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Introduction: Bone mineral density (BMD) is reduced in patients with human immunodeficiency virus (HIV) infection. Trabecular bone score (TBS) is an additional feature calculated by dual-energy X ray absorption (DXA) that measures texture inhomogeneity at lumbar spine level, providing an index of bone microarchitecture. However, its clinical value still needs to be fully addressed. Aims of the study were to assess BMD and TBS in a cohort of patients with HIV compared to a population of healthy subjects and to investigate the prognostic value of TBS in HIV infected patients. Method: Bone health was assessed by DXA in 165 patients with HIV infection (120 men, mean age 40 ± 7 years) and in 164 healthy subjects (53 male, mean age 37 ± 10 years). BMD was measured at level of lumbar spine (L1-L4), femoral neck and total hip. TBS was computed from the images of lumbar spine using machine proprietary software. Results: BMD at femoral neck level was similar in HIV infected patients and healthy subjects (p = 0.57), whereas BMD measured in total femur was lower in HIV infected patients compared to healthy subjects (p < 0.05). Although mean BMD in lumbar spine was similar between HIV infected patients and healthy subjects (p = 0.90), mean lumbar TBS was lower in patients with HIV infection compared to healthy subjects (p < 0.05). Age, sex and HIV infection resulted independent predictors of reduced TBS. In HIV infected patients age, sex and protease inhibitor duration resulted independent predictors of reduced TBS. TBS was a significant predictor of vertebral fractures during follow-up (p < 0.05). Conclusion: Patients with HIV infection have a significant reduction of TBS, a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement.

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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 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.

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BACKGROUND: The prevalence of traditional cardiovascular risk factors shows different age-specific patterns. It is not known whether the prognostic impact of risk factors is similarly age-specific. We evaluated the profiles of cardiovascular risk factors and their prognostic impact on coronary artery disease (CAD) in relation to age. METHODS: We included 3667 patients with suspected or known CAD undergoing stress myocardial perfusion imaging (MPI). We evaluated the risk for major adverse cardiac events (MACE) within three years from the index MPI in patients belonging to three groups according to age tertile distribution: <59, 59-68, and >68 years. Gender, body mass index, diabetes, hypertension, dyslipidemia, family history of CAD, smoking, angina, dyspnea, previous CAD, and MPI outcome were assessed as risk factors by a multivariable Cox's regression. RESULTS: The three-year risk of MACE increased progressively with age and was 9%, 13%, and 18% for each group, respectively (p < 0.0001). Dyspnea and abnormal MPI outcome were significant risk factors for all age groups. Diabetes and smoking were significant from the age of 59 onwards, while hypertension resulted significant for patients older than 68 years. CONCLUSIONS: The number of risk factors was significantly associated with the occurrence of MACE increase with age. It is noteworthy that a personal history of CAD was not useful for risk stratification, while MPI results were.

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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.

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Advances in the prevention and treatment of cardiovascular disease (CVD) over the last decades have led to a marked reduction in mortality for CVD. Nevertheless, atherosclerosis leading to coronary artery disease and stroke remains one of the most common causes of death in the world. The usefulness of imaging tests in the early identification of disease led to identify subjects at major risk of poor outcomes, suggesting risk factor modification. The aim of this article is to analyze the state of art of combined imaging in patients at risk of CVD referred to MPI evaluation, to highlight the present and potential features able to provide incremental prognostic information to help clinicians in patient management and to reduce adverse events.

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Myocardial perfusion imaging by nuclear cardiology is widely validated for the diagnosis, risk stratification, and management of patients with suspected or known coronary artery disease. Numerous radiopharmaceuticals are available for single-photon emission computed tomography and PET modalities. Each tracer shows advantages and limitations that should be taken into account in performing an imaging examination. This review aimed to summarize the state-of-the-art radiotracers used for myocardial perfusion imaging and blood flow quantification, highlighting the new technologic advances and promising possible applications.

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BACKGROUND: Advances in treatment and optimization of chemotherapy protocols have greatly improved survival in cancer patients. Unfortunately, treatment can cause a reduction in left ventricular (LV) ejection fraction (EF) leading to cancer therapy-related cardiac dysfunction (CTRCD). We conducted a scoping review of published literature in order to identify and summarize the reported prevalence of cardiotoxicity evaluated by noninvasive imaging procedures in a wide-ranging of patients referred to cancer treatment as chemotherapy and/or radiation therapy. METHODS: Different databases were checked (PubMed, Embase, and Web of Science) to identify studies published from January 2000 to June 2021. Articles were included if they reported data on LVEF evaluation in oncological patients treated with chemotherapeutic agents and/or radiotherapy, measured by echocardiography and/or nuclear or cardiac magnetic resonance imaging test, providing criteria of CTRCD evaluation such as the specific threshold for LVEF decrease. RESULTS: From 963 citations identified, 46 articles, comprising 6841 patients, met the criteria for the inclusion in the scoping review. The summary prevalence of CTRCD as assessed by imaging procedures in the studies reviewed was 17% (95% confidence interval, 14-20). CONCLUSIONS: The results of our scoping review endorse the recommendations regarding imaging modalities to ensure identification of cardiotoxicity in patients undergoing cancer therapies. However, to improve patient management, more homogeneous CTRCD evaluation studies are required, reporting a detailed clinical assessment of the patient before, during and after treatment.

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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.

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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: 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.

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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.

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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.

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BACKGROUND: We performed a systematic review and meta-analysis to investigate the prognostic value of stress myocardial perfusion single-photon emission computed tomography (MPS) in predicting adverse cardiovascular events in patients with chronic kidney disease (CKD). METHODS: Studies published from inception until July 2020 were identified by PubMed and Embase databases search. Studies were included if they evaluated CKD patients referred for stress MPS, providing data on adjusted hazard ratio (HR) for the occurrence of adverse events. For studies providing only non-adjusted HR, the univariable risk estimate was included in the analysis. Pooled HR and 95% confidence interval (CI) were estimated using a random effects model to compare patients with abnormal and normal MPS. Whenever possible, incidence rate ratio (IRR) was also calculated and pooled. RESULTS: Sixteen eligible studies were identified including 7834 patients with a follow-up range from 1 to 4.4 years. Eleven articles included patients with end-stage renal disease (IV-V CKD stage), 3 articles with III-V CKD stage and 2 articles with I-V CKD stage. The pooled HR for the occurrence of adverse events was 2.02 (95% CI 1.68-2.42) and heterogeneity was 34%. Among the included studies, 5 reported the HR for the occurrence of hard events, with a pooled HR of 2.36 (95% CI 1.77-3.13). A total of 8 studies reported data useful to calculate the IRR in patients with normal and abnormal perfusion. The pooled IRR was 2.37 (95% CI 1.63-3.47) and heterogeneity was 60%. At meta-regression analysis, we found an association between HR for adverse events and age, hypertension and smoking, while no significant association was found between HR for hard events and demographic and clinical variables. CONCLUSIONS: In patients with CKD an abnormal myocardial perfusion at stress MPS is associated with adverse cardiovascular events.

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BACKGROUND: We evaluated if risk scores commonly used to predict the absence of significant stenosis at coronary computed tomography (CT) angiography are useful to predict a normal stress myocardial perfusion imaging (MPI) study. METHODS: Our cohort included a total of 1422 consecutive patients with zero coronary artery calcium score (ZCS) who underwent 82Rb PET/CT for evaluation of suspected coronary artery disease (CAD). Predictive models were constructed as reported by Genders et al. and Alshahrani et al., and the probability of abnormal summed stress score (SSS) and of reduced myocardial perfusion reserve (MPR) based on these risk scores was assessed. RESULTS: In the overall population, the prevalence of abnormal SSS was 0.10 and the prevalence of reduced MPR was 0.17 (both P < .001).The observed frequencies of abnormal SSS and reduced MPR vs the probabilities predicted by the Genders and Alshahrani models were above the diagonal identity line, highlighting an underestimation of the observed occurrence by these models. The areas under the receiver operating characteristic curve of the Genders and Alshahrani models indicated lack of discriminative ability for predicting abnormal SSS (0.547 and 0.527) and reduced MPR (0.509 and 0.538). The Hosmer-Lemeshow test revealed that both models underestimated the observed occurrence of abnormal SSS and reduced MPR. CONCLUSIONS: Available models were unable to identify among patients with ZCS those with a low probability of a normal stress MPI study. Thus, an optimal approach to rule out from MPI patients without detectable coronary calcium still needs to be improved.

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Anderson-Fabry disease (AFD) is a multisystem X-linked disorder of lipid metabolism frequently associated with progressive glycosphingolipid accumulation in cardiac, renal, and nervous cells. The diagnosis of AFD is usually assessed by enzyme assay and genetic tests, but advanced cardiac imaging can be useful in detecting early signs of the disease. Echocardiography and cardiac magnetic resonance are the first-line imaging modalities to investigate cardiac involvement in AFD, but the recent introduction of new molecular and hybrid imaging techniques opens to a wider range of diagnostic applications. This article aims to provide an overview of nuclear cardiology techniques in diagnosis and clinical management of AFD.

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BACKGROUND: We evaluated the performance of conventional (C) single-photon emission computed tomography (SPECT) and cadmium-zinc-telluride (CZT)-SPECT in a large cohort of patients with suspected or known coronary artery disease (CAD) and compared the diagnostic accuracy of the two systems using machine learning (ML) algorithms. METHODS AND RESULTS: A total of 517 consecutive patients underwent stress myocardial perfusion imaging (MPI) by both C-SPECT and CZT-SPECT. In the overall population, an excellent correlation between stress MPI data and left ventricular (LV) functional parameters measured by C-SPECT and by CZT-SPECT was observed (all P < .001). ML analysis performed through the implementation of random forest (RF) and k-nearest neighbors (NN) algorithms proved that CZT-SPECT has greater accuracy than C-SPECT in detecting CAD. For both algorithms, the sensitivity of CZT-SPECT (96% for RF and 60% for k-NN) was greater than that of C-SPECT (88% for RF and 53% for k-NN). CONCLUSIONS: MPI data and LV functional parameters obtained by CZT-SPECT are highly reproducible and provide good correlation with those obtained by C-SPECT. ML approach showed that the accuracy and sensitivity of CZT-SPECT is greater than C-SPECT in detecting CAD.

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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.

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