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Background Cardiovascular risk models are based on traditional risk factors and investigations such as imaging tests. External validation is important to determine reproducibility and generalizability of a prediction model. We performed an external validation of t the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS) model, developed from a cohort of patients undergoing stress myocardial perfusion imaging. Methods We included 3623 patients with suspected or known coronary artery disease undergoing stress single-photon emission computer tomography (SPECT) myocardial perfusion imaging at our academic center between January 2001 and December 2019. Results In our study population, the J-ACCESS model underestimated the risk of major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and severe heart failure requiring hospitalization) within three-year follow-up. The recalibrations and updated of the model slightly improved the initial performance: C-statistics increased from 0.664 to 0.666 and Brier score decreased from 0.075 to 0.073. Hosmer–Lemeshow test indicated a logistic regression fit only for the calibration slope (P = .45) and updated model (P = .22). In the update model, the intercept, diabetes, and severity of myocardial perfusion defects categorized coefficients were comparable with J-ACCESS. Conclusion The external validation of the J-ACCESS model as well as recalibration models have a limited value for predicting of three-year major adverse cardiac events in our patients. The performance in predicting risk of the updated model resulted superimposable to the calibration slope model.

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Background. To assess the incremental value of 18F-fluorodeoxyglucose (FDG) cardiac positron emission tomography (PET) over dobutamine stress echocardiography (DSE) in predicting myocardial ischemia in patients with suspected coronary artery disease (CAD). Methods. Forty-one patients with suspected CAD underwent within 7 days apart rest-stress cardiac PET with 82Rb and DSE followed by cardiac 18F-FDG PET imaging. 18F-FDG images were scored on a 0 (no discernible uptake) to 2 (intense uptake) scale. Logistic regression analysis was performed to identify predictors of stress-induced ischemia. The incremental value of 18F-FDG PET over DSE in detecting ischemia at 82Rb PET cardiac imaging was assessed by the likelihood ratio chi-square and net reclassification index. Results. On 82Rb-PET imaging, myocardial ischemia (ischemic total perfusion defect > 5%) was detected in 20 (49%) patients. Inducible ischemia was found in 22 (54%) patients on DSE (biphasic or worsening response pattern in > 1 segment) and in 21 (51%) patients on 18FFDG PET (uptake score of 2 in ‡ 1 segment). 18F-FDG PET resulted as statistically significant predictor of ischemia on 82Rb-PET. The addition of 18F-FDG PET to DSE increased the likelihood of ischemia on 82Rb-PET (P < .05). 18F-FDG PET was able to reclassify the probability of stress-induced myocardial ischemia on both patient and vessel analyses. Conclusion. 18F-FDG PET performed after dobutamine stress test may provide incremental value to DSE in the evaluation of myocardial ischemia. These results suggest that stress induced myocardial ischemia can be imaged directly using 18F-FDG PET after dobutamine stress test.

Background. The purpose of this study was to assess the prognostic value of cardiac 82Rb positron emission tomography (PET)/computed tomography (CT) imaging in patients with myocardial ischemia of nonobstructive coronary arteries (INOCA). Methods. We retrospectively evaluated 311 INOCA patients who underwent rest stress 82Rb PET/CT. Cardiac end points were cardiac death, myocardial infarction, or late coronary revascularization. A parametric survival model was also used to identify how the variables influenced time to event. Results. During a median follow-up of 37 months (range 6–108), 23 (7%) cardiac events occurred. In patients with events total perfusion defect (TPD) was higher and myocardial flow reserve (MFR) lower compared to those without events (both P < .001). At multivariable Cox analysis, increased TPD (i.e., ‡ 5%) and reduced MFR (i.e., < 2) were predictors of events (both P < .001). At Weibull survival analysis, the highest probability of cardiac events and risk acceleration were observed in patients with both increased TPD and reduced MFR. Annualized event rate was higher in patients with reduced MFR compared to those with preserved MFR (P < .001). Conclusion. In patients with INOCA, the combined evaluation of myocardial perfusion and coronary vascular function by 82Rb PET/CT is able to identify those at higher risk of cardiac events.

BACKGROUND: We measured myocardial blood flow (MBF) and perfusion reserve (MPR) by dynamic CZT-SPECT and 82Rb-PET in patients with suspected or known coronary artery disease (CAD) and compared the accuracy of the two methods in predicting obstructive CAD. METHODS: Twenty-five patients with available coronary angiography data underwent 99mTc-sestamibi CZT-SPECT and 82Rb-PET cardiac imaging. Stress and rest MBF and MPR were calculated by both methods and compared. Diagnostic accuracies of CZT-SPECT and PET were also assessed using a receiver-operator-characteristic curve. RESULTS: CZT-SPECT yielded similar baseline MBF, but higher hyperemic MBF and MPR values compared to PET. There was a modest correlation between the two methods for MPR (r = 0.56, P < .01). MPR by CZT-SPECT showed a good ability in identify a reduced MPR by PET, with an area under the curve of 0.85. A MPR cut-off of 2.5 was identified by CZT-SPECT for detection of abnormal MPR by PET, with a sensitivity, specificity and accuracy of 86%, 73% and 80%. The area under the curve for the identification of obstructive CAD by regional MPR were 0.83 for CZT-SPECT and 0.84 for PET (P = .90). At CZT-SPECT, a regional MPR of 2.1 provided the best trade-off between sensitivity and specificity for identifying obstructive CAD. Diagnostic accuracy of CZT-SPECT and PET using respective cut-off values was comparable (P = .62). CONCLUSION: Hyperemic MBF and MPR values obtained by CZT-SPECT are higher than those measured by 82Rb-PET imaging, with a moderate correlation between the two methods. CZT-SPECT shows good diagnostic accuracy for the identification of obstructive CAD. These findings may encourage the use of this new technique to a better risk stratification and patient management.

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Background. We performed a meta-analysis to compare the diagnostic performance of conventional SPECT (C-SPECT) and cadmium-zinc-telluride (CZT)-SPECT systems in detecting angiographically proven coronary artery disease (CAD). Methods. Studies published between January 2000 and February 2018 were identified by database search. We included studies assessing C-SPECT or CZT-SPECT as a diagnostic test to evaluate patients for the presence of CAD, defined as at least 50% diameter stenosis on invasive coronary angiography. A study was eligible regardless of whether patients were referred for suspected or known CAD. Results. We identified 40 eligible articles (25 C-SPECT and 15 CZT-SPECT studies) including 7334 patients (4997 in C-SPECT and 2337 in CZT-SPECT studies). The pooled sensitivity and specificity were 85% and 66% for C-SPECT and 89% and 69% for CZT-SPECT imaging studies. The area under the curve was slightly higher for CZT-SPECT (0.89) compared to C-SPECT (0.83); accordingly, the summary diagnostic OR was 17 for CZT-SPECT and 11 for C-SPECT. The accuracy of the two tests slightly differs between C-SPECT and CZT-SPECT (chi-square 11.28, P < .05). At meta-regression analysis, no significant association between both sensitivity and specificity and demographical and clinical variables considered was found for C-SPECT and CZT-SPECT studies. Conclusions. C-SPECT and CZT-SPECT have good diagnostic performance in detecting angiographic proven CAD, with a slightly higher accuracy for CZT-SPECT. This result supports the use of the novel gamma cameras in clinical routine practices also considering the improvements in acquisition time and radiation exposure reduction.

Background. The frequency of abnormal stress single-photon emission computed tomography myocardial perfusion imaging (MPS) has decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. This study evaluated the temporal trend of abnormal stress MPS and its relationship with risk factors in a cohort of Italian subjects. Methods. We included all patients who underwent clinically indicated stress MPS at our academic center between January 2006 and December 2017. Patients were assessed for change in demographics, clinical symptoms, risk factors, and frequency of abnormal and ischemic MPS. Results. A total of 8,886 stress MPS studies were performed (3,350 abnormal). Age, male gender, diabetes, smoking, and angina were independent predictors of abnormal MPS. There was a slight decline in the frequency of abnormal (from 39% to 36%, P < .05) and ischemic (from 25% to 22%, P < .01) MPS during the study period, while the percentage of patients with hypertension, hypercholesterolemia, smoking, and angina increased. The Cochran-Mantel-Haenszel test indicates that the likelihood of having an abnormal MPS did not change over time for age, diabetes, smoking, and a history of coronary artery disease (CAD), increased for hypertension and hypercholesterolemia and decreased for male compared to female gender. Conclusions. In our cohort of Italian subjects, there was a slight temporal decline in the frequency of abnormal and ischemic MPS despite an increase over time in the prevalence of many cardiac risk factors. These results strengths the need to develop more effective strategies for appropriately referring patients to cardiac imaging procedures.

Background: We evaluated the warranty period of a normal stress myocardial perfusion single-photon emission computed tomography (MPS) in hypertensive patients. Methods and Results: A total of 471 consecutive hypertensive patients with suspected coronary artery disease and normal perfusion at stress MPS were followed for a mean of 76 ± 21 months. Endpoint events were cardiac death or nonfatal myocardial infarction. With Cox analysis, age (hazard ratio 1.1, P < .005) and stress test type (hazard ratio 2.7, P < .005) were independent predictors of events. With parametric Weibull analysis, patients ≤60 years old undergoing exercise stress test remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration were observed in those > 60 years old who underwent pharmacologic stress test. In patients undergoing exercise test, peak systolic blood pressure (BP; hazard ratio 1.1, P < .005) emerged as predictor of events, and only subjects with peak systolic BP < 160 mmHg remained at low risk for the entire length of follow-up. In contrast, for patients with peak systolic BP ≥180 mmHg, the time to achieve a cumulative cardiac risk level of 3% was 18 months. Conclusions: In hypertensive patients, the warranty period of a normal stress MPS varies according to stress type and peak systolic BP. A normal stress MPS can be considered reassuring in subjects ≤60 years old who performed exercise stress test and a peak systolic BP < 160 mmHg.

BACKGROUND: Comparing the prognostic value of a negative finding by stress single-photon emission computed tomography myocardial perfusion imaging (MPI) and coronary computed tomography angiography (CCTA) may be useful to evaluate how better identify low-risk patients. We performed a meta-analysis to compare the long-term negative predictive value (NPV) of normal stress MPI and normal CCTA in subjects with suspected coronary artery disease (CAD). METHODS AND RESULTS: Studies published between January 2000 and November 2016 were identified by database search. We included MPI and CCTA studies that followed-up ≥100 subjects for ≥5 years and providing data on clinical outcome for patients with negative tests. Summary risk estimates for normal perfusion at MPI or

Background. Breast attenuation may impact the diagnostic accuracy of stress myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT). We compared the performance of conventional (C)-SPECT and cadmium-zinc-telluride (CZT)-SPECT systems in women with low-intermediate likelihood of coronary artery disease (CAD). Methods and Results. A total of 109 consecutive women underwent stress-optional rest MPI by both C-SPECT and CZT-SPECT. In the overall study population, a weak albeit significant correlation between total perfusion defect (TPD) measured by C-SPECT and CZT-SPECT was observed (r = 0.38, P < .001) and at Bland-Altman analysis the mean difference in TPD (C-SPECT minus CZT-SPECT) was 2.40% (P < .001). Overall concordance of semiquantitative diagnostic performance between C-SPECT and CZT-SPECT was observed in 52 (48%) women with a κ value of 0.09. Normalcy rate was significantly higher using CZT-SPECT compared to C-SPECT (P < .001). Machine learning analysis performed through the implementation of J48 algorithm proved that CZT-SPECT has higher sensitivity, specificity, and accuracy than C-SPECT. Conclusions. In women with low-intermediate likelihood of CAD, there is a poor concordance of diagnostic performance between C-SPECT and CZT-SPECT and CZT-SPECT allows better normalcy rate detection compared to C-SPECT.

BACKGROUND: We compared the long-term prognostic value of coronary artery calcium (CAC) scanning, coronary computed tomographic angiography (CCTA), and stress single-photon emission computed tomography myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: A total of 164 patients were studied. CAC score was measured according to the Agatston method and patients were categorized into 3 groups (0, 1-300, and >300). The following events were recorded: cardiac death, nonfatal infarction, and unstable angina requiring revascularization. Follow-up was 95% complete during a mean period of 82 ± 34 months. During follow-up, 22 events occurred (14% cumulative event rate). Event-free survival decreased with worsening of CAC score category (P < .001) and it was worse (P < .001) in patients with significant CAD (≥50% stenosis) and in those with stress-induced ischemia (summed difference score >2). At multivariable analysis, CAC (P = .001) and ischemia (P = .012) were independent predictors of events. MPI data added prognostic information to a model including clinical variables, CAC and CCTA findings, increasing the global Chi-square from 36.2 to 41.9 (P = .013). The decision curve analyses in patients with CAC score >0 indicate that the prognostic model including MPI resulted in a higher net benefit across a wide range of decision threshold probabilities. CONCLUSIONS: CAC and MPI, but not CCTA, are independent predictors of cardiac events. Stress MPI appears to improve risk stratification over clinical variables, CAC scanning and CCTA findings.

Assessment of risk of future events in patients with suspected or known coronary artery disease (CAD) is challenging. Many studies are published every month on prognostic factors, and novel prognostic models and flowchart are proposed for clinical use. A quantity of data accumulated since the 70’ demonstrates the strength of stress single-photon emission-computed tomographymyocardial perfusion imaging (MPI) in predicting outcome. MPI is also commonly used as a gatekeeper to select patients for coronary revascularization. The degree of left ventricular (LV) dysfunction and the extent and magnitude of inducible myocardial ischemia are important prognostic variables that can be assessed by MPI. Transient ischemic LV cavity dilation is another high-risk variable associated with the presence of severe angiographic CAD and with an adverse outcome. Serial MPI imaging has been used to compare the effectiveness of intercurrent treatments, within the framework of randomized controlled trials. Moreover, an analysis of the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study not including patients with intervening cardiac events or revascularization found unexpected resolution of ischemia in most of these patients, potentially because of more aggressive medical treatment of cardiovascular risk factors.

However, improving nuclear cardiology practiceis required to maximize its role in the presence ofmultiple concurrent imaging modalities.REGADENOSON SPECT MYOCARDIALPERFUSION IMAGINGThe United States Food and Drug Administrationapproved the use of regadenoson, a selective adenosineA2A receptor agonist, on April 10, 2008 for SPECTmyocardial perfusion imaging as vasodilator stressagent.

BACKGROUND: We assessed the prognostic value of coronary flow reserve (CFR) estimated by single-photon emission computed tomography (SPECT) in patients with suspected myocardial ischemia. METHODS AND RESULTS: Myocardial perfusion and CFR were assessed in 106 patients using dipyridamole/rest Tc-99m sestamibi SPECT and follow-up was obtained in 103 (97%) patients. Four early revascularized patients were excluded and 99 were assigned to normal (summed stress score 60 months in those with normal and

Background. We evaluated the incremental prognostic value of viability assessment by nitrate single-photon emission computed tomography (SPECT) in patients with ischemic left ventricular (LV) dysfunction. Methods and Results. One hundred and sixty-four patients with previous myocardial infarction and LV dysfunction (ejection fraction 29% ± 15%) underwent two Tc-99m sestamibi SPECT studies, under control conditions and after sublingual nitrate administration, for evaluation of myocardial viability. In each patient, viability was defined as the presence of ?2 severely dysfunctional segments with preserved tracer uptake (?55% of peak activity). Cardiac death, myocardial infarction, and late (>2 months) revascularization were considered events. Follow-up was 98% complete at a mean period of 30 ± 24 months. At baseline SPECT, 119 (73%) patients had evidence of viable myocardium, while 45 (27%) did not. Of these latter patients, 18 (40%) had evidence of viability after nitrate administration. Cardiac events occurred in 58 (35%) patients. Cumulative probability of event-free survival was similar in patients with and without viability at baseline SPECT (log rank 0.3, P 5 NS), while it was lower in patients with viability at nitrate SPECT compared to those without (log rank 6.3, P < .01). The addition of nitrate SPECT data significantly improved the prognostic power of the model including clinical, functional, angiographic, and baseline SPECT data (P < .01). Conclusions. In patients with previous myocardial infarction and LV dysfunction, nitrate SPECT imaging provides incremental prognostic information over those obtained from clinical, functional, angiographic variables, and baseline SPECT data.

The quantitative assessment of coronary flow reserve (CFR) may be useful for the functional evaluation of coronary artery disease (CAD), allowing judgment of its severity, tracking of disease progression, and evaluation of the anti-ischemic efficacy of therapeutic strategies. Invasive techniques, such as intracoronary Doppler ultrasound and the pressure-derived method, which directly assess CFR velocity and fractional flow reserve, have been used for the evaluation of the physiologic significance of coronary lesions. Considerable progress has been made in the improvement of technologies directed toward the noninvasive quantification of myocardial blood flow and CFR. Positron emission tomography has emerged as an accurate technique to quantify CFR. The absolute measurements obtained with this noninvasive approach have been widely validated. Nevertheless, it has not been applied to routine studies because of its high cost and complexity. On the other hand, technetium 99m-labeled tracers have been largely used for the evaluation of myocardial perfusion with single photon emission computed tomography (SPECT) imaging in patients with suspected or known CAD. Recently, attempts to estimate CFR with SPECT tracers have been made to obtain, with noninvasive methods, data for quantitative functional assessment of CAD. This review analyzes the relative merit and limitations of CFR measurements by cardiac SPECT imaging with Tc-99m-labeled tracers and describes the potential clinical applications of this technique.

This study evaluated the prognostic value of combined assessment of left ventricular (LV) function and regional myocardial thallium activity in patients with nonrecent myocardial infarction and LV dysfunction. Eighty-two patients with previous myocardial infarction (>8 weeks) and echocardiographic evidence of LV dysfunction underwent thallium-201 rest-redistribution tomography and cardiac catheterization. During the follow-up period (mean 25 months) there were 18 cardiac events (14 deaths and 4 nonfatal myocardial infarctions). Multivariate Cox regression analysis on clinical, angiographic, and thallium variables showed that the number of echocardiographic dysfunctional segments with preserved thallium uptake (≥50% of peak activity; chi-square 11.03; p

patients (*36%) were correctly reclassified and the NRI also was *0.36. 5 However, the NRI value is not merely the ratio between the number of patients correctly reclassified and the total study population. The NRI is based on event-specific reclassification tables and only for the particular distribution of reclassification between ‘‘event’’ and ‘‘no event,’’ the two values (NRI and percent of correct reclassification) may coincide. As an example, consider a study of 1,000 subjects with 300 events (30%) and a new marker that correctly reclassified 30% of the total study population. If all the 300 subjects reclassified are ‘‘event’’ subjects, then the NRI is 1 (300/300), while if the 300 subjects reclassified are ‘‘no event’’ subjects, then the NRI is 0.43 (300/700). In fact, if all ‘‘event’’ and ‘‘no event’’ subjects are correctly reclassified, the NRI is 2 (the maximum possible value), and thus NRI is perhaps better expressed in absolute units than in percentage, to avoid misleading interpretation. As an ancillary question, the authors of that study stated that only 40% of patients underwent an exercise stress test and the remaining underwent a pharmacologic stress test, with monitoring procedures similar to an exercise test. 5 It is unclear how the Duke treadmill score was calculated in patients undergoing pharmacologic stress test and whether this score has been validated for pharmacologic stress test for diagnostic and/or prognostic purposes.