changing patient treatment and influencing outcomes. As the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015 is implemented, the net value of the imaging procedure will directly impact on levels of reimbursement.

Thus, as the cost of diagnostic testing now plays a greater role in clinical decision making, clinicians have to be well educated in the science and economics of medicine as it impacts their daily practice. This chapter will discuss approaches to optimize the efficiency and quality of care based on patient selection for testing. This will be followed by a review of the definitions currently used for analysis and determination of cost-effectiveness. Finally, we will discuss sentinel studies that have examined value-based comparative approaches to diagnostic testing using nuclear stress tests as compared to other imaging modalities among patients presenting with stable ischemic heart disease or acute chest pain.

The value of a test can be directly correlated to the selection of an appropriate test for a particular patient. In 2005, the AUC were first released by the American College of Cardiology to help guide clinicians in the selection of nuclear stress tests for the most common indications.⁴ These were revised in 2009⁵ as the initial AUC document was incorporated into payer decisions for test reimbursement. The AUC for stable ischemic heart disease have been updated as part of a new set of multimodality AUC.⁶ This latest document also reflects changes in terminology to now include: appropriate, may be appropriate, and rarely appropriate.⁶ Refer to Chapter 13 for a more detailed discussion of AUC.

The use of clinical decision support for the selection of appropriate tests is mandatory for most commercial payers and is also a central portion of Medicare health care reform policies. The Protecting Access to Medicare Act of 2014 (PAMA) includes stipulations that require the use of clinical decision support tools as part of the reimbursement process for imaging including nuclear cardiology.⁸

The passing of the Affordable Care Act of 2010 in the United States brought increased attention to value-based purchasing,¹⁰ which examined health care value and included factors of quality and cost. Value-based purchasing can be mathematically written as:

From this equation, it is clear that value increases as either quality increases or costs decrease. However, how is quality defined? In general, quality has been expressed as efficiency relating the processes incorporated to attain a certain goal. In health care, it is often associated with outcomes, which include survival or quality of life.¹¹ For cost, the question remains for what period of time the cost is impacted (e.g., episode of care). In value-based imaging, for example, we can compare two test modalities such as an exercise treadmill stress test and a nuclear stress test. For the actual test performed, there is a monetary cost associated with the specific test, which is one portion of the diagnostic evaluation cost.¹² Based on the results of a certain test, additional diagnostic testing, procedures and/or treatments may be required, which result in a higher cost of the diagnostic test approach beyond the index procedure.¹³ However, over what timeframe do we allow these additional costs to be attributed to the index imaging procedure? There is as of yet no clear definition to incorporate associated downstream costs, but the length of time must be long enough to see the full benefit of the test and its subsequent results to fruition.¹⁴ Moreover, an episode of care can be quite short for an acute evaluation, but may also be protracted for lower risk, stable patients.

Cost-effectiveness in cardiac imaging may involve two different approaches and compares the costs and outcomes of these testing strategies. It is important to keep in mind that one of the comparators can be no testing at all.¹⁴ Quality-adjusted life-year (QALY) can be used to measure this outcome, which incorporates survival adjusted for quality of life.¹⁴ The incremental cost-effectiveness ratio (ICER) is the summed calculation and allows for comparison of two diagnostic approaches. This can be mathematically written (with 1 and 2 representing the two diagnostic tests) as:

It is important for the definition of cost-effectiveness to identify both absolute thresholds as well as the impact of selecting one modality over another while incorporating downstream-related expenses. The thresholds of QALY have varied in studies, but have often been designated as $50,000 in previous literature.^14,15 Recently, the World Health Organization has suggested an alternative calculation based on an individual country's gross domestic product (GDP). Using the recommendation of three times the GDP would result in a new threshold in the United States of <$150,000 per life-year saved.¹⁴

The American College of Cardiology and the American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines now mandates that in addition to "Level of Evidence" for clinical guideline recommendations, that there also be a category of "Level of Value."¹⁴ This proposal would include four categories: high value (H); intermediate value (I); low value (L); uncertain value (U). The dollar amount associated with these categories is linked with previously defined benchmarks of ICER (Table 20-1).

It has now been almost 20 years since one of the most sentinel papers regarding cost-effectiveness in cardiac imaging was published. The Economics of Noninvasive Diagnosis (END) Multicenter Study Group examined the cost impact of an approach using an initial referral for stress myocardial perfusion tomography versus direct referral for coronary angiography without initial noninvasive testing.¹⁶ In this study, 11,372 patients were prospectively evaluated for costs of care both in their initial diagnostic testing and in composite costs over a 3-year period. The costs of care using radionuclide myocardial perfusion imaging (range, $2,387–$3,010) were lower than for patients undergoing direct angiography (range, $2,878–$4,579) (p < 0.0001) despite similar rates of death or myocardial infarction (p > 0.20). Part of this increased cost was due to higher rates of revascularization among patients in the invasive arm. Reductions in cost were also seen due to only one-third of patients assigned to the initial imaging strategy undergoing subsequent coronary angiography. Although some interpreted these results as a license to use nuclear stress testing as a "gatekeeper," it should instead be viewed as a precursor to trials such as COURAGE and BARI-2D, in that revascularization based solely on anatomic disease increases cost without a clinical benefit in terms of event-free survival (i.e., death or myocardial infarction-free survival).^17–19

Figure 20-2 shows a graph from the END Multicenter Study Group comparing both the diagnostic and follow-up costs for different clinical risk subsets of patients for stress-first versus invasive-first approaches. Upon review of this finding, several factors have to be kept in mind: (1) The dollar amounts in this figure reflect health care costs from 1995 which would clearly underestimate current costs¹⁶; (2) Both guideline-directed medical therapy and revascularization technologies have improved, which also underestimate the costs to both arms if reproduced at present day; (3) Referral patterns for patients undergoing ischemic heart disease evaluation have changed with recent studies showing lower abnormality rates for single-photon emission computed tomography (SPECT) testing.²⁰ These factors taken together would suggest a greater cost-effectiveness for a cardiac imaging first approach in stable ischemic heart disease.

In 1999, the Economics of Myocardial Perfusion Imaging in Europe (EMPIRE) study retrospectively examined 396 patients for the cost-effectiveness of several diagnostic strategies, as well as the quality of diagnosis in a patient population undergoing initial evaluation of suspected coronary artery disease.¹³ The diagnostic approaches evaluated in this trial were exercise stress testing, nuclear stress testing and coronary angiography with differentiation between institutions using nuclear stress testing routinely and for those who did not. The results from the EMPIRE study revealed that costs associated with both initial diagnostic approaches were reduced for institutions utilizing SPECT stress testing as well as a 32% lower 2-year diagnostic and management costs in these populations among patients without identified obstructive coronary artery disease. In patients where the algorithm was SPECT stress testing followed by coronary angiography versus angiography alone, 2-year costs were reduced 54% and 36% in patients without disease and those with disease, respectively, when using SPECT first (Fig. 20-3).¹³

More recent data presented in the Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease (SPARC) registry evaluated 1703 patients who were prospectively monitored after SPECT, positron emission tomography (PET), or 64-slice coronary computed tomography angiography (CCTA) for their 90-day cardiac catheterization rates.^3,21 The results showed that referral to catheterization was relative to the severity of the noninvasive test abnormalities across all modalities, 2.8% catheterization rate in those with normal/nonobstructive results, 20.3% catheterization rate in those with mildly abnormal results, and 48.2% catheterization rate in those with moderate or severe abnormal results (p < 0.001). However, the referral rate to catheterization for patients in the CCTA arm (13.2%) was higher when compared to SPECT (4.3%) and PET (11.1%) (p < 0.001).³

For the purposes of this discussion on cost-effectiveness, subsequent analysis from the SPARC registry was performed to evaluate resource use, medical costs, and clinical outcomes for this cohort, allowing calculation of cost-effectiveness for the varying diagnostic test strategies.²² These results revealed that 2-year costs were lowest for those who underwent initial SPECT testing compared to CCTA and PET (mean $3,965 vs. $4,909 vs. $6,647, respectively), which persisted after multivariable adjustment for clinical characteristics. Furthermore, patients undergoing CCTA had costs that were 15% higher than those undergoing SPECT. However, after controlling for longer survival, the cost-effectiveness of one modality over another became uncertain.²² Notably, this registry was based on physician choice for test selection, and not randomization, and thus selection biases and additional confounders may have been present.

In the Cost-Effectiveness of Noninvasive Cardiac Testing (CECat) trial, 898 patients at high risk for obstructive coronary artery disease were randomized to SPECT, stress echocardiography, magnetic resonance perfusion imaging or index coronary angiography.²³ The goal was to compare the index noninvasive test versus direct coronary angiography. Survival was generally similar across the patients randomized to stress echocardiography and radionuclide stress testing when compared to coronary angiography (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.4–2.9; and HR 1.6, 95% CI 0.6–4.0, respectively). However, magnetic resonance perfusion imaging was noted to have a nearly threefold increased risk of death (HR 2.6, 95% CI 1.1–6.2). In the quality-of-life analysis, no difference was found in any of the four arms, thus revealing a similar pattern across all of the compared patient subsets. Notably, the cost of the index coronary angiography compared to index noninvasive testing was lower, but this was partially attributed to the high rate of subsequent coronary angiography among patients undergoing index noninvasive testing (75–80%). Of note is a key statement made in their report, "Our data clearly demonstrate a limited future role for cost-effective noninvasive imaging if referring physicians are not willing to accept a negative result as ground truth."²³ This underlines the utilization of noninvasive testing results in determining patients who would benefit from coronary angiography.

A different conclusion was reached from the results of the single-center clinical evaluation of magnetic resonance imaging in coronary heart disease (CeMARC). A total of 752 patients with suspected angina and at least one cardiovascular risk factor were recruited to undergo SPECT, CMR, or coronary angiography in order to evaluate the sensitivity, specificity, positive predictive value, and negative predictive value of SPECT versus CMR when using coronary angiography as the gold standard.²⁴ A subsequent decision analytic model was applied to this data to identify the most cost-effective diagnostic approach in a similar patient population.²⁵ Two diagnostic approaches using CMR (one with index ETT testing followed by CMR after a positive or inconclusive ETT and the other with index CMR) were concluded to be the most cost-effective with a threshold range cost of £20,000 (index ETT) to £30,000 (index CMR). In the recently published CE-MARC 2 trial, CMR and SPECT both reduced the probability of unnecessary angiography compared with NICE guideline-directed care. There was no statistical significance between the CMR and SPECT arms.²⁶

Importantly, one of the least costly of initial noninvasive tests has been the exercise treadmill test (ETT). In the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial, 824 women with intermediate pretest likelihood of coronary artery disease were randomized to an index diagnostic test of ETT versus exercise SPECT imaging.¹² Of note, all enrolled patients had interpretable EKGs for ischemia and predetermined exercise tolerance >5 METs. Two-year major adverse cardiac event (MACE)-free survival was similar in the two groups with 98.0% in the ETT arm and 97.7% in the MPI arm (p = 0.59). The index testing costs for patients undergoing ETT averaged $154.28 compared to exercise MPI of $495.24 (p ≤ 0.001). This cost benefit was sustained when follow-up testing was also added with the ETT arm averaging $337.80 versus the exercise MPI at $643.24 (p ≤ 0.001) (Table 20-2). These results support the cost-effectiveness of index diagnostic testing using ETT in lower-risk women who have an ability to exercise and have an interpretable EKG. Although not a cost-effectiveness trial by design, Borque et al. evaluated a similar question of additive benefit of myocardial perfusion imaging among patients who were able to exercise beyond 10 METS without ischemic ECG changes.²⁷ This study demonstrated that the prevalence of >10% ischemia in this group was very low (0.6%) with an annual cardiac mortality rate of 0.1% per year. Given these low event rates, it appears that there is little incremental value of SPECT MPI for patients who can perform a high-level exercise without ECG evidence for myocardial ischemia.

In 2015, the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial published results comparing noninvasive anatomic assessment versus functional testing for patients presenting with chest pain.²⁸ A total of 10,003 symptomatic outpatients who required nonurgent, noninvasive cardiac evaluation were randomized to initial evaluation with CCTA versus stress testing (67% stress radionuclide imaging, 23% stress echocardiography, and 10% ETT). The primary endpoint of a composite of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar between the diagnostic arms with an event rate of 3.3% in the CCTA group and 3.0% in the functional-testing group (HR 1.04; 95% CI 0.83–1.29, p = 0.75). An economic analysis of 9649 of the enrolled patients was subsequently published.²⁹ The costs were divided into three sections: First, was the cost of the index testing. The range of mean costs for different modalities ranged from $174 for ETT and up to $1132 for pharmacologic SPECT. The second analysis examined cumulative costs through 90 days. In comparing treatment approaches, the CCTA strategy had mean costs of $2494 compared to the functional strategy costs of $2240. A major component of this cost difference was attributed to coronary angiography and revascularization. In the CCTA group, 12.2% of the patients underwent invasive angiography with 6.2% undergoing revascularization compared to 8.1% of the functional testing group undergoing invasive angiography and 3.2% undergoing revascularization. Through 3 years of follow-up, using bootstrap analysis, the cost differences between anatomic versus functional diagnostic testing were minimal after the first year ($26 in year 2 and $91 in year 3 after removal of an outlier representing a noncardiovascular hospitalization). Figure 20-4 shows the cost differences between the two diagnostic approaches. Similarly, a retrospective analysis of Medicare spending from a sample of 282,830 patients from 2005 to 2008 showed that those undergoing evaluation with CCTA had a higher rate of subsequent invasive angiography compared to patients undergoing SPECT evaluation (22.9% vs. 12.1%, p < 0.001),³⁰ which led to higher total costs for CCTA. Importantly, medication use was not included as part of the cost calculations in either of these studies. As revealed in a secondary analysis of SPARC, aspirin and statin utilization were greater following an index CCTA as compared to an index SPECT.³ Whether these changes in medication use could have prevented clinical worsening, additional downstream testing, or coronary hospitalizations are unknown, but are important variables to consider in cost-effectiveness analysis.

A subset of patients where cost-effectiveness of nuclear stress testing is important has been evaluated among those undergoing evaluation in the emergency department (ED) for acute chest pain. Each year, over 8 million patients are evaluated in the ED in the United States for low-risk chest pain with costs in excess of $10 billion per year,^31–34 which has recently gained even more importance as medicine has seen a substantive movement from inpatient to outpatient care. The cost-effectiveness of different diagnostic modalities has additional components in this patient population including: time to diagnosis, hospital length of stay, and need for follow-up testing postdischarge. Thus, within nuclear cardiology, significant attention had been paid to the concept of acute chest pain imaging,³¹ which uses an injection of a radiopharmaceutical while the patient is at rest but during or shortly after an episode of chest pain. Using this approach, an injection of radioisotope, in the setting of suspected acute myocardial ischemia, can be used to help differentiate focal-decreased perfusion from ischemia. In a sentinel article looking at early patient hospital discharge, Udelson et al. reported that hospitalizations among patients without evidence of acute ischemia on nuclear testing were reduced by 10% (52% of patients with usual care compared to 42% with sestamibi imaging).³² Although only modest cost savings per patient ($60–72) were realized due to the added expense of SPECT imaging, the overall impact could be translated into savings of more than $14 million annually. Heller et al. similarly found in a patient sample of 357 patients that normal SPECT findings during the evaluation of acute chest pain resulted in more prompt and higher rates of discharge from the ED, with a mean cost savings of $4258 per patient.³² Stowers et al. looked at a sample of 46 patients who were assigned to perfusion imaging-guided diagnostic approach versus conventional evaluation (blinded to the perfusion results) and found a $1843 median reduction in in-hospital costs in the perfusion imaging-guided approach.³⁴ These results have been replicated in several additional studies.³⁵

More commonly, an evaluation to exclude acute coronary syndrome consists of serial cardiac enzymes followed by rest–stress radionuclide imaging. In the Coronary Computed Tomographic Angiography for Systemic Triage of Acute Chest Pain Patients to Treatment (CT-STAT) trial, 699 patients presenting to the ED for evaluation of low-risk chest pain were randomized to index testing with CCTA versus SPECT.³⁶ Two key findings were relevant to our cost-effectiveness discussion. First, the time to diagnosis was 54% shorter in the arm undergoing index CCTA (median 2.9 hours in the CCTA arm compared to 6.2 hours in the SPECT arm, p < 0.0001). However, the amount of time for test completion should be considered given the increased time required for SPECT versus CCTA as well as need for serial biomarker testing. Second, the total ED costs were reduced in the CCTA arm by over 38%. The median CCTA cost was $2137 compared to $3458 for SPECT (p < 0.0001) despite no difference in the actual cost of the diagnostic test. Of note, these costs do not take into effect subsequent costs after the initial emergency room discharge and also include the required additional emergency room time needed for serial cardiac enzymes. In the Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain by the ROMICAT-II investigators, early CCTA was compared to standard ED treatment for 1000 patients with suspected acute coronary syndromes.³⁷ No difference was seen in the cost of the two approaches with the CCTA at $4289 cumulative mean cost and the standard evaluation group at $4060.

The above studies relate times to discharge from the ED. However, new MPI protocols have resulted in reduction in time for testing. One particular protocol using selective stress-only testing can result in significant reduction in time required prior to a negative result. In a retrospective analysis performed by Duvall et al., the utilization of a selective stress-only protocol revealed a lower rate of follow-up testing in the nuclear stress arm as compared to the CCTA arm, which may reduce overall costs associated with SPECT.³⁸ In addition, multiple studies have shown that the prognosis associated with a normal stress-only scan is similar to that of a normal rest/stress MPI scan.^39–41

In this chapter, we have highlighted the economic evidence and provided clinicians with a clearer understanding of the factors determining varying cost-effectiveness of diagnostic imaging test strategies. Both in patients with suspected stable ischemic heart disease and in those who present to the ED with acute chest pain, radionuclide stress testing has been shown to be a cost-effective approach to the management of these patients. When comparing direct invasive angiography first approaches to radionuclide stress testing, the data have repeatedly shown cost-effectiveness to using a noninvasive testing first approach. In the ED evaluation, studies have shown a more equipoise in the cost-effectiveness among noninvasive tests when comparing radionuclide imaging to coronary CT angiography. As newer technologies become available for clinical use, the comparative cost-effectiveness of these new diagnostic testing modalities will need to be investigated against those which have been our mainstay testing for almost the last half-century.