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.

Evaluation of sympathetic vasomotor fibres in carpal tunnel syndrome using continuous wave Doppler ultrasonography.

Sympathetic vasomotor fibres carried by the median nerve and ulnar nerve innervate their respective sensory territories. The sympathetic vasomotor fibres of the median nerve were evaluated in patients with carpal tunnel syndrome and in healthy volunteers using continuous wave Doppler ultrasonography. The pulsatility index of the radialis indicis artery and the radial palmar digital artery of the little finger were measured at baseline and after stimulation. The maximal increase in the pulsatility index of each artery was measured. This was significantly lower for the radialis indicis artery in the CTS group than in the healthy controls. However, there was no significant difference in the maximal increase in pulsatility index of the radial palmar digital artery of the little finger between both groups. Sympathetic vasomotor fibres of the median nerve are affected in carpal tunnel syndrome. Continuous wave Doppler ultrasonography is easy to use and should be investigated further as a possible diagnostic tool for the confirmation of carpal tunnel syndrome.

Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine.

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES: This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS: Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS: Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS: Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

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.

Bromine-76-metabromobenzylguanidine: a PET radiotracer for mapping sympathetic nerves of the heart.

Iodine-123-metaiodobenzylguanidine (MIBG) is used to qualitatively assess heart innervation with single-photon emission computed tomography (SPECT). This approach is clinically useful in the prognostic evaluation of congestive heart failure. To improve quantification of uptake of the tracer using positron emission tomography (PET), we studied the characteristics of the bromoanalog of MIBG. Bromine-76-metabromobenzylguanidine (76Br-MBBG) was prepared from a heteroisotopic exchange between radioactive bromine atoms (noncarrier-added (76Br) BrNH4) and the cold iodine atoms of the precursor metaiodobenzylguanidine. Biodistribution was studied in rats and PET cardiac imaging performed in dogs. Myocardial uptake was high and prolonged in both species (mean half-life in dogs: 580 min). In rats, myocardial uptake was inhibited by desipramine by 64%, whereas after pretreatment with 6-hydroxydopamine uptake was reduced by 84%. In dogs pretreated with 6-hydroxydopamine or with desipramine, a steep washout of the tracer occurred (mean half-life: 136 min and 118 min, respectively). The non-specific uptake plus the passive neuronal diffusion of the tracer could be estimated at about 25%-30% of the total fixation. In dogs, analysis of unchanged 76Br-MBBG in plasma showed that radiotracer metabolism was slow: 60 min after injection, 80% of the radioactivity was related to unchanged 76Br-MBBG. These preliminary findings suggest that 76Br-MBBG could be used to quantitatively assess adrenergic innervation in heart disease using PET. When combined with use of 11C-CGP 12177, cardiac adrenergic neurotransmission can be assessed.

Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man.

Metaiodobenzylguanidine (MIBG) localizes in adrenergic neurons; MIBG labeled with 123I then serves as an analog of norepinephrine, and concentrations of [123I]MIBG reflect sites of adrenergic neurons in organs. Movements of [123I]MIBG into and out of organs were measured by quantitative scintigraphy in man. We perturbed adrenergic neuron function in several ways, and [123I]MIBG concentrations in the heart were subsequently altered in patterns consistent with the concept that [123I]MIBG resides mostly in adrenergic neurons. Uptake of [123I]MIBG into the heart was inhibited by the tricyclic drug, imipramine, and this agent also accelerated the rate of loss of [123I]MIBG. Phenylpropanolamine, a sympathomimetic drug that acts by displacing norepinephrine from neurons, increased the rates of loss of [123I]MIBG from the heart. Exercise was followed by a movement of [123I]MIBG into blood and urine. Generalized autonomic neuropathies were associated with marked diminutions of [123I]MIBG uptake into the heart. We conclude that quantitative scintigraphy in patients will enable determinations of regional disturbances in integrity (by measuring uptake of [123I]MIBG) and function (by measuring rates of loss of [123I]MIBG) of the adrenergic nervous system in the heart.

Effects of carvedilol on cardiac function and cardiac adrenergic neuronal damage in rats with dilated cardiomyopathy.

UNLABELLED: Metaiodobenzylguanidine (MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating beta-adrenoceptor-blocking agent, were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. METHODS: Twenty-eight days after immunization, surviving rats (41/55, or 75%) were divided into 2 groups treated with carvedilol, 2 mg/kg/d (group C, n = 19), or vehicle alone (0.5% methylcellulose, group V, n = 22). After oral administration for 2 mo, heart weight, heart rate, left ventricular end-diastolic pressure (LVEDP), and myocardial fibrosis were measured and compared with those in untreated rats (group N, n = 19). Myocardial uptake of (125)I-MIBG (differential absorption ratio) in the left ventricle was measured by autoradiography at 10, 30, or 240 min after tracer injection. RESULTS: Four (18%) of 22 rats in group V died between days 28 and 84 after immunization. None of the rats in group C or N died. Heart weight, heart rate, LVEDP, and area of myocardial fibrosis in group C (1.14 +/- 0.04 g, 345 +/- 16 beats per minute, 7.6 +/- 1.5 mm Hg, and 12% +/- 1%) were significantly lower than those in group V (1.34 +/- 0.04 g, 389 +/- 10 beats per minute, 12.3 +/- 1.3 mm Hg, and 31% +/- 2%). Although the differential absorption ratio was lower at all time points in group V than in group N, uptake after treatment increased in group C, compared with group V, at 10 min (12.5 +/- 1.0 vs. 7.6 +/- 0.8, not significant), 30 min (10.1 +/- 1.1 vs. 6.3 +/- 0.9, not significant), and 240 min (6.5 +/- 0.5 vs. 2.5 +/- 0.2, P < 0.05). The late washout ratio from myocardial radioactivity between 30 and 240 min in group C was lower than that in group V (36% vs. 60%). CONCLUSION: These observations indicated that carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.

Reappearance of cardiac presynaptic sympathetic nerve terminals in the transplanted heart: correlation between PET using (11)C-hydroxyephedrine and invasively measured norepinephrine release.

UNLABELLED: Previously, sympathetic reinnervation of the transplanted heart has been described using invasive catheterization techniques and noninvasive radionuclide imaging techniques. However, little is known about the agreement between these 2 methods. Thus, correlation between (11)C-hydroxyephedrine (HED) PET and invasively measured norepinephrine (NE) release was investigated in transplant recipients in this study. METHODS: Using PET and the catecholamine analog HED, 17 patients were studied between 2 mo and 13.6 y after transplantation. Based on results in completely denervated hearts, areas with HED retention >7%/min were defined as reinnervated. Additionally, transcardiac NE release induced by intravenous tyramine (55 microg/kg) was measured by coronary sinus and aortic catheterization within 1 wk of the PET study. NE levels between coronary sinus and aortic root, DeltaNE(CS-AO), were calculated at baseline and after tyramine administration. Differences of more than 3 SD of baseline (>163 pg/mL) were interpreted as reinnervation. RESULTS: HED retention indicated reinnervation in 10 patients. Maximal HED retention ranged from 4.3%/min to 16.4%/min. DeltaNE(CS-AO) 1 min after tyramine administration ranged between -10 pg/mL and 1157 pg/mL, and 8 patients were above the reinnervation threshold. Fisher's exact test demonstrated good agreement between results of PET and DeltaNE(CS-AO) measurements (P = 0.002). Maximal HED retention was also significantly correlated with NE release (r = 0.69; P = 0.001). CONCLUSION: Results of invasively measured NE release and noninvasive (11)C-HED PET are well correlated. This study further supports the usefulness of PET as a noninvasive approach for detection of reappearance of catecholamine uptake sites after heart transplantation.

Recent advances in nuclear cardiology in the study of coronary artery disease.

A variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. This review will introduce these new techniques which have recently been available in Japan. Tc-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use of first-pass angiography or ECG-gated acquisition. Positron emission tomography enables metabolic assessment in vivo. Preserved FDG uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently I-123 BMIPP, a branched fatty acid analog, has been clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. Such perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Both of them are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. I-123 MIBG uptake in the myocardium reflects adrenergic neuronal function in vivo. In the study of coronary artery disease, neuronal denervation is often observed around the infarcted myocardium and post ischemic region as well. More importantly, reduced MIBG uptake in these patients can identify high risk for ventricular arrhythmias and assess severity of congestive heart failure. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment in these patients.

Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy.

We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6 +/- 10.0 yrs) and 15 with DCM (45.3 +/- 8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac 123I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. LVEF was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21 +/- 0.44 vs. 2.10 +/- 0.42, 35.3 +/- 13.1 vs. 36.0 +/- 10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41 +/- 0.34 vs. 0.08 +/- 0.20, 20.5 +/- 14.4 vs. -2.1 +/- 9.6%, p < 0.01). In TC, heart failure improved after a shorter duration of treatment (p < 0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM.

Localized reduction in 123I-MIBG accumulation in the lung.

A patient with old myocardial infarction underwent 123I-MIBG scintigraphy to evaluate the adrenergic nerve system in the heart following the treatment of pneumonia. Decreased accumulation of MIBG was observed in the right lower lung field, corresponding to the area affected by pneumonia, as well as in the left ventricle with myocardial infarction. 99mTc-MAA lung perfusion scan demonstrated hypoperfusion in the region of reduced MIBG uptake. Regional decrease in MIBG uptake in the lung is considered to suggest lung pathology, and lung perfusion scan is recommended to discriminate selective endothelial damage from loss of vascular bed.

Differences in myocardial sympathetic degeneration and the clinical features of the subtypes of Parkinson's disease.

Parkinson's disease (PD) can be divided into the akinetic-rigid (ART), mixed (MT), and tremor-dominant (TDT) subtypes according to the clinically dominant symptoms. We analyzed the correlations between (123)I-meta-iodobenzylguanidine (MIBG) uptake and the clinical features of patients with various PD subtypes. In addition, we evaluated the relationship between MIBG uptake and the severity of the cardinal motor symptoms among patients with PD subtypes. The mean Unified Parkinson's Disease Rating Scale motor scores differed significantly among patients with different PD subtypes (± standard deviation [SD]) (ART, 34.6 ± 18.28; MT, 24.63 ± 7.78; TDT, 16.22 ± 4.15, p=0.002), especially between the ART and TDT subtypes (p=0.022). The mean MIBG uptake (± SD) was decreased in the TDT (1.69 ± 0.39), MT (1.35 ± 0.32), and ART (1.35 ± 0.22) subtypes (p=0.049). The MIBG uptake values differed significantly between the ART and TDT subtypes (p=0.02). The MIBG uptake was inversely correlated with the severity of hypokinesia in the ART subtype (r=-0.75; p=0.01) and the MT subtype (r=-0.8; p=0.02), but it was not correlated with the severity of any of the parkinsonian motor symptoms in the TDT subtype. These results imply that hypokinesia is strongly associated with sympathetic myocardial degeneration and that sympathetic myocardial degeneration can reflect the progression of the disease in patients with the ART and mixed MT subtypes of PD.

Cardiac adrenergic nerve function and microvascular dysfunction in patients with cardiac syndrome X.

OBJECTIVE: To assess whether abnormalities in cardiac uptake of (123)I-metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction in patients with cardiac syndrome X (CSX). SETTING: University hospital. PATIENTS: 29 patients (aged 59 (SD 7) years, 11 men) with typical CSX and a matched group of 20 healthy subjects (aged 56 (7) years, 8 men) were studied. INTERVENTIONS: Planar and single photon emission computed tomography (SPECT) MIBG myocardial scintigraphy was performed in all subjects. Coronary flow response (CFR) to adenosine and to cold pressor test (CPT) in the left anterior descending (LAD) coronary artery was assessed in all CSX patients and in 12 controls by transthoracic Doppler echocardiography. MAIN OUTCOME MEASURES: Abnormalities in cardiac MIBG scintigraphy were observed in 25 CSX patients (86.2%), but in no healthy control (p<0.001). Compared to controls, CSX patients showed a lower heart/mediastinum (H/M) ratio of MIBG uptake (1.69 (0.24) vs 2.2 (0.3), p<0.001) and a higher cardiac MIBG defect score (25 (22) vs 4 (2), p = 0.002). Both CFR to adenosine (3.31 (1.1) vs 1.94 (0.6), p<0.001) and CFR to CPT (2.35 (0.5) vs 1.63 (0.4), p<0.001) were lower in CSX patients than in controls. In CSX patients, however, no correlation was found between MIBG H/M ratio and CFR to adenosine (r = 0.17; p = 0.38) and to CPT (r = -0.28; p = 0.13), as well as between MIBG uptake score in the LAD territory and CFR to adenosine (r = 0.14; p = 0.47) and to CPT (r = 0.06; p = 0.73). CONCLUSION: Our data show striking abnormalities in cardiac adrenergic nerve function and in coronary microvascular function in CSX patients. However, no significant relation between the two abnormalities was found. Further studies are needed to clarify the mechanisms and the role of MIBG defects in CSX patients.

Cardiac adrenergic innervation within the first 3 months after acute myocardial infarction.

It is widely accepted that myocardial infarction results in adrenergic denervation of the infarcted and peri-infarcted myocardium. On the contrary, the concept of re-innervation of adrenergic nerve fibres is less well established. Although there is evidence of partial re-innervation occuring several months after myocardial infarction, the extent and time scale of re-innervation are only poorly known. In this study we investigated changes in cardiac adrenergic innervation and myocardial perfusion during the early convalescence period (the first 3 months) after an acute myocardial infarction. Single-photon emission computed tomographic imaging was conducted in 15 men 1 week and 3 months after an acute myocardial infarction with I123-metaiodobentzylguanidine (MIBG) and Tc99m-sestamibi (MIBI) to determine the extent of adrenergic denervation and impaired perfusion, respectively. A MIBG and MIBI defect was determined as regional uptake

Myocardial dysfunction and adrenergic innervation in patients with Type 1 diabetes mellitus.

In this study we assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with Type 1 diabetes mellitus (T1DM) without coronary artery disease. Fourteen patients and 10 volunteers were enrolled. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. Diabetic subjects were classified into group A (n=7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n=7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients. In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV after load. No significant changes in LVEF occurred during dobutamine, whereas post-extrasystolic potentiation (PESP) significantly increased LVEF (60 +/- 6% vs 74 +/- 6%,p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than in normal subjects (1.69 +/- 0.30 vs 2.98 +/- 0.82 cpm/MBq per g,p = 0.01) and group B diabetic patients (vs 2.79 +/- 0.94 cpm/MBq per g,p = 0.01). A linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. A defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy.

I-123 metaiodobenzylguanidine (MIBG) is a new radiopharmaceutical with properties that allow the characterization of the sympathetic innervation of several organ systems. In this study, we used MIBG with tomographic imaging to evaluate noninvasively the differences in myocardial sympathetic innervation in 14 healthy volunteers and 16 patients with severe dilated cardiomyopathy (CM). Initial (15-minute) images demonstrated no significant differences in MIBG concentration in the hearts of patients with CM and of healthy volunteers. However, the myocardial retention of MIBG was significantly reduced in the patients with CM. Expressed as the percent washout from 15 to 85 minutes, the patients with CM had a 28 +/- 12% washout rate compared with 6 +/- 8% in the controls (p less than 0.001). A small subset of patients from each group imaged at 4-hour intervals demonstrated even greater disparity in washout rates. In addition, the patients with CM had significantly greater heterogeneity in the MIBG activity distribution within the myocardial images. There was 47 +/- 15% intraimage variability in MIBG distribution in the patients with CM and 22 +/- 9% variation in the controls (p less than 0.001). We conclude from these data that the myocardial distribution and kinetics of MIBG in images obtained from patients with CM differ significantly from those of controls and that the MIBG patterns may be used as a relatively noninvasive means to evaluate the severity of altered adrenergic innervation in the hearts of these patients.

Scintigraphic detection of regional disruption of the adrenergic nervous system in sarcoid heart disease.

The presence of defects on resting thallium (201Tl) myocardial scintigraphy has been previously demonstrated in myocardial sarcoidosis. To examine cardiac sympathetic nerve activity in patients with cardiac sarcoidosis, we performed 201Tl and I-123 MIBG (meta-iodobenzylguanidine) myocardial scintigraphy in patients with sarcoidosis. Sixteen patients with sarcoidosis were classified into 2 groups according to the presence or absence of defects on 201Tl scintigraphy. Myocardial images by both 201Tl and I-123 MIBG were then divided into 20 segments and scored using a 6-point scoring system. Defect Score was defined as a the sum of significant scores in each image. The mean Defect Score in I-123 MIBG images was higher in the 201Tl defect group (44.3 +/- 13.3) than in both the normal 201Tl group (25.1 +/- 10.5) and the control group (22.7 +/- 11.4). Moreover, the locations of defects on I-123 MIBG scans were consistent with those on 201Tl scans. This study suggests that cardiac adrenergic function may be impaired in cardiac sarcoidosis, and I-123 MIBG scintigraphy may be more sensitive in detecting cardiac sarcoidosis than 201Tl scintigraphy, although the clinical significance of these findings requires further study.