Emanuele Nicolai

Left ventricular function in young adults with childhood and adulthood onset growth hormone deficiency

The impairment of heart structure and function in adults with childhood onset GH deficiency has been recently described. However, previous echocardiographic studies have reported no differences in cardiac mass and function between adulthood onset GH deficient patients and healthy subjects.

Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans

This study aimed at evaluating the role of consolidation radiation in a setting of Hodgkins lymphoma (HL) patients, using event-free survival (EFS) as end point. Among 260 patients treated with induction chemotherapy for bulky HL, 160 patients achieved negative residual masses at 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scans. They were randomly divided into two well-matched groups to receive either 32 Gy radiotherapy to bulky area or no further therapy. At a median follow-up of 40 months, histology showed a malignancy in 14% of patients in the chemotherapy-only group (HL, 11 patients) and in 4% of patients in the chemotherapy + radiotherapy group (HL, 2 patients; carcinoma in previously irradiated area, 1 patient) (P = 0.03). All the relapses in the chemotherapy-only group involved the bulky site and the contiguous nodal regions. Thus, the overall diagnostic accuracy of FDG-PET to exclude future relapses in the patients nonprotected by radiotherapy was 86% with a false-negative rate of 14%. Our study suggests that the addition of irradiation helps improve EFS in HL patients with post-chemotherapy FDG-PET-negative residual masses.

Clinical Impact of PET/MR Imaging in Patients with Cancer Undergoing Same-Day PET/CT: Initial Experience in 134 Patients—A Hypothesis-generating Exploratory Study

PURPOSE To compare the clinical impact of combined positron emission tomography (PET) and magnetic resonance (MR) imaging to that of combined PET and computed tomography (CT) performed on the same day in patients with cancer. MATERIALS AND METHODS This HIPAA-compliant retrospective study was approved by the institutional review board. Patients gave written informed consent for study enrollment, including the possibility to use their imaging and clinical data in future evaluations. A total of 134 patients with cancer with a non-central nervous system primary neoplasm underwent same-day fluorodeoxyglucose (FDG) PET/CT and FDG PET/MR imaging. PET/CT and PET/MR studies were independently interpreted by teams of radiologists and nuclear medicine physicians. Four readers, divided into two teams composed of one radiologist and one nuclear medicine physician each, read all 134 studies. The referring physician classified discordance between PET/CT and PET/MR observations either as findings affecting clinical management or as findings not affecting clinical management. Data were compared with the χ(2) test. RESULTS Findings affecting clinical management were noted for PET/CT studies but not for PET/MR studies in two (1.5%) of 134 patients and for PET/MR studies but not for PET/CT studies in 24 (17.9%) of 134 patients. The discrepancies between findings affecting clinical management detected with PET/MR imaging over those detected with PET/CT were significant (P < .001). CONCLUSION In these patients, PET/MR imaging alone contributed to clinical management more often than did PET/CT alone. PET/MR imaging provides information that affects the care of patients with cancer and is unavailable from PET/CT. Online supplemental material is available for this article.

Independent and incremental prognostic value of heart rate variability in patients with chronic heart failure

BACKGROUND Decreased heart rate variability (HRV), indicating derangement in cardiac autonomic control, has been reported in patients with chronic heart failure. However, the independent and incremental prognostic value of HRV over clinical data and measures of left ventricular dysfunction has been less thoroughly investigated. This study was designed to evaluate the predictive value of HRV and Poincaré plots as assessed by 24-hour Holter recording in patients with chronic heart failure. METHODS Ninety-seven patients, mean age 55 +/- 13 years, with radionuclide left ventricular ejection fraction </=40% underwent echocardiographic examination and 24-hour Holter recording. Heart failure was caused by coronary artery disease in 57 patients (59%) and idiopathic dilated cardiomyopathy in 40 (41%). RESULTS During follow-up (39 +/- 18 months), 32 cardiac deaths occurred. By Cox multivariate analysis, significant predictors of death were left ventricular end-systolic volume (hazard ratio 1.04), low- to high-frequency ratio (hazard ratio 0.09), percentage of differences between successive normal R-R intervals >50 ms (hazard ratio 0.93), and age (hazard ratio 1.06). Furthermore, HRV analysis improved (P <. 001) the prognostic power of a model including clinical and echocardiographic data, left ventricular ejection fraction, and ventricular arrhythmias at Holter recording, whereas the inclusion of Poincaré plots did not add further predictive value. CONCLUSIONS Our investigation demonstrated that HRV has independent and incremental prognostic value in patients with chronic heart failure and seems useful to stratify patients at high risk of cardiac death.

Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: Lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues

PURPOSE To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues. METHODS A total of 36 patients underwent a whole-body PET/CT scan 1h after injection and an average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle. RESULTS Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data (ρ=0.71-0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found (ρ=0.95-0.97; p<0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (ρ=0.91; p<0.0001), while moderate correlations were found for the other normal organ tissues (ρ=0.36-0.61; p<0.05). CONCLUSIONS PET/MRI showed equivalent performance in terms of qualitative lesion detection to PET/CT. Despite significant differences in tracer uptake quantification, due to either methodological and biological factors, PET/MRI and PET/CT measurements in lesions and normal organ tissues correlated well. This study demonstrates that integrated whole-body PET/MRI is feasible in a clinical setting with high quality and in a short examination time.

Improved left ventricular function after growth hormone replacement in patients with hypopituitarism: assessment with radionuclide angiography.

Prolonged growth hormone deficiency (GHD) leads to marked cardiac dysfunction; however, whether reversal of this abnormality may be achieved after specific replacement therapy has not yet been completely clarified. Fourteen patients with childhood-onset GHD (nine men and five women, mean age 27±4 years) and 12 normal control subjects underwent equilibrium radionuclide angiography under control conditions at rest. Patients with GHD were also studied 6 months after recombinant human (rh) GH treatment (0.05 IU/kg per day). Normal control subjects and patients with GHD did not differ with respect to age, gender and heart rate. In contrast, left ventricular ejection fraction (53%±9% vs 66%±6%,P <0.001), stroke volume index (41±11 vs 51±8 ml/m2,P <0.01) and cardiac index (2.8±0.6 vs 3.±0.51/min/m2,P <0.001) were significantly lower in GHD patients than in normal control subjects. None of the GHD patients showed adverse or side-effects during rhGH therapy; thus none required a reduction in GH dose during the treatment period. Heart rate and arterial blood pressure were not significantly modified by rhGH treatment. After 6 months of rhGH therapy a significant improvement in left ventricular ejection fraction (from 53%±9% to 59%±9%,P <0.01), stroke volume index (from 41±11 to 47±13 ml/m2,P <0.05) and cardiac index (from 2.8±0.6 to 3.3±0.8 1/min/m2,P <0.01) was observed in GHD patients. In conclusion, prolonged lack of GH leads to impaired left ventricular function at rest. Reversal of this abnormality may be observed after 6 months of specific replacement therapy in patients with childhood-onset GHD.

Successful coronary revascularization improves prognosis in patients with previous myocardial infarction and evidence of viable myocardium at thallium-201 imaging

Abstract. The role of coronary revascularization of dysfunctional myocardium with preserved thallium-201 uptake in determining the prognosis in patients after myocardial infarction remains to be defined. This study was designed to evaluate the effects of successful revascularization on survival and left ventricular (LV) function in patients with previous myocardial infarction and evidence of dysfunctional but still viable myocardium at rest-redistribution 201Tl imaging. Seventy-six consecutive patients with LV dysfunction related to previous myocardial infarction and evidence of viable myocardium at rest-redistribution 201Tl tomography were followed for 17±8 months. LV ejection fraction (EF) was assessed by radionuclide angiography at baseline and after 13±2 months. Thirty-nine patients were revascularized (group A) and 37 treated medically (group B). During the follow-up there were nine cardiac deaths. Survival rate was 97% in group A and 66% in group B (P<0.01). By Cox multivariate analysis, the extent of viable myocardium was the best predictor of cardiac death (χ2=8.67, P<0.01) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global χ2 of the model from 14.1 to 21.9 (P<0.01). At follow-up, EF had improved by ≥5% in 16 patients. By multivariate logistic analysis, the extent of viable myocardium was the best predictor of EF improvement (χ2=15.49, P<0.001) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global χ2 of the model from 16.8 to 22.5 (P<0.01). These results demonstrate that the total extent of dysfunctional myocardium with preserved 201Tl uptake is the strongest predictor of cardiac death in patients after myocardial infarction. Successful revascularization of dysfunctional but viable myocardium improves survival and LVEF in such patients.

Relationship between simultaneously acquired resting-state regional cerebral glucose metabolism and functional MRI: A PET/MR hybrid scanner study

Recently introduced hybrid PET/MR scanners provide the opportunity to measure simultaneously, and in direct spatial correspondence, both metabolic demand and functional activity of the brain, hence capturing complementary information on the brains physiological state. Here we exploited PET/MR simultaneous imaging to explore the relationship between the metabolic information provided by resting-state fluorodeoxyglucose-PET (FDG-PET) and fMRI (rs-fMRI) in neurologically healthy subjects. Regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and degree of centrality (DC) maps were generated from the rs-fMRI data in 23 subjects, and voxel-wise comparison to glucose uptake distribution provided by simultaneously acquired FDG-PET was performed. The mutual relationships among each couple of these four metrics were explored in terms of similarity, both of spatial distribution across the brain and the whole group, and voxel-wise across subjects, taking into account partial volume effects by adjusting for grey matter (GM) volume. Although a significant correlation between the spatial distribution of glucose uptake and rs-fMRI derived metrics was present, only a limited percentage of GM voxels correlated with PET across subjects. Moreover, the correlation between the spatial distributions of PET and rs-fMRI-derived metrics is spatially heterogeneous across both anatomic regions and functional networks, with lowest correlation strength in the limbic network (Spearman rho around -0.11 for DC), and strongest correlation for the default-mode network (up to 0.89 for ReHo and 0.86 for fALFF). Overall, ReHo and fALFF provided significantly higher correlation coefficients with PET (p=10(-8) and 10(-7), respectively) as compared to DC, while no significant differences were present between ReHo and fALFF. Local GM volume variations introduced a limited overestimation of the rs-fMRI to FDG correlation between the modalities under investigation through partial volume effects. These novel results provide the basis for future studies of alterations of the coupling between brain metabolism and functional connectivity in pathologic conditions.

Direct comparison of technetium 99m—sestamibi and technetium 99m—tetrofosmin cardiac single photon emission computed tomography in patients with coronary artery disease

BackgroundTechnetium 99m-labeled sestamibi and tetrofosmin tomography have shown high diagnostic accuracy in the detection of coronary artery disease (CAD). However, few data are available comparing sestamibi and tetrofosmin imaging in the same patients. The aim of the study was to determine the image quality of the two tracers and to compare the results of exercise sestamibi and tetrofosmin tomography in the same patients.MethodsThe results of exercise-rest sestamibi and tetrofosmin myocardial tomography were compared in 32 patients with suspected or known CAD who underwent coronary angiography. Image quality was evaluated subjectively. Regional tracer distribution was visually assessed and quantitatively measured in 22 segments/patient.ResultsAt coronary angiography 7 patients had normal coronary vessels, 11 single-vessel, and 14 multivessel CAD (≥50% luminal stenosis). Image quality judged visually was comparable with the two tracers. Heart/lung and heart/liver ratios for sestamibi and tetrofosmin were not different. At visual analysis, 68% of the patients with CAD had abnormal findings with sestamibi and 76% with tetrofosmin (p=NS). At quantitative analysis, 92% of the patients with CAD had abnormal findings with sestamibi and 96% with tetrofosmin (p=NS). At both visual and quantitative analyses, sensitivity, specificity, and diagnostic accuracy in the detection of individual stenosed vessels were not different between the two tracers. Moreover, for both tracers sensitivity, specificity, and diagnostic accuracy in the detection of diseased vessels were significantly higher (all p<0.05) at quantitative compared with visual analysis. Finally, defect size and severity were similar for the two tracers.ConclusionsExercise-rest sestamibi and tetrofosmin tomography yielded images of comparable quality and provided similar results in the identification of patients with CAD and in the detection of the individual stenosed coronary vessels.

Does the age of onset of growth hormone deficiency affect cardiac performance? A radionuclide angiography study

BACKGROUND GH and IGF‐I seem to play a relevant role in cardiac development and performance. Longstanding GH deficiency (GHD) causes several abnormalities in cardiac structure and performance which ultimately determine an increased cardiovascular morbidity and mortality.