Kevin C. Allman

Myocardial glucose uptake in patients with insulin-dependent diabetes mellitus assessed quantitatively by dynamic positron emission tomography.

BackgroundAnimal studies have demonstrated reduced myocardial glucose utilization in the diabetic heart, suggesting abnormalities in glucose transport. This study was designed to evaluate myocardial glucose uptake as assessed by 2-fluoro-(fluorine-18)2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in patients with insulin-dependent diabetes mellitus (IDDM) under standardized metabolic conditions. Methods and ResultsA hyperinsulinemic-euglycemic clamp technique was used during PET data acquisition in nine healthy male volunteers and seven young male patients with a history ofIDDM for less than 5 years. Oxidative metabolism was assessed with C-11 acetate, and glucose uptake was quantitatively measured with FDG using Patlak graphic analysis. Hemodynamic data and C-11 acetate kinetics were comparable. Myocardial glucose uptake averaged 0.44 ± 0.12, umol g−1 minm in normal subjects and 0.43 ± 0.16, mol· g−1. min-1 in patients with IDDM (P=NS). Blood tracer clearance was also similar in both groups as determined by the ratio of peak blood tracer activity to the activity at 55 to 60 minutes after tracer injection. F-18 activity ratio between myocardium and blood pool averaged 7.2 ± 3.4 in the normal heart and 7.5 ± 3.0 in the diabetic heart (P=NS). ConclusionThese data indicate that metabolic standardization and supplementation with insulin in young patients with IDDM is associated with myocardial glucose uptake similar to that observed in the normal heart. Chronic therapy with insulin may prevent the metabolic abnormalities observed in diabetic animal models.

Positron emission tomography detects evidence of viability in rest technetium-99m sestamibi defects.

OBJECTIVES The purpose of this study was to determine the relative value of single-photon emission computed tomographic (SPECT) imaging at rest using technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi) with positron emission tomography for detection of viable myocardium. BACKGROUND Recent studies comparing positron emission tomography and thallium-201 reinjection with rest technetium-99m sestamibi imaging have suggested that the latter technique underestimates myocardial viability. METHODS Twenty patients with a previous myocardial infarction underwent rest technetium-99m sestamibi imaging and positron emission tomography using fluorine (F)-18 deoxyglucose and nitrogen (N)-13 ammonia. In each patient, circumferential profile analysis was used to determine technetium-99m sestamibi, F-18 deoxyglucose and N-13 ammonia activity (expressed as percent of peak activity) in nine cardiac segments and in the perfusion defect defined by the area having technetium-99m sestamibi activity < 60%. Technetium-99m sestamibi defects were graded as moderate (50% to 59% of peak activity) and severe (< 50% of peak activity). Estimates of perfusion defect size were compared between technetium-99m sestamibi and N-13 ammonia. RESULTS Sixteen (53%) of 30 segments with moderate defects and 16 (47%) of 34 segments with severe defects had > or = 60% F-18 deoxyglucose activity considered indicative of viability. Fluorine-18 deoxyglucose evidence of viability was still present in 50% of segments with technetium-99m sestamibi activity < 40%. There was no significant difference in the mean (+/- SD) technetium-99m sestamibi activity in segments with viable (40 +/- 7%) and nonviable segments (49 +/- 7%, p = 0.84). Of the 18 patients who had adequate F-18 deoxyglucose studies, the area of the technetium-99m sestamibi defect was viable in 5 (28%). In 16 patients (80%), perfusion defect size determined by technetium-99m sestamibi exceeded that measured by N-13 ammonia. The difference in defect size between technetium-99m sestamibi and N-13 ammonia was significantly greater in patients with viable (21 +/- 9%) versus nonviable segments (7 +/- 9%, p = 0.007). CONCLUSIONS Moderate and severe rest technetium-99m sestamibi defects frequently have metabolic evidence of viability. Technetium-99m sestamibi SPECT yields larger perfusion defects than does N-13 ammonia positron emission tomography when the same threshold values are used.

Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans☆

OBJECTIVES The purpose of this study was to assess the extent and reversibility of neuronal abnormalities in patients with an acute myocardial infarction. BACKGROUND Previous experimental studies have described ischemic injury to sympathetic neurons exceeding the area of myocardial necrosis. Carbon-11 (C-11) hydroxyephedrine (HED) is a norepinephrine analogue that can be used for the noninvasive evaluation of neuronal integrity using positron emission tomography. METHODS We studied 14 volunteers and 16 patients experiencing a first acute myocardial infarction. Positron emission tomographic imaging was used to quantitatively compare regional perfusion, as assessed with nitrogen-13 ammonia, with myocardial retention of C-11 hydroxyephedrine early after myocardial infarction as well as > 6 months after the acute event. RESULTS C-11 hydroxyephedrine and flow images demonstrated homogeneous tracer retention in volunteers but were abnormal in all patients. C-11 hydroxyephedrine abnormalities were more extensive than those for blood flow assessed by semiquantitative polar map analysis (31 +/- 15% vs. 17 +/- 17% left ventricle; p < 0.05), particularly in five patients with non-Q wave infarction (31 +/- 11% vs. 3.5 +/- 2.5% left ventricle; p = 0.008). Eleven patients with Q wave infarction had matched defects (28 +/- 17% vs. 21 +/- 17% left ventricle; p = NS). C-11 hydroxyephedrine tissue retention fraction was quantified in three tissue zones: zone 1 (abnormal rest flow) had retention fraction 0.037 +/- 0.022-min; zone 2 (normal rest flow but decreased carbon-11 hydroxyephedrine retention) had retention fraction 0.068 +/- .034-min, and zone 3 (normal flow and carbon-11 hydroxyephedrine retention) had retention fraction 0.087 +/- 0.041-min (p = 0.0004). Follow-up studies at 8 +/- 3 months in eight patients revealed no change in extent of abnormalities or absolute tissue tracer retention in infarct and peri-infarct territories. CONCLUSIONS The results of abnormal regional sympathetic innervation in patients with infarction confirm previous experimental data and suggest persistent neuronal damage in infarct and peri-infarct territories, without evidence of reinnervation of reversibly injured myocardium.

Scintigraphic assessment of regionalized defects in myocardial sympathetic innervation and blood flow regulation in diabetic patients with autonomic neuropathy.

OBJECTIVES This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions. BACKGROUND Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown. METHODS We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 microg/kg body weight per min). RESULTS Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments. CONCLUSIONS DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.

Correlation between scintigraphic evidence of regional sympathetic neuronal dysfunction and ventricular refractoriness in the human heart.

Backgrund. Denervation supersensitivity has been proposed as a mechanism for the relation between ventricular arrhythmias and the sympathetic nervous system. Evaluation of this phenomenon in humans has become feasible only recently with the development of noninvasive scintigraphic methods for evaluating the pattern of sympathetic innervation. The purpose of this study was to determine if scintigraphic evidence of sympathetic neuronal dysfunction correlates with measurements of ventricular refractoriness and to evaluate the phenomenon of denervation supersensitivity in humans. Methods and ResultsEleven patients with a history of sustained ventricular tachycardia or sudden cardiac death who were referred for placement of an implantable defibrillator participated in this study (seven men and four women; age, 51

Noninvasive assessment of cardiac diabetic neuropathy by carbon-11 hydroxyephedrine and positron emission tomography

18 years). Preoperative scintigraphic evaluation of the pattern of sympathetic innervation was performed with 11C-hydroxyephedrine in conjunction with positron emission tomography. At the time of surgery, ventricular refractoriness was determined in regions of myocardium demonstrating normal and reduced 11C-hydroxyephedrine retention in the baseline state and during an nfusion of norepinephrine. Scintigraphic evaluation demonstrated regions of reduced 11C-hydroxyephedrine retention in each patient. The effective refractory period in areas of myocardium that demonstrated reduced 11C-hydroxyephedrine retention was significantly longer than in areas of myocardium demonstrating normal 11C-hydroxyephedrine retention (273

Regression and progression of cardiac sympathetic dysinnervation complicating diabetes: An assessment by C-11 hydroxyephedrine and positron emission tomography

32 versus 243

Assessing the need for nuclear cardiology and other advanced cardiac imaging modalities in the developing world

32 msec, p < 0.001). Norepinephrine shortened the effective refractory period in regions of myocardium demonstrating normal and reduced 1C-hydroxyephedrine retention to a similar degree. ConclusionsThere is a correlation between scintigraphic evidence of sympathetic neuronal dysfunction and ventricular refractoriness in the human heart. These observations help validate the use of scintigraphic techniques for evaluation of sympathetic innervation and may assist in the further evaluation of the relation between the sympathetic nervous system and ventricular arrhythmias.

Scintigraphic pattern of regional cardiac sympathetic innervation in patients with familial long QT syndrome using positron emission tomography.

OBJECTIVES The purpose of this investigation was to evaluate the sympathetic nervous system of the heart by positron emission tomographic (PET) imaging in patients with diabetes mellitus with and without diabetic autonomic neuropathy. BACKGROUND The clinical assessment of cardiac involvement in diabetic autonomic neuropathy has been limited to cardiovascular reflex testing. With the recent introduction of radiolabeled catecholamines such as carbon (C)-11 hydroxyephedrine, the sympathetic innervation of the heart can be specifically visualized with PET imaging. METHODS Positron emission tomographic imaging was performed with C-11 hydroxyephedrine and rest myocardial blood flow imaging with nitrogen-13 ammonia. Three patient groups were studied, including healthy volunteers as control subjects, diabetic patients with normal autonomic function testing and diabetic patients with varying severity of autonomic neuropathy. Homogeneity of cardiac tracer retention as well as absolute tracer retention was determined by relating myocardial tracer retention to an arterial C-11 activity input function. RESULTS Abnormal regional C-11 hydroxyephedrine retention was seen in seven of eight patients with autonomic neuropathy. Relative tracer retention was significantly reduced in apical, inferior and lateral segments. The extent of the abnormality correlated with the severity of conventional markers of autonomic dysfunction. Absolute myocardial tracer retention index measurements showed a 45 +/- 21% decrease in distal compared with proximal myocardial segments in autonomic neuropathy (0.069 +/- 0.037 min-1 vs. 0.13 +/- 0.052 min-1, p = 0.02). CONCLUSIONS This study demonstrates a heterogeneous pattern of neuronal abnormalities in patients with diabetic cardiac neuropathy. The extent of this abnormality correlated with the severity of neuropathy assessed by conventional tests. Future studies in larger groups of patients are required to define the relative sensitivity of this imaging approach in detecting cardiac neuropathy and to determine the clinical significance of these scintigraphic findings in comparison with conventional markers of autonomic innervation.

Eikenella corrodens vertebral osteomyelitis.

Cardiovascular denervation complicating diabetes has been implicated in sudden cardiac death potentially by altering myocardial electrical stability and impairing myocardial blood flow. Scintigraphic evaluation of cardiac sympathetic integrity has frequently demonstrated deficits in distal left ventricular (LV) sympathetic innervation in asymptomatic diabetic subjects without abnormalities on cardiovascular reflex testing. However, the clinical significance and subsequent fate of these small regional defects is unknown. This study reports the results of a prospective observational study in which positron emission tomography (PET) with (-)-[11C]-meta-hydroxyephedrine ([11C]-HED) was used to evaluate the effects of glycemic control on the progression of small regional LV [11C]-HED retention deficits in 11 insulin-dependent diabetic subjects over a period of 3 years. The subjects were divided into two groups based on attained glycemic control during this period: group A contained six subjects with good glycemic control (individual mean HbA1c <8%), and group B contained five subjects with poor glycemic control (individual mean HbAlc > or =8%). Changes in regional [11C]-HED retention were compared with reference values obtained from 10 healthy aged-matched nondiabetic subjects. At baseline, abnormalities of [11C]-HED retention affected 7.3%+/-1.4% and 9.9%+/-6.6% of the LV in group A and B subjects, respectively, with maximal deficits of LV [ C]-HED retention involving the distal myocardial segments. At the final assessment in group A, the extent of the deficits in [11C]-HED retention decreased to involve only 1.7%+/-0.7% of LV (P<.05 v. baseline scan), with significant increases in [11C]-HED retention occurring in both the distal and proximal myocardial segments. In contrast, in group B with poor glycemic control, the extent of [11C]-HED deficits increased to involve 34%+/-3.5% of the LV (P<.01 v. baseline), with retention of [11C]-HED significantly decreasing in the distal segments ([11C]-HED retention index, 0.066+/-0.003 v. 0.057+/-0.002, P<.05, at baseline and final assessment, respectively). Poor glycemic control was associated with increased heterogeneity of LV [11C]-HED retention, since three of five group B subjects developed abnormally increased [11C]-HED retention in the proximal myocardial segments. In conclusion, defects in LV sympathetic innervation can regress or progress in diabetic subjects achieving good or poor glycemic control, respectively. In diabetic subjects with early cardiovascular denervation, institution of good glycemic control may prevent the development of myocardial sympathetic dysinnervation and enhanced cardiac risk.