Abstract Introduction Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional ...homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III–IV) after CRT using11 C-hydroxyephedrine (HED) PET/CT. Methods Ten IHF patients (mean age = 68; range = 55–81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. Results At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with “impaired innervation” (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). Conclusion As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. Advances in Knowledge These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation. Implication for patient care This work might contribute to identify imaging parameters that could predict the response to CRT therapy.
Aim
This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population ...of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study.
Methods and results
Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3092€/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure.
Conclusion
In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization.
Purpose
To identify both clinical and FDG PET/CT-derived factors predicting the occurrence of relapse, or conversely, the likelihood of false positive findings in surveillance FDG-PET/CT studies ...(PETsv).
Methods
The study included 149 asymptomatic patients with Hodgkin’s lymphoma (HL) (n = 55) or diffuse large B cell lymphoma (DLBCL) (n = 94) in first remission. PETSv studies were performed 12, 18, 24 and 36 months thereafter. Logistic regression analysis was performed to identify clinical and imaging-derived predictors of either PET-detected relapse or false-positive (FP) results. Tested clinical variables were: 1) age, 2) HL vs. DLBCL, 3) stage of disease, 4) bulky disease, 5) previous radiotherapy. PET/CT-derived variables were: 1) maximum standardized uptake value at baseline, 2) size-incorporated maximum standardized uptake value (SIMaxSUV) at baseline, 3) positive interim PET(PET-2), 4) presence of hot spots likely to be unrelated to the disease in final PET, 5) residual non-FDG avid mass.
Results
Accuracy was 88 % for PETsv1, 95 % for PETsv2, 95 % for PETsv3 and 91 % for PETsv4. However, PPV was relatively low in all PETsv. Best predictors of relapse were result of interim PET, HL versus NHL type, SIMaxSUV, age ≥ 60. Best predictors of FP were previous radiotherapy and hot spots unrelated to the disease in final PET.
Conclusions
The present study confirms the need of restricting the use of surveillance PET/CT to patients at high risk of relapse. Information derived from PET/CT performed at baseline (metabolic disease burden), in the course (PET2) and at the end of therapy (unrelated hot spots) can help to select high-risk patients and also to identify patients more likely to present equivocal findings at PETsv.
Purpose
Reversible ischaemia at radionuclide myocardial perfusion imaging (MPI) accurately predicts risk of cardiac death and nonfatal myocardial infarction (major adverse cardiac events, MACE). This ...prognostic penetrance might be empowered by accounting for exercise tolerance as an indirect index of ischaemia severity. The present study aimed to verify this hypothesis integrating imaging assessment of ischaemia severity with exercise maximal rate pressure product (RPP) in a large cohort of patients with suspected or known coronary artery disease (CAD).
Methods and results
We analysed 1,502 consecutive patients (1,014 men aged 59 ± 10 years) submitted to exercise stress/rest MPI. To account for exercise tolerance, the summed difference score (SDS) was divided by RPP at tracer injection providing a clinical prognostic index (CPI). Reversible ischaemia was documented in 357 patients (24 %) and was classified by SDS as mild (SDS 2–4) in 180, moderate (SDS 5–7) in 118 and severe (SDS >7) in 59. CPI values of ischaemic patients were clustered into tertiles with lowest and highest values indicating low and high risk, respectively. CPI modified SDS risk prediction in 119/357 (33 %) patients. During a 60-month follow-up, MACE occurred in 68 patients. Kaplan-Meier analysis revealed that CPI significantly improved predictive power for MACE incidence with respect to SDS alone. Multivariate Cox analysis confirmed the additive independent value of CPI-derived information.
Conclusion
Integration of ischaemic threshold and ischaemia extension and severity can improve accuracy of exercise MPI in predicting long-term outcome in a large cohort of patients with suspected or known CAD.
Objective
To compare the diagnostic value of striatal 123I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (123I‐FP‐CIT) single photon emission computed tomography (SPECT) and ...123I‐metaiodobenzylguanidine (123I‐MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types.
Methods
This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non‐DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent 123I‐FP‐CIT SPECT and 123I‐MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re‐evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data.
Results
Overall, sensitivity and specificity to DLB were respectively 93% and 100% for 123I‐MIBG myocardial scintigraphy, and 90% and 76% for 123I‐FP‐CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased 123I‐FP‐CIT uptake in 7 non‐DLB subjects (3 with concomitant parkinsonism) who had normal 123I‐MIBG myocardial uptake. Notably, in our non‐DLB group, myocardial imaging gave no false‐positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with 123I‐MIBG uptake.
Interpretation
123I‐FP‐CIT SPECT and 123I‐MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non‐DLB dementias, especially when parkinsonism is the only “core feature” exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on 123I‐MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368–378
Objective To compare the diagnostic value of striatal super(123)I-2 beta -carbomethoxy-3 beta -(4-iod ophenyl)-N-(3-fluoropropyl) nortropane ( super(123)I-FP-CIT) single photon emission computed ...tomography (SPECT) and super(123)I-metaiodobenzylguanidine ( super(123)I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. Methods This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n=16; behavioral variant frontotemporal dementia, n=13). All patients underwent super(123)I-FP-CIT SPECT and super(123)I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. Results Overall, sensitivity and specificity to DLB were respectively 93% and 100% for super(123)I-MIBG myocardial scintigraphy, and 90% and 76% for super(123)I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased super(123)I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal super(123)I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n=7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with super(123)I-MIBG uptake. Interpretation super(123)I-FP-CIT SPECT and super(123)I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only "core feature" exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on super(123)I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016; 80:368-378
Objective
To compare the diagnostic value of striatal
123
I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐
N
‐(3‐fluoropropyl) nortropane (
123
I‐FP‐CIT) single photon emission computed tomography (SPECT) and
...123
I‐metaiodobenzylguanidine (
123
I‐MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types.
Methods
This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non‐DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent
123
I‐FP‐CIT SPECT and
123
I‐MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re‐evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data.
Results
Overall, sensitivity and specificity to DLB were respectively 93% and 100% for
123
I‐MIBG myocardial scintigraphy, and 90% and 76% for
123
I‐FP‐CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased
123
I‐FP‐CIT uptake in 7 non‐DLB subjects (3 with concomitant parkinsonism) who had normal
123
I‐MIBG myocardial uptake. Notably, in our non‐DLB group, myocardial imaging gave no false‐positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with
123
I‐MIBG uptake.
Interpretation
123
I‐FP‐CIT SPECT and
123
I‐MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non‐DLB dementias, especially when parkinsonism is the only “core feature” exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on
123
I‐MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368–378
Objective To compare the diagnostic value of striatal 123I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT) and ...123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. Methods This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n=16; behavioral variant frontotemporal dementia, n=13). All patients underwent 123I-FP-CIT SPECT and 123I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. Results Overall, sensitivity and specificity to DLB were respectively 93% and 100% for 123I-MIBG myocardial scintigraphy, and 90% and 76% for 123I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased 123I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal 123I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n=7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with 123I-MIBG uptake. Interpretation 123I-FP-CIT SPECT and 123I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only "core feature" exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on 123I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368-378
Oxidative stress and its interference on myocardial metabolism play a major role in Doxorubicin (DXR) cardiotoxic cascade.
Mice models of neuroblastoma (NB) were treated with 5 mg DXR/kg, either free ...(Free-DXR) or encapsulated in untargeted (SLDXR) or in NB-targeting Stealth Liposomes (pep-SLDXR and TP-pep-SLDXR). Control mice received saline. FDG-PET was performed at baseline (PET1) and 7 days after therapy (PET2). At PET2 Troponin-I and NT-proBNP were assessed. Explanted hearts underwent biochemical, histological, and immunohistochemical analyses. Finally, FDG uptake and glucose consumption were simultaneously measured in cultured H9c2 in the presence/absence of Free-DXR (1 μM).
Free-DXR significantly enhanced the myocardial oxidative stress. Myocardial-SUV remained relatively stable in controls and mice treated with liposomal formulations, while it significantly increased at PET2 with respect to baseline in Free-DXR. At this timepoint, myocardial-SUV was directly correlated with both myocardial redox stress and hexose-6-phosphate-dehydrogenase (H6PD) enzymatic activity, which selectively sustain cellular anti-oxidant mechanisms. Intriguingly, in vitro, Free-DXR selectively increased FDG extraction fraction without altering the corresponding value for glucose.
The direct correlation between cardiac FDG uptake and oxidative stress indexes supports the potential role of FDG-PET as an early biomarker of DXR oxidative damage.
Objective:
The present study was planned to investigate, by means of quantitative FDG‐PET, how bariatric surgery (BS) modifies the metabolic pattern of the whole body and different tissues in ...slightly obese patients with type 2 diabetes mellitus (T2DM).
Design and Methods:
Before, 1 and 4 months after BS, 21 consecutive slightly obese T2DM patients underwent blood sampling to estimate plasma levels of glucose, insulin, glycosylated hemoglobin. At the same time points, these patients underwent a dynamic 18F‐FDG PET study of thorax and upper abdomen in fasting state and after washout of T2DM therapy. Gjedde‐Patlak analysis was applied to estimate glucose uptake in the whole body and in different tissues (myocardium, skeletal back muscle, adipose tissue, and liver).
Results:
Surgical intervention quickly lowered levels of both insulin and glucose documenting an amelioration of glucose tolerance. Similarly, skeletal muscle and myocardial glucose uptake significantly increased soon after surgery (P < 0.001 and P < 0.01 at 1 month versus baseline, respectively) and remained substantially stable thereafter. By contrast, glucose uptake slightly decreased from its baseline values in the liver (P < 0.01 at 4 months) while no response could be documented over time in the adipose tissue.
Conclusions:
These findings document that BS‐induced modification of glucose homeostasis in slightly obese T2DM patients is mostly due to an increase in muscle glucose consumption. The surgically modified metabolic pattern of these patients might be of interest as a new model to investigate mechanism underlying insulin resistance.
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