Lutetium [177Lu]-DOTA-TATE in gastroenteropancreatic-neuroendocrine tumours: rationale, design and baseline characteristics of the Italian prospective observational (REAL-LU) study.

PURPOSE: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. METHODS: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. RESULTS: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. CONCLUSION: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. STUDY REGISTRATION: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1.

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.

Tumor Burden of Iodine-Avid Bone Metastatic Thyroid Cancer Identified via 18F-Sodium Fluoride PET/CT Imaging.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) are referred to radioactive 131I (RAI) therapy and post-therapy 131I whole-body scintigraphy (WBS) to identify local and/or remote metastases. Positron emission tomography (PET)/computed tomography (CT) imaging with 18F-fluoro-D-glucose (FDG) or 18F-sodium fluoride (NaF) may also be used with these patients for the evaluation of bone metastases. We compared the role of 18F-NaF PET/CT and 18F-FDG-PET/CT in patients with DTC and documented bone metastases at post-therapy WBS. METHODS: Ten consecutive DTC patients with iodine avid bone metastasis at post-therapy WBS referred to 18F-NaF PET/CT and 18F-FDG PET/CT were studied. The findings of the three imaging procedures were compared for abnormal detection rates and concordance. RESULTS: At post-therapy 131I WBS, all patients had skeletal involvement with a total of 21 bone iodine avid lesions. At 18F-FDG PET/TC, 19 bone lesions demonstrated increased tracer uptake and CT pathological alterations, while 2 lesions did not show any pathological finding. At 18F-NaF PET/CT, the 19 bone lesions detected at 18F-FDG PET/TC also demonstrated abnormal tracer uptake, and the other 2 bone iodine avid foci did not show any pathological finding. CONCLUSIONS: In patients with DTC, 18F-NaF PET/CT did not obtain more information on the metastatic skeletal involvement than post-therapy 131I WBS and 18F-FDG PET/CT.

Late-onset mucopolysaccharidosis type IIIA mimicking Usher syndrome.

Mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo syndrome type A) is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the SGSH gene encoding N-sulfoglucosamine sulfohydrolase, an enzyme involved in the degradation of heparan sulfate. MPS IIIA is typically characterized by neurocognitive decline and hepatosplenomegaly with childhood onset. Here, we report on a 53-year-old male subject initially diagnosed with Usher syndrome for the concurrence of retinitis pigmentosa and sensorineural hearing loss. Clinical exome sequencing identified biallelic missense variants in SGSH, and biochemical assays showed complete deficiency of sulfamidase activity and increased urinary glycosaminoglycan excretion. Reverse phenotyping revealed left ventricle pseudo-hypertrophy, hepatosplenomegaly, bilateral deep white matter hyperintensities upon brain MRI, and decreased cortical metabolic activity by PET-CT. On neuropsychological testing, the proband presented only partial and isolated verbal memory deficits. This case illustrates the power of unbiased, comprehensive genetic testing for the diagnosis of challenging mild or atypical forms of MPS IIIA.

Age-Specific Cardiovascular Risk Factors for Major Adverse Cardiac Events in Patients Undergoing Myocardial Perfusion Imaging.

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.

Efficacy of Empirical Radioiodine Therapy in Patients with Differentiated Thyroid Cancer and Elevated Serum Thyroglobulin without Evidence of Structural Disease: A Propensity Score Analysis.

We assessed the outcome of administration of empiric radioactive iodine (RAI) therapy to patients with differentiated thyroid cancer (DTC), in a propensity-score-matched cohort of patients with biochemical incomplete response (BIR) and without evidence of structural disease. We retrospectively evaluated 820 DTC patients without distant metastases, who underwent total thyroidectomy followed by RAI therapy, with available BIR at 12 months and follow-up evaluations. The patients were categorized according to the administration of empiric therapy (ET). To account for differences between patients with (n = 119) and without (n = 701) ET, a propensity-score-matched cohort of 119 ET and 119 no-ET patients was created. The need for additional therapy and the occurrence of structural disease were considered as end-points. During a median follow-up of 53 months (range 3-285), 57 events occurred (24% cumulative event rate). The rate of events was significantly higher in the no-ET compared to the ET patients (30% vs. 18% p < 0.001). The multivariate Cox analysis identified age (p < 0.01), pre-therapy Tg (p < 0.05) and empiric RAI therapy (p < 0.01) as predictors of outcome. The Kaplan-Meier analysis found that progression-free survival was lower in no-ET patients compared to the ET group (p < 0.01). In patients with DTC treated with surgery and RAI, and with biochemical incomplete response at the 12-month evaluation, their prognosis seemed to be affected by Tg values and the empiric treatment. The identification of candidates for this approach may improve prognosis.

Diagnosis, Management and Theragnostic Approach of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms.

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) constitute an ideal target for radiolabeled somatostatin analogs. The theragnostic approach is able to combine diagnosis and therapy by the identification of a molecular target that can be diagnosed and treated with the same radiolabeled compound. During the last years, advances in functional imaging with the introduction of somatostatin analogs and peptide receptor radionuclide therapy, have improved the diagnosis and treatment of GEP-NENs. Moreover, PET/CT imaging with 18F-FDG represents a complementary tool for prognostic evaluation of patients with GEP-NENs. In the field of personalized medicine, the theragnostic approach has emerged as a promising tool in diagnosis and management of patients with GEP-NENs. The aim of this review is to summarize the current evidence on diagnosis and management of patients with GEP-NENs, focusing on the theragnostic approach.

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.

Combined evaluation of CAC score and myocardial perfusion imaging in patients at risk of cardiovascular disease: where are we and what do the data say.

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.

Left Ventricular Mechano-Energetic Efficiency Identifies an Early Impairment of Myocardial Blood Flow in Arterial Hypertension.

BACKGROUND: Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated possible relationships between positron emission tomography/computed tomography-derived myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi). METHODS: Seventy-eight hypertensive patients without flow-limiting epicardial coronary artery disease underwent echocardiography, including MEEi computation, and cardiac positron emission tomography/computed tomography with assessment of MBF/mass ratio at rest and after stress and myocardial flow reserve. The lowest MEEi tertile (MEEi<0.031 mL/s/g) was compared to the merged second and third tertiles (MEEi≥0.031). RESULTS: Patients in the lowest MEEi tertile were older, had higher systolic blood pressure and body mass index. They also had higher prevalence of LV hypertrophy, whereas lower resting and stress MBF/mass ratio. MEEi was significantly correlated with both resting (r=0.51; P<0.0001) and hyperemic (r=0.54; P<0.0001) MBF/mass ratios, whereas it was not related to myocardial flow reserve. Delta of MBF/mass ratio was lower in the lowest MEEi tertile than in the highest (P<0.0001). In separate multiple linear regression models, after adjusting for sex, systolic blood pressure, body mass index, prevalence of LV hypertrophy, left atrial volume index, and diuretic therapy, the association between LV MEEi and both hyperemic (beta coefficient=0.44; P=0.003) and resting (beta coefficient=0.35; P=0.008) MBF/mass ratio remained significant. CONCLUSIONS: In hypertensive patients without flow-limiting epicardial coronary artery disease, low values of MEEi could detect an early LV dysfunction involving an impairment of both resting and hyperemic MBF/mass ratios. MEEi has the advantage of simpler detection, cheaper costs than positron emission tomography/computed tomography, and a lack of radiation exposure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02211365.

Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives.

There is increasing evidence that in patients with atherosclerotic cardiovascular disease (ASCVD) under optimal medical therapy, a persisting dysregulation of the lipid and glucose metabolism, associated with adipose tissue dysfunction and inflammation, predicts a substantial residual risk of disease progression and cardiovascular events. Despite the inflammatory nature of ASCVD, circulating biomarkers such as high-sensitivity C-reactive protein and interleukins may lack specificity for vascular inflammation. As known, dysfunctional epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) produce pro-inflammatory mediators and promote cellular tissue infiltration triggering further pro-inflammatory mechanisms. The consequent tissue modifications determine the attenuation of PCAT as assessed and measured by coronary computed tomography angiography (CCTA). Recently, relevant studies have demonstrated a correlation between EAT and PCAT and obstructive coronary artery disease, inflammatory plaque status and coronary flow reserve (CFR). In parallel, CFR is well recognized as a marker of coronary vasomotor function that incorporates the haemodynamic effects of epicardial, diffuse and small-vessel disease on myocardial tissue perfusion. An inverse relationship between EAT volume and coronary vascular function and the association of PCAT attenuation and impaired CFR have already been reported. Moreover, many studies demonstrated that 18F-FDG PET is able to detect PCAT inflammation in patients with coronary atherosclerosis. Importantly, the perivascular FAI (fat attenuation index) showed incremental value for the prediction of adverse clinical events beyond traditional risk factors and CCTA indices by providing a quantitative measure of coronary inflammation. As an indicator of increased cardiac mortality, it could guide early targeted primary prevention in a wide spectrum of patients. In this review, we summarize the current evidence regarding the clinical applications and perspectives of EAT and PCAT assessment performed by CCTA and the prognostic information derived by nuclear medicine.

Prognostic value of 12-month response to therapy in pediatric patients with differentiated thyroid cancer.

PURPOSE: In pediatric patients with differentiated thyroid cancer (DTC) we assessed the prognostic value of the 12-month response to therapy after initial treatment with surgery and radioactive iodine (RAI). METHODS: We retrospectively evaluated 94 pediatric patients with DTC, treated with surgery and RAI who were initially classified as low, intermediate or high risk of relapse of disease according to the American Thyroid Association (ATA) guidelines. Twelve months after RAI administration the response to therapy was assessed by serum thyroglobulin (Tg) measurement and neck ultrasound and patients were classified as having excellent response (ER) or no-ER. RESULTS: At the 12 months evaluation, 62 (66%) patients had ER and 32 (34%) no-ER. During a mean follow-up time of 86 months (range 9-517), 19 events occurred (20% cumulative event rate). Events occurred more frequently in younger patients (p < 0.05), in those at ATA intermediate/high risk (p < 0.01) and with a pre-RAI therapy Tg level > 10 ng/mL (p < 0.001), and in those with no-ER (p < 0.001). At multivariate analysis, the evidence of no-ER was the only independent predictor of events. CONCLUSION: In pediatric patients with DTC, the response to therapy evaluated 12 months after initial treatment has an independent prognostic impact and is able to predict mid-term outcome. Patients with no-ER at 12 months after RAI therapy should be closely followed-up.

External validation and update of the J-ACCESS model in an Italian cohort of patients undergoing stress myocardial perfusion imaging.

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.

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.

Altered Patterns of Brain Glucose Metabolism Involve More Extensive and Discrete Cortical Areas in Treatment-resistant Schizophrenia Patients Compared to Responder Patients and Controls: Results From a Head-to-Head 2-[18F]-FDG-PET Study.

BACKGROUND AND HYPOTHESIS: Treatment resistant schizophrenia (TRS) affects almost 30% of patients with schizophrenia and has been considered a different phenotype of the disease. In vivo characterization of brain metabolic patterns associated with treatment response could contribute to elucidate the neurobiological underpinnings of TRS. Here, we used 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) to provide the first head-to-head comparative analysis of cerebral glucose metabolism in TRS patients compared to schizophrenia responder patients (nTRS), and controls. Additionally, we investigated, for the first time, the differences between clozapine responders (Clz-R) and non-responders (Clz-nR). STUDY DESIGN: 53 participants underwent FDG-PET studies (41 patients and 12 controls). Response to conventional antipsychotics and to clozapine was evaluated using a standardized prospective procedure based on PANSS score changes. Maps of relative brain glucose metabolism were processed for voxel-based analysis using Statistical Parametric Mapping software. STUDY RESULTS: Restricted areas of significant bilateral relative hypometabolism in the superior frontal gyrus characterized TRS compared to nTRS. Moreover, reduced parietal and frontal metabolism was associated with high PANSS disorganization factor scores in TRS (P < .001 voxel level uncorrected, P < .05 cluster level FWE-corrected). Only TRS compared to controls showed significant bilateral prefrontal relative hypometabolism, more extensive in CLZ-nR than in CLZ-R (P < .05 voxel level FWE-corrected). Relative significant hypermetabolism was observed in the temporo-occipital regions in TRS compared to nTRS and controls. CONCLUSIONS: These data indicate that, in TRS patients, altered metabolism involved discrete brain regions not found affected in nTRS, possibly indicating a more severe disrupted functional brain network associated with disorganization symptoms.

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.

Diagnostic value of clinical risk scores for predicting normal stress myocardial perfusion imaging in subjects without coronary artery calcium.

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.

A machine learning-based approach to directly compare the diagnostic accuracy of myocardial perfusion imaging by conventional and cadmium-zinc telluride SPECT.

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.