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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 82 Rb positron emission tomography (PET)/computed tomography (CT) imaging., Methods: The study included 102 patients referred to 82 Rb 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 82 Rb PET/CT may improve risk stratification in patients submitted to coronary revascularization., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

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 &lt; 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., (© 2022. The Author(s).)

Purpose: We assessed the impact of COVID-19 infection on cardiovascular events in patients with suspected or known coronary artery disease (CAD) referred to stress single-photon emission computed tomography myocardial perfusion imaging (MPS)., Methods: A total of 960 consecutive patients with suspected or known CAD were submitted by referring physicians to stress MPS for assessment of myocardial ischemia between January 2018 and June 2019. All patients underwent stress-optional rest MPS. Perfusion defects were quantitated as % of LV myocardium and expressed as total perfusion defect (TPD), representing the defect extent and severity. A TPD ≥ 5% was considered abnormal., Results: During a mean follow-up of 27 months (range 4-38) 31 events occurred. Moreover, 55 (6%) patients had a COVID-19 infection. The median time from index MPS to COVID-19 infection was 16 months (range 6-24). At Cox multivariable analysis, abnormal MPS and COVID-19 infection resulted as independent predictors of events. There were no significant differences in annualized event rate in COVID-19 patients with or without abnormal MPS (p = 0.56). Differently, in patients without COVID-19, the presence of abnormal MPS was associated with higher event rate (p < .001). Patients with infection compared to those without had a higher event rate in the presence of both normal and abnormal TPD., Conclusion: In patients with suspected or known CAD, the presence of COVID-19 infection during a short-term follow-up was associated with a higher rate of cardiovascular events., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We performed a systematic review and a meta-analysis to investigate the successful ablation rate after radioiodine (RAI) administration in patients with differentiated thyroid cancer (DTC) at intermediate-high risk of recurrence., Methods: A comprehensive literature search of the PubMed, Scopus, and Web of Science databases was conducted according to the PRISMA statement., Results: The final analysis included 9 studies accounting for 3103 patients at intermediate-high risk of recurrence. In these patients, the successful ablation rates ranged from 51 to 94% with a 71% pooled successful ablation and were higher in intermediate (72%) than in high (52%)-risk patients. Despite the rigorous inclusion standards, a significant heterogeneity among the evaluated studies was observed. Higher administered RAI activities are associated with a lower successful ablation rate in the whole population and in the subgroup of high-risk patients. Furthermore, pooled recurrence rate in intermediate-risk patients achieving successful ablation was only 2% during the subsequent 6.4-year follow-up while the pooled recurrence rate was 14% in patients who did not achieve a successful ablation., Conclusion: In a large sample of 3103 patients at intermediate-high risk of persistent/recurrent disease, 71% of patients achieved a successful ablation. In these intermediate-risk patients, the probability of subsequent recurrence is low and most recurrence occurred in those with already abnormal findings at the first control., (© 2021. The Author(s).)

Purpose: The identification of coronary vascular dysfunction may enhance risk stratification in patients with resistant hypertension (RH). We evaluated if impaired coronary vascular function, assessed by rubidium-82 ( 82 Rb) positron emission tomography/computed tomography (PET/CT) imaging, is associated with increased cardiovascular risk in patients with hypertension without overt coronary artery disease (CAD)., Methods: We studied 517 hypertensive subjects, 26% with RH, without overt CAD, and with normal stress-rest myocardial perfusion imaging at 82 Rb PET/CT. The outcome end points were cardiac death, nonfatal myocardial infarction, coronary revascularization, and admission for heart failure., Results: Over a median of 38 months (interquartile range 26 to 50), 21 cardiac events (4.1% cumulative event rate) occurred. Patients with RH were older (p < 0.05) and had a higher prevalence of left ventricular hypertrophy (p < 0.001), a lower hyperemic myocardial blood flow (MBF), and myocardial perfusion reserve (MPR) (both p < 0.001) compared to those without. Conversely, coronary artery calcium content and baseline MBF were not different between patients with and without RH. At univariable Cox regression analysis, age, RH, left ventricular ejection fraction, coronary artery calcium score, and reduced MPR were significant predictors of events. At multivariable analysis, age, RH, and reduced MPR (all p < 0.05) were independent predictors of events. Patients with RH and reduced MPR had the highest risk of events and the major risk acceleration over time., Conclusion: The findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension., (© 2021. The Author(s).)

Purpose: We assessed the effects of the COVID-19 pandemic on myocardial perfusion imaging (MPI) for ischemic heart disease during the lockdown imposed by the Italian Government., Methods: We retrospectively reviewed the number and the findings of stress single-photon emission computed tomography (SPECT)-MPI performed between February and May 2020 during the COVID-19 pandemic at the University of Napoli Federico II. The number and the findings of stress SPECT-MPI studies acquired in the corresponding months of the years 2017, 2018, and 2019 were also evaluated for direct comparison., Results: The number of stress SPECT-MPI studies performed during the COVID-19 pandemic (n = 123) was significantly lower (P < 0.0001) compared with the mean yearly number of procedures performed in the corresponding months of the years 2017, 2018, and 2019 (n = 413). Yet, the percentage of abnormal stress SPECT-MPI studies was similar (P = 0.65) during the pandemic (36%) compared with the mean percentage value of the corresponding period of the years 2017, 2018, and 2019 (34%)., Conclusion: The number of stress SPECT-MPI studies was significantly reduced during the COVID-19 pandemic compared with the corresponding months of the previous 3 years. The lack of difference in the prevalence of abnormal SPECT-MPI studies between the two study periods strongly suggests that many patients with potentially abnormal imaging test have been missed during the pandemic.

Aims: 18 F-FDG PET/CT is the most accurate imaging modality in differentiated thyroid cancer (DTC) patients with either an aggressive histology, an absence of radioiodine uptake in neoplastic foci, or in the absence of imaging abnormalities in patients with an elevated serum thyroglobulin (Tg) level that progresses with time. We evaluated the diagnostic performance of FDG PET/MR in comparison with that of PET/CT., Methods and Results: Following the injection of a single 18 F-FDG activity, PET/MR and PET/CT were sequentially performed in 40 consecutive patients with DTC previously treated with total thyroidectomy and radioiodine ablation. All patients were then followed up for at least 6 months. PET/MR was positive in 11 patients and PET/CT in 10. PET/MR detected 33 tumor foci and PET/CT 30. During the follow-up of the 12 patients with negative initial PET studies and with a detectable serum Tg, only one patient had a neck recurrence and the administration of an empiric high activity of 131 I in the other 11 patients did not reveal any tumor focus. In the 17 patients with an initial serum Tg level < 2 ng/mL, no recurrence occurred., Conclusion: This study confirms the high diagnostic accuracy of FDG PET studies in DTC patients with elevated serum Tg levels and shows that PET/MR brings similar information as compared to PET/CT imaging.

Purpose: Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC), stress-induced myocardial ischemia and myocardial perfusion reserve (MPR). We evaluated the prognostic role of the combined assessment of regional CAC score, ischemic total perfusion defect (ITPD) and MPR in predicting lesion-related outcome in patients with suspected coronary artery disease (CAD)., Methods: We studied 206 patients with suspected CAD referred to 82 Rb PET/CT cardiac imaging and available coronary angiographic data. The outcome end points were cardiac death, target vessel-related myocardial infarction or coronary revascularization., Results: Compared to vessels without event, those with event showed higher CAC score and ITPD, and lower hyperemic myocardial blood flow and MPR (all p < 0.001). At Cox regression multivariable analysis, significant CAD (≥50% stenosis) (p < 0.001), CAC score ≥ 300 (p < 0.01) and MPR <2 (p < 0.01) were independent predictors of events. The decision trees analysis for the identification of events produced five terminal nodes. The initial split was on CAC score values. For vessels with CAC <300 and MPR ≥2, no further split was performed, while vessels with CAC <300 and MPR <2 were further stratified by ITPD. For vessels with CAC ≥300 a further stratification was performed only by MPR. The worst prognosis was observed in vessels with CAC ≥300 and MPR <2 and in vessels with CAC <300, MPR <2 and ITPD ≥5%., Conclusion: The combination of CAC score and MPR is useful to predict the lesion-related outcome in the presence of significant CAD.

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 99m Tc-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.

Purpose: Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD)., Methods: We analyzed 113 patients with suspected CAD referred to 82 Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD., Results: Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6 ± 6.2 vs. 0.6 ± 1.3) and lower hyperemic MBF (1.01 ± 0.5 vs. 1.75 ± 0.6 ml/min/g) and CFR (1.56 ± 0.6 vs. 2.38 ± 0.7; all p < 0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p < 0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365-1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64-1.26) for the CAC/ITPD/CFR model., Conclusion: Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD.

Purpose: To evaluate the prognostic value of coronary atherosclerotic burden, assessed by coronary artery calcium (CAC) score, and coronary vascular function, assessed by coronary flow reserve (CFR) in patients with suspected coronary artery disease (CAD)., Methods: We studied 436 patients undergoing hybrid 82 Rb positron emission tomography/computed tomography imaging. CAC score was measured according to the Agatston method, and patients were categorized into three groups (0, <400, and ≥400). CFR was calculated as the ratio of hyperemic to baseline myocardial blood flow, and it was considered reduced when <2., Results: Follow-up was 94% complete during a mean period of 47±15 months. During follow-up, 17 events occurred (4% cumulative event rate). Event-free survival decreased with worsening of CAC score category (p < 0.001) and in patients with reduced CFR (p < 0.005). At multivariable analysis, CAC score ≥400 (p < 0.01) and CFR (p < 0.005) were independent predictors of events. Including CFR in the prognostic model, continuous net reclassification improvement was 0.51 (0.14 in patients with events and 0.37 in those without). At classification and regression tree analysis, the initial split was on CAC score. For patients with a CAC score < 400, no further split was performed, while patients with a CAC score ≥400 were further stratified by CFR values. Decision curve analyses indicate that the model including CFR resulted in a higher net benefit across a wide range of decision threshold probabilities., Conclusions: In patients with suspected CAD, CFR provides significant incremental risk stratification over established cardiac risk factors and CAC score for prediction of adverse cardiac events.

Purpose: To assess the relationship between coronary atherosclerotic burden and vascular function in diabetic and nondiabetic patients after balancing for coronary risk factors., Methods: We studied 672 patients without overt coronary artery disease and normal myocardial perfusion on stress 82 Rb PET/CT imaging. To account for differences in baseline characteristics between diabetic patients and nondiabetic patients, we created a propensity score-matched cohort considering clinical variables and coronary risk factors., Results: Before matching, diabetic patients had higher coronary artery calcium (CAC) scores (p < 0.001) and lower coronary flow reserve (CFR; p < 0.001) than nondiabetic patients. After matching, CAC scores were comparable between diabetic and nondiabetic patients, but diabetic patients still had lower hyperaemic myocardial blood flow (p < 0.001) and CFR (p < 0.05). Patients were categorized by ln(CAC score) quartiles. There was a decrease in CFR with increasing CAC score quartile in both diabetic patients (p for trend < 0.01) and nondiabetic patients (p for trend < 0.005). Diabetes was associated with lower CFR across quartile categories (p < 0.002). In a multivariable linear regression analysis, CAC score was inversely related to CFR in both diabetic patients (p < 0.05) and nondiabetic patients (p < 0.001)., Conclusion: Diabetic patients had higher CAC scores than nondiabetic patients, but the difference disappeared when clinical characteristics were taken into account. Of note, diabetic patients also had lower CFR regardless of CAC score than nondiabetic patients after matching. Thus, coronary atherosclerotic burden and vascular function have to be seen as two different entities.

Purpose: Reversible ischaemia at radionuclide myocardial perfusion imaging (MPI) accurately predicts risk of cardiac death and nonfatal myocardial infarction (major adverse cardiac events, MACE). This prognostic penetrance might be empowered by accounting for exercise tolerance as an indirect index of ischaemia severity. The present study aimed to verify this hypothesis integrating imaging assessment of ischaemia severity with exercise maximal rate pressure product (RPP) in a large cohort of patients with suspected or known coronary artery disease (CAD)., Methods and Results: We analysed 1,502 consecutive patients (1,014 men aged 59 ± 10 years) submitted to exercise stress/rest MPI. To account for exercise tolerance, the summed difference score (SDS) was divided by RPP at tracer injection providing a clinical prognostic index (CPI). Reversible ischaemia was documented in 357 patients (24 %) and was classified by SDS as mild (SDS 2-4) in 180, moderate (SDS 5-7) in 118 and severe (SDS >7) in 59. CPI values of ischaemic patients were clustered into tertiles with lowest and highest values indicating low and high risk, respectively. CPI modified SDS risk prediction in 119/357 (33 %) patients. During a 60-month follow-up, MACE occurred in 68 patients. Kaplan-Meier analysis revealed that CPI significantly improved predictive power for MACE incidence with respect to SDS alone. Multivariate Cox analysis confirmed the additive independent value of CPI-derived information., Conclusion: Integration of ischaemic threshold and ischaemia extension and severity can improve accuracy of exercise MPI in predicting long-term outcome in a large cohort of patients with suspected or known CAD.

Purpose: Exercise training might exert its beneficial effects on myocardial perfusion by inducing coronary vascular adaptations or enhancing collateralization. We evaluated whether long-term exercise-based cardiac rehabilitation started early after ST-elevation acute myocardial infarction (STEMI) improves myocardial perfusion and left ventricular (LV) function., Methods: Forty-six patients with recent STEMI and residual inducible hypoperfusion were randomized into two groups: 25 enrolled in a 6-month outpatient exercise-based cardiac rehabilitation programme (group T) and 21 discharged with generic instructions for maintaining physical activity and correct lifestyle (group C). All patients underwent cardiopulmonary exercise test and dipyridamole rest gated myocardial perfusion single photon emission computed tomography within 1 week after STEMI and at 6-month follow-up., Results: At follow-up, group T showed an improvement in peak oxygen consumption, oxygen pulse and in the slope of increase in ventilation over carbon dioxide output (all p < 0.01) associated with a reduction of stress-induced hypoperfusion (p < 0.01) and an improvement in resting and post-stress wall motion score indexes (both p < 0.01), resting and post-stress wall thickening score indexes (both p < 0.05) and resting and post-stress LV ejection fraction (both p < 0.05). On the contrary, no changes in cardiopulmonary indexes, myocardial perfusion and LV function parameters were observed in group C at follow-up., Conclusion: Exercise training started early after STEMI reduces stress-induced hypoperfusion and improves LV function and contractility. Exercise-induced changes in myocardial perfusion and function were associated with the absence of unfavourable LV remodelling and with an improvement of cardiovascular functional capacity.