Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus.

The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure >/=140 and/or diastolic blood pressure >/=90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55+/-11 vs 63+/-12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120+/-12 vs 145+/-16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1. 81+/-0.29 vs 2.27+/-0.20, respectively, P<0.01). During the follow-up period (18+/- 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%+/-16.87% vs 12.89%+/-11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant statistical differences between the control group and non-survivors in terms of age (54+/-11 vs 73+/-11 years, respectively, P<0.01), H/M ratio (2. 27+/- 0.20 vs 1.64+/-0.36, respectively, P<0.01) and %WR (12. 89%+/-11.94% vs 42.52%+/-22.39%, respectively, P<0.01). In conclusion, cardiac sympathetic denervation using MIBG scintigraphy observed in hypertensive NIDDM patients, and was more profound in non-survivors. MIBG scintigraphy proved useful for the evaluation of NIDDM patients with new onset hypertension, and it was found that NIDDM patients with abnormalities on MIBG scintigraphy needed to be observe carefully.     

Cardiac adrenergic denervation in patients with non-Q-wave versus Q-wave myocardial infarction

In spite of smaller infarct size and better preserved left ventricular function the long-term prognosis after a non-Q-wave infarction is not better than after a Q-wave infarction. In fact, the risk of sudden cardiac death is higher in patients with a non-Q-wave infarction than in patients with a Q-wave infarction. One possible reason for postinfarction arrhythmias is cardiac adrenergic denervation resulting from myocardial infarction. In this study we compared cardiac adrenergic innervation after non-Q-wave and Q-wave infarctions. Single-photon emission tomography using iodine-123 metaiodobentzylguanidine (MIBG) and technetium-99m sestamibi (MIBI) tracers were conducted in order to compare cardiac adrenergic denervation and myocardial perfusion in 12 patients with a non-Q-wave infarction and 15 patients with a Q-wave infarction. MIBG and MIBI defects were determined as regional uptake ≤30% of maximal myocardial activity. The size of MIBI defects calculated as a percentage of left ventricular mass was significantly smaller in patients with a non-Q-wave infarction than in patients with a Q-wave infarction (4%±3% vs 9%±7%, P<0.05, respectively). According to the maximal serum creatine kinase activity, less myocardium was damaged in patients with a non-Q-wave infarction than in patients with a Q-wave infarction (502±436 IU/l vs 1878± 1265 IU/l, P<0.001). In spite of this, the extent of MIBG defects was similar in patients with a non-Q-wave and patients with a Q-wave infarction (21%±18% vs 23%± 12%, respectively). In addition, the size of MIBG defect correlated with the infarct size (maximal creatine kinase activity) (r=0.52, P<0.05) after a Q-wave infarction but not after a non-Q-wave infarction. In conclusion, despite a smaller infarct size in non-Q-wave infarct patients, the extent of cardiac adrenergic denervation was similar in patients with a non-Q-wave and patients with a Q-wave infarction. In addition, the extent of cardiac adrenergic denervation was related to the infarct size in patients with a Q-wave infarction but not in patients with a non-Q-wave infarction. Received 19 January 2000 and in revised form 24 March 2000     

Impact of exercise rehabilitation on cardiac neuronal function in heart failure: an iodine-123 metaiodobenzylguanidine scintigraphy study

Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36–66 years) with stable chronic heart failure of NYHA class II–III and an initial resting radionuclide left ventricular ejection fraction (LVEF) <50% were enrolled in the study. Patients underwent progressive, supervised endurance training (treadmill test, Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a cardiac rehabilitation referral centre in order to measure exercise parameters. Planar ¹²³I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801±428 vs 1229±245 kpm·min^–1, P = 0.001), exercise duration (504±190 vs 649±125 s, P = 0.02), and myocardial MIBG uptake (135%±19% vs 156%±25%, P = 0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%±9% vs 21%±10%, p = NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. Received 23 September and in revised form 24 November 1997     

Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific

The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson’s disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63±9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61±0.29) was significantly lower than that in the control group (2.24±0.14, P<0.01), P-nism (2.15±0.31, P<0.01), MSA (2.08±0.31, P<0.05) and PSP (2.30±0.24, P<0.01). The delayed H/M ratio in PD (1.47±0.34) was also significantly lower than that in the control group (2.37±0.14, P<0.01), P-nism (2.13±0.38, P<0.01), PSP (2.36±0.36, P<0.01) and MSA (2.17±0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%±8.0% vs 11%±4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA were significantly lower than those in the control group (P<0.05). In conclusion: In patients with PD without autonomic failure, only cardiac MIBG uptake was severely reduced in the earliest phase of the disease (stage I). Parkinsonian syndromes other than PD did not demonstrate significant reduction in MIBG uptake in any organs except for the lower legs in MSA. In patients with PD without autonomic failure, reduction in MIBG uptake occurs selectively in the heart; this is considered to be a specific finding for PD and useful for the differential diagnosis of the parkinsonian syndromes. Received 13 September and in revised form 29 December 1999     

Effect of spinal cord stimulation on cardiac adrenergic nerve function in patients with cardiac syndrome X

Background. In patients with cardiac syndrome X (CSX) who present with refractory angina episodes, spinal cord stimulation (SCS) has beneficial effects. The mechanisms of SCS, however, remain speculative. We assessed the effects of SCS on cardiac sympathetic function in these patients. Methods and Results. We studied 11 CSX patients treated by SCS for refractory angina (mean age, 60±9 years; 5 men and 6 women), both during SCS therapy (SCS-ON) and after withdrawal of SCS therapy (SCS-OFF), using a randomized crossover design. Planar and single photon emission computed tomography iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and technetium 99m sestamibi (MIBI) bicycle exercise stress testing were performed at the end of each period. Compared with 10 healthy control subjects, CSX patients showed a lower heart-mediastinum ratio for MIBG uptake (2.19±0.3 vs 1.69±0.3,P=.001) and a higher cardiac MIBG uptake score (4.0±2.5 vs 19.7±27,P=.08). There were no differences in CSX patients during the SCS-ON and SCS-OFF phases of the study in heart-mediastinum ratio (1.74±0.3 vs 1.69±0.3,P=.13), cardiac washout rate of MIBG (42.9%±14% vs 43.3%±14%,P=.08), or MIBG defect score (18.7±25 vs 19.7±27,P=.22). Reversible perfusion defects during the SCS-OFF phase were detected in 8 patients; an improvement in perfusion defects was observed in 2 patients (25%) during the SCS-ON phase. Conclusions. Our data confirm the presence of abnormal cardiac adrenergic nerve function in CSX patients. SCS was unable to result in significant improvement of cardiac MIBG uptake abnormalities, suggesting that its therapeutic effects are unlikely to be mediated by modulation of cardiac adrenergic nerve activity.     

A novel clinical indicator using Tc-99m sestamibi for evaluating cardiac mitochondrial function in patients with cardiomyopathies

Background  Technetium 99m sestamibi (MIBI) is a technetium-labeled myocardial perfusion agent that is taken up by the myocardial cell in proportion to myocardial regional blood flow and remains fixed in the myocardial cell over a long period of time. Previous studies have suggested that MIBI shows very slow myocardial clearance after its initial uptake in an animal model, which is related to mitochondrial function. This study was designed to test the hypothesis that MIBI washout can be used to evaluate the severity of congestive heart failure in comparison to other clinical parameters in patients with cardiomyopathies. Methods and Results  After administration of MIBI, 61 patients with nonischemic congestive heart failure (49 with dilated cardiomyopathy and 12 with other cardiomyopathies) and 7 normal control subjects were examined by electrocardiography-gated myocardial perfusion single photon emission computed tomography and planar data acquisition in the early and delayed phases (interval of 3 hours). Myocardial MIBI washout rates were calculated from the early and delayed planar images. Left ventricular function (systolic and diastolic) was analyzed by use of QGS data. Plasma levels of B-type natriuretic peptide and iodine 123 metaiodobenzylguanidine (MIBG) parameters were also measured. Patients were followed up for a mean of 12 months (range, 1–19 months). As the severity of the New York Heart Association (NYHA) functional class advanced, the washout rate of MIBI increased (21.6%±2.4% in those with NYHA class I [n=23], 28%±4% in those with NYHA class II [n=27], and 35%±5% in those with NYHA class III [n=10]; P<.05, analysis of variance). The washout rate of MIBI was positively correlated with the level of B-type natriuretic peptide (r=0.31, P<.05), and-diastolic volume (r=0.396, P<.01). and end-systolic volume (r=0.496, P<.01) and was negatively correlated with left ventricular ejection fraction (r=0.523, P<.01), peak filling rate (r=0.444, P<.01), and first-third ejection fraction (r=0.414, P<.01). The parameters of MIBG scintigraphy were calculated as the heart-mediastinum count ratio (1.9±3) and washout rate (38%±4%). We found a significant relationship between the washout rate of MIBI and the heart-mediastinum count ratio of MIBG (r=0.51, P<.01). Patients with a higher washout rate of MIBI had a higher cardiac event rate (≥28%) than those with a lower washout rate (<28%) (P<.05). Conclusions  The myocardial washout rate of MIBI is thought to be a novel marker for the diagnosis of myocardial damage or dysfunction, providing prognostic information in patients with congestive heart failure.     

Clinical evaluation of no-carrier-added meta-[123I]iodobenzylguanidine for myocardial scintigraphy

In clinical and research studies, images obtained using carrier-added meta-[¹²³I]iodobenzylguanidine (c.a. [¹²³I]MIBG) have shown quite variable quality, with varying levels of uptake in lung, liver and mediastinum; this is a significant problem for quantification of the myocardial uptake by means of region ratios. First experimental and preliminary human data in respect of no-carrier-added (n.c.a.) [¹²³I]MIBG are indicative of improved imaging quality. The aim of the present study was to evaluate the clinical value of myocardial scintigraphy with n.c.a. [¹²³I]MIBG in patients with tachyarrhythmias. The study population comprised 24 patients with tachyarrhythmogenic diseases routinely studied by cardiac single-photon emission tomography (SPET) with [¹²³I]MIBG. Twelve of the 24 patients were studied with c.a. [¹²³I]MIBG (seven females and five males; mean age 42±13 years, range 20–60 years), whereas the other 12 were studied with n.c.a. [¹²³I]MIBG (ten females, two males; mean age 41±11 years, range 18–60 years, P=NS). For quantification of the specific uptake in the different organs, count ratios were calculated on SPET images acquired 4 h p.i. Visual analysis of all [¹²³I]MIBG scans showed improved image quality (improved contrast between heart and neighbouring organs) in n.c.a. studies as compared with c.a. studies. A significantly higher heart/left atrial blood ratio was found in the n.c.a. studies as compared with the c.a. studies (10.3±3.2 vs 5.3±1.3, P=0.0003); furthermore, significantly higher heart/lung and heart/liver ratios (2.5±0.6 vs 1.5±0.3, P=0.0002, and 0.8±0.2 vs 0.6±0.1, P=0.0006, respectively) were obtained in the c.a. studies, whereas lung/left atrial blood and liver/left atrial blood ratios showed no significant differences (4.2±1.3 vs 3.6±1.1, P=0.39, and 13.7±5.2 vs 9.6±2.2, P=0.21, respectively). In conclusion, the use of n.c.a. [¹²³I]MIBG yields a significantly higher myocardial uptake associated with improvement in contrast between the heart and neighbouring organs and is therefore superior to the commercially available c.a. [¹²³I]MIBG for use in clinical and research studies of the myocardial presynaptic sympathetic nervous system. Furthermore, our data indicate that for quantification the use of a left atrial blood reference region of interest, which is only available on SPET studies, is to be recommended. Received 22 September and in revised form 2 November 1999     

Potential of iodine-123 metaiodobenzylguanidine single-photon emission tomography to detect abnormal functional status of the pulmonary neuroadrenergic system in irradiated lung

The potential of iodine-123 metaiodobenzylguanidine (MIBG) to detect functional abnormalities of the pulmonary neuroadrenergic system (PNS) in irradiated lung areas (ILAS) was preliminarily explored using single-photon emission tomography (SPET). The subjects included five healthy subjects and a total of 31 patients with peripheral-type lung cancer treated by radiation; 15 patients (group A) had received a dose of less than 36 Gy (mean ± SD: 28.2 ±6.2 Gy), and 16 patients (group B) had received a higher dose (mean ± SD: 51.2 ± 3.5 Gy) at the time of examination. MIBG SPET scans aquired 15 min and 3 h after injection were used to measure the MIBG uptake ratio (count ratio of the ILA to the contralateral non-ILA) and the clearance rate [percentage of (early counts – delayed counts)/early counts] from the ILAs without noticeable abnormal opacities on chest computed tomography scan. Lung perfusion changes were also assessed by technetium-99m macroaggregated albumin SPET. By contrast to the homogeneous MIBG uptake in the lungs of the healthy subjects, MIBG uptake was folcally decreased in correspondence with the ILAs in all patients, including 11 patients (73.3%) of group A with relatively preserved lung perfusion. The reduction MIBG uptake was significant (P<0.0001), and the MIBG clearance rate from the ILAs was also significantly faster than the clearance rates from the normal lungs and contralateral non-ILAs (both P<0.01). Group B patients showed significantly lower MIBG uptake and faster clearance from the ILAs than group A patients (P<0.001 and P<0.05, respectively), although there was no significant difference in the clearance from the non-ILAs. Overall, MIBG uptake/clearance from the ILAs correlated significantly with the radiation dose in the 31 patients (r = –0.656; P<0.0001 and r = 0.387; P<0.05, respectively). Perfusion changes were inversely correlated with the clearance from the ILAs (r = –0.432, P<0.05), but did not correlate with MIBG uptake. These preliminary results suggest that MIBG may have the potential to be a marker of abnormal functional status of the PNS produced by irradiation and may facilitate investigation of irradiation lung injury independently of morphological or lung perfusion changes. Received 11 December 1998 and in revised form 10 February 1999     

Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42±12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36±0.26 versus 1.98±0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac sympathetic denervation in FAP patients. Received 19 October 1998 and in revised form 6 January 1999     

Proximal femur bone marrow blood perfusion indices are reduced in hypertensive rats: A dynamic contrast‐enhanced MRI study

Purpose:

To investigate the differences in proximal femoral bone marrow blood perfusion indices between hypertensive and normotensive rats using perfusion magnetic resonance imaging (MRI).

Materials and Methods:

Six‐month‐old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were used (12 of each). Dynamic contrast‐enhanced MRI of the right hip was performed after bolus injection of Gd‐DOTA administered through a tail vein cannula. In all, 800 images were acquired at 0.6 sec/image. Regions of interest (ROIs) were drawn comprising the medullary component of proximal femoral shaft and femoral head. MRI maximum enhancement (E^max) and enhancement slope (E^slope) were analyzed.

Results:

The E^max and E^slope of proximal femoral shaft and femoral head of SHR were significantly lower than those of WKY (E^max: 107.4 ± 18.2% vs. 130.6 ± 21.5%, P = 0.009, and 76.0 ± 12.5% vs. 97.9 ± 6.9%, P < 0.001, respectively; E^slope: 3.01 ± 0.63%/sec vs. 3.75 ± 0.74%/sec, P = 0.016, and 1.95 ± 0.33%/sec vs. 2.28 ± 0.28%/sec, P = 0.012, respectively). The E^max and E^slope of femoral head were significantly lower than those of proximal femoral shaft in both SHR and WKY (P < 0.001). In both SHR and WKY, proximal femoral shaft and femoral head had a rather different contrast enhancement pattern.

Conclusion:

Proximal femoral shaft and femoral head bone marrow blood perfusion indices were significantly lower in hypertensive rats than in normotensive rats. Femoral head bone marrow was less perfused than proximal femoral shaft in both rats. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.     

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 epalrestat (ARI group) in three divided 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. Received 16 May and in revised form 30 July 1998     

Age-related decrease in cardiopulmonary adrenergic neuronal function in children as assessed by I-123 metaiodobenzylguanidine imaging

Background  Radioiodinated metaiodobenzylguanidine (MIBG) imaging has been used to evaluate adrenergic nerve activity in different organs Cardiac and pulmonary MIBG uptake is important in predicting the prognosis of certain cardiopulmonary diseases. It has been reported that cardiac MIBG uptake decreases with age and is significantly lower in the elderly. However, there has been no systemic study on age-related changes in cardiac and pulmonary MIBG uptake in children. This study was undertaken to determine the changes in MIBG uptake in the developing heart and lung in children and adolescents. Methods and Results  MIBG scans of 44 children (16 female and 28 male; age range, 2 months to 19 years) without abnormal uptake were selected from a large pool of patients with whole-body MIBG imaging performed for evaluation of neuroblastoma. All of the selected subjects had a normal physiologic distribution of MIBG and no history of heart or lung diseases. The patients were divided into 4 groups by age: group 1, 0 to 24 months; group 2, 25 to 48 months; group 3, 49 to 72 months; and group 4, 73 months or greater. Cardiac and pulmonary MIBG uptake values (expressed as heart-to-mediastinum [H/M] ratio and lung-to-mediastinum [L/M] ratio, respectively) were determined and compared among the 4 groups. H/M and L/M ratios were noted to decrease with age. The mean H/M and L/M ratios were in group 1, 4.13±0.66 and 1.53±0.18, respectively; in group 2, 3.46±0.71 and 1.26±0.18, respectively; in group 3, 3.19±0.94 and 1.13±0.17, respectively; and in group 4, 2.84±0.48 and 1.14±0.14, respectively. There was a significant inverse correlation between H/M ratio and age (r=0.711, P<.001) as well as between L/M ratio and age (r=0.718, P<.001). Conclusion  Cardiac and pulmonary MIBG uptake is inversely related to age in children.     

Endothelial dysfunction in patients with antiphospholipid syndrome assessed with positron emission tomography

Background  There is limited knowledge about endothelial dysfunction in patients with primary antiphospholipid syndrome (PAPS). The purpose of this study was to evaluate endothelial function in patients with PAPS assessed by positron emission tomography. Methods and Results  A 3-phase protocol—rest, cold pressor test (CPT), and adenosine positron emission tomography with nitrogen 13 ammonia—was used in 18 patients with PAPS and 18 healthy volunteers (HVs). Myocardial blood flow (MBF) was measured in each phase, with calculation of the endothelial-dependent vasodilation index, the increase in the MBF in response to CPT, and the myocardial flow reserve. An important trend was found in the myocardial flow reserve (2.76±1.04 in PAPS group vs 3.27±0.72 in HV group,P>.05), in the endothelial-dependent vasodilation index (1.19±0.31 in PAPS group vs 1.55±0.37 in HV group,P<.05), and in the percent change in the MBF in response to CPT (from rest) (19%±31% in PAPS group vs 55%±37% in HV group,P<.05). Conclusion  The CPT results obtained in this study showed that the PAPS patients studied have endothelial dysfunction.     

Influence of the postexercise acquisition delay on the detection of functional abnormalities in sestamibi-gated SPECT

Background  Gated single photon emission computed tomography (SPECT) identifies functional changes produced by ischemia, but the influence of acquisition delay on their detection is not established. Methods and Results  In 80 patients with known or suspected coronary artery disease, gated SPECT was acquired twice: first, less than 30 minutes after peak exercise (stress 1), and second, more than 45 minutes after peak exercise (stress 2). End-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were compared with perfusion. The relationship between the ΔEF (stress EF — resting EF) and the summed difference score (SDS) was −0.443 (P<.0001) for stress 1 and −0.416 (P<.0001) for stress 2. In stress 2. In stress 1, EF increased in patients without inducible ischemia (SDS=0) (57%±10% vs 54%±9% at rest, P <.02) and decreased in those with an SDS of 1 or greater (53%±10.8% vs 55%±9.6% at rest, P <.05). In stress 2, EF was unchanged in patients without ischemia (55.8%±9.7%, P=.06) and decreased in the other patients (52.8%±10.2%, P<.01). In patients without ischemia, both the EDV and ESV decreased significantly in stress 1 and were unchanged in stress 2. In patients with an SDS of 1 or greater, the EDV remained unchanged and the ESV minimally decreased in stress 1, whereas both volumes clearly and significantly increased in stress 2. Conclusions  The early acquisition of postexercise gated SPECT is slightly more effective in detecting ischemia-related functional changes; however, a delayed acquisition within 60 minutes still permits the detection of functional abnormalities in most patients.     

Evaluation of the endothelial function in hypertensive patients with 13N-ammonia PET

Background

Essential hypertension is one of the main risk factors for the development of coronary artery disease (CAD). Hypertension causes endothelial dysfunction which is considered an early sign for the development of CAD. Positron emission tomography is a non-invasive imaging technique that measures myocardial blood flow (MBF), allowing us to identify patients with endothelial dysfunction.

Methods and Results

19 patients without comorbidities recently diagnosed hypertensive, as well as 21 healthy volunteers were studied. A three-phase (rest, cold pressor test, and adenosine-induced hyperemia) ¹³N-ammonia PET was performed, and MBF was measured. Endothelial-Dependent Vasodilation Index, ??MBF, and coronary flow reserve (CFR) were calculated for each patient. Hypertensive patients had a significantly higher systolic and diastolic blood pressures compared with the control group (134.6?±?11.7/86.4?±?10.6?mm?Hg and 106.0?±?11.8/71.4?±?6.6?mm?Hg, respectively, P?<?.001). The ENDEVI (1.28?±?0.26 vs 1.79?±?0.30, P?<?.001), the ??MBF (0.81?±?0.50 vs 0.25?±?0.21, P?<?.001) and the CFR (2.18?±?0.88 vs 3.17?±?0.68, P?=?.001) were significantly lower in the hypertensive patients compared to the control group, 84% of the former group had endothelial dysfunction i.e., ENDEVI?<?1.5 and 58% had vasomotor abnormalities, i.e., CFR?<?2.5.

Conclusions

In this study, we showed that recently diagnosed hypertensive patients have coronary endothelial dysfunction and vasomotor disturbances which are early signs for the development of CAD.     

MRI evaluation of right ventricular pressure overload in chronic obstructive pulmonary disease

In chronic obstructive pulmonary disease (COPD), the development of pulmonary hypertension is common. This study was performed to assess the signs of right ventricular (RV) pressure overload and RV failure in COPD. In 8 COPD patients without primary cardiac disease, RV wall thickness, mass, and end-diastolic volume were measured by cardiac-triggered cine MRI. MR phase-contrast velocity quantification was used to measure stroke volume and the patterns of flow into and out of the RV. Data of patients were tested versus those of a control group matched for age (n = 8). Results showed that the RV wall thickness was increased (.6 ± 0.1 vs 0.4 ± 0.1 cm, P < .001). RV mass was increased (67 ± 11 vs 57 ± 5 g, P < .005). RV stroke volume was decreased (57 ± 13 vs 71 ± 13 ml, P < .01), but RV ejection fraction was not different. In the main pulmonary artery flow, the quotient of acceleration time divided by ejection time was decreased (33 ± 5% vs 38 ± 4%, P < .05), which is indicative of pulmonary hypertension. In conclusion, this MRI protocol provides a tool to assess the effects of RV pressure overload in COPD before heart failure has become manifest.     

Similar effect of revascularization on technetium-99msestamibi and 15-(p-iodophenyl)pentadecanoic acid uptake in myocardial infarction patients

To study its usefulness as a tracer for assessment of the perfusion and viability of myocardium, 15-(p-iodophenyl)pentadecanoic acid (IPPA) was compared with technetium-99m sestamibi (MIBI). Dual-tracer single-photon emission tomography rest imaging was performed no more than 2 months before and 3 months after coronary artery bypass grafting in 28 patients with previous anterior (n=13) or inferior (n=15) infarction. The size of MIBI and IPPA defects decreased from 14%±12% and 13%±9% to 10%±11% and 9%±7%, respectively (P<0.001 for both). The MIBI uptake increased in the infarct zones from 35%±11% to 43%±8% (P<0.001), and in the peri-infarct zones from 50%±11% to 55%±10% (P<0.05). The IPPA uptake increased in the infarct zones from 37%±11% to 44%±13% (P<0.001), and in the peri-infarct zones from 51%±11% to 57%±12% (P<0.05). In nine patients with improved regional echocardiographic wall motion score after bypass surgery, the pre-operative uptake values of both MIBI and IPPA in the infarct and peri-infarct zones were on average slightly but not significantly higher than in 19 patients with no observed improvement in regional wall motion score. In patients with improved regional wall motion, the MIBI scans and the IPPA scans showed (non-significant) decreases in defect size and increases in infarct and peri-infarct zone uptake after bypass surgery. Similar (in some cases significant) changes were observed in the patients without improvement in wall motion. Thus IPPA and MIBI provided similar information about perfusion and viability in pre- and postoperative evaluation of patients with clinically evident myocardial infarction and with normal global ejection fraction. Regardless of the tracer used, the resolution capability of the dual-tracer method with a rest imaging protocol was not sufficient to differentiate viable from non-viable infarction defects in unselected individual patients with a normal ejection fraction. Received 5 March and in revised form 5 May 1999     

Abnormal blood-pressure response to exercise and oxygen consumption in patients with hypertrophic cardiomyopathy

Background Abnormal blood-pressure response during exercise occurs in about one third of patients with hypertrophic cardiomyopathy (HCM), and it has been associated with a high risk of sudden cardiac death. We assessed the hemodynamics of exercise in HCM patients with abnormal blood-pressure response by using ambulatory radionuclide monitoring (VEST) of left-ventricular (LV) function, and exercise tolerance by oxygen consumption. Methods Twenty-two HCM patients uderwent treadmill exercise during VEST monitoring. A cardiopulmonary exercise test was performed a few days after. The VEST data were averaged for 1 minute. Stroke volume, cardiac output, and systemic vascular resistance were expressed as percent of baseline. Exercise tolerance was assessed as maximal oxygen consumption. Results In eight HCM patients (36%) with an abnormal blood-pressure response, endsystolic volume increased more (52%±21% vs 31%±28%, P=.012), and the ejection fraction (−31%±17% vs−14%±22%, P=.029) and stroke volume (−21%±21% vs 3%±28%, P=.026) fell more, than in patients with normal response. Cardiac output increased less in the former patients (49%±44% vs 94%±44%, P=.012). Systemic vascular resistance decreased similarly, irrespective of blood-pressure response (−28%±26% vs −34%±26%. P=N.S.). Percent of maximal predicted oxygen consumption was lower in HCM patients with an abnormal blood-pressure response (63%±11% vs 78%±15%, P=.025). Conclusions In HCM patients, abnormal blood-pressure response was associated with exercise-induced LV systolic dysfunction and impairment in oxygen consumption. This may cause hemodynamic instability, associated with a high risk of sudden cardiac death.     

Use of <Superscript>123</Superscript>I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using ¹²³I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1–168 months) with DCM and left ventricular dysfunction underwent ¹²³I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20–75 MBq of ¹²³I-MIBG. Cardiac neuronal uptake of ¹²³I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality.     

Comparison of flow capacities of arterial and venous grafts for coronary artery bypass grafting: evaluation with exercise thallium-201 single-photon emission tomography

Stress thallium-201 tomography was performed to compare the flow capacities of arterial and saphenous vein grafts in patients with coronary artery bypass grafting (CABG). One hundred and seven consecutive patients (95 male and 12 female; mean age 58±9.1 years) underwent exercise-redistribution ²⁰¹Tl myocardial single-photon emission tomography 4–5 weeks after CABG. When a reversible perfusion defect was present in the area covered by a patent bypass graft, the flow capacity of the graft was defined as insufficient. Of all 285 grafts, 211 were considered as complete bypass. Reversible perfusion defects were present in 29 (27%) of 108 myocardial areas supplied by patent arterial grafts but in only 5 (5%) of 103 myocardial areas supplied by patent saphenous vein grafts (P<0.0001). In the LAD area reversible defects were observed in 22 of 82 areas covered by arterial grafts, in contrast to only 1 of 29 areas covered by venous grafts (P<0.01); in the RCA area reversible defects were observed in 7 of 17 and 4 of 41 areas respectively (P<0.01). There was no difference between the native coronary artery stenosis bypassed by patent arterial and venous grafts (88%±12% vs 86%±14% respectively, P=0.27). In conclusion, flow capacities during peak myocardial demand were more frequently insufficient in arterial bypass grafts than in saphenous vein grafts. Received 23 May and in revised form 7 August 1997