Abstract
Purpose:
Myocardial perfusion imaging (MPI) is frequently used to improve cardiac risk prediction in patients undergoing non-cardiac surgery. However, the data supporting this practice is derived from single center studies and predates current therapy for coronary artery disease (CAD). We evaluated the association between pre-operative testing indication and outcomes as well as predictors of death or myocardial infarction (MI) in these patients.
Methods:
We include patients from the international, multicenter REFINE-SPECT registry (13 sites). Based on referral indication patients were classified as pre-operative testing indications and non-pre-operative testing. We evaluated the associations between pre-operative testing and incidence of death or MI. We then evaluated associations with death or MI in patients referred for pre-operative testing compared to other patients.
Results:
In total, 32,714 patients were included with pre-operative testing as the indication in 2,173(6.6%) patients. Patients referred for pre-operative testing were more likely to experience death or MI (annualized rate 4.4% vs 1.6%, p<0.001). In patients referred for pre-operative testing, stress, rest, and ischemic total perfusion deficit were associated with death or MI. Rest total perfusion deficit (adjusted hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.07 – 1.45) was independently associated with death or MI, but pharmacologic stress testing was not (adjusted HR 0.88, 95% CI 0.70 – 1.12).
Conclusion:
Patients undergoing pre-operative SPECT MPI are at increased cardiovascular risk which may reflect selection bias or unmeasured confounders. Resting perfusion abnormalities may identify patients at higher risk, potentially helping guide peri-operative care.
Keywords: Myocardial perfusion imaging, Single photon emission computed tomography, prognosis, peri-operative, Pre-operative testing
INTRODUCTION
Cardiovascular events are a leading cause of mortality in patients undergoing non-cardiac surgery[1]. Risk stratification can aid in discussions with patients regarding overall risk of surgery and directing intensive postoperative care. Risk calculators, such as the revised cardiac risk index and National Surgical Quality Improvement Program score[2], are currently endorsed by guidelines[3] despite their limited sensitivity and specificity[4]. Myocardial perfusion imaging (MPI) is one potential tool to further elucidate cardiac risk and is often used in patients with significant comorbidities or undergoing higher risk surgeries[5–7].
Previous literature shows that MPI findings improve upon major adverse cardiac events (MACE) prediction algorithms based on clinical variables[8]. Coley et al. demonstrated that MPI could discriminate MACE risk in moderate- to high-risk patients[8]. Notably, variances exist in the ability of imaging modalities to predict MACE risk[9]. In a meta-analysis of studies evaluating pre-operative testing, MPI (with the majority of studies describing planar imaging with thallium) had poor accuracy for predicting cardiac death or non-fatal myocardial infarctions (MI)[9]. However, this analysis predated current MPI technology, which have led to significant advances in diagnostic accuracy[10]. In spite of limited contemporary data, guidelines currently suggest stress imaging in patients undergoing intermediate or high-risk non-cardiac surgery if they have poor functional capacity and either known coronary artery disease (CAD) or a high likelihood of CAD[11]. Given the emergence of coronary computed tomography angiography (CCTA) and positron emission tomography (PET) MPI in diagnosing and managing CAD[12], there is a need to confirm the utility of contemporary single photon emission computed tomography (SPECT) MPI for pre-operative assessment.
The current study evaluates the prognostic significance of SPECT MPI findings in a large, multicenter cohort of contemporary patients undergoing pre-operative testing compared to patients with other indications.
METHODS
We included consecutive patients undergoing clinically indicated SPECT MPI from the international, multicenter, REFINE SPECT registry[13]. Patients without information regarding testing indication (n=2,214) and patients with known coronary artery disease (CAD) (n=10,327), defined as previous revascularization or MI[14], were excluded. We excluded patients with known CAD since the appropriateness of pre-operative testing is given special consideration in this group[15]. Clinical indications were recorded at the time of SPECT MPI imaging and could include multiple selections. In our primary analysis, patients were considered to be referred for pre-operative testing if pre-operative testing was included as any one of the indications. However, we also considered patients with pre-operative testing as the only indication in a separate analysis. The study was approved by the institutional review boards at each participating institution and the overall study was approved by the institutional review board at Cedars-Sinai Medical Center.
Clinical Data
Demographic information included: age, gender, body mass index (BMI), family history of CAD, smoking status, history of previous MI, previous revascularization, hypertension, diabetes, dyslipidemia, and peripheral vascular disease. Stress types were divided into pharmacologic or exercise stress. Data regarding type of surgical intervention, timing of intervention, and anesthetic care were not available.
Image Acquisition and Interpretation
Patients were included from 13 different sites, with MPI performed between 2009 and 2020 as previously described in detail[13]. De-identified image datasets were transferred to the core laboratory (Cedars-Sinai Medical Center) where automated quantitation was performed by experienced technologists. Myocardial contours were generated automatically with Quantitative Perfusion SPECT (QPS) /Quantitative Gated SPECT (QGS) software (Cedars-Sinai Medical Center, Los Angeles, CA). Myocardial perfusion was quantified by total perfusion deficit (TPD) which incorporates severity and extent of perfusion abnormalities and is more reproducible compared to visual ischemia scoring[16]. Left ventricular ejection fraction (LVEF) was assessed on the supine resting study with reduced LVEF defined as <40%[17].
Outcomes
Patients were followed for development of MACE which includes all-cause mortality, non-fatal MI, hospitalization for unstable angina, and revascularization. Unstable angina was defined as recent onset or escalating cardiac chest pain with negative cardiac biomarkers. All outcomes were adjudicated by cardiologists after considering all available investigations. The primary outcome in this study was death or MI. However, we performed secondary analyses evaluating associations with MACE as well as evaluating associations with outcomes during the first 180 days following testing.
Statistical Analysis
The normality of continuous variables was assessed with the Shapiro-Wilk test. Continuous variables were summarized as mean (SD) and compared using a Student’s t-test or Mann-Whitney U test as appropriate. Categorical variables were summarized as number (proportion) and compared using a chi-square test or Fisher exact test as appropriate.
Univariable Cox proportional hazards analysis was used to determine associations between clinical and imaging factors with the primary clinical outcome of death or MI. Multivariable Cox proportional hazards analysis was performed to assess associations with death or MI and MACE. Associations with outcomes within 180 days were assessed using multivariable logistic regression models. All statistical tests were two-sided, with a p-value < 0.05 considered significant. All analyses were performed using Stata version 13 (StataCorp, College Station, Texas).
RESULTS
Population Characteristics
In total, 32,711 patients were included with pre-operative testing as the indication in 2173(6.6%) patients. A comparison of clinical and imaging features for patients referred for pre-operative testing compared to other indications is shown in Table 1. Patients referred for pre-operative testing were more likely to be male (52.8% vs 49.8%, p=0.008) and had a higher prevalence of diabetes (30.0% vs 24.8%, p<0.001) and peripheral vascular disease (15.8% vs 11.8%, p<0.001). Of the patients referred for pre-operative testing, 363 (16.2%) had at least one additional indication recorded, with patient characteristics in Supplemental Table 1.The additional indications included: abnormal resting electrocardiogram n=125, dyspnea n=77, chest pain n=73, arrhythmias/palpitations n=34, peripheral vascular disease n=22, high cardiovascular risk n=16, heart failure/cardiomyopathy n=11, abnormal treadmill test n=10, syncope n=4, and valve disease n=2.
Table 1:
| Pre-Operative Indication N=2,173 |
Other Indications N= 30,538 |
P-value | |
|---|---|---|---|
| Age, median (IQR) | 64 (56, 72) | 64 (56, 72) | 0.86 |
| Male | 1147 (52.8%) | 15213 (49.8%) | 0.008 |
| BMI (Body mass index), median (IQR) | 27.9 (24.3, 33.0) | 28.6 (25.2, 33.1) | <0.001 |
| Past Medical History | |||
| Hypertension | 1416 (65.2%) | 18490 (60.5%) | <0.001 |
| Diabetes Mellitus | 652 (30.0%) | 7577 (24.8%) | <0.001 |
| Dyslipidemia | 1082 (49.8%) | 13962 (45.9%) | <0.001 |
| Family History | 456 (21.0%) | 10406 (34.1%) | <0.001 |
| Smoking | 564 (26.0%) | 6713 (22.0%) | <0.001 |
| Peripheral vascular disease | 343 (15.8%) | 3603 (11.8%) | <0.001 |
| Exercise stress | 774 (35.6%) | 15758 (51.6%) | <0.001 |
| Stress TPD, median (IQR)* | 2.1 (0.8, 4.8) | 2.4 (0.8, 5.2) | 0.008 |
| Rest TPD, median (IQR) | 0.6 (0.0, 1.6) | 0.5 (0.0, 2.5) | 0.15 |
| Ischemic TPD, median (IQR) | 1.6 (0.4, 3.7) | 1.7 (0.4, 3.9) | 0.050 |
| Stress EF, median (IQR) | 64.2 (56.9, 70.9) | 64.8 (57.5, 72.2) | <0.001 |
| Rest EF, median (IQR)* | 63.3 (55.4, 70.4) | 63.5 (55.5, 71.5) | 0.050 |
Table 1: Baseline population characteristics. * - stress only imaging was performed in 6971 patients. EF – ejection fraction, IQR – interquartile range, TPD – total perfusion deficit.
Clinical Outcomes
During a median follow-up of 3.6 years (IQR 2.7-4.8), death or MI occurred in 2,226 (6.8%) patients. Kaplan-Meier survival estimates curve for non-preoperative and preoperative indication groups are shown in Figure 1. Patients undergoing testing for pre-operative indications were more likely to experience death or MI (annualized rate 4.4% vs 1.6%, log rank p<0.001). There was no difference in incidence of death or MI between patients with only pre-operative indication compared to patients with pre-operative and other indications (annualized rate 4.4% vs 4.4%, log-rank p=0.675).
Figure 1:
Survival free of death or myocardial infarction by testing indication. There was no significant difference in outcomes between patients referred only for pre-operative(pre-op) testing compared to patients referred for pre-op testing and other indications (p=0.675).
Associations with Death or MI
In unadjusted analysis (Table 2), pre-operative testing was associated with an increased risk of death or MI (unadjusted hazard ratio [HR] 2.70, 95% CI 2.41 – 3.02, p<0.001). Additionally, stress TPD, rest TPD, ischemic TPD, and stress ejection fraction (EF) were associated with risk of death or MI (all p<0.001). When the multivariable model was evaluated in the overall patient population, pre-operative testing continued to be associated with an increased risk of death or MI (adjusted HR 2.33, 95% CI 2.08 – 2.62, p<0.001).
Table 2:
Associations with death or myocardial infarction in overall population
| Unadjusted HR (95% CI) |
p-value | Adjusted HR (95% CI) |
p-value | |
|---|---|---|---|---|
| Pre-operative indication | 2.70 (2.41 – 3.02) | <0.001 | 2.33 (2.08 - 2.62) | <0.001 |
| Age (per 10 years) | 1.66 (1.60 – 1.72) | <0.001 | 1.50 (1.43 - 1.56) | <0.001 |
| Male | 1.35 (1.24 – 1.47) | <0.001 | 1.15 (1.05 - 1.27) | 0.002 |
| BMI (per kg/m2) | 0.98 (0.97 – 0.99) | <0.001 | 0.98 (0.97 - 0.99) | <0.001 |
| Hypertension | 1.58 (1.44 – 1.73) | <0.001 | 1.10 (1.00 - 1.22) | 0.050 |
| Diabetes | 1.73 (1.59 – 1.89) | <0.001 | 1.52 (1.39 - 1.67) | <0.001 |
| Dyslipidemia | 1.11 (1.02 – 1.20) | 0.016 | 0.93 (0.85 - 1.01) | 0.102 |
| Family History | 0.70 (0.64 – 0.77) | <0.001 | 0.92 (0.83 - 1.01) | 0.081 |
| Smoker | 1.18 (1.07 – 1.30) | 0.001 | 1.07 (0.96 - 1.18) | 0.219 |
| Peripheral vascular disease | 1.88 (1.72 – 2.06) | <0.001 | 1.05 (0.93 - 1.18) | 0.418 |
| Exercise stress | 0.34 (0.31 – 0.37) | <0.001 | 0.48 (0.43 - 0.53) | <0.001 |
| Stress TPD (per 5%) | 1.29 (1.25 – 1.32) | <0.001 | -- | -- |
| Rest TPD (per 5%) | 1.38 (1.34 – 1.43) | <0.001 | 1.14 (1.10 - 1.19) | <0.001 |
| Ischemic TPD (per 5%) | 1.34 (1.28 – 1.39) | <0.001 | 1.08 (1.02 - 1.14) | 0.004 |
| Stress EF (per 5%) | 0.86 (0.85 – 0.87) | <0.001 | 0.90 (0.89 - 0.92) | <0.001 |
Associations with death or myocardial infarction in unadjusted and multivariable models in the overall cohort. Stress total perfusion deficit (TPD) was excluded from the multivariable model due to the inclusion of rest and ischemic TPD. Significant associations in bold. BMI – body mass index, CI – confidence interval. EF – ejection fraction, HR – hazard ratio, IQR – interquartile range
Unadjusted associations with death or MI in patients referred for pre-operative testing were generally similar to those seen in patients referred for non-preoperative indications (Figure 2). In patients referred for pre-operative testing, the risk associated with increasing age (unadjusted HR 1.33 per 10 years, 95% CI 1.22 – 1.46, p<0.001) and hypertension (unadjusted HR 1.02, 95% CI 0.82 – 1.27, p=0.865) were less than the risk seen in patients referred for non-preoperative indications (both interaction p-value <0.001). Additionally, there was less of a decrease in risk associated with exercise stress testing (unadjusted HR 0.79, 95% CI 0.63 – 0.99, p=0.044). However, there was no significant difference between preoperative and non-preoperative patients in the risk associated with stress TPD, rest TPD, ischemic TPD, or stress LVEF.
Figure 2:
Unadjusted hazard ratios for death or myocardial infarction (MI) in patients with (blue) and without (red) pre-operative (pre-op) testing indications. * indicates significant interaction, such that the association with death or MI significantly differs by testing indication (p<0.001 to adjust for multiple testing). BMI – body mass index, CI – confidence interval, EF – ejection fraction, HR – hazard ratio, PVD – peripheral vascular disease, TPD – total perfusion deficit
Adjusted associations with death or MI in patients referred for pre-operative and indications other than pre-operative testing are shown in Figure 3, with additional details in Table 3. Rest TPD was an independent predictor of death or MI (adjusted HR 1.25 per 5% increase, 95% CI 1.07 – 1.45, p<0.001). Increasing age was associated with death or MI in patients undergoing pre-operative testing (adjusted HR 1.31 per 10 years, 95% CI 1.19 – 1.44), but with less of an increase compared to patients undergoing testing for other indications (interaction p=0.001). Exercise stress was not associated with death or MI in patients referred for pre-operative testing (adjusted HR 0.88, 95% CI 0.70 – 1.12, p=0.306, interaction p-value<0.001). Stress EF was also not associated with death or MI in patients referred for pre-operative testing (adjusted HR 0.99, 95% CI 0.95 – 1.04, p=0.711; interaction p-value <0.001).
Figure 3:
Adjusted hazard ratios for death or myocardial infarction (MI) in patients with (blue) and without (red) pre-operative (pre-op) testing indications. * indicates significant interaction, such that the association with death or MI significantly differs by testing indication (p<0.001 to adjust for multiple testing). BMI – body mass index, CI – confidence interval, EF – ejection fraction, HR – hazard ratio, PVD – peripheral vascular disease, TPD – total perfusion deficit
Table 3:
Multivariable model in pre-operative testing patients
| Adjusted HR (95% CI) |
p-value | |
|---|---|---|
| Age (per 10 years) | 1.31 (1.19 - 1.44) | <0.001 |
| Male | 1.67 (1.32 - 2.11) | <0.001 |
| BMI (per kg/m2) | 0.96 (0.94 - 0.97) | <0.001 |
| Hypertension* | 0.99 (0.78 - 1.26) | 0.918 |
| Diabetes | 1.57 (1.25 - 1.98) | <0.001 |
| Dyslipidemia | 0.73 (0.58 - 0.92) | 0.007 |
| Family History | 0.92 (0.69 - 1.22) | 0.542 |
| Smoker | 0.80 (0.60 - 1.05) | 0.112 |
| Peripheral vascular disease | 0.78 (0.56 - 1.08) | 0.135 |
| Exercise stress* | 0.88 (0.70 - 1.12) | 0.306 |
| Rest TPD (per 5%) | 1.25 (1.07 - 1.45) | 0.004 |
| Ischemic TPD (per 5%) | 1.08 (0.92 - 1.27) | 0.333 |
| Stress EF (per 5%)* | 0.99 (0.95 - 1.04) | 0.711 |
Associations with death or myocardial infarction in multivariable models in patients referred for pre-operative testing. Stress total perfusion deficit (TPD) was excluded from the multivariable model due to the inclusion of rest and ischemic TPD. Significant associations in bod. * indicates significant interaction between the variable and pre-operative testing with respect to association with death or myocardial infarction (p<0.001 to adjust for multiple testing). BMI – body mass index, CI – confidence interval, EF – ejection fraction, HR – hazard ratio, IQR – interquartile range
Adjusted associations with death or MI in patients referred for pre-operative testing, stratified by mode of stress, is shown in Supplemental Table 2. Rest TPD was associated with an increased risk of death or MI in patients undergoing exercise stress (adjusted HR 1.51, 95% CI 1.03 – 2.19) or pharmacologic stress (adjusted HR 1.21, 95% CI 1.02 – 1.44). Adjusted associations with death or MI in patients referred only for pre-operative testing are shown in Table 4. Results were similar to the analysis including all patients with a pre-operative testing indication. Age, sex, BMI, diabetes, dyslipidemia, and rest TPD were significantly associated with death or MI.
Table 4:
| Adjusted HR (95% CI) |
p-value | |
|---|---|---|
| Age (per 10 years) | 1.30 (1.17 - 1.45) | <0.001 |
| Male | 1.61 (1.23 - 2.09) | <0.001 |
| BMI (per kg/m2) | 0.96 (0.94 - 0.98) | <0.001 |
| Hypertension | 1.01 (0.77 - 1.33) | 0.942 |
| Diabetes | 1.63 (1.26 - 2.12) | <0.001 |
| Dyslipidemia | 0.78 (0.60 – 1.00) | 0.051 |
| Family History | 0.98 (0.71 - 1.34) | 0.881 |
| Smoker | 0.88 (0.65 - 1.19) | 0.400 |
| Peripheral Vascular Disease | 0.61 (0.41 - 0.90) | 0.012 |
| Exercise stress | 0.85 (0.65 - 1.11) | 0.227 |
| Rest TPD (per %) | 1.20 (1.01 - 1.43) | 0.039 |
| Ischemic TPD (per %) | 1.11 (0.93 - 1.32) | 0.244 |
| Stress EF (per %) | 0.99 (0.94 - 1.05) | 0.820 |
Associations with death or myocardial infarction in in patients referred for pre-operative testing only. Stress total perfusion deficit (TPD) was excluded from the multivariable model due to the inclusion of rest and ischemic TPD. Significant associations shown in bold. CI – confidence interval, EF – ejection fraction, HR – hazard ratio, IQR – interquartile range
Associations with MACE
MACE occurred in 4,152 (12.7%) patients including first events of: 2006 revascularizations, 170 admissions for unstable angina, 408 MI, and 1,568 deaths. Associations with MACE in the overall population are shown in Supplemental Table 3 and were similar to associations with death or MI, with the exception of ischemic TPD which was associated with a greater risk for MACE (adjusted HR 1.54, 95% CI 1.51-1.59 per 5% increase). Associations with MACE in patients referred for pre-operative indications are shown in Supplemental Table 4. Again, results were generally similar except for ischemic TPD being associated with increased risk for MACE (adjusted HR 1.29, 95% CI 1.13-1.48 per 5% increase).
Associations with outcomes within 180 days
Death or MI within 180 days occurred in 350 (1.1%) patients. Adjusted associations with death or MI within 180 days in the overall population is shown in Supplemental Table 5. This demonstrated similar results as associations with death or MI at any time. Associations with death or MI within 180 days in patients referred for pre-operative testing indications is shown in Supplemental Table 6 and showed similar results as associations with death or MI at any time.
DISCUSSION
This study assessed the prognostic significance of preoperative indication for MPI and predictors of MACE in these patients. We found that pre-operative indication for testing was independently associated with an increased risk of death or MI. In patients referred for pre-operative testing, increasing stress, rest, and ischemic TPD were associated with an increased risk of death or MI. After multivariable adjustment, rest TPD remained a significant independent predictor of death or MI. Lastly, we noted significant differences in the risk associated with other features, such as requirements for pharmacologic stress testing, in patients undergoing pre-operative testing. Overall, our results suggest that MPI plays a role in predicting risk in select patients in the pre-operative setting.
In our analysis, patients referred for pre-operative testing had a two-fold increased risk of death or MI compared to patients referred for other indications. This is at least in part due to a greater burden of comorbidities. For example, patients referred for pre-operative testing were more likely to have hypertension, diabetes, and peripheral vascular disease. The residual risk may be a result of selection bias, with referring physicians selecting higher risk patients for pre-operative MPI (with lower-risk patients proceeding to surgery without pre-operative testing). Importantly, there has been a shift in pre-operative testing recommendations to focus on patients unable to complete at least 4 Metabolic Equivalent of Tasks (METs)[11]. This would be expected to lead to higher-risk patients selected for pre-operative testing given the known prognostic utility of exercise capacity[18]. Additionally, there may be unmeasured confounders, such as cerebrovascular disease, which differ systematically between the groups based on current guidelines for pre-operative risk estimation[11]. Lastly, the planned operations may introduce additional cardiac risk, through factors such as physiological stress, increased adrenergic drive, tachycardia, and fluid shifts[3]. Regardless, this increased risk may explain why previous literature has shown that 1/3 of individuals with normal preoperative MPI results continue to experience MACE[9, 19].
In patients referred for pre-operative testing, all imaging features were associated with risk of death or MI in unadjusted analyses. However, only rest TPD was a significant independent predictor of events in the multivariable model. This is similar to results from Hashimoto et al. which demonstrated that integrating imaging SPECT MPI results with clinical risk factors improves perioperative MACE prediction[20]. Interestingly, rest perfusion defect was the only variable found to be statistically significant on both univariate and multivariate analysis in their work as well[20]. Ischemic TPD was associated with an increased risk of MACE, but not death or MI, suggesting that physicians may be targeting revascularization procedures to those patients with more significant ischemia[21]. This revascularization selection bias may underly the lack of associations with hard outcomes. Notably, age, sex, and the presence of diabetes were associated with an increased risk of death or MI in both populations. Additionally, higher BMI was protective in both preoperative and non-preoperative populations. This is not a surprising finding, as previous literature shows that higher BMI patients may have advantages in postoperative survival[22].
While many variables were associated with similar risk in both populations, there were several variables associated with less risk in the pre-operative testing group. Of those, the difference risk was most discrepant for utilization of pharmacologic stress testing. The need for pharmacologic stress testing is associated with increased risk after correcting for differences in coronary atherosclerosis and perfusion findings[23]. The increase in risk may be a reflection of frailty, since pharmacologic stress is reserved for patients unable to complete exercise testing. However, the testing in the pre-operative setting is typically limited to patients with poor functional capacity, potentially removing this bias related to mode of stress. Additionally, in the pre-operative setting patients may be unable to walk for transient reasons, such as orthopedic conditions, which could help explain the differential in associated risk.
Our analysis provides clinicians with a few important insights into how to best utilize results from SPECT MPI in the pre-operative context. As isolated measures, of risk, stress, rest, and ischemic perfusion abnormalities carry the same prognostic significance in patients referred for pre-operative testing. Therefore, patients with significant abnormalities may benefit from more aggressive peri-operative monitoring strategies[24]. Prior studies have shown that beta-blockers are prescribed more commonly in patients with significant ischemia on MPI[25] and patients with significant ischemia may derive greater expected benefit from initiating beta-blocker therapy prior to surgery[26, 27]. Lastly, physicians could utilize this information to provide a more refined estimate of risk for patients in whom there is uncertainty regarding the balance between the risks and benefits of a potential surgery. Randomized trials would suggest similar outcomes with functional and anatomic testing in patients with suspected CAD[28], but no similar data exists specific to pre-operative testing. It is important to perform similar analyses, identifying key predictors of risk, for other modalities (eg: stress echocardiogram, CCTA and PET MPI) used in the pre-operative setting. As a whole these analyses would not only allow physicians to better understand how to utilize pre-operative imaging results but could also inform comparative cost-effectiveness analyses and help develop a framework for optimal pre-operative testing strategies in future guidelines.
A key limitation to this paper is that the type of planned surgery and surgical date are not available. While this is not feasible to collect in a large, international, multicenter registry, it is worth noting that different surgeries vary in risk for MACE[29]. Similarly, we do not know how clinicians responded to the SPECT MPI results to modify, or cancel, operative plans. Previous studies have shown that physicians respond to the presence of myocardial ischemia by intensifying medical therapy for CAD in those patients[25]. However, changes to operative plans or medical therapy in patients with myocardial ischemia or abnormal ventricular function would be expected to reduce the risk associated with those factors and may explain the lack of association with death or MI. Lastly, we are not able to evaluate associations with cardiovascular mortality given difficulties in adjudicating this from administrative records[30].
CONCLUSIONS
Patients undergoing pre-operative SPECT MPI are at increased cardiovascular risk, even after adjusting for comorbidities and MPI findings, which may reflect risk related to the condition requiring surgical intervention, selection bias related to pre-operative testing recommendations, or other unmeasured confounders. Resting perfusion abnormalities can help identify patients at higher risk, potentially helping guide peri-operative care.
Supplementary Material
FUNDING
This research was supported in part by grants R01HL089765 and R35HL161195 from the National Heart, Lung, and Blood Institute at the National Institutes of Health (PI: Piotr Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. MCW (FS/ICRF/20/26002) is supported by the British Heart Foundation.
CONFLICTS OF INTEREST DISCLOSURES
Drs. Berman, Dorbala, and Edward Miller have served as consultants for GE Healthcare. Dr. Dorbala has served as a consultant to Bracco Diagnostics; her institution has received grant support from Astellas. Dr. DiCarli has received research grant support from Spectrum Dynamics and consulting honoraria from Sanofi and GE Healthcare. Dr. Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. Dr. Edward Miller has served as a consultant for Bracco Inc; he and his institution has received grant support from Bracco Inc. Dr. Berman’s institution has received grant support from HeartFlow. Dr. Einstein’s institution has received research support from GE Healthcare, Philips Healthcare, Toshiba America Medical Systems, Roche Medical Systems, and W. L. Gore & Associates. Dr. Robert Miller has received consulting and research support from Pfizer and research support from Alberta Innovates. Drs Berman and Slomka participate in software royalties for QPS software at Cedars-Sinai Medical Center. Dr. Slomka has received research grant support from Siemens Medical Systems. The remaining authors have nothing to disclose.
ABBREVIATIONS
- CAD
coronary artery disease
- CI
confidence interval
- HR
hazard ratio
- IQR
interquartile range
- LVEF
left ventricular ejection fraction
- MI
myocardial infarction
- MPI
myocardial perfusion imaging
- REFINE SPECT
Registry of Fast Myocardial Perfusion Imaging With Next Generation SPECT
- SPECT
single photon emission computed tomography
- TPD
total perfusion deficit
- ACC/AHA
American College of Cardiology/American Heart Association
- HTN
hypertension
- DM
diabetes mellitus
- BMI
body mass index
Footnotes
ETHICS APPROVAL
The study was approved by the institutional review boards at each participating institution and the overall study was approved by the institutional review board at Cedars-Sinai Medical Center.
CONSENT
Patients either provided written informed consent or a waiver of consent was granted according to site-specific protocols.
DATA AVAILABILITY
To the extent allowed by existing data use agreements, the data underlying this manuscript can be made available upon written request to the corresponding author.
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Data Availability Statement
To the extent allowed by existing data use agreements, the data underlying this manuscript can be made available upon written request to the corresponding author.