Teresa Pellegrino

Impact of Diabetes on Cardiac Sympathetic Innervation in Patients With Heart Failure: A 123I meta-iodobenzylguanidine (123I MIBG) scintigraphic study

OBJECTIVE Impaired parasympathetic and sympathetic nervous system activity have been demonstrated in patients with diabetes mellitus (DM) and correlated with worse prognosis. Few data are available on the effect of DM on cardiac neuropathy in heart failure (HF). The aim of the current study was to assess cardiac sympathetic activity in HF patients with and without DM. RESEARCH DESIGN AND METHODS Patients with severe HF (n = 75), with (n = 37) and without DM (n = 38), and 14 diabetic patients with normal cardiac function underwent 123I meta-iodobenzylguanidine scintigraphy from which early and late heart-to-mediastinum (H/M) ratios were calculated. Clinical, echocardiographic, and biochemical data were measured. RESULTS DM compared with non-DM patients showed significantly lower early (1.65 ± 0.21 vs. 1.75 ± 0.21; P < 0.05) and late H/M ratios (1.46 ± 0.22 vs. 1.58 ± 0.24; P < 0.03). Early and late H/M were significantly higher in DM patients without HF (2.22 ± 0.35 and 1.99 ± 0.24, respectively) than HF patients with (P < 0.0001) and without (P < 0.0001) DM. In HF patients, an inverse correlation between early or late H/M ratio and hemoglobin A1c (HbA1c) (Pearson = −0.473, P = 0.001; Pearson = −0.382, P = 0.001, respectively) was observed. In DM, in multivariate analysis, HbA1c and ejection fraction remained significant predictors of early H/M; HbA1c remained the only significant predictor of late H/M. No correlation between early or late H/M and HbA1c was found in non-DM patients. CONCLUSIONS Diabetic patients with HF show lower cardiac sympathetic activity than HF patients not having DM or than DM patients with a similar degree of autonomic dysfunction not having HF. HbA1c correlated with the degree of reduction in cardiac sympathetic activity.

Relations of left ventricular mass and systolic function to endothelial function and coronary flow reserve in healthy, new discovered hypertensive subjects

Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47±10 years old, 26.6±2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (β=−0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (β=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.

Increased Epicardial Adipose Tissue Volume Correlates With Cardiac Sympathetic Denervation in Patients With Heart Failure

RATIONALE It has been reported that epicardial adipose tissue (EAT) may affect myocardial autonomic function. OBJECTIVE The aim of this study was to explore the relationship between EAT and cardiac sympathetic nerve activity in patients with heart failure. METHODS AND RESULTS In 110 patients with systolic heart failure, we evaluated the correlation between echocardiographic EAT thickness and cardiac adrenergic nerve activity assessed by (123)I-metaiodobenzylguanidine ((123)I-MIBG). The predictive value of EAT thickness on cardiac sympathetic denervation ((123)I-MIBG early and late heart:mediastinum ratio and single-photon emission computed tomography total defect score) was tested in a multivariate analysis. Furthermore, catecholamine levels, catecholamine biosynthetic enzymes, and sympathetic nerve fibers were measured in EAT and subcutaneous adipose tissue biopsies obtained from patients with heart failure who underwent cardiac surgery. EAT thickness correlated with (123)I-MIBG early and late heart:mediastinum ratio and single-photon emission computed tomography total defect score, but not with left ventricular ejection fraction. Moreover, EAT resulted as an independent predictor of (123)I-MIBG early and late heart:mediastinum ratio and single-photon emission computed tomography total defect score and showed a significant additive predictive value on (123)I-MIBG planar and single-photon emission computed tomography results over demographic and clinical data. Although no differences were found in sympathetic innervation between EAT and subcutaneous adipose tissue, EAT showed an enhanced adrenergic activity demonstrated by the increased catecholamine levels and expression of catecholamine biosynthetic enzymes. CONCLUSIONS This study provides the first evidence of a direct correlation between increased EAT thickness and cardiac sympathetic denervation in heart failure.

Assessment of Metabolic Response to Radioimmunotherapy with 90Y–Ibritumomab Tiuxetan in Patients with Relapsed or Refractory B-Cell Non–Hodgkin Lymphoma

PURPOSE To prospectively compare the assessment of metabolic response to yttrium 90 ((90)Y)-ibritumomab tiuxetan radioimmunotherapy (RIT) by using fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomographic-computed tomographic (PET/CT) imaging at 2 and 6 months to determine the most appropriate time to detect therapeutic response in refractory non-Hodgkin lymphoma (NHL) patients treated with RIT. MATERIALS AND METHODS The ethical committee of the university approved the protocol and all patients signed informed consent. Twenty-three consecutive patients (10 women, 13 men; mean age, 51.8 years +/-7.3 [standard deviation]) treated by using RIT for relapsed or refractory follicular NHL were enrolled. For all patients, (18)F FDG PET/CT scanning was performed at baseline and at 2 and 6 months after RIT. Response was assessed by using the International Workshop Criteria (IWC) and revised criteria (IWC + PET) as well as the criteria of the European Organization for Research and Treatment of Cancer. One-way analysis of variance for repeated measures, receiver operator curve analysis, and Kaplan-Meier curves were used for statistical analysis. RESULTS PET/CT performed at 2 months revealed complete (n = 12) or partial (n = 4) metabolic response in 16 of 23 patients with complete or partial clinical response. These findings were all confirmed at 6-month scanning. PET/CT indicated refractory or persistent disease at 2 and 6 months in the remaining seven patients. Better overall survival was observed for patients with a reduction in the maximum standard uptake value of 49% or higher (both at 2 and 6 months after RIT) when compared with those with a decrease of less than 49% (P < .05). CONCLUSION Early assessment of response to RIT by using PET/CT might be useful in the identification of patients needing additional therapeutic strategies.

Assessment of coronary flow reserve by sestamibi imaging in patients with typical chest pain and normal coronary arteries

PurposeWe assessed coronary flow reserve (CFR) by sestamibi imaging in patients with typical chest pain, positive exercise stress test and normal coronary vessels.MethodsThirty-five patients with typical chest pain and normal angiogram and 12 control subjects with atypical chest pain underwent dipyridamole/rest 99mTc-sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Estimated CFR was expressed as the ratio of stress to rest MBF. Rest MBF and CFR were corrected for rate–pressure product (RPP) and expressed as normalised MBF (MBFn) and normalised CFR (CFRn). Coronary vascular resistances (CVR) were calculated as the ratio between mean arterial pressure and estimated MBF.ResultsAt rest, estimated MBF and MBFn were lower in controls than in patients (0.98 ± 0.4 vs 1.30 ± 0.3 counts/pixel/s and 1.14 ± 0.5 vs 1.64 ± 0.6 counts/pixel/s, respectively, both p < 0.02). Stress MBF was not different between controls and patients (2.34 ± 0.8 vs 2.01 ± 0.7 counts/pixel/s, p=NS). Estimated CFR was 2.40 ± 0.3 in controls and 1.54 ± 0.3 in patients (p < 0.0001). After correction for the RPP, CFRn was still higher in controls than in patients (2.1 ± 0.5 vs 1.29 ± 0.5, p < 0.0001). At baseline, CVR values were lower (p < 0.01) in patients than in controls. Dipyridamole-induced changes in CVR were greater (p < 0.0001) in controls (−63%) than in patients (−35%). In the overall study population, a significant correlation between dipyridamole-induced changes in CVR and CFR was observed (r = −0.88, p < 0.0001).ConclusionSPECT might represent a useful non-invasive method for assessing coronary vascular function in patients with angina and a normal coronary angiogram.

Quantitative Assessment of Myocardial Blood Flow with SPECT

The quantitative assessment of myocardial blood flow (MBF) and coronary flow reserve (CFR) may be useful for the functional evaluation of coronary artery disease, allowing judgment of its severity, tracking of disease progression, and evaluation of the anti-ischemic efficacy of therapeutic strategies. Quantitative estimates of myocardial perfusion and CFR can be derived from single-photon emission computed tomography (SPECT) myocardial perfusion images by use of equipment, tracers, and techniques that are available in most nuclear cardiology laboratories. However, this method underestimates CFR, particularly at high flow rates. The recent introduction of cardiac-dedicated gamma cameras with solid-state detectors provides very fast perfusion imaging with improved resolution, allowing fast acquisition of serial dynamic images during the first pass of a flow agent. This new technology holds great promise for MBF and CFR quantification with dynamic SPECT. Future studies will clarify the effectiveness of dynamic SPECT flow imaging.

Prognostic role of 18F-FDG PET/CT in the postoperative evaluation of differentiated thyroid cancer patients

Purpose The aim of this study was to evaluate the role of 18F-FDG PET/CT performed after surgery but before radioiodine therapy in patients with differentiated thyroid cancer. Procedures FDG PET/CT was performed off l-thyroxine in 60 newly diagnosed differentiated thyroid cancer patients. Clinical and hematological evaluation as well as high-resolution neck ultrasound were performed. All patients underwent a complete follow-up (range, 6-67 months; mean [SD], 31.7 [20.6] months). The date of recurrence or the most recent office visit was recorded. Progression-free survival (PFS) is the primary end point of this study. Analysis was performed by Cox proportional hazards model. Survival curves were generated using Kaplan-Meier estimates, and the log-rank test was used to assess significance. Results FDG PET/CT was negative in 63% of patients, 20% had FDG thyroid bed uptake, 5% distant metastases, and 12% lymph node FDG uptake. In patients with positive FDG PET/CT scan (ie, those with distant metastases or lymph node uptake), a higher rate of recurrence was observed (50% vs 6%, P < 0.05). Thyroglobulin, neck ultrasound, stage, and FDG PET/CT correlated with PFS at univariate analysis. At multivariate analysis, only thyroglobulin and FDG PET/CT continued to be predictors of PFS. Patients with a negative FDG PET/CT scan have a better PFS either in the whole group or in those with elevated thyroglobulin level (both >2 ng/mL and >10 ng/mL). Conclusions FDG PET/CT was abnormal in 17% of patients. Moreover, FDG PET/CT has an independent prognostic role, with a better PFS in patients with a negative scan.

Beyond ultrasound: advances in multimodality cardiac imaging

The rapid technological evolution accomplished in noninvasive cardiac imaging techniques over the past few decades has provided physicians with a large armamentarium for the evaluation of patients with known or suspected coronary heart disease. Noninvasive assessment of coronary artery calcium or noninvasive coronary angiography may be performed using computed tomography or magnetic resonance imaging. These techniques evaluate the presence of atherosclerosis rather than ischemia. Conversely, nuclear cardiology is the most widely used noninvasive approach for the assessment of myocardial perfusion and function. These techniques coupled with the development of dedicated image fusion software packages to merge data sets from different modalities have paved the way for hybrid imaging. This article provides a description of the available noninvasive imaging techniques in the assessment of coronary anatomy, myocardial perfusion, and cardiac function in patients with known or suspected coronary heart disease.

Cardiac neuronal imaging with 123I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions [1]. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with I has been widely used and validated as a marker of adrenergic neuron function [2–4]. The first study addressing the prognostic value of I-MIBG imaging in heart failure (HF) was that of Merlet et al. [5] in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-tomediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters [6]. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest [7]. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published [8]. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late H/M ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a H/M ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. [9] present the results of a secondary analysis of the ADMIRE-HF study exploring the association of abnormal MIBG imaging and hospitalization events. The results of this study indicate that the H/M ratio may risk-stratify HF patients for cardiacrelated hospitalization, especially when used in conjunction with BNP.

Noninvasive quantification of coronary endothelial function by SPECT imaging in children with a history of Kawasaki disease

PurposeThe feasibility of coronary function estimation by single photon emission computed tomography (SPECT) has been recently demonstrated. The aim of this study was to apply SPECT imaging in patients with previous Kawasaki disease (KD) to assess the coronary functional status at long-term follow-up of the acute phase of the disease.MethodsSixteen children with a history of KD underwent 99mTc-sestamibi imaging at rest and during the cold pressor test (CPT). Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Coronary endothelial function was expressed as the ratio of the CPT to rest MBF.ResultsSix KD patients without coronary artery lesions served as controls and ten with coronary artery aneurysms during the acute phase of the disease were separated into two groups: group 1 (n = 4) with regressed and group 2 (n = 6) with persistent aneurysm at follow-up. The estimated coronary endothelial function was higher in controls compared to patients with coronary artery aneurysms (2.5 ± 0.3 vs 1.7 ± 0.7, p < 0.05). A significant difference in coronary endothelial function among groups was found (F = 5.21, p < 0.02). Coronary endothelial function was higher in patients of group 1 than in those of group 2 (1.9 ± 0.6 vs 1.4 ± 0.7, p < 0.02).ConclusionSPECT may be applied as a noninvasive method for assessing coronary vascular function in children with a history of KD, demonstrating an impaired response to the CPT, an endothelial-dependent vasodilator stimulus. These findings reinforce the concept that coronary endothelial dysfunction may represent a long-term sequela of KD.