Direct evidence of impaired cardiac sympathetic innervation in essential hypertensive patients with left ventricular hypertrophy

Increased sympathetic nervous activity has been proposed as one of the causes of left ventricular hypertrophy (LVH) associated with hypertension. However, the precise relationship is not fully understood. METHODS: To elucidate the relationship between myocardial sympathetic nervous activity and LVH in patients with essential hypertension EHT), we performed 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 49 patients with EHT and 17 normotensive control subjects. Sympathetic innervation of the left ventricle was evaluated using SPECT, and the whole heart uptake of the tracer was quantitatively assessed as the heart-to-mediastinum uptake ratio on both the early (15-min) and delayed (5-hr) images. Myocardial washout rate (MWR) of the tracer from 15 min to 5 hr after the isotope administration was also calculated. The left ventricular mass index (LVMI) was determined echocardiographically. RESULTS: In 49 hypertensive patients, there was a negative correlation between LVMI and heart-to-mediastinum uptake ratio on both the early and delayed images (r=-0.55, p < 0.0001; r=-0.63, p < 0.0001, respectively). In addition, there was a positive correlation between the LVMI and MWR of 123I-MIBG in these hypertensive patients (r=0.59, p < 0.0001). As for the regional uptake of the tracer, there was no significant difference between control subjects and hypertensive patients without cardiac hypertrophy, but a significant decrease of the uptake in the inferior and lateral regions was observed in hypertensive patients with cardiac hypertrophy. CONCLUSION: Patients with EHT had decreased accumulation and increased MWR of 123I-MIBG in proportion to the degree of LVH. Hypertensive patients with cardiac hypertrophy had impaired sympathetic innervation in the inferior and lateral regions of the left ventricle.     

Evaluation of long-term prognosis in patients with heart failure: is cardiac imaging with iodine-123 metaiodobenzylguanidine useful?

The effect of cardiac sympathetic activity on long-term prognosis in patients with heart failure was evaluated by cardiac imaging with iodine-123 metaiodobenzylguanidine (123I-MIBG) in 46 patients admitted for the first episode of heart failure (idiopathic dilated cardiomyopathy: 18, ischemic heart disease: 10, hypertensive heart disease: 7, valvular heart disease: 4, others: 7). Cardiac imaging was performed with 123I-MIBG and thallium-201 (201Tl) at rest on separate days before discharge. Using whole body imaging, the ratio of cardiac uptake of the isotope to total injected dose was calculated (percentage uptake). The cardiac uptake ratio of 123I-MIBG (percentage uptake of 123I-MIBG divided by percentage uptake of 201Tl) and percentage washout of 123I-MIBG from the heart over 3 hours were calculated as scintigraphic parameters. Cardiac events were defined as cardiac death or deterioration of heart failure requiring readmission. Scintigraphic parameters, clinical parameters, left ventricular function obtained by echocardiography and neurohumoral parameters were compared between the event group and event-free group. During the follow-up period of 26.9 +/- 13.9 (7.1-53.8 months), cardiac events developed in 14 patients (cardiac death in 10 and deterioration of heart failure in 4; 30%). Univariate analysis showed uptake ratio and washout rate of 123I-MIBG, percentage uptake of 201Tl, New York Heart Association class at discharge, fractional shortening of the left ventricle, serum norepinephrine and atrial natriuretic peptide levels differed significantly between the two groups. Cox proportional-hazard analysis showed that the uptake ratio was an independent predictor of cardiac events (p < 0.0001). When a cut-off point in the uptake ratio equal to or less than 0.50 and age equal to or more than 65 years old were included in the Cox proportional-hazard analysis instead of actual numbers, relative risks of cardiac events by each index were 31.2 (95% confidence interval, 3.9 to 247.6; p = 0.001) and 4.2 (p = 0.025), respectively. These data suggest that cardiac uptake of 123I-MIBG is a strong and independent predictor of long-term prognosis in patients with heart failure.     

Scientific challenges in environmental carcinogenesis

Myocardial uptake of iodine-123 meta-iodobenzylguanidine (123I-MIBG) was measured using scintigrams at rest in 12 patients with isolated, nonischemic mitral regurgitation (MR; regurgitant fraction 64% +/- 7%) and was related to the left ventricular (LV) function assessed by cardiac catheterization. Iodine-123 meta-iodobenzylguanidine activity in the upper mediastinum, liver, and lung was comparable between MR and control (n = 8) patients. The heart-to-mediastinum 123I-MIBG activity ratio 4 hours after injection was significantly (p < 0.01) decreased in MR (2.0 +/- 0.1, mean +/- SE) compared with control (2.7 +/- 0.1) with the increased clearance of MIBG. In addition, MR patients had significantly greater heterogeneity in the 123I-MIBG distribution within the myocardial images (26.1% +/- 2.1% intraimage variability for MR versus 15.6% +/- 0.8% for control, p < 0.01). Myocardial 123I-MIBG activity correlated positively with cardiac index and negatively with pulmonary capillary wedge pressure and LV volume indexes. Thus, 123I-MIBG scintigrams can be a noninvasive method for assessing the contractile dysfunction in MR.     

Dental fear with and without blood-injection fear: implications for dental health and clinical practice

BACKGROUND: It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (123I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of 123I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm. METHODS AND RESULTS: Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2+/-12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n = 18) comprised subjects with a positive provocative test result, and group 2 (n = 8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using 123I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal 123I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of 123I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of 123I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval [CI] 55% to 89%) and 100%, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively. CONCLUSION: 123I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in 123I-MIBG SPECT.     

Acromegalic cardiomyopathy: an echocardiographic study

Thirty eight acromegalic patients (A) and a control group (C) of subjects without heart disease, were studied with echocardiography. Acromegalies were divided in two groups, A1 and A2, who had increase or normal serum growth hormone (GH) levels respectively after treatment (pituitary adenectomy and/or bromocriptine), at the time of the study. In acromegalic patients (A) mean left ventricular (LV) dimensions were normal while LV wall and septal thickness, LV mass and left atrial (LA) dimension were increased compared to control subjects. LVH was present in 79% of acromegalic patients. Asymmetric septal hypertrophy (ASH) was found in 10,5% of our patients. In group A1, IVS, LVPW, LVMM/m2 were significantly increased as compared to group A2. Fractional shortening (FS), ejection fraction (EF), mean velocity of circumferential fibre shortening (Vcf), frequency-normalized Vcf (Vcfn), posterior left ventricular wall velocity (PWV), and normalized PWV (PWVn) were normal in both groups. In patients with active acromegaly (Al) IVS and LVMM/m2 correlated well with the total duration of the disease (r=0.550 p less than 0.01 for IVS; r=0.624 p less than 0.01 for LVMM/m2) and with the duration of acromegaly before treatment (r=0.568, p less than 0.01 for IVS; r=0.500 p less than 0.01 for LVMM/m2). Furthermore a positive correlation was found between IVS and GH levels (r=0,550 p less than 0.01). Concomitant coronary artery disease and or hypertension did not seem to play any role in causing the above mentioned echocardiographic changes. Echocardiography is useful in assessing the cardiac involvement in patients with acromegaly.     

Managed care and outcomes of hospitalization among elderly patients with congestive heart failure

123I-radiolabeled metaiodobenzylguanidine (123I-MIBG) cardiac imaging has been used to evaluate the distribution of sympathetic nervous system (SNS) in the heart. Different heart diseases have shown impaired cardiac SNS distribution as reflected by MIBG activity. The aim of this study was to assess the cardiac distribution of SNS in normal subjects, using MIBG imaging. Ten normal subjects (1 male and 9 females, mean age 46 +/- 9 years) with no cardiac abnormalities underwent myocardial 123I-MIBG scintigraphy, Tc-99m methoxyisobutylisonitrile (MIBI) cardiac perfusion imaging and equilibrium radionuclide angiography (RNA). Regional myocardial MIBG and MIBI activities were quantitatively evaluated using a region of interest analysis. For this purpose, the left ventricle was divided into 6 myocardial regions as anterior, apical, inferior, septum, lateral and posterolateral. In particular, myocardial MIBG and MIBI activities were measured as myocardium to mediastinum ratio. Regional left ventricular function was assessed by RNA. Myocardial MIBG uptake was homogeneous in anterior (2.2 +/- 0.5), inferior (2.5 +/- 0.7), septal (2.4 +/- 0.4), lateral (2.3 +/- 0.4), and posterolateral (2.3 +/- 0.4) regions. Conversely, MIBG uptake was significantly lower in the apical region (1.9 +/- 0.3) compared to all other left ventricular segments (p < 0.05). Regional myocardial perfusion, as measured by MIBI uptake, was homogeneous in all regions. No regional left ventricular wall motion abnormalities were observed by RNA. In conclusion, our data suggest that a decreased MIBG uptake may be observed in the left ventricular apical region of normal subjects reflecting reduced sympathetic innervation of the apex. This finding is not related to myocardial perfusion or wall motion abnormalities. The knowledge of cardiac sympathetic innervation in normal subjects may be helpful to assess SNS abnormalities in heart disease.     

G1 accumulation caused by iron deprivation with deferoxamine does not accompany change of pRB status in ML-1 cells

In hypertension, several factors disturb coronary circulation and the metabolic reserve of the heart. This study was undertaken to test whether in hypertensive patients global and regional left ventricular (LV) function is related during exercise to the presence of significant coronary stenosis and whether lowering of coronary perfusion pressure through rapid normalization of the diastolic pressure may modify the dynamics of the left ventricle. Thirty-five patients with mild to moderate hypertension undergoing coronary angiography for the evaluation of chest pain were included in the study; upright bicycle exercise echocardiography tests were performed without therapy and 1 day later 1 h after sublingual administration of nifedipine. LV ejection fraction and regional wall motion scores were evaluated and compared at baseline, peak exercise, immediate postexercise, and recovery phases in each test through digital on-line storing of echocardiographic images. Twenty-one patients had normal coronary arteries (group 1) and 14 significant coronary stenoses (group 2); age, gender, heart rate, blood pressure, left ventricular diameter and mass index, and ejection fraction were similar in the two groups. At peak exercise LV ejection fraction slightly increased in group 1, whereas it slightly decreased in group 2 (both during the test without therapy and after nifedipine administration). All patients in group 1 had normal left ventricular wall motion during exercise; 13 of 14 patients in group 2 had LV wall motion abnormalities at peak exercise. Nifedipine did not produce any effect on LV regional wall motion in group 1, but it induced significant changes in LV regional wall motion in seven patients in group 2. Changes in LV wall motion between the two test groups were related to the number of the stenotic coronary vessels: the normal exercise test before and after therapy and the two normalized tests after nifedipine administration were in fact observed in patients with one-vessel disease, whereas worsening or changes in the site of ischemia were observed only in patients with multivessel disease. Regional and global left ventricular dynamics during exercise is mainly dependent on the existence of significant coronary artery disease. Rapid decrease of blood pressure does not alter the regional dynamics of the left ventricle during exercise in patients without coronary artery disease, but it may induce normalization, worsening, or changes in the site of wall motion abnormalities in hypertensives with significant coronary stenoses.     

Parallel increase in carotid, brachial and left ventricular cross-sectional areas in arterial hypertension

Few data have been published about the relation between the vessels geometry and development of left ventricular (LV) hypertrophy in patients with arterial hypertension. The aim of this study is to describe arterial and LV geometry changes due to mild-to-moderate arterial hypertension in an untreated hypertensive population. In 95 untreated patients with mild-to-moderate hypertension and 23 age- and sex-matched healthy normotensives, we measured the end-diastolic diameter and wall thickness of the left ventricle and the internal diameter and intimal-medial thickness (IMT) of carotid and brachial arteries. From these data, the cross-sectional areas (CSAs) of arterial and myocardial walls were calculated. Hypertensive patients were further subdivided on the basis of the presence of LV hypertrophy defined according to Devereux et al as anatomical LV mass >125 g/m. In hypertensive patients with hypertrophy, carotid and brachial CSAs increased, without significant changes in thickness/diameter ratio (arterial 'enlargement'), while the left ventricle developed 'concentric' hypertrophy. Arterial and LV CSAs showed a significant direct correlation with systolic blood pressure (BP). However, when data were corrected for BP, the correlation between the increase in arterial and LV CSAs became much improved than for the raw data. In conclusion patients with untreated mild-to-moderate hypertension, both carotid and brachial arterial walls showed an enlargement that was proportional to the development of LV hypertrophy. These results suggest that the effects of arterial hypertension on carotid, brachial and LV wall geometry have a common modulation.     

Optic nerve dysplasia associated with meningeal defect in Sprague-Dawley rats

The relationship between the myocardial uptake of iodine-123 metaiodobenzylguanidine (123I-MIBG) and heart rate variability parameters has not been determined. This study determined the relationship between the change in myocardial uptake of 123I-MIBG and improvement in left ventricular function after treatment, to determine the usefulness of 123I-MIBG imaging to assess the effect of therapy on heart failure due to dilated cardiomyopathy (DCM). 123I-MIBG imaging and power spectral analysis of heart rate variability were performed before and after treatment in 17 patients with heart failure due to DCM. The following parameters were compared before and after treatment: New York Heart Association (NYHA) functional class, radiographic cardiothoracic ratio (CTR), blood pressure, echocardiographic data [left ventricular end-systolic (LVDs) and end-diastolic (LVDd) diameters, left ventricular ejection fraction (LVEF)], plasma concentrations of norepinephrine and epinephrine, heart rate variability power spectral analysis data [mean low frequency (MLF) and high frequency power (MHF)] and the myocardium to mediastinum activity ratio (MYO/M) obtained in early and late images, and washout rate calculated by anterior planar imaging of 123I-MIBG. The NYHA functional class, LVEF, LVDs, CTR, MLF and MHF improved after treatment. Early MYO/M and late MYO/M improved after treatment. The rate of increase in late MYO/M was positively correlated with the rate of improvement of LVEF after treatment. Furthermore, the late MYO/M was negatively correlated with MLF. Washout rate revealed no correlation with hemodynamic parameters. These findings suggest that late MYO/M is more useful than washout rate to assess the effect of treatment on heart failure due to DCM. Furthermore, the 123I-MIBG imaging and heart rate variability parameters are useful to assess the autonomic tone in DCM with heart failure.     

Single irradiation of the pituitary with a narrow beam of protons having 200 MeV of energy in generalized breast cancer

Eighteen patients with congestive cardiomyopathy were studied by echocardiography and cardiac catheterization. Patients with coronary disease on angiography or primary valvular disease were excluded. Six patients showed mild or no mitral regurgitation; in 12 others the degree of mitral regurgitation was moderate or severe. The echocardiographic features in these patients were: (1) a dilated left ventricle (LV), (2) normal LV wall thickness, (3) reduced LV posterior wall motion, and (4) reduced or absent systolic thickening of the interventricular septum (IVS). IVS motion was reduced in 10 patients, and appeared "normal" or increased in another eight, all of whom showed moderate or severe mitral regurgitation on angiography. It is concluded that an apparent normal or increased motion of the IVS with reduced or absent systolic thickening in congestive cardiomyopathy is evidence for coexistence of significant mitral regurgitation. Reduced or absent systolic thickening can distinguish these patients from those with segmental myocardial disease and normal septa or dilated LV's due to volume overload.     

An evaluation of the British Army spatial disorientation sortie in U.S. Army aviation

A 68-year-old female whose myocardial sympathetic function was severely damaged with multi-vessel vasospastic angina is presented. She had no signs of autonomic dysfunction or diabetes mellitus. Myocardial imaging with 123I-MIBG showed extremely diminished uptake, but 201TlCl and 123I-BMIPP SPECT images were almost normal. Coronary arteriography revealed no significant atherosclerotic stenosis, multivessel spasm was observed by provocation test using acetylcholine. The extremely diminished uptake of 123I-MIBG was slightly increased in response to medication and the subsequent improvement of the patient's condition. Markedly decreased uptake with 123I-MIBG myocardial scintigraphy was considered to be due to multi-vessel spastic angina. We believe that this method of imaging study is useful for evaluating the healing stage of myocardial sympathetic dysfunction.     

Parameters of dynamic and static iodine-123-MIBG cardiac imaging

Dynamic and static 123I-MIBG studies were used to investigate various parameters with regard to their usefulness in evaluating cardiac disorders. METHODS: Four patient groups and one control group were included in this study. Dynamic study was acquired immediately after injection at 1 frame/sec for 2 min and at 1 frame/6 sec for the next 30 min using a 64 x 64 matrix format. Static study consisted of planar images at the anterior and left anterior oblique 45 degrees views in a 512 x 512 matrix format for 1 min. The early and delayed planar images were acquired soon after dynamic acquisition and approximately 4 hr after injection, respectively. Net injection dose was calculated as the difference in syringe counts before and after injection. From the dynamic and static studies, the heart uptake ratios at 3 min and 30 min, early uptake ratio and delayed uptake ratio were calculated at various intervals. Early and delayed clearance rates, Ke and Kd, respectively were also determined. These parameters were compared and correlated with each other. RESULTS: Three-minute heart uptake ratios were significantly higher than early or delayed uptake ratios or uptake ratios at 30 min in all groups. All uptake ratios in hemodialysis patients were significantly higher than those in other groups. The Kd values in dilated cardiomyopathy, doxorubicin therapy and vasospastic angina patients were significantly higher than those in hemodialysis patients and normal controls. At least bi-exponential clearance patterns of MIBG from the heart were observed in all groups. CONCLUSION: Three-minute and delayed heart uptake ratios calculated from dynamic and static studies are helpful in elucidating the uptake at nonvesicular sites, which reflect the severity of sympathetic nervous system abnormalities in the heart.     

Impaired regional fatty acid uptake and systolic dysfunction in hypertrophied right ventricle

Little information is available regarding the determinants of systolic contractile function of the hypertrophied right ventricle (RV). The purpose of this study was to clarify the relationship between myocardial metabolism and contractile function in the hypertrophied RV due to pulmonary hypertension (PH). METHODS: Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-sestamibi (MIBI) SPECT were performed to calculate the RV-to-left ventricle (LV) tracer uptake ratio (RV/LV) in 21 patients with PH (6 with primary PH and 15 with chronic thromboembolic PH). The patients also underwent electron-beam CT to assess RV ejection function (RVEF) and percentage systolic wall thickening (%SWT) and right heart catheterization to measure mean pulmonary arterial pressure (mPAP). RESULTS: There were significant positive correlations between mPAP and MIBI-RV/LV (r = 0.89, p < 0.001) and between mPAP and BMIPP-RV/LV (r = 0.86, p < 0.001). However, 8 patients showed lower BMIPP-RV/LV than MIBI-RV/LV, indicating the impairment of myocardial fatty acid uptake in the RV. These patients had lower RVEF and %SWT compared to those with normal myocardial fatty acid uptake (RVEF = 28% +/- 10% compared to 40% +/- 9% and %SWT = 33% +/- 27% compared to 74% +/- 30%, respectively; p < 0.05 for both comparisons). Although mPAP did not differ between the groups, the RVEF-mPAP and %SWT-mPAP regression lines drawn from the patients with impaired myocardial fatty acid uptake were located below the lines from the patients with normal myocardial fatty acid uptake, suggesting disproportionately decreased RV myocardial contractility for a given mPAP in patients with impaired myocardial fatty acid uptake. The patients with the impaired fatty acid uptake in the RV had a significantly higher death rate (log-rank test, p < 0.05). CONCLUSION: The results from this preliminary study suggest that myocardial fatty acid uptake is impaired in the failing hypertrophied RV due to PH.     

Diastolic function parameters and atrial arrhythmias in patients with arterial hypertension

OBJECTIVE: To investigate in patients with arterial hypertension (HT) the extent of left ventricular (LV) hypertrophy and diastolic function in relation to atrial arrhythmias. PATIENTS AND METHODS: In 112 hypertensive patients (40 women, 72 men; mean age 50 +/- 6.6 years) with a mean systolic blood pressure for the cohort of 170 +/- 5 mmHg, their first invasive coronary angiography was performed between July 1995 and October 1997 because of angina pectoris and/or an abnormal stress electrocardiogram. After excluding coronary heart disease LV dimensions and diastolic function were measured by echocardiography; in 59 of the 112 patients LV hypertrophy was demonstrated. In addition, long-term blood pressure monitoring, exercise and long-term electrocardiography, late-potential analysis and measurement of heart rate variability were undertaken. The control group consisted of 51 patients without arterial hypertension after exclusion of coronary heart disease. RESULTS: Even in the hypertensive patients without LV hypertrophy diastolic LV function and ergometric exercise capacity were reduced. The risk of LV arrhythmias was significantly higher in patients with LV hypertrophy than those without and in the control group, as measured by the complexity of atrial arrhythmias (P < 0.001), the incidence of abnormal late potentials (P < 0.001) and reduction in heart rate variability (29.3 +/- 5.3 ms vs 47.8 +/- 12.1 ms vs 60.7 +/- 6.6 ms; P < 0.001). There were similar results regarding severe complex atrial arrhythmias (38.5 vs 15.0 vs 0%; P < 0.001). The incidence of atrial arrhythmias correlated with the LV diameter (r = 0.68, P < 0.001), LV morphological dimensions and diastolic function (isovolumetric relaxation time r = 0.44, P < 0.001) and the ratio of early to late diastolic inflow (r = 0.46; P < 0.001). CONCLUSIONS: Hypertensive patients have a higher risk of atrial and ventricular arrhythmias, depending on the degree of LV hypertrophy. But atrial arrhythmias, in contrary to ventricular arrhythmias, are also closely related to abnormalities in LV diastolic function.     

Mechanism of impaired left ventricular wall motion in the diabetic heart without coronary artery disease

OBJECTIVE: To elucidate whether impairment of the myocardial free fatty acid (FFA) metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease. RESEARCH DESIGN AND METHODS: We performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum. RESULTS: Nine patients with reduced wall motion documented by left ventriculography (LVG), (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 +/- 0.2, mean +/- SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 +/- 0.2, P < 0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P < 0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients. CONCLUSIONS: Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes.     

Scintigraphic assessment of silent myocardial ischaemia after early infarction using myocardial SPET imaging with 201Tl and 123I-MIBG

To test the hypothesis that myocardial sympathetic denervation reflects silent myocardial ischaemia early after infarction, 12 patients with myocardial infarction but without post-infarction angina pectoris underwent single photon emission tomography (SPET) at rest with 201Tl and 123I-metaiodobenzylguanidine (MIBG) shortly after and 3 months after infarction. Short-axis SPET images at the basal, mid-ventricular and apical portions of the left ventricle were selected, and each short-axis image was divided into eight segments. Tracer uptake in each of the 24 segments was scored using a 4-point scale. The total score in each segment was calculated as the defect score for each image, and the difference between the total defect score for the 201Tl and 123I-MIBG images was calculated as the delta defect score. All 12 patients underwent exercise stress 201Tl scintigraphy 1 month after infarction, and they were divided into two groups: those patients with (Group A, n = 7) and those patients without (Group B, n = 5) transient perfusion defects in the peri-infarcted region without chest pain. For the 123I-MIBG defect score, a marked reduction at 3 months was observed in Group A (24 +/- 12 vs 13 +/- 6; P < 0.01), whereas the defect score remained unchanged in Group B (25 +/- 7 vs 23 +/- 8; N.S.). The delta defect score was significantly reduced in Group A (10 +/- 5 vs 6 +/- 4; P < 0.05), whereas it remained unchanged in Group B. The 123I-MIBG defect score early after infarction was higher than the exercise-induced 201Tl defect score (24 +/- 12 vs 20 +/- 9; P < 0.01), whereas at 3 months post-infarction it was lower than the exercise-induced 201Tl defect score (13 +/- 6 vs 20 +/- 9; P < 0.05). Moreover, effort chest pain during daily activities was noted in 5 of the 7 (71%) patients in Group A within 3 months post-infarction. The results of this study suggest that viable but denervated myocardium (mismatched 123I-MIBG defects) is present in peri-infarcted regions, and that myocardial sensory nervous disturbance, which may co-exist with sympathetic nervous denervation, may induce silent myocardial ischaemia in patients with myocardial infarction.     

A case of hypertensive hypertrophy in which both regression of hypertrophy and improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG) myocardial imagings were observed after antihypertensive therapy

A case of hypertensive hypertrophy is described in which both regression of hypertrophy and improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG) myocardial imagings were seen after 7 months of antihypertensive therapy. A 58-year-old man was diagnosed as having essential hypertension and hypertensive hypertrophy. The patient was treated with antihypertensive drugs and showed regression of left ventricular hypertrophy on electrocardiograms and echocardiograms. MIBG observations made before and after antihypertensive therapy showed increased heart-to-mediastinum activity ratio and decreased cardiac washout ratio. Despite the many theories addressing the mechanisms of regression of left ventricular hypertrophy, the process is still unclear. In the present case, the improvement of cardiac sympathetic nervous dysfunction might have been related to the regression of left ventricular hypertrophy because the abnormality in MIBG images improved. MIBG, therefore, may be helpful in clarifying the mechanisms of the regression of hypertensive hypertrophy.     

Viability after myocardial infarction: can it be assessed within five minutes by low-dose dynamic iodine-123-iodophenylpentadecanoic acid imaging with a multicrystal gamma camera?

Although positron emission tomography (PET) assesses myocardial viability (V) accurately, a rapid, inexpensive substitute is needed. Therefore, the authors developed a low-dose (1 mCi) Iodine-123-Iodophenylpentadecanoic Acid (IPPA) myocardial viability scan requiring analysis of only the first three minutes of data acquired at rest with a standard multicrystal gamma camera. Twenty-one patients > 2 weeks after myocardial infarction (MI) (24 MIs, 10 anterior, 14 inferoposterior, 21 akinetic or dyskinetic) had cardiac catheterization and resting IPPA imaging. V was determined by either transmural myocardial biopsy during coronary bypass surgery (12 patients, 14 MIs) or reinjection tomographic thallium scan (9 patients, 10 MIs), and 50% of MIs were viable. The IPPA variables analyzed were: time to initial left ventricular (LV) uptake in the region of interest (ROI), the ratio of three-minute uptake in the ROI to three-minute LV uptake, three-minute clearing (counts/pixel) in the ROI (decrease in IPPA after initial uptake), and three-minute accumulation (increase in IPPA after initial uptake) in the ROI. Rules for detecting V were generated and applied to 10 healthy volunteers to determine normalcy. While three-minute uptake in nonviable MIs was only 67% of volunteers (P < 0.0001) and 75% of viable MIs, uptake alone identified only 50% of viable MIs and 75% of nonviable MIs. IPPA clearing, however, was > or = 13.5 counts/pixel in 10/12 (83%) of viable MIs, and IPPA accumulation > or = 6.75 counts/pixel identified one more viable MI, for a sensitivity for V of 11/12 (92%), with a specificity of 11/12 (92%), and a 100% normalcy rate. The authors conclude low-dose IPPA (five-minute acquisition with analysis of the first three minutes of data) has potential for providing rapid, inexpensive V data after MI. Since newer multicrystal cameras are mobile, IPPA scans can be done in emergency rooms or coronary care units generating information that might be useful in decisions regarding thrombolysis, angioplasty, or bypass surgery.     

Sympathetic re-innervation after heart transplantation: dual-isotope neurotransmitter scintigraphy, norepinephrine content and histological examination

Cardiac transplantation entails surgical disruption of the sympathetic nerve fibres from their somata, resulting in sympathetic denervation. In order to investigate the occurrence of sympathetic re-innervation, neurotransmitter scintigraphy using the norepinephrine analogue iodine-123 metaiodobenzylguanidine (MIBG) was performed in 15 patients 2-69 months after transplantation. In addition, norepinephrine content and immunohistochemical reactions of antibodies to Schwann cell-associated S100 protein, to neuron-specific enolase (NSE) and to norepinephrine were examined in 34 endomyocardial biopsies of 29 patients 1-88 months after transplantation. Anterobasal 123I-MIBG uptake indicating partial sympathetic re-innervation could be shown in 40% of the scintigraphically investigated patients 37-69 months after transplantation. In immunohistochemical studies 83% of the patients investigated 1-72 months after transplantation showed nerve fibres in their biopsies but not positive reaction to norepinephrine. Significant norepinephrine content indicating re-innervation could not be detected in any biopsy. It was concluded that in spite of the lack of norepinephrine content there seemed to be immunohistological and scintigraphic evidence of sympathetic re-innervation. An explanation for this contradictory finding may be the reduced or missing norepinephrine storage ability compared to the restored uptake ability of regenerated sympathetic nerve fibres.     

111In-pentetreotide scintigraphy is superior to 123I-MIBG scintigraphy in the diagnosis and location of chemodectoma

Chemodectomas, or glomus tumours, are unusual head and neck paragangliomas. A non-invasive imaging technique, 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy, has long been used for the diagnosis of all types of paraganglioma. The aim of this study was to evaluate and compare classic 123I-MIBG scintigraphy with the more recent 111In-pentetreotide scintigraphy in the diagnosis and location of chemodectomas. We performed 123I-MIBG and 111In-pentetreotide scintigraphy in eight patients (7 females, 1 male) with histologically or radiologically confirmed chemodectomas (five carotid body and three jugulotympanic chemodectomas). 123I-MIBG uptake was visualized in four patients on planar views and SPET images (sensitivity 50%); uptake was low in three patients. Using 111In-pentetreotide scintigraphy, all chemodectomas in eight patients were visualized (sensitivity 100%) and 111In-pentetreotide uptake was high in all cases. In conclusion, our results indicate that 111In-pentetreotide scintigraphy is superior to 123I-MIBG scintigraphy in the diagnosis and location of chemodectomas. In-pentetreotide or 123I-MIBG uptake suggests a neuroendocrine origin, providing important functional information in the diagnosis of chemodectomas. Moreover, 111In-pentetreotide scintigraphy permits a good classification of patients with or without somatostatin receptors in the chemodectoma in the application of pharmacological therapy with somatostatin analogues to inoperable tumours. The main therapeutic action of cold somatostatin analogues is to inhibit hormonal hypersecretion in different neuroendocrine tumours. In chemodectomas, however, the most important effect of somatostatin analogues is to reduce tumour volume or inhibit growth progression.