Economic and healthcare resource utilization assessments of PET imaging in Coronary Artery Disease diagnosis: a systematic review and discussion of opportunities for future economic evaluations.

AIMS: This systematic literature review (SLR) consolidated economic and healthcare resource utilization (HCRU) evidence for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to inform future economic evaluations. MATERIALS AND METHODS: An electronic search was conducted in MEDLINE, Embase, and Cochrane databases from 2012-2022. Economic and HCRU studies in adults who underwent PET- or SPECT-MPI for coronary artery disease (CAD) diagnosis were eligible. A qualitative methodological assessment of existing economic evaluations, HCRU, and downstream cardiac outcomes was completed. Exploratory meta-analyses of clinical outcomes were performed. RESULTS: The search yielded 13,439 results, with 71 records included. Economic evaluations and comparative clinical trials were limited in number and outcome types (HCRU, downstream cardiac outcomes, and diagnostic performance) assessed. No studies included all outcome types and only one economic evaluation linked diagnostic performance to HCRU. The meta-analyses of comparative studies demonstrated significantly higher rates of early- and late-invasive coronary angiography and revascularization for PET- compared to SPECT-MPI; however, the rate of repeat testing was lower with PET-MPI. The rate of acute myocardial infarction was lower, albeit non-significant with PET- vs. SPECT-MPI. LIMITATIONS AND CONCLUSIONS: This SLR identified economic and HCRU evaluations following PET- and SPECT-MPI for CAD diagnosis and determined that existing studies do not capture all pertinent outcome parameters or link diagnostic performance to downstream HCRU and cardiac outcomes, thus, resulting in simplified assessments of CAD burden. A limitation of this work relates to heterogeneity in study designs, patient populations, and follow-up times of existing studies. Resultingly, it was challenging to pool data in meta-analyses. Overall, this work provides a foundation for the development of comprehensive economic models for PET- and SPECT-MPI in CAD diagnosis, which should link diagnostic outcomes to HCRU and downstream cardiac events to capture the full CAD scope.

Combined stress myocardial CT perfusion and coronary CT angiography as a feasible strategy among patients presenting with acute chest pain to the emergency department.

BACKGROUND: A combined approach of myocardial CT perfusion (CTP) with coronary CT angiography (CTA) was shown to have better diagnostic accuracy than coronary CTA alone. However, data on cost benefits and length of stay when compared to other perfusion imaging modalities has not been evaluated. Therefore, we aim to perform a feasibility study to assess direct costs and length of stay of a combined stress CTP/CTA and use SPECT myocardial perfusion imaging (SPECT-MPI) as a benchmark, among chest pain patients at intermediate-risk for acute coronary syndrome (ACS) presenting to the emergency department (ED). METHODS: This is a prospective two-arm clinical trial (NCT02538861) with 43 patients enrolled in stress CTP/CTA arm (General Electric Revolution CT) and 102 in SPECT-MPI arm. Mean age of the study population was 65 â€‹± â€‹12 years; 56% were men. We used multivariable linear regression analysis to compare length of stay and direct costs between the two modalities. RESULTS: Overall, 9 out of the 43 patients (21%) with CTP/CTA testing had an abnormal test. Of these 9 patients, 7 patients underwent invasive coronary angiography and 6 patients were found to have obstructive coronary artery disease. Normal CTP/CTA test was found in 34 patients (79%), who were discharged home and all patients were free of major adverse cardiac events at 30 days. The mean length of stay was significantly shorter by 28% (mean difference: 14.7 â€‹h; 95% CI: 0.7, 21) among stress CTP/CTA (20 â€‹h [IQR: 16, 37]) compared to SPECT-MPI (30 â€‹h [IQR: 19, 44.5]). Mean direct costs were significantly lower by 44% (mean difference: $1535; 95% CI: 987, 2082) among stress CTA/CTP ($1750 [IQR: 1474, 2114] compared to SPECT-MPI ($2837 [IQR: 2491, 3554]). CONCLUSION: Combined stress CTP/CTA is a feasible strategy for evaluation of chest pain patients presenting to ED at intermediate-risk for ACS and has the potential to lead to shorter length of stay and lower direct costs.

Cost-effectiveness of cardiovascular imaging for stable coronary heart disease.

OBJECTIVE: To assess the cost-effectiveness of management strategies for patients presenting with chest pain and suspected coronary heart disease (CHD): (1) cardiovascular magnetic resonance (CMR); (2) myocardial perfusion scintigraphy (MPS); and (3) UK National Institute for Health and Care Excellence (NICE) guideline-guided care. METHODS: Using UK data for 1202 patients from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 trial, we conducted an economic evaluation to assess the cost-effectiveness of CMR, MPS and NICE guidelines. Health outcomes were expressed as quality-adjusted life-years (QALYs), and costs reflected UK pound sterling in 2016-2017. Cost-effectiveness results were presented as incremental cost-effectiveness ratios and incremental net health benefits overall and for low, medium and high pretest likelihood of CHD subgroups. RESULTS: CMR had the highest estimated QALY gain overall (2.21 (95% credible interval 2.15, 2.26) compared with 2.07 (1.92, 2.20) for NICE and 2.11 (2.01, 2.22) for MPS) and incurred comparable costs (overall £1625 (£1431, £1824) compared with £1753 (£1473, £2032) for NICE and £1768 (£1572, £1989) for MPS). Overall, CMR was the cost-effective strategy, being the dominant strategy (more effective, less costly) with incremental net health benefits per patient of 0.146 QALYs (-0.18, 0.406) compared with NICE guidelines at a cost-effectiveness threshold of £15 000 per QALY (93% probability of cost-effectiveness). Results were similar in the pretest likelihood subgroups. CONCLUSIONS: CMR-guided care is cost-effective overall and across all pretest likelihood subgroups, compared with MPS and NICE guidelines.

Cost-effectiveness of myocardial perfusion SPECT and stress test according to coronary revascularization therapy, cardiac events and total mortality: Register of 8,496 patients. / Coste-efectividad de la SPECT de perfusión miocárdica y de la prueba de esfuerzo en relación con la revascularización coronaria, eventos cardíacos y mortalidad total. Registro de 8.496 pacientes.

OBJECTIVE: The aim was to analyze the cost-effectiveness ratio (CER) of stress electrocardiogram (ES) and stress myocardial perfusion imaging (SPECT-MPI) according to coronary revascularization (CR) therapy, cardiac events (CE) and total mortality (TM). MATERIAL AND METHODS: A total of 8,496 consecutive patients who underwent SPECT-MPI were followed-up (mean 5.3±3.5years). Cost-effectiveness for coronary bypass (CABG) or percutaneous CR (PCR) (45.6%/54.4%) according to combined electrocardiographic ischemia and scintigraphic ischemia were evaluated. Effectiveness was evaluated as TM, CE, life-year saved observed (LYSO) and CE-LYSO; costs analyses were conducted from the perspective of the health care payer. A sensitivity analysis was performed considering current CABG/PCR ratios (12%/88%). RESULTS: When electrocardiogram and SPECT approaches are combined, the cost-effectiveness values for CABG ranged between 112,589€ (electrocardiographic and scintigraphic ischemia) and 2,814,715€ (without ischemia)/event avoided, 38,664 and 2,221,559€/LYSO; for PCR ranged between 18,824€ (electrocardiographic and scintigraphic ischemia) and 46,377€ (without ischemia)/event avoided, 6,464 and 36,604€/LYSO. To CE: the cost-effectiveness values of the CABG and CPR in presence of electrocardiographic and scintigraphic ischemia were 269,904€/CE-avoided and 24,428€/CE-avoided, respectively; and the €/LYSO of the CABG and PCR were 152,488 and 13,801, respectively. The RCE was maintained for the current proportion of revascularized patients (12%/88%). CONCLUSIONS: Combined ES and SPECT-MPI results, allows differentiation between patient groups, where the PCR and CABG are more cost-effective in different economic frameworks. The major CER in relation to CR, CE and TM occurs in patients with electrocardiographic and scintigraphic ischemia. PCR is more cost-effective than CABG.

MRI perfusion in patients with stable chest-pain.

Perfusion-cardiovascular MR (CMR) imaging has been shown to reliably identify patients with suspected or known coronary artery disease (CAD), who are at risk for future cardiac events and thus, allows for guiding therapy including revascularizations. Accordingly, it is an ideal test to exclude prognostically relevant coronary artery disease. Several guidelines, such as the ESC guidelines, currently recommend CMR as non-invasive testing in patients with stable chest pain. CMR has as an advantage over the more conventional pathways as it lacks radiation and it potentially reduces costs.

Design of CTP-PRO study (impact of stress Cardiac computed Tomography myocardial Perfusion on downstream resources and PROgnosis in patients with suspected or known coronary artery disease: A multicenter international study).

BACKGROUND: CT myocardial perfusion imaging (CTP) represents one of the newly developed CT-based techniques but its cost-effectiveness in the clinical pathway is undefined. The aim of the study is to evaluate the usefulness of combined evaluation of coronary anatomy and myocardial perfusion in intermediate to high-risk patients for suspected CAD or with known disease in terms of clinical decision-making, resource utilization and outcomes in a broad variety of geographic areas and patient subgroups. METHODS: CTP-PRO study is a cooperative, international, multicentre, prospective, open-label, randomized controlled study evaluating the cost-effectiveness of a CCTA+CTP strategy (Group A) versus usual care (Group B) in intermediate-high risk patients with suspected or known CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 2000 subjects will be enrolled and followed up for 24 months. The primary endpoint is the reclassification rate of CCTA in group A due to the addition of CTP. The secondary endpoint will be the comparison between groups in terms of non-invasive and invasive downstream testing, prevalence of obstructive CAD at ICA, revascularization, cumulative ED and overall cost during the follow-up at 1- and 2-years. The tertiary endpoint will be the comparison between each group in terms of MACE and cost-effectiveness at 1- and 2-years. CONCLUSIONS: The study will provide information to patients, health care providers and other stakeholders about which strategy could be more effective in the diagnosis of suspected CAD in intermediate to high-risk patients or in the symptomatic patients with known CAD and previous history of revascularization.

PET-Based Imaging of Ischemic Heart Disease.

PET-based cardiac nuclear imaging plays a large role in the management of ischemic heart disease. Compared with conventional single-photon emission CT myocardial perfusion imaging, PET provides superior accuracy in diagnosis of coronary artery disease and, with the incorporation of myocardial blood flow and coronary flow reserve, adds value in assessing prognosis for established coronary and microvascular disease. This review describes these and other uses of PET in ischemic heart disease, including assessing myocardial viability in ischemic cardiomyopathy. Developments in novel PET flow tracers and molecular imaging tools to assess atherosclerotic plaque vulnerability, vascular calcification, and vascular remodeling also are described.

Specificity of Myocardial Perfusion Imaging: Issues With Proposed MBS Item Review.

Myocardial perfusion scanning (MPS) is commonly used to assess patients with an intermediate to high risk of coronary artery disease. Concerns have been raised about the accuracy of this test. There is little recent data regarding the specificity of the MPS in the context of current medical therapy. The primary objective of this study is to determine the specificity of MPS in diagnosing obstructive coronary artery disease. A total of 184 patients fulfilled study criteria. The overall specificity of MPS for obstructive coronary artery disease was 54%.The only demographic variable that influenced specificity was gender: males with a specificity of 66% and females with a specificity of 29% (p-value=0.001). These results suggest that the real world specificity of MPS is lower than previously indicated, particularly in the female population. The limitations proposed by the Cardiac Services Committee Report are therefore unlikely to improve patient outcomes.

Coronary computed tomography angiography vs. myocardial single photon emission computed tomography in patients with intermediate risk chest pain: a randomized clinical trial for cost-effectiveness comparison based on real-world cost.

AIMS: To compare the cost-effectiveness of coronary computed tomography angiography (CCTA) vs. myocardial single photon emission computed tomography (SPECT) in patients with stable intermediate risk chest pain. METHODS AND RESULTS: Non-acute patients with 10-90% pre-test probability of coronary artery disease from three high-volume centres in Korea (n = 965) were randomized 1:1 to CCTA or myocardial SPECT as the initial non-invasive imaging test. Medical costs after randomization, the downstream outcome, including all-cause death, acute coronary syndrome, cerebrovascular accident, repeat revascularization, stent thrombosis, and significant bleeding following the initial test and the quality-adjusted life-years (QALYs) gained by the EuroQoL-5D questionnaire was compared between the two groups. In all, 903 patients underwent the initially randomized study (n = 460 for CCTA, 443 for SPECT). In all, 65 patients underwent invasive coronary angiography (ICA) in the CCTA and 85 in the SPECT group, of which 4 in the CCTA and 30 in the SPECT group demonstrated no stenosis on ICA [6.2% (4/65) vs. 35.3% (30/85), P-value < 0.001]. There was no difference in the downstream clinical events. QALYs gained was higher in the SPECT group (0.938 vs. 0.955, P-value = 0.039) but below the threshold of minimal clinically important difference of 0.08. Overall cost per patient was lower in the CCTA group (USD 4514 vs. 5208, P-value = 0.043), the tendency of which was non-significantly opposite in patients with 60-90% pre-test probability (USD 5807 vs. 5659, P-value = 0.845). CONCLUSION: CCTA is associated with fewer subsequent ICA with no difference in downstream outcome. CCTA may be more cost-effective than SPECT in Korean patients with stable, intermediate risk chest pain.

Contrast-Enhanced Stress Echocardiography and Myocardial Perfusion Imaging in Patients Hospitalized With Chest Pain: A Randomized Study.

Ultrasound contrast-enhanced stress echocardiography improves endocardial visualization, but diagnostic test rates versus stress myocardial perfusion imaging (MPI) have not been studied. A prospective randomized trial was performed between April 2012 and October 2014 at a single-center, safety net hospital. Hospitalized patients referred for noninvasive stress imaging were randomized 1:1 to stress echocardiography or stress MPI. The primary outcome was diagnostic test rate defined as interpretable images and achievement of >85% of age-predicted maximal heart rate (for dobutamine and exercise). Rates were assessed among those completing testing and then based solely on image interpretability. Charges and length of stay were secondary outcomes. A total of 240 patients were randomized, and 229 completed testing. Diagnostic test rates were similar for stress echocardiography versus MPI {89.4% [95% confidence interval (CI), 82.2-94.4] vs. 94.8% [95% CI, 89.1-98.1], P = 0.13} and did not differ with multivariable adjustment. Modalities requiring a diagnostic heart rate criteria were more frequently ordered with stress echocardiography (100% vs. 26%; P < 0.001). Therefore, an imaging-based analysis without the 12 individuals who failed to achieve target heart rate (n = 217) was evaluated with diagnostic test rates of 100% versus 94.8% (95% CI, 89.1%-98.1%; P = 0.03) for stress echocardiography and MPI, respectively. Median length of stay did not differ. Median (interquartile range) test-related charges were lower with stress echocardiography: $2,424 ($2400-$2508) versus $3619 ($3584-$3728), P < 0.0001. Overall, tests were positive for ischemia in 8% of patients. In conclusion, contrast-enhanced stress echocardiography provides comparable diagnostic test rates to MPI with lower associated charges.

Comparative efficiency of exercise stress testing with and without stress-only myocardial perfusion imaging in patients with low-risk chest pain.

OBJECTIVES: To compare major adverse cardiac event (MACE), downstream resource utilization, and direct cost of care for low-risk chest pain patients observed in the clinical decision unit (CDU) with exercise treadmill testing (ETT) and with stress-only myocardial perfusion imaging (sMPI). BACKGROUND: CDUs are poised to increase efficiency and resource utilization. However, the optimal testing strategy that would assure favorable outcomes while decreasing cost is not defined. METHODS: 1016 subjects from 2 locations were propensity score-matched (PSM) by age, gender, pre-test likelihood, Duke treadmill score, and test results. Outcomes were length of stay >24 hours, MACE (acute coronary syndrome, revascularization, cardiac death), downstream resource use (admission for chest pain, repeat testing, angiography), and mean direct cost per patient. RESULTS: PSM yielded 680 patients (340 matches). 98% of all tests were normal. 96.6% of patients were discharged from the CDU within 24 hours but twice as many exceeded 24 hours in the sMPI group. There were no cardiac deaths. MACE rate was 1.47% at 72 hours and 1% at 1 year. Downstream resource use was 4.82% at 72 hours, and 7.69% at 1 year. The sMPI group was event-free longer than the ETT group reflecting less repeat testing. The mean direct cost was 30% higher for sMPI ($3168.70) vs. ETT ($2226.96). CONCLUSION: Low-risk chest pain patients in the observation unit had low MACE rate, not different for ETT vs. sMPI. The majority of ETT and sMPI tests were normal. The sMPI reduced additional testing, but resulted in greater expense and longer stay.

Impact of the Publication of Appropriate Use Criteria on Utilization Rates of Myocardial Perfusion Imaging Studies in Ontario, Canada: A Population-Based Study.

BACKGROUND: Concern regarding overutilization of cardiac imaging has led to the development of appropriate use criteria (AUC). Myocardial perfusion imaging (MPI) is one of the most commonly used cardiac imaging modalities worldwide. Despite multiple iterations of AUC, there is currently no evidence regarding their real-world impact on population-based utilization rates of MPI. Our goal was to assess the impact of the AUC on rates of MPI in Ontario, Canada. We hypothesized that publication of the AUC would be associated with a significant reduction in MPI rates. METHODS AND RESULTS: We conducted a retrospective cohort study of the adult population of Ontario from January 1, 2000, to December 31, 2015. Age- and sex-standardized rates were compared from 4 different periods intersected by 3 published iterations of the AUC. Overall, 3 072 611 MPI scans were performed in Ontario during our study period. The mean monthly rate increased from 14.1/10 000 in the period from January 2000 to October 2005 to 18.2/10 000 between November 2005 and June 2009. After this point in time, there was a reduction in rates, falling to a mean monthly rate of 17.1/10 000 between March 2014 and December 2015. Time series analysis revealed that publication of the 2009 AUC was associated with a significant reduction in MPI rates (P<0.001). This translated into ≈88 849 fewer MPI scans at a cost savings of ≈72 million Canadian dollars. CONCLUSIONS: Our results reflect a potential real-world impact of the 2009 MPI AUC by demonstrating evidence of a significant effect on population-based rates of MPI.

Regadenoson versus Dipyridamole: A Comparison of the Frequency of Adverse Events in Patients Undergoing Myocardial Perfusion Imaging.

STUDY OBJECTIVE: To compare the frequency of adverse events in patients undergoing myocardial perfusion imaging (MPI) with either regadenoson or dipyridamole. DESIGN: Single-center, retrospective cohort study. SETTING: Large community teaching hospital. PATIENTS: A total of 568 adults who underwent single-photon emission tomography MPI with either regadenoson (284 patients) or dipyridamole (284 patients) as a vasodilator agent, following an institution conversion from regadenoson to dipyridamole in the MPI protocol on July 15, 2013, for cost-saving purposes. MEASUREMENTS AND MAIN RESULTS: Data were collected from the patients' electronic medical records. The primary endpoint was the composite occurrence of any documented adverse event in each group. Secondary endpoints were individual components of the primary endpoint, reason for termination of the MPI examination (protocol completion or premature end due to an adverse event), use of an interventional agent to an treat adverse event, and cost-related outcomes. A higher proportion of patients in the regadenoson group experienced an adverse event than those who received dipyridamole (84.9% vs 56.7%, p<0.0001). None of the patients in either group required early MPI study termination due to an adverse event. No significant differences were noted between groups regarding use of aminophylline or other interventions to treat adverse events. The overall drug cost savings in the postconversion dipyridamole group was $51,526. CONCLUSION: Dipyridamole was associated with fewer adverse events than regadenoson in patients undergoing MPI. Dipyridamole offers a safe and cost-effective alternative to regadenoson for cardiac imaging studies.

Systematic review of cost-effectiveness of myocardial perfusion scintigraphy in patients with ischaemic heart disease: A report from the cardiovascular committee of the European Association of Nuclear Medicine. Endorsed by the European Association of Cardiovascular Imaging.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

Cost-effectiveness of diagnostic evaluation strategies for individuals with stable chest pain syndrome and suspected coronary artery disease.

PURPOSE: To determine lifetime cost-effectiveness of diagnostic evaluation strategies for individuals with stable chest pain and suspected coronary artery disease (CAD). METHODS: Exercise treadmill testing (ETT), stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), coronary computed tomographic angiography (CCTA), and invasive coronary angiography (ICA) were assessed alone, or in succession to each other. RESULTS: Initial ETT followed by imaging wherein ETT was equivocal or unable to be performed appeared more cost-effective than any strategy employing initial testing by imaging. CONCLUSION: As pre-test likelihood of CAD varies, different modalities including SE, CCTA, and MPS result in improved costs and enhanced effectiveness.

Critical appraisal of appropriateness in nuclear cardiology.

Radionuclide myocardial perfusion imaging (MPI) is a large component of the healthcare spending both in developed and developing countries. MPI is also responsible for a significant increase in the exposition of patients and health care operators to ionizing radiations for medical purposes. Thus, health-care systems and pertinent scientific societies were involved in developing criteria to contain the non-appropriate use by implementing Appropriate Use Criteria and Clinical Indications Guidelines. The present manuscript will review the concept and limitations of such an approach.

Impact of Stress Cardiac Magnetic Resonance Imaging on Clinical Care.

Given the rising costs of imaging, there is increasing pressure to provide evidence for direct additive impact on clinical care. Appropriate use criteria (AUC) were developed to optimize test-patient selection and are increasingly used by payers to assess reimbursement. However, these criteria were created by expert consensus with limited systematic validation. The aims of this study were therefore to determine (1) rates of active clinical change resulting from stress cardiovascular magnetic resonance (CMR) imaging and (2) whether the AUC can predict these changes. We prospectively enrolled 350 consecutive outpatients referred for stress CMR. Categories of "active changes in clinical care" due to stress CMR were predefined. Appropriateness was classified according to the 2013 AUC. Multivariate logistic regression analysis was used to identify factors independently associated with active change. Overall, stress CMR led to an active change in clinical care in about 70% of patients. Rates of change in clinical care did not vary significantly across AUC categories (p = 0.767). In a multivariate model adjusting for clinical variables and AUC, only ischemia (odds ratio [OR] 6.896, 95% CI 2.637 to 18.032, p <0.001), known coronary artery disease (OR 0.300, 95% CI 0.161 to 0.559, p <0.001), and age (OR 0.977, 95% CI 0.954 to 1.000, p = 0.050) independently predicted significant clinical change. In conclusion, stress CMR made a significant impact on clinical management, resulting in active change in clinical care in about 70% of patients. AUC categories were not an independent predictor of clinical change. Clinical change was independently associated with the presence of ischemia, absence of known coronary artery disease, and younger age.

Nuclear cardiology and CVD in the developing world: Are we applying our scarce resources appropriately? Why is our mortality rate so high?

While mortality rates from cardiovascular diseases have progressively decreased in developed nations, this has not been observed to the same extent in the developing world. Nuclear Cardiology utilization remains low or non-existent for most of those living in the low-to-middle-income countries. How much of the decline in mortality observed in the developed world has to do with advanced cardiac imaging? Are we applying our scarce resources appropriately for myocardial perfusion imaging? Are myocardial revascularizations being guided by appropriate use criteria? Is more imaging necessary to reduce the mortality rates further in the developing world?