Impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic perfusion defect and myocardial flow reserve.

PURPOSE: We evaluated the impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic total perfusion defect (ITPD) and myocardial flow reserve (MFR) as assessed by 82Rb positron emission tomography (PET)/computed tomography (CT) imaging. METHODS: The study included 102 patients referred to 82Rb PET/CT myocardial perfusion imaging before and after coronary revascularization. All patients were followed for the occurrence of cardiovascular events (cardiac death, nonfatal myocardial infarction, repeated revascularization, and heart failure) after the second imaging study. RESULTS: During a median follow-up of 20 months, 21 events occurred. The clinical characteristics were comparable between patients with and without events. In the overall study population, after revascularization, there was a significant reduction (P < 0.001) of ITPD, while hyperemic myocardial blood flow (MBF) (P < 0.01) and MFR (P < 0.05) significantly improved. Event rate was higher in patients with ITPD (P < 0.005) or MFR (P < 0.001) worsening compared to those with unchanged or improved ITPD or MFR. At Cox univariable analysis, ITPD and MFR worsening resulted in predictors of events (both P < 0.05). Patients with worsening of both ITPD and MFR had the worst event-free survival (log-rank 32.9, P for trend < 0.001). CONCLUSIONS: In patients with stable CAD, worsening of ITPD and MFR after revascularization procedures is associated with higher risk of cardiovascular events. Follow-up MPI with 82Rb PET/CT may improve risk stratification in patients submitted to coronary revascularization.

Prognostic value of myocardial perfusion imaging by cadmium zinc telluride single-photon emission computed tomography in patients with suspected or known coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: Aim of this study was to define the prognostic value of stress myocardial perfusion imaging by cadmium zinc telluride (CZT) single-photon emission computed tomography (SPECT) for prediction of adverse cardiovascular events in patients with known or suspected coronary artery disease (CAD). METHODS AND RESULTS: Studies published until November 2022 were identified by database search. We included studies using stress myocardial perfusion imaging by CZT-SPECT to evaluate subjects with known or suspected CAD and providing primary data of adverse cardiovascular events. Total of 12 studies were finally included recruiting 36,415 patients. Pooled hazard ratio (HR) for the occurrence of adverse events was 2.17 (95% confidence interval, CI, 1.78-2.65) and heterogeneity was 66.1% (P = 0.001). Five studies reported data on adjusted HR for the occurrence of adverse events. Pooled HR was 1.69 (95% CI, 1.44-1.98) and heterogeneity was 44.9% (P = 0.123). Seven studies reported data on unadjusted HR for the occurrence of adverse events. Pooled HR was 2.72 (95% CI, 2.00-3.70). Nine studies reported data useful to calculate separately the incidence rate of adverse events in patients with abnormal and normal myocardial perfusion. Pooled incidence rate ratio was 2.38 (95% CI, 1.39-4.06) and heterogeneity was 84.6% (P < 0.001). The funnel plot showed no evidence of asymmetry (P = 0.517). At meta-regression analysis, we found an association between HR for adverse events and presence of angina symptoms and family history of CAD. CONCLUSIONS: Stress myocardial perfusion imaging by CZT-SPECT is a valuable noninvasive prognostic indicator for adverse cardiovascular events in patients with known or suspected CAD.

Myocardial blood flow evaluation with dynamic cadmium-zinc-telluride single-photon emission computed tomography: Bright and dark sides.

Myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) assessment with non-invasive techniques represent an important tool to evaluate both coronary artery disease severity and extent. Currently, cardiac positron emission tomography-computed tomography (PET-CT) is the "gold standard" for the assessment of coronary function and provides accurate estimations of baseline and hyperemic MBF and MFR. Nevertheless, due to the high cost and complexity, PET-CT is not widely used in clinical practice. The introduction of cardiac-dedicated cadmium-zinc-telluride (CZT) cameras has renewed researchers' interest on MBF quantitation by single-photon emission computed tomography (SPECT). Indeed, many studies evaluated MPR and MBF measurements by dynamic CZT-SPECT in different cohorts of patients with suspected or overt coronary artery disease. As well, many others have compared the values obtained by CZT-SPECT to the ones by PET-CT, showing good correlations in detecting significant stenosis, although with different and non-standardized cut-off values. Nevertheless, the lack of standardized protocol for acquisition, reconstruction and elaboration makes more difficult to compare different studies and to further assess the real advantages of MBF quantitation by dynamic CZT-SPECT in clinical routine. Many are the issues involved in the bright and dark sides of dynamic CZT-SPECT. They include different type of CZT cameras, different execution protocols, different tracers with different myocardial extraction fraction and distribution, different software packages with different tools and algorithms, often requiring manual post-processing elaboration. This review article provides a clear summary of the state of the art on MBF and MPR evaluation by dynamic CZT-SPECT and outlines the major issues to solve to optimize this technique.

Prediction of outcome by 82Rb PET/CT in patients with ischemia and nonobstructive coronary arteries.

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.

Regional myocardial perfusion imaging in predicting vessel-related outcome: interplay between the perfusion results and angiographic findings.

BACKGROUND: Despite myocardial perfusion imaging (MPI) by cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera is largely used in the diagnosis and risk stratification of patients with suspected or known coronary artery disease (CAD), no data are available on the prognostic value of a regional MPI evaluation. We evaluated the prognostic value of regional MPI by the CZT camera in predicting clinical outcomes at the vessel level in patients with available angiographic data. METHODS AND RESULTS: Five hundred and forty-one subjects with suspected or known CAD referred to 99mTc-sestamibi gated CZT-SPECT cardiac imaging and with available angiographic data were studied. Both regional total perfusion deficit (TPD) and ischemic TPD (ITPD) were calculated separately for each vascular territory (left anterior descending, left circumflex, and right coronary artery). The outcome end points were cardiac death, target vessel-related myocardial infarction, or late coronary revascularization. The prevalence of CAD ≥ 50%, regional stress TPD, and regional ITPD was significantly higher in vessels with events as compared to those without (both P < 0.001). The receiver operating characteristics area under the curve for regional ITPD for the identification of vessel-related events was 0.81 (95% confidence interval 0.75-0.86). An ITPD value of 2.0% provided the best trade-off for identifying the vessel-related event. At multivariable analysis, both CAD ≥ 50% and ITPD ≥ 2.0% resulted in independent predictors of events. CONCLUSIONS: Regional myocardial perfusion assessed by the CZT camera demonstrated good reliability in predicting vessel-related events in patients with suspected or known CAD.

Simultaneous assessment of myocardial perfusion and adrenergic innervation in patients with heart failure by low-dose dual-isotope CZT SPECT imaging.

BACKGROUND: In patients with heart failure (HF) sequential imaging studies have demonstrated a relationship between myocardial perfusion and adrenergic innervation. We evaluated the feasibility of a simultaneous low-dose dual-isotope 123I/99mTc-acquisition protocol using a cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera. METHODS AND RESULTS: Thirty-six patients with HF underwent simultaneous low-dose 123I-metaiodobenzylguanidine (MIBG)/99mTc-sestamibi gated CZT-SPECT cardiac imaging. Perfusion and innervation total defect sizes and perfusion/innervation mismatch size (defined by 123I-MIBG defect size minus 99mTc-sestamibi defect size) were expressed as percentages of the total left ventricular (LV) surface area. LV ejection fraction (EF) significantly correlated with perfusion defect size (P < .005), innervation defect size (P < .005), and early (P < .05) and late (P < .01) 123I-MIBG heart-to-mediastinum (H/M) ratio. In addition, late H/M ratio was independently associated with reduced LVEF (P < .05). Although there was a significant relationship (P < .001) between perfusion and innervation defect size, innervation defect size was larger than perfusion defect size (P < .001). At multivariable linear regression analysis, 123I-MIBG washout rate (WR) correlated with perfusion/innervation mismatch (P < .05). CONCLUSIONS: In patients with HF, a simultaneous low-dose dual-isotope 123I/99mTc-acquisition protocol is feasible and could have important clinical implications.

Incremental value of 18F-FDG cardiac PET imaging over dobutamine stress echocardiography in predicting myocardial ischemia in patients with suspected coronary artery disease.

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 18F-FDG 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.

External validation of the CRAX2MACE model in an Italian cohort of patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging.

BACKGROUND: Prevention and development of diagnostic and therapeutic techniques reduced morbidity and mortality for coronary artery disease (CAD). In this context, the cardiovascular risk assessment for major adverse cardiac events (MACE) at 2-year (CRAX2MACE) model for prediction of 2-year major adverse cardiac events was developed. We performed an external validation of this model. METHODS: We included 1003 patients with suspected CAD undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging at our academic center between March 2015 and April 2019. RESULTS: Considering the occurrence of MACE (death from any cause, acute myocardial infarction, or late coronary revascularization), for the CRAX2MACE model the area under the receiver operating characteristic curve was 0.612 and the Brier score was 0.061. The Hosmer-Lemeshow test estimated a non-optimal fit (χ2 28, P < .001). Considering only hard events (cardiac death, acute myocardial infarction), the external validation of the CRAX2MACE model revealed a Brier score of 0.053 and an area under the receiver operating characteristic curve of 0.621. Hosmer-Lemeshow test was calculated by deciles and showed a poor fit (χ2 31, P < .001). CONCLUSION: CRAX2MACE model had a limited value for predicting 2-year major adverse cardiovascular events in an external validation cohort of patients with suspected CAD.

Quantification of myocardial perfusion reserve by CZT-SPECT: A head to head comparison with 82Rubidium PET imaging.

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.

Low-dose dynamic myocardial perfusion imaging by CZT-SPECT in the identification of obstructive coronary artery disease.

BACKGROUND: We measured myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by a dynamic low-dose CZT-SPECT protocol in patients with suspected or known coronary artery disease (CAD) and investigated the capability of dynamic data in predicting obstructive CAD. A total of 173 patients with suspected or known CAD underwent dynamic CZT-SPECT after the injection of 155 MBq and 370 MBq of 99mTc-sestamibi for rest and stress imaging, respectively. Standard rest and stress imaging were performed at the end of each dynamic scan. A total perfusion defect (TPD) < 5% were considered normal. Obstructive CAD was defined as ≥ 70% stenosis at coronary angiography. RESULTS: Global MPR was lower (p < 0.05) in patients with abnormal compared with those with normal MPI (2.40 ± 0.7 vs. 2.70 ± 0.8). A weak, albeit significant correlation between TPD and MPR (r = - 0.179, p < 0.05) was found. In 91 patients with available angiographic data, hyperemic MBF (2.59 ± 1.2 vs. 3.24 ± 1.1 ml/min/g) and MPR (1.96 ± 0.7 vs. 2.74 ± 0.9) were lower (both p < 0.05) in patients with obstructive CAD (n = 21) compared with those without (n = 70). At univariable analysis, TPD, hyperemic MBF, and MPR were significant predictors of obstructive CAD, whereas only MPR was independent predictor at multivariable analysis (p < 0.05). At per vessels analysis, regional hyperemic MBF (2.59 ± 1.2 vs. 3.24 ± 1.1 ml/min/g) and regional MPR (1.96 ± 0.7 vs. 2.74 ± 0.9) were lower in the 31 vessels with obstructive CAD compared with 242 vessels without (both p < 0.05). CONCLUSIONS: In patients with suspected or known CAD, MPR assessed by low-dose dynamic CZT-SPECT showed a good correlation with myocardial perfusion imaging findings and it could be useful to predict obstructive CAD.

A New Relational Database Including Clinical Data and Myocardial Perfusion Imaging Findings in Coronary Artery Disease.

BACKGROUND: The aim of this study was to test a relational database including clinical data and imaging findings in a large cohort of subjects with suspected or known Coronary Artery Disease (CAD) undergoing stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging. METHODS: We developed a relational database including clinical and imaging data of 7995 subjects with suspected or known CAD. The software system was implemented by PostgreSQL 9.2, an open source object-relational database, and managed from remote by pgAdmin III. Data were arranged according to a logic of aggregation and stored in a schema with twelve tables. Statistical software was connected to the database directly downloading data from server to local personal computer. RESULTS: There was no problem or anomaly for database implementation and user connections to the database. The epidemiological analysis performed on data stored in the database demonstrated abnormal SPECT findings in 46% of male subjects and 19% of female subjects. Imaging findings suggest that the use of SPECT imaging in our laboratory is appropriate. CONCLUSION: The development of a relational database provides a free software tool for the storage and management of data in line with the current standard.

Negative predictive value of stress myocardial perfusion imaging and coronary computed tomography angiography: A meta-analysis.

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 <50% coronary stenosis at CCTA were derived in random effect regression analysis, and causes of heterogeneity were determined in meta-regression analysis. We identified 12 eligible articles (6 MPI and 6 CCTA) including 33,129 patients (26,757 in MPI and 6372 in CCTA studies) with suspected CAD. The pooled annualized event rate (AER) for occurrence of hard events (death and nonfatal myocardial infarction) was 1.06 (95% confidence interval, CI 0.49-1.64) in MPI and 0.61 (95% CI 0.35-0.86) in CCTA studies. The pooled NPV was 91% (95% CI 86-96) in MPI and 96 (95% CI 95-98) in CCTA studies. The summary rates between MPI and CCTA were not statistically different. At meta-regression analysis, no significant association between AER and clinical and demographical variables considered was found for overall studies. CONCLUSIONS: Stress MPI and CCTA have a similar ability to identify low-risk patients with suspected CAD.