Iodine-123 Metaiodobenzylguanidine Uptake Research Articles

Impact of concomitant medication use on myocardial 123I-mIBG imaging results in patients with heart failure.

Medications that interfere with sympathetic neuronal norepinephrine uptake and storage, such as neuropsychiatrics (NP) and sympathomimetic amines, are most likely to affect cardiac uptake of iodine-123 metaiodobenzylguanidine (I-mIBG). The present study examined these and other medications reported to affect I-mIBG uptake using measurements of cardiac I-mIBG uptake on the heart failure (HF) patients in the ADMIRE-HF extension (X) study. Baseline concomitant medications taken by the 961 HF patients were categorized into five groups: calcium channel blockers, NP medications, β agonists and sympathomimetics, α antagonists, and other antihypertensives. NP medications were further subcategorized into those expected to have high and low impact on norepinephrine transporter (NET) function. Myocardial I-mIBG heart/mediastinum (H/M) uptake ratios on 4 h planar images were compared among the groups. Impact of medication group on the prognostic value of the H/M ratio for all-cause (AC) and cardiac death during a median 2-year follow-up was also examined. A total of 283 (29%) patients were using at least one calcium channel blocker, NP medication, or β agonist or sympathomimetic. These patients had a lower mean H/M ratio than the other study patients (1.42±0.20 vs. 1.45±0.20; P=0.022). However, the 2-year AC mortality rates in the two groups were the same [11.3% (95% confidence interval: 7.5-15.2%) vs. 11.8% (95% confidence interval: 9.2-14.4%)]. In terms of medication categories, there were no significant differences in the mean H/M ratios between patients who did and did not use NP medications, β agonists, calcium channel blockers, and α antagonists. Across all categories, patients with H/M ratio greater than or equal to 1.60 had lower AC and cardiac mortality. Patients using higher potency (for NET inhibition) NP medications had significantly lower H/M ratio values, but the prognostic significance of H/M ratio greater than or equal to 1.60 was unchanged. Only a small number of higher potency NET-inhibiting NP medications have a measurable effect on the results of I-mIBG myocardial imaging. There appears to be no basis for restricting the use of calcium channel blockers and β agonist respiratory medications in HF patients referred for cardiac I-mIBG imaging.

Iodine-123 metaiodobenzylguanidine scintigraphy for the assessment of cardiac sympathetic innervation and the relationship with cardiac autonomic function in healthy adults using standardized methods.

Global iodine-123 metaiodobenzylguanidine (I-MIBG) uptake is predictive of cardiovascular events and mortality in patients with heart failure. Normal variations in global and regional uptake, however, are not well defined and few studies have addressed the functional relevance of I-MIBG uptake and distribution in healthy individuals. We performed I-MIBG scintigraphy and cardiac autonomic function testing using the standardized methodology in 15 healthy individuals (mean age 54.6±5.3 years, male : female 10 : 5) with no evidence of previous myocardial infarction or ischaemic heart disease. Early heart to mediastinum ratio (HMR) was 1.67±0.13, late HMR was 1.73±0.16 and washout rate was 19.09±7.63% (4.20-31.30). Regional analysis showed reduced tracer uptake at the apex, base and inferior wall in all individuals. Early and late HMR correlated negatively with RFa (r=-0.603; P=0.05 and r=-0.644; P=0.033) and expiration and inspiration ratio (r=-0.616; P=0.043 and r=-0.676; P=0.022) and positively with LFa/RFa (r=0.711; P=0.014 and r=0.784; P=0.004). Washout rate correlated only with RFa (r=0.642; P=0.033). Healthy adults show a heterogeneous pattern of cardiac innervation with reduced regional uptake of I-MIBG. Furthermore, HMR correlates with indices of cardiac sympathetic function, suggesting that it might not only be a useful prognostic marker but may also provide insight into the functional integrity of the cardiac autonomic nervous system.

Abstract 18957: Modulation of Ganglionated Plexi as an Addition to Pv Isolation in Persistent Atrial Fibrillation Ablation

Introduction: Catheter ablation of ganglionated plexi (GP) as an add on to pulmonary vein (PV) isolation has been reported to significantly improve outcome of atrial fibrillation (AF) ablation. In order to facilitate localization of these GPs, a novel imaging study is proposed that investigates the uptake of iodine-123 metaiodobenzylguanidine (mIBG, an analogon for norepinephrine) on the atrial level. This information is combined with 3D surface reconstruction from contrast computed tomography (cCT) or cardiac magnetic resonance (CMR). Methods: A total of 7 patients (5 male, mean age 64.3 yrs) with AF underwent mIBG nuclear studies using a dedicated solid state cardiac camera (D-SPECT, Spectrum Dynamics). Four patient had 4 persistent AF (3 prev. abl.) with less than 1 year of sustained AF, whereas 3 patient were in longstanding persistent AF (all prev. abl). The acquired data was merged with the 3D imaging and subsequently imported into the 3D electroanatomical mapping system (CARTO, Biosense Webster). During invasive AF ablations these sites were mapped to perform high frequency stimulation (HFS) to confirm GP locations. Results: In all pts, both the mIBG and CT scans were performed without any complications. Locations of high mIBG uptake corresponded to anatomical GP sites (LA & RA) in the majority of patients, but individual variations were observed. PV isolation was added in all but 1 pt (who had previous ablation) plus CFAE ablation if necessary. Follow-up of in median of 10.4 months demonstrated SR in all persistent AF patients (1 redo for atrial reentry). In patients with longstanding persistent AF: 2 pts are in SR (both AF at 1 week and 1 pt in AT at 6 weeks), while 1 pt remained in AF. Conclusion: The combination of mIBG and 3D imaging provides a novel type of “road map” for localizing GPs during AF ablation. As an add-on to PV (re-) isolation, this strategy was found to be beneficial for patients with persistent and longstanding persistent AF. Interestingly, pts with longstanding persistent AF (and multiple previous ablations) all recurred early in F/U but showed reversal to AT and finally SR at later stages. Further studies in larger patient cohorts need to confirm these initial observations.

Abstract 19466: Preliminary Experience Using Multiplexed Imaging of the Sympathetic Autonomic Nervous System - Impact on Outcome of Catheter Ablation of Atrial Fibrillation

Introduction: Catheter ablation of ganglionated plexi (GP) as an add on to pulmonary vein (PV) isolation has been reported to significantly improve outcome of atrial fibrillation (AF) ablation. In order to facilitate localization of these GPs, a novel imaging study is proposed, assessing the uptake of iodine-123 metaiodobenzylguanidine (mIBG, an analog of norepinephrine)in combination with 3D surface reconstruction from contrast computed tomography (cCT) or cardiac magnetic resonance (CMR). Methods: A total of 8 patients (5 male, median age 58 yrs) underwent mIBG SPECT using a dedicated cardiac camera (D-SPECT, SUMO, Spectrum Dynamics). This data was merged with 3D CMR or cCT and finally imported into CARTO (Biosense Webster). Using the individual mediastinum uptake as a normalizing factor, high uptake sites in the epicardial fat pads around the left atrium (LA) were identified. Five patients had paroxysmal AF whilst 3 present in persistent (n=2) or longstanding persistent (n=1) AF. Only 3 patients were treated de-novo, with the remaining failing in median 2 previous ablation procedures. Invasively, high uptake sites were mapped using high frequency stimulation (HFS) to confirm GP locations, which were subsequently ablated. PV (re) isolation and CFAE ablation was performed as needed. Results: Both the mIBG and CT or CMR scans were performed without complications. Focal mIBG uptake sites corresponded to anatomical GP sites, but individual variations of additional GPs were observed. Using HFS stimulation, GP sites were confirmed, but exact localization was highly depending on accurate image registration. Median follow-up of 9.2 months with all PAF and persistent AF patients in SR (1 AT redo), while the long-standing AF relapsed. Conclusion: The combination of mIBG SPECT and 3D anatomical imaging (SUMO protocol) provides a novel type of “road map” for localizing GPs during AF ablation. GPs were variable in number and location and were invasively confirmed using high frequency stimulation. Addition of GP ablation to standard AF ablation strategies seems beneficial in patients with paroxysmal or persistent AF. Further studies in larger patient cohorts are needed to confirm these initial observations.

Renal dysfunction does not affect the prognostic value of myocardial iodine-123 meta-iodobenzylguanidine imaging in heart failure

Iodine-123 meta-iodobenzylguanidine (I-mIBG) imaging has prognostic value in patients with heart failure (HF). Renal dysfunction is prevalent in HF patients. I-mIBG is excreted by the kidneys, and the effect of renal dysfunction on its myocardial uptake and established prognostic value in HF patients is unknown. The data analysed are from patients with New York Heart Association (NYHA) class II or III HF enrolled in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study. Myocardial uptake and retention of I-mIBG were assessed by the early and late heart-to-mediastinal (HM) ratio. Effect of renal dysfunction on the prognostic value of I-mIBG was determined by multivariable-predicted survival analysis stratified by glomerular filtration rate (GFR) and late HM ratio. Cox proportional hazard models were used to determine the predictors of cardiac events (CEs, defined as death, HF progression or life-threatening arrhythmia). Complete data were available on 867 patients. The GFR range was 19-140 ml/min, and 344 (40%) patients had renal dysfunction (GFR<60 ml/min). A total of 523 (60%) and 689 (80%) patients had early and late HM ratios below the previously established prognostic cutoff of 1.6. There was no relationship between early or late HM ratios and GFR after controlling for HF severity (NYHA class and norepinephrine levels), indicating a lack of effect of renal dysfunction on the HM ratio. Significant independent predictors of CE were (hazard ratio, P), b-type natriuretic peptide level (1.4, <0.001), left ventricular ejection fraction (0.95, <0.001), BMI (1.04, 0.002), cardiac glycoside use (1.42, 0.019) and late HM ratio (7.04, 0.008). Neither GFR nor its interaction with late HM ratio was a significant predictor of CE. Renal dysfunction does not affect the HM ratios or the prognostic value of I-mIBG imaging in HF patients.

Clinical significance of lung iodine-123 metaiodobenzylguanidine uptake assessment in Parkinson’s and heart diseases

Decreased heart iodine-123 metaiodobenzylguanidine ((123)I-MIBG) uptake [heart-to-mediastinum count ratio (H/M)] is reported in heart disease (HD) or Lewy body disease (LBD). When LBD is merged, therefore, information regarding HD severity may be ambiguous. We aimed to examine whether lung (123)I-MIBG uptake [lung-to-mediastinum count ratio (L/M)] assessment might be useful for differentiating two clinical conditions of HD and LBD, and to investigate whether L/M could reflect the grade of left ventricular (LV) dysfunction. Three groups were examined: LBD (patient group with Parkinson's disease or dementia with Lewy bodies, n = 33), PS (group with other Parkinsonian syndromes, n = 20) and HD (group with heart disease). HD consisted of 4 subgroups: HD(I) [H/M(<2.30)-matched group with LBD, n = 34), HD(II) [H/M(≥2.30)-matched group with PS, n = 33], HD(III) [group for functional analysis, LV ejection fraction, first-third and peak filling rates (1/3FR and PFR) and time to PFR were calculated using gated SPECT, n = 35] and HD(IV) (group for examining cardiac prognosis, follow-up period of 1283 ± 506 days, n = 54). Using Doppler echocardiography, a diastolic parameter E/e' and pulmonary artery pressure (ePAP) were estimated. H/Ms did not differ between HD(I) and LBD, or between PS and HD(II). However, L/Ms were increased in the order of LBD, PS, HD(II) and HD(I) groups. In combined LBD, PS, HD(I) and HD(II), L/Ms correlated positively with a diastolic parameter E/e'. L/Ms correlated with ePAP, while H/Ms did not. H/Ms correlated with a systolic parameter EF (r = 0.56) and diastolic parameters 1/3FR (r = 0.51) and PFR (r = 0.51), and L/Ms correlated with diastolic parameters 1/3FR (r = -0.36) and PFR (r = -0.36) but not with EF in HD(III). Kaplan-Meier analysis showed earlier cardiac death in patients with decreased H/Ms, but not in patients with increased L/Ms in HD(IV). Our study suggest that increased lung (123)I-MIBG uptake is useful as a reference marker for differentiating two clinical conditions of HD and LBD, and can reflect the degree of LV diastolic dysfunction. Elevated ePAP caused by LV diastolic dysfunction may be involved in the mechanism(s) of increased lung uptake.

Glucose hypometabolism in primary visual cortex is commonly associated with clinical features of dementia with Lewy bodies regardless of cognitive conditions

Although metabolic reduction in the primary visual cortex on [(18) F]-fluoro-d-glucose (FDG) positron emission tomographic (PET) scans is the hallmark of dementia with Lewy bodies (DLB) for differential diagnosis from Alzheimer's disease, the clinical significance of the metabolic pattern in patients without dementia remains unknown. The purpose of this study was to investigate the clinical profiles of patients without dementia with the metabolic pattern and its relevance to DLB. Of 145 individuals who underwent (18) F-FDG PET, 25 patients with glucose hypometabolism in the primary visual cortex were identified based on three-dimensional stereotactic surface projection images through comparison with a normative database. The frequency of core and suggestive clinical features of DLB was compared between the groups with and without the metabolic pattern. Of 25 patients with glucose hypometabolism in the primary visual cortex, 12 exhibited more than two core features of DLB (probable DLB group) and 6 had rapid eye movement sleep behavior disorder (possible DLB group). Three patients exhibited memory loss without any core or suggestive features but with reduced cardiac iodine-123 metaiodobenzylguanidine uptake. Ten of these 21 patients exhibited no dementia. The proportion of individuals in the probable and possible DLB groups was significantly higher in the group with glucose hypometabolism in the primary visual cortex. Glucose hypometabolism in the primary visual cortex is commonly associated with the clinical features of DLB regardless of cognitive conditions. Continued follow-up of these patients without dementia with the metabolic pattern is warranted to determine if they represent the prodromal state of DLB.

Iodine‐123 metaiodobenzylguanidine scintigraphic assessment of pulmonary vascular status in patients with chronic obstructive pulmonary disease

Lung uptake of iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) is used as an indicator of pulmonary endothelial function. Decreased lung uptake of ¹²³I-MIBG has been demonstrated in patients with COPD as compared with normal subjects. The present study was performed to examine the relationship between lung uptake of ¹²³I-MIBG and pulmonary artery pressure (Ppa) at rest and during exercise, in patients with COPD. ¹²³I-MIBG scintigraphy was performed in 19 patients with COPD. Anterior planar images were acquired 15 min after the injection of ¹²³I-MIBG, and the total lung to upper mediastinum ratio (LMR) was calculated for both lungs. Right heart catheters were used to monitor Ppa continuously at rest and during exercise. Exercise was performed on an electrically braked bicycle ergometer at a constant workload of 25 W for 3 min. In COPD patients the LMR were not correlated with the pulmonary function parameters measured before exercise, including FEV₁, PaO₂, DL(CO), or Ppa at rest. However, the percentage increase in Ppa during exercise was significantly correlated with LMR. Evaluation of the kinetics of lung uptake of ¹²³I-MIBG may be a novel scintigraphic tool for the assessment of exercise-induced pulmonary hypertension in patients with COPD.

Myocardial adrenergic innervation in patients with vasovagal syncope measured with 123I-MIBG uptake

Data about biochemical abnormalities (catecholamines) during vasovagal syncope (VVS) are available, but adrenergic myocardial structural damage may be hypothesized as well. To study the global and regional adrenergic myocardial innervations in patients with VVS that was shown by head-up tilt table testing. Fifteen adult patients with VVS were studied. The age of patients was 44+/-18 years (17-73), nine were female and six were male. According to the tilt test results, five patients had cardioinhibition, six patients had vasodepressor syncope and four patients suffered from mixed-type VVS. Ischemic heart diseases were excluded by normal Tc-MIBI rest-stress dipyridamol single-photon emission computed tomography (SPECT) results. A control group was formed from six healthy adult volunteers. To investigate cardiac sympathetic innervations 250-370 MBq iodine-123 meta-iodobenzylguanidine (I-MIBG) was used. Fifteen minutes after the intravenous administration of I-MIBG early, and 2-3 h later, delayed planar myocardial and tomographic (SPECT) scintigraphies were performed. The heart-to-mediastinum count ratio (H/M) was calculated for both early and delayed images, together with the decay-corrected change rates. The regional I-MIBG uptake was visualized on SPECT slices and polar map images. The regional uptake was considered pathological below 50% compared with normal uptake sites. Delayed H/M ratios significantly depended on group (analysis of variance: P=0.005), whereas early H/M values did not. Although the decay-corrected myocardial MIBG uptake increased in time in controls, less wash-in or even wash-out could be observed in the VVS groups; however, difference from the controls was significant only in the vasodepressor group (Dunnett's t-test: P<0.05). All patients had regional I-MIBG uptake deficit in different regions. In our patients with VVS, global I-MIBG deficit was present frequently, and all patients had regional adrenergic nerve function deficit. These alterations may play a role in causing clinical symptoms and have importance in staging and treatment planning.

Mutation Analysis of the PINK1 Gene in 391 Patients With Parkinson Disease

To determine the frequency, distribution, and clinical features of Parkinson disease (PD) with PINK1 mutations. Retrospective clinical and genetic review. University hospital. We performed extensive mutation analyses of PINK1 in 414 PD patients negative for parkin mutations (mean [SD] age at onset, 42.8 [14.3] years), including 391 unrelated patients (190 patients with sporadic PD and 201 probands of patients with familial PD) from 13 countries. We found 10 patients with PD from 9 families with PINK1 mutations and identified 7 novel mutations (2 homozygous mutations [p.D297MfsX22 and p.W437R] and 5 single heterozygous mutations [p.A78V, p.P196QfsX25, p.M342V, p.W437R, and p.N542S]). No compound heterozygous mutations were found. The frequency of homozygous mutations was 4.26% (2 of 47) in families with autosomal recessive PD and 0.53% (1 of 190) in patients with sporadic PD. The frequency of heterozygous mutations was 1.89% (2 of 106) in families with potential autosomal dominant PD and 1.05% (2 of 190) in patients with sporadic PD. The mean (SD) age at onset in patients with single heterozygous mutations (53.6 [11.1] years; range, 39-69 years) was higher than that in patients with homozygous mutations (34.0 [20.3] years; range, 10-55 years). Myocardial iodine-123 metaiodobenzylguanidine uptake was low in patients with heterozygous mutations but not in those with homozygous mutations. Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of PD. Single heterozygous mutations may contribute to the development of sporadic PD and also could be an additional genetic predisposition for developing familial PD. The reduced myocardial iodine-123 metaiodobenzylguanidine uptake observed in patients with single heterozygous PINK1 mutations is similar to that seen in patients with sporadic PD.

Risk Stratification Assessed by Combined Lung and Heart Iodine-123 Metaiodobenzylguanidine Uptake in Patients With Idiopathic Dilated Cardiomyopathy

Iodine-123 metaiodobenzylguanidine (123I-MIBG) has been used to assess myocardial sympathetic nervous activity and severity of heart failure. (123)I-MIBG is also used as a potential marker of pulmonary endothelial cell function and may be related to pulmonary hypertension. Thus, we hypothesized that combined assessment of lung and heart 123I-MIBG kinetics predicts future clinical outcome more accurately than myocardial evaluation alone in patients with chronic heart failure. To test this hypothesis, we examined 123I-MIBG scintigrams in 62 consecutive patients with idiopathic dilated cardiomyopathy. Anterior planar images were obtained 15 minutes and 3 hours after 123I-MIBG injection. Cardiac and pulmonary 123I-MIBG activities were quantified as heart-to-mediastinum activity ratio and lung-to-mediastinum activity ratio. We introduced lung-to-heart activity ratio as the new 123I-MIBG parameter including myocardial sympathetic nerve activity and pulmonary endothelial cell function. Delayed lung-to-heart ratio was correlated with pulmonary vascular resistance (r = 0.48, p <0.0001), disease duration (r = 0.49, p <0.0001), and number of heart failure episodes (r = 0.55, p <0.0001). During a mean follow-up of 25 months, 15 patients had a cardiac event. Area under receiver operating characteristic curves for prediction of the event was greatest in delayed lung-to-heart ratio (lung to heart 0.92, heart to mediastinum 0.83, lung to mediastinum 0.80). In multivariate analysis, the lung-to-heart ratio (hazard ratio 2.76/0.1 increase, p = 0.002) was selected as an independent predictor for a future cardiac event. In conclusion, the combined assessment of lung and heart 123I-MIBG uptake may help to predict future clinical outcome for patients with idiopathic dilated cardiomyopathy more accurately than myocardial evaluation alone.

Reduced Lung Uptake of Iodine-123 Metaiodobenzylguanidine in Patients with Myeloperoxidase Antineutrophil Cytoplasmic Antibodies-Positive Vasculitis

Background: Iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) lung uptake in the early phase has been proposed as a potential marker of endothelial function because MIBG behaves qualitatively similarly to norepinephrine in pulmonary circulation. Objectives: The purpose of the present study was to examine the lung uptake of ¹²³I-MIBG in patients diagnosed with myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis without clinical or radiological abnormalities of the thorax. Methods: Six patients with MPO-ANCA-associated vasculitis were enrolled. They had severe renal damage (mean creatinine: 5.1 mg/dl, mean blood urea nitrogen: 54.6 mg/dl), but no respiratory symptoms clinically or radiographic findings on chest computed tomography. The total lung to upper mediastinum ratio of ¹²³I-MIBG uptake (L/M) 15 min after the injection was measured. The result was compared with those for 6 patients with renal damage due to other diseases (mean creatinine: 6.2 mg/dl, blood urea nitrogen: 51.7 mg/dl) and for 8 healthy subjects. Results: The mean value of L/M in patients with MPO-ANCA-positive vasculitis was 1.21 ± 0.04, which was significantly less than that of other groups (1.41 ± 0.06 for patients with renal failure and 1.45 ± 0.03 for normal volunteers). There were no significant differences in MIBG accumulation in the heart among the groups. Conclusions: The reduction in kinetic behavior of MIBG in the lung reflects the presence of pulmonary endothelial impairment in patients with MPO-ANCA-associated vasculitis, even though there are no clinical manifestations in the lungs.

Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium.

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with 123I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%+/-3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 microM. This indicates an unsaturable uptake process in the tested concentrations. Preincubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism.

Effects of aldose reductase inhibitor and vitamin B12 on myocardial uptake of iodine-123 metaiodobenzylguanidine in patients with non-insulin-dependent diabetes mellitus.

This study was undertaken to examine the effects of aldose reductase inhibitor (ARI) and vitamin B12 (VB12) on myocardial uptake of iodine-123 metaiodobenzylguanidine (MIBG) in patients with diabetic autonomic disorder. Myocardial scintigraphy using 123I-MIBG was performed on 20 healthy volunteers (controls) and 56 patients with non-insulin-dependent diabetes mellitus (NIDDM), in order to obtain the heart/mediastinum ratio in the initial (HMi) and the delayed images (HMd), and the washout rate (%WR). Thirty-four of the 56 NIDDM patients could be diagnosed as having diabetic autonomic disorder by evaluating their scintigraphic findings in comparison with the controls. Seventeen of these 34 patients received 150 mg/day of doses before meals, and the other 17 received 1.5 mg/day of mecobalamin (VB12 group) in three divided doses after meals, for 3-5 months. According to the presence or absence of clinical symptoms of autonomic or peripheral somatic nerve disorder, the patients were subclassified into four groups. group 1=patients, with autonomic symptoms or somatosensory disorder in the ARI group; group 2=patients without autonomic symptoms or somatosensory disorder in the ARI group; group 3=patients with autonomic symptoms or somatosensory disorder in the VB12 group; and group 4=patients without autonomic symptoms or somatosensory disorder in the VB12 group. After completion of the treatment, myocardial scintigraphy was performed again. Comparing the results obtained before and after the treatment, it was seen that ARI improved only the HMi in group 1 (P=0.046), whereas VB12 significantly improved HMi in the group 3 (P=0.018) and HMi, HMd and %WR in group 4 (P=0.043, P=0.018 and P=0.043, respectively). We conclude that VB12 is more efficacious than ARI in the treatment of diabetic cardiovascular autonomic disorder.

Association between QT dispersion and autonomic dysfunction in patients with diabetes mellitus

We hypothesized that QT dispersion would be increased in patients with diabetes mellitus and autonomic dysfunction and that QT dispersion would be related to abnormal iodine-123 (I-123) metaiodobenzylguanidine (MIBG) uptake. Patients with diabetes mellitus and autonomic dysfunction have an increased incidence of sudden death. This event may be due to a sympathetic imbalance causing disturbances of repolarization. QT dispersion has recently been demonstrated to reflect dispersion of ventricular refractoriness and is a marker of arrhythmogenic potential. Uptake of I-123 MIBG is a reliable measure of whether the tissue examined receives sympathetic neuronal innervation. Fifty-one diabetic patients and 11 normal subjects were studied. All patients had clinical evaluation for autonomic dysfunction (defined as at least two abnormal heart rate and blood pressure responses to five validated tests). Rest 12-lead electrocardiograms were recorded for measurement of QT dispersion, defined as the longest QT interval minus the shortest QT interval, and corrected for heart rate using Bazett's formula. Visual and quantitative measurements of I-123 MIBG uptake were performed using I-123 MIBG, and technetium-99m sestamibi uptake was used to assess perfusion. Thirty-five diabetic patients had autonomic dysfunction. Corrected QT dispersion was significantly greater in the patients than in the normal subjects (p = 0.02). The I-123 MIBG scores were also significantly greater in patients with than without autonomic dysfunction (p = 0.0004) and in normal subjects (p = 0.008). There was no correlation between QT dispersion and I-123 MIBG uptake score (r = 0.006, p = 0.97). Diabetic patients with autonomic dysfunction have increased QT dispersion and larger I-123 MIBG uptake defects. This finding suggests that such patients have a greater inhomogeneity of repolarization. The lack of correlation between QT dispersion and I-123 MIBG uptake suggests that these abnormalities are mediated by different mechanisms.

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: Evidence for late reinnervation

This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure.

Assessment of anthracycline-related myocardial adrenergic derangement by [123i]metaiodobenzylguanidine scintigraphy

Myocardial adrenergic neuron integrity and function were evaluated in 21 patients who had received doxorubicin or epirubicin for various malignancies. Myocardial uptake of iodine-123 metaiodobenzylguanidine ([123I]MIBG), a marker suitable for the study of myocardial neuron injury, was calculated from planar scintigraphic images after 4 h and the washout between 15 min and 4 h. In 13 patients with normal left ventricle ejection fraction (LVEF) analysed at three cumulative dose levels (no, low and middle dose), [123I]MIBG uptake tended to be significantly impaired (z = -2.772, P = 0.0056), at higher cumulative dose levels, before significant LVEF changes were observed. [123I]MIBG values were considerably decreased in 2/7 patients investigated at low cumulative dose and in 3/8 cases at the middle dose level. On follow-up, 1 of these patients, who had normal LVEF after completion of chemotherapy but whose [123I]MIBG values had progressively deteriorated during anthracycline therapy, subsequently developed congestive heart failure; another patient, whose [123I]MIBG values were impaired at the middle dose level, developed persistent reduced LVEF 5 months after completing therapy. In 8 patients, who had developed persistently, reduced LVEF at high doxorubicin cumulative dose levels, [123I]MIBG, performed in the period after chemotherapy discontinuation, was invariably abnormal. These data suggest that myocardial adrenergic derangement plays a role in anthracycline-associated cardiotoxicity: its appearance, even at low cumulative anthracycline dose levels, may reflect impairment of the intravesicular norepinephrine storage by incipient anthracycline-associated cardiac neuron injury. [123I]MIBG scintigraphy may be useful to assess myocardial adrenergic derangement during and in the follow-up of anthracycline therapy and potentially detect patients who are at risk.

Iodine-123 meta-iodobenzylguanidine scintigraphy: A noninvasive method to demonstrate myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy

Iodine-123 (I-123) meta-iodobenzylguanidine (MIBG) imaging was performed in 31 patients. Three patients were without cardiac disease and 28 had idiopathic dilated cardiomyopathy with various degrees of left ventricular dysfunction. The quantitatively assessed myocardial I-123 MIBG scintigrams and the myocardial versus mediastinal I-123 MIBG uptake ratio were related to I-123 MIBG activity and norepinephrine concentration determined from endomyocardial biopsy samples taken from the right side of the interventricular septum. Scintigrams and the MIBG uptake ratio were also related to plasma catecholamine concentrations, left ventricular ejection fraction and New York Heart Association functional class.Patients with distinct myocardial I-123 MIBG uptake (score 1) had a normal ejection fraction (58 ± 16%). Patients with diffusely reduced uptake or scintigraphic defects (score 2) had a significantly lower ejection fraction (38 ± 9%, p < 0.05), whereas patients with shadowy or no visible myocardial uptake (score 3) had the lowest ejection fraction (23 ± 6%, p < 0.002 versus patients with score 2). The scintigraphically determined I-123 MIBG activity in the septal region correlated significantly with I-123 MIBG activity from the endomyocardial biopsy samples (r = 0.78, p < 0.001, n = 9). The myocardial versus mediastinal I-123 MIBG activity ratio was significantly related to myocardial norepinephrine concentration (r = 0.63, n = 28) and to left ventricular ejection fraction (r = 0.74, n = 31).These data suggest that myocardial I-123 MIBG scintigraphy is a useful noninvasive method for the assessment of myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy.