Imiglucerase, cholecalciferol, and bone-diet in skeletal health management of type I Gaucher disease patients: a pilot study and systematic review.

Skeletal anomalies represent a characteristic feature of type 1 Gaucher disease (GD1). Here we evaluated the impact of an integrated therapy comprising enzyme-replacement therapy (ERT), cholecalciferol, and a normocalcemic-normocaloric-hyposodic diet (bone diet) on bone health in GD1 patients. We also performed a systematic review to compare our results with available data. From January 1, 2015 to February 28, 2019, all GD1 patients referred to Federico II University were enrolled and treated with the integrated therapy. Bone turnover markers and bone mineral density (BMD) were evaluated at baseline (T0) and after 24 months (T24). We enrolled 25 GD1 patients, all showing 25-hydroxy vitamin D (25OHD) levels < 50 nmol/l (hypovitaminosis D) at T0. Response to cholecalciferol treatment was effective, showing a direct relationship between 25OHD levels before and after treatment. At T0, 2 GD1 patients showed fragility fractures, 5 the Erlenmeyer flask deformity, 3 osteonecrosis, and 7 a BMD Z-score ≤ -2. Overall, GD1 patients with bone anomalies showed higher C-terminal telopeptide levels compared with those without bone anomalies. No new bone anomalies occurred during 2 years of follow-up. At T24, BMD remained stable across the entire study cohort, including in patients with bone anomalies. The systematic review showed that our study is the first that evaluated all bone health parameters. Hypovitaminosis D is prevalent in GD1 patients. The response to cholecalciferol treatment was effective but different to healthy subjects and in patients with metabolic bone disorders. Integrated therapy including ERT, cholecalciferol, and bone diet guarantees bone health.

Salvage Therapy with Rezafungin for Candida parapsilosis Spondylodiscitis: A Case Report from Expanded Access Program.

Candida spp. spondylodiscitis is a rare condition for which treatment options are often limited. A further obstacle is the duration of therapy, which should be administered for up to twelve months. In view of the long duration of therapy, azoles are, so far, the only oral treatment strategy that can be given as home therapy. In the case of resistance or reduced susceptibility to azoles, there are not enough comfortable treatment opportunities with adequate bone penetration and limited toxicity. We report the first case of the successful use of rezafungin for spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. A 68-year-old patient, affected by paraplegia and short bowel syndrome, was diagnosed with Candida parapsilosis spondylodiscitis, confirmed with a culture on vertebral biopsy after an 18-FDG PET/CT scan. He received 200 mg of rezafungin weekly for 26 weeks, after 10 weeks of previous antifungal treatment that was not well tolerated with voriconazole plus liposomal amphotericin B. He had a full clinical, radiologic, and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin can be a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective, poorly tolerated, or contraindicated.

Emerging Role of Nuclear Medicine in Prostate Cancer: Current State and Future Perspectives.

Prostate cancer is the most frequent epithelial neoplasia after skin cancer in men starting from 50 years and prostate-specific antigen (PSA) dosage can be used as an early screening tool. Prostate cancer imaging includes several radiological modalities, ranging from ultrasonography, computed tomography (CT), and magnetic resonance to nuclear medicine hybrid techniques such as single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET)/CT. Innovation in radiopharmaceutical compounds has introduced specific tracers with diagnostic and therapeutic indications, opening the horizons to targeted and very effective clinical care for patients with prostate cancer. The aim of the present review is to illustrate the current knowledge and future perspectives of nuclear medicine, including stand-alone diagnostic techniques and theragnostic approaches, in the clinical management of patients with prostate cancer from initial staging to advanced disease.

R0 surgical resection of giant dedifferentiated retroperitoneal liposarcomas in the COVID era with and without nephrectomy: A case report.

Retroperitoneal sarcomas (RPSs) are rare findings that can grow into large masses without eliciting severe symptoms. At present, surgical resection is the only radical therapy, whenever it can be performed with the aim to achieve a complete removal of the tumor. The present report describes two consecutive cases of RPSs that resulted in dedifferentiated liposarcomas (DDLPSs) and these patients underwent R0 surgical resection with and without a nephron-sparing procedure. The diagnostic workup, the surgical approach, the impact of late surgical management due to the COVID pandemic and the latest literature on the topic are discussed and analyzed. The patients, who refused to undergo any medical examination during the prior 2 years due to the COVID pandemic, were admitted to Federico II University Hospital (Naples, Italy) complaining about weight loss and general abdominal discomfort. In the first case, a primitive giant abdominal right neoplasm of retroperitoneal origin enveloping and medializing the right kidney was observed. The second patient had a similar primitive retroperitoneal giant left neoplasm, which did not affect the kidney. Given the characteristics of the masses and the absence of distant metastases, after a multidisciplinary discussion, radical surgical removal was carried out for both patients. The lesions appeared well-defined from the surrounding tissues, and markedly compressed all the adjacent organs, without signs of infiltration. In the first patient, the right kidney was surrounded and undetachable from the tumor and it was removed en bloc with the mass. The second patient benefited from a nephron-sparing resection, due to the existence of a clear cleavage plane. The postoperative courses were uneventful. Both the histological examinations were oriented towards a DDLPS and both patients benefited from adjuvant chemotherapy. In conclusion, the treatment of giant RPS is still challenging and requires multidisciplinary treatment as well as, when possible, radical surgical removal. The lack of tissue infiltration and the avoidance of excision or reconstruction of major organs (including the kidney) could lead to an easier postoperative course and an improved prognosis. When possible, surgical management of recurrences or incompletely resected masses must be pursued. Since the COVID pandemic caused limited medicalization of a number of population groups and delayed diagnosis of other oncologic diseases, an increased number of DDLPSs could be expected in the near future.

Prediction of 2-[18F]FDG PET-CT SUVmax for Adrenal Mass Characterization: A CT Radiomics Feasibility Study.

BACKGROUND: Indeterminate adrenal masses (AM) pose a diagnostic challenge, and 2-[18F]FDG PET-CT serves as a problem-solving tool. Aim of this study was to investigate whether CT radiomics features could be used to predict the 2-[18F]FDG SUVmax of AM. METHODS: Patients with AM on 2-[18F]FDG PET-CT scan were grouped based on iodine contrast injection as CT contrast-enhanced (CE) or CT unenhanced (NCE). Two-dimensional segmentations of AM were manually obtained by multiple operators on CT images. Image resampling and discretization (bin number = 16) were performed. 919 features were calculated using PyRadiomics. After scaling, unstable, redundant, and low variance features were discarded. Using linear regression and the Uniform Manifold Approximation and Projection technique, a CT radiomics synthetic value (RadSV) was obtained. The correlation between CT RadSV and 2-[18F]FDG SUVmax was assessed with Pearson test. RESULTS: A total of 725 patients underwent PET-CT from April 2020 to April 2021. In 150 (21%) patients, a total of 179 AM (29 bilateral) were detected. Group CE consisted of 84 patients with 108 AM (size = 18.1 ± 4.9 mm) and Group NCE of 66 patients with 71 AM (size = 18.5 ± 3.8 mm). In both groups, 39 features were selected. No statisticallyf significant correlation between CT RadSV and 2-[18F]FDG SUVmax was found (Group CE, r = 0.18 and p = 0.058; Group NCE, r = 0.13 and p = 0.27). CONCLUSIONS: It might not be feasible to predict 2-[18F]FDG SUVmax of AM using CT RadSV. Its role as a problem-solving tool for indeterminate AM remains fundamental.

Algorithm for Reducing Overall Biological Detriment Caused by PET/CT: an Age-Based Study.

Purpose: This study is to use a simple algorithm based on patient's age to reduce the overall biological detriment associated with PET/CT. Materials and Methods: A total of 421 consecutive patients (mean age 64 ± 14 years) undergoing PET for various clinical indications were enrolled. For each scan, effective dose (ED in mSv) and additional cancer risk (ACR) were computed both in a reference condition (REF) and after applying an original algorithm (ALGO). The ALGO modified the mean dose of FDG and the PET scan time parameters; indeed, a lower dose and a longer scan time were reported in the younger, while a higher dose and a shorter scan time in the older patients. Moreover, patients were classified by age bracket (18-29, 30-60, and 61-90 years). Results: The ED was 4.57 ± 0.92 mSv in the REF condition. The ACR were 0.020 ± 0.016 and 0.0187 ± 0.013, respectively, in REF and ALGO. The ACR for the REF and ALGO conditions were significantly reduced in males and females, although it was more evident in the latter gender (all p < 0.0001). Finally, the ACR significantly reduced from the REF condition to ALGO in all three age brackets (all p < 0.0001). Conclusion: Implementation of ALGO protocols in PET can reduce the overall ACR, mainly in young and female patients.

Endocrine system involvement in patients with RASopathies: A case series.

Background and Objectives: Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies. Study Design: 72 patients with a genetically confirmed RASopathy (Noonan syndrome [NS], N=53; 29 LEOPARD syndrome [LS], N=2; cardiofaciocutaneous syndrome [CFCS], N=14; subjects showing co-occurring pathogenic variants in PTPN11 and NF1, N=3) and an age- and sex-matched healthy controls were included in the study. Endocrine system involvement was investigated by assessing the thyroid function, pubertal development, auxological parameters, adrenal function and bone metabolism. Results: Short stature was detected in 40% and 64% of the NS and CFCS subcohorts, respectively. Patients showed lower Z-scores at DXA than controls (p<0.05) when considering the entire case load and both NS and CFCS groups. Vitamin D and Calcitonin levels were significantly lower (p< 0.01), Parathormone levels significantly higher (p<0.05) in patients compared to the control group (p<0.05). Patients with lower BMD showed reduced physical activity and joint pain. Finally, anti-TPO antibody levels were significantly higher in patients than in controls when considering the entire case load and both NS and CFCS groups. Conclusions: The collected data demonstrate a high prevalence of thyroid autoimmunity, confirming an increased risk to develop autoimmune disorders both in NS and CFCS. Reduced BMD, probably associated to reduced physical activity and inflammatory cytokines, also occurs. These findings are expected to have implications for the follow-up and prevention of osteopenia/osteoporosis in both NS and CFCS.

Hyperfunctioning parathyroid gland and skeletal involvement on [18F]fluorocholine PET/CT: one look with two views.

Hyperparathyroidism is an endocrine disorder that may be associated with other metabolic diseases. Non-invasive imaging techniques including [99mTc]Tc-sestamibi single-photon emission computed tomography (SPECT) and [18F]fluorocholine positron emission tomography (PET)/computed tomography (CT) play a key role on management of patients with hyperparathyroidism. We report for the first time a case of a patient with evidence of both hyperfunctioning parathyroid tissue and multiple lytic bone lesions on [18F]fluorocholine PET/CT imaging. The present case report highlights the potential role of whole-body [18F]fluorocholine PET/CT for the identification of both parathyroid adenoma and multiple bone lesions in a single diagnostic setting.

Liposomal doxorubicin supercharge-containing front-line treatment in patients with advanced-stage diffuse large B-cell lymphoma or classical Hodgkin lymphoma: Preliminary results of a single-centre phase II study.

We evaluated the impact of liposomal doxorubicin (NPLD) supercharge-containing therapy on interim fluorodeoxyglucose positron emission tomography (interim-FDG-PET) responses in high-risk diffuse large B-cell lymphoma (DLBCL) or classical Hodgkin lymphoma (c-HL). In this phase II study (2016-2021), 81 adult patients with advanced-stage DLBCL (n = 53) and c-HL (n = 28) received front-line treatment with R-COMP-dose-intensified (DI) and MBVD-DI. R-COMP-DI consisted of 70 mg/m2 of NPLD plus standard rituximab, cyclophosphamide, vincristine and prednisone for three cycles (followed by three cycles with NPLD de-escalated at 50 mg/m2 ); MBVD-DI consisted of 35 mg/m2 of NPLD plus standard bleomycin, vinblastine and dacarbazine for two cycles (followed by four cycles with NPLD de-escalated at 25 mg/m2 ). Patients underwent R-COMP-DI and MBVD-DI with a median dose intensity of 91% and 94% respectively. At interim-FDG-PET, 72/81 patients (one failed to undergo interim-FDG-PET due to early death) had a Deauville score of ≤3. At end of treatment, 90% of patients reached complete responses. In all, 20 patients had Grade ≥3 adverse events, and four of them required hospitalisation. At a median 21-months of follow-up, the progression-free survival of the entire population was 77.3% (95% confidence interval 68%-88%). Our data suggest that the NPLD supercharge-driven strategy in high-risk DLBCL/c-HL may be a promising option to test in phase III trials, for improving negative interim-FDG-PET cases incidence.

Impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow in a single medical institution: comparison among the three Italian waves.

PURPOSE: To compare the impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow during the three waves in a medical institution of southern of Italy. METHODS: We retrospectively reviewed the numbers and results of 2-[18F]FDG PET/CT studies acquired during the following three periods of the COVID-19 waves: 1) February 3-April 30, 2020; 2) October 15, 2020-January 15, 2021; and 3) January 18-April 16, 2021. RESULTS: A total of 861 PET/CT studies in 725 patients (388 men, mean age 64 ± 4 years) was acquired during the three waves of COVID-19 pandemic. The majority (94%) was performed for diagnosis/staging (n = 300) or follow-up (n = 512) of neoplastic diseases. The remaining 49 studies (6%) were acquired for non-oncological patients. The distribution of number and type of clinical indications for PET/CT studies in the three waves were comparable (p = 0.06). Conversely, the occurrence of patients positive for COVID-19 infection progressively increased (p < 0.0001) from the first to third wave; in particular, patients with COVID-19 had active infection before PET/CT study as confirmed by molecular oro/nasopharyngeal swab. CONCLUSION: Despite the restrictive medical measures for the emergency, the number of 2-[18F]FDG PET/CT studies was unchanged during the three waves guaranteeing the diagnostic performance of PET/CT imaging for oncological patients.

Prognostic value of heart rate reserve in patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging.

BACKGROUND: Chronotropic incompetence is common in patients with cardiovascular disease and is associated with increased risk of adverse events. We assessed the incremental prognostic value of heart rate reserve (HRR) over stress myocardial perfusion single-photon emission computed tomography (MPS) findings in patients with suspected coronary artery disease (CAD). METHODS: We studied 866 patients with suspected CAD undergoing exercise stress-MPS as part of their diagnostic program. The primary study endpoint was all-cause mortality. All patients were followed for at least 5 years. HRR was calculated as the difference between peak exercise and resting HR, divided by the difference of age-predicted maximal and resting HR and expressed as percentage. RESULTS: During 7 years follow-up, 61 deaths occurred, with a 7% cumulative event rate. Patients experiencing death were older (P < .001), and had a higher prevalence of male gender (P < .001) and diabetes (P < .05). Patients with event also had lower values of HRR (65% ± 27% vs 73% ± 18%, P < .0001) and higher prevalence of stress-induced myocardial ischemia (25% vs 8%, P < .0001). Male gender, HRR and stress-induced ischemia were independent predictors of all-cause mortality (all P < .01). HRR improved the prognostic power of a model including clinical data and MPS findings, increasing the global χ2 from 66 to 82 (P < .005). CONCLUSIONS: Chronotropic incompetence has independent and incremental prognostic value in predicting all-cause mortality in patients with suspected CAD undergoing exercise stress-MPS. Hence, the evaluation of HRR may further improve patients' risk stratification.

Effect of changes in perfusion defect size during serial stress myocardial perfusion imaging on cardiovascular outcomes in patients treated with primary percutaneous coronary intervention after myocardial infarction.

BACKGROUND: We evaluated the prognostic value of changes in perfusion defect size (PDS) on serial MPS in patients treated with primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI). METHODS: We enrolled 112 patients treated with primary PCI after AMI who underwent two stress MPS within 1 month and after 6 months. Improvement in PDS was defined as a reduction ≥5%. Remodeling was defined as an increase in left ventricular (LV) end-diastolic volume index ≥20%. Cardiac events included cardiac death, nonfatal MI, unstable angina, repeated revascularization, and heart failure. RESULTS: During a median follow-up of 86 months, 22 events occurred. Event rate was higher (P < .01) in patients with worsening of PDS compared to those with unchanged or improved PDS. Moreover, patients with remodeling had a higher (P < .001) event rate compared to those without. At Cox analysis, worsening of PDS and remodeling resulted independent predictors of events (both P < .01). Patients with both worsening of PDS and remodeling had the worst event-free survival (P <.001). CONCLUSION: In patients treated with primary PCI after AMI, worsening of PDS and remodeling are associated to higher risk of events at long-term follow-up. Gated stress MPS improves risk stratification in these patients.

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.

Impact of COVID-19 infection on short-term outcome in patients referred to stress myocardial perfusion imaging.

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.

State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation.

AIM: The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. METHODS: In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [18F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. RESULTS: Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. CONCLUSIONS: Currently, [18F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40336-021-00445-w.

Ileal inflammatory pseudotumor in adolescent male patient with prior Burkitt lymphoma: A challenging diagnosis.

Inflammatory pseudotumor is a rare benign mesenchymal pediatric neoplasm, that can mimic tumoral residue or relapse at metabolic imaging with nonspecific clinical presentation and difficult diagnosis. We present the case of a 14year old male patient with fever of unknown origin and large ileal mass, diagnosed with and treated for Burkitt lymphoma, who performed several 18-fluoro-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) scans, during and after first line chemotherapy, showing persistent and focal uptake, while ileal mass volume decreased dramatically and the patient was clinically asymptomatic. Histopathological analysis of residual ileal mass was suggestive for xanthomatous pseudotumor, a type of inflammatory pseudotumor. No more treatment was performed and a short-term follow up with 18F-FDG PET/CT showed tracer uptake intensity decreasing progressively over the next few months. This case reports an uncommon presentation of a rare disease, inflammatory pseudotumor of the small bowel developed at the site of treated Burkitt lymphoma, underscoring the potential role of 18F-FDG PET/CT imaging in the diagnosis and management of these rare neoplasms, particularly in asymptomatic patients.

Relation between myocardial blood flow and cardiac events in diabetic patients with suspected coronary artery disease and normal myocardial perfusion imaging.

BACKGROUND: We assessed the prognostic value of structural abnormalities and coronary vasodilator function in diabetic patients referred to a PET/CT for suspected coronary artery disease (CAD). METHODS: We studied 451 diabetics and 451 nondiabetics without overt CAD and normal myocardial perfusion. Myocardial blood flow (MBF) was computed from the dynamic rest and stress imaging. Myocardial flow reserve (MFR) was defined as ratio of hyperemic to baseline MBF and was considered reduced when < 2. RESULTS: During a mean follow-up of 44 months 33 events occurred. Annualized event rate (AER) was higher in diabetic than nondiabetic patients (1.4% vs 0.3%, P < .001). Diabetic patients with reduced MFR had higher AER compared to those with preserved MFR (3.3% vs 0.4%, P < .001). At Cox analysis, age, BMI and reduced MFR were independent predictors of events in diabetic patients. Patients with diabetes and reduced MFR had lower event-free survival compared to nondiabetic patients and MFR < 2 (P < .001). Event-free survival was similar in patients with diabetes and normal MFR and those without diabetes and reduced MFR. CONCLUSIONS: Diabetic patients with reduced MFR had higher AER and lower event-free survival compared to those with preserved MFR and to nondiabetic patients.