Cardiac autonomic nervous system in heart failure: imaging technique and clinical implications

The autonomic nervous system interacts in the pathophysiology of heart failure. Dysfunction of the sympathetic nervous system has been identified as an important prognostic marker in patients with chronic heart failure. At present, cardiac sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine [123-I MIBG] has been employed most frequently for the assessment of cardiac sympathetic innervation and activation pattern. The majority of studies have shown that cardiac sympathetic dysfunction as assessed with 123-I MIBG imaging is a powerful predictor for heart failure mortality and morbidity. Additionally, 123-I MIBG imaging can be used for prediction of potentially lethal ventricular tachyarrhythmias in heart failure patients. At present however, the lack of standardization of 123-I MIBG imaging procedures represents an evident issue. Standardized criteria on the use of 123-I MIBG imaging will further strengthen the clinical use of 123-I MIBG imaging in heart failure patients.     

The role of nuclear imaging in the failing heart: myocardial blood flow,sympathetic innervation,and future applications

Heart failure represents a common disease affecting approximately 5 million patients in the United States. Several conditions play an important role in the development and progression of heart failure, including abnormalities in myocardial blood flow and sympathetic innervation. Nuclear imaging represents the only imaging modality with sufficient sensitivity to assess myocardial blood flow and sympathetic innervation of the failing heart. Although nuclear imaging with single-photon emission computed tomography (SPECT) is most commonly used for the evaluation of myocardial perfusion, positron emission tomography (PET) allows absolute quantification of myocardial blood flow beyond the assessment of relative myocardial perfusion. Both techniques can be used for evaluation of diagnosis, treatment options, and prognosis in heart failure patients. Besides myocardial blood flow, cardiac sympathetic innervation represents another important parameter in patients with heart failure. Currently, sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine (123-I MIBG) is often used for the assessment of cardiac innervation. A large number of studies have shown that an abnormal myocardial sympathetic innervation, as assessed with 123-I MIBG imaging, is associated with increased mortality and morbidity rates in patients with heart failure. Also, cardiac 123-I MIBG imaging can be used to risk stratify patients for ventricular arrhythmias or sudden cardiac death. Furthermore, novel nuclear imaging techniques are being developed that may provide more detailed information for the detection of heart failure in an early phase as well as for monitoring the effects of new therapeutic interventions in patients with heart failure.     

Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure.

OBJECTIVE: To assess non-invasively the effect of enalapril on cardiac sympathetic neuronal uptake function in patients with congestive heart failure, by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline analogue. Cardiac MIBG uptake was visualised by single photon emission tomography (SPET). In addition, plasma noradrenaline concentration, indicating systemic sympathetic activity, was measured to see whether it was related to cardiac MIBG uptake. DESIGN: Consecutive patients were treated with enalapril and served as their own controls. SETTING: Cardiac unit of a tertiary care centre. PATIENTS: 23 Patients with chronic, mild to moderate, stable congestive heart failure, and a left ventricular ejection fraction less than 40%. Heart failure was caused by ischaemic heart disease or was idiopathic. INTERVENTIONS: Cardiac MIBG SPET was performed and plasma noradrenaline concentration was measured before and after 6 weeks treatment with enalapril. MAIN OUTCOME MEASURES: Cardiac uptake of MIBG was measured by using the left ventricular cavity and a venous blood sample as a reference. RESULTS: Cardiac uptake of MIBG increased significantly after enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake was not related to plasma noradrenaline concentration. CONCLUSIONS: Cardiac MIBG SPET can be used to assess changes in cardiac sympathetic neuronal uptake function caused by pharmacological intervention. Enalapril seemed to improve cardiac sympathetic neuronal uptake function but did not significantly affect plasma noradrenaline concentrations in a group of patients with predominantly moderate heart failure. These results accord with the hypothesis that restoration of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of enalapril in such patients.     

Scintigraphic evidence for cardiac sympathetic dysinnervation in long-term IDDM patients with and without ECG-based autonomic neuropathy

Summary To analyse the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in long-term insulin-dependent diabetes mellitus (IDDM) without myocardial perfusion abnormalities (^99mTc-methoxy isobutyl isonitrile study), ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy was performed in two clinically-comparable groups (20 diabetic patients with and 22 diabetic patients without ECG-based cardiac autonomic neuropathy). For comparison nine control subjects without heart disease were investigated. Only six diabetic patients (27%) without and one diabetic patient (5%) with ECG-based autonomic neuropathy were found to have a uniform homogeneous uptake of ¹²³I-MIBG, in contrast to a uniform homogeneous uptake in all control subjects. The uptake of ¹²³I-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral and septal myocardium (p<0.001, p<0.001, p=0.001). In addition, diabetic patients with cardiac autonomic neuropathy ( two of five age-related cardiac reflex tests abnormal) demonstrated a more reduced uptake in the global, lateral and posterior myocardium than diabetic patients without (p<0.01, p<0.01, p<0.001). A correlation between global or regional myocardial ¹²³I-MIBG uptake, however, and duration of diabetes, HbA_1c, body mass index or QT interval length was not observed. Our study demonstrates that cardiac sympathetic dysinnervation is common in long-term IDDM even in patients without ECG-based cardiac autonomic neuropathy and that the posterior myocardium is predominantly affected. We conclude that ¹²³I-MIBG scintigraphy is a promising approach to further elucidate the pattern and natural history of myocardial dysinnervation in IDDM.Abbreviations CAN-negative Without cardiac autonomic neuropathy - CAN-positive with cardiac autonomic neuropathy - MIBG metaiodobenzylguanidine - SPECT single-photon emission computed tomography - MU myocardial uptake - ^99mTc-MIBI ^99mTc-methoxy isobutyl isonitrile     

Myocardial adrenergic denervation in patients with primary (AL) amyloidosis.

Three patients, 2 women and 1 man, with primary (AL) amyloidosis without congestive heart failure are described; all 3 patients presented reduced I-123 metaiodobenzylguanidine (MIBG) myocardial uptake suggesting marked cardiac sympathetic denervation. This is the first time myocardial adrenergic denervation is described in patients with AL amyloidosis without evidence of congestive heart failure; the observed denervation could be implicated in the pathogenesis of cardiac conduction disturbances which are common in this disease.     

Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

OBJECTIVES: Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5 +/- 6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. METHODS: Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). RESULTS: The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33 +/- 0.22 in chronic heart failure class I, 2.50 +/- 0.34 in class II, 1.95 +/- 0.61 in class III, and 1.39 +/- 0.29 in class IV (p < 0.05). %WR was 24.8 +/- 12.8% in chronic heart failure class I, 23.3 +/- 10.2% in class II, 49.2 +/- 24.5% in class III, and 66.3 +/- 26.5% in class IV (p < 0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. CONCLUSIONS: Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure.     

Cardiac sympathetic innervation and blood flow regulation of the diabetic heart

A key problem in ischemia‐induced impairment of the vascular performance of the diabetic heart is the often‐unrecognized cardiac sympathetic dysfunction. Advanced single‐photon emission computed tomography (SPECT) and positron emission tomography (PET) using the radiopharmaceuticals, ¹²³I‐metaiodobenzylguanidine (¹²³I‐MIBG) and ¹¹C‐hydroxyephedrine (¹¹C‐HED), have shown that dysfunction of cardiac sympathetic nerves is present to a large extent in both type 1 and type 2 diabetes. The pattern of sympathetic disturbances is heterogeneous with a predominant effect in the posterior myocardial region. Furthermore, myocardial blood flow assessment with PET has shown that endothelial‐dependent vasodilatation is reduced in proportion to the magnitude of cardiac sympathetic dysfunction. These mechanisms are currently proposed to lead from early changes to advanced impairment of cardiac function in diabetes. Copyright © 2001 John Wiley & Sons, Ltd.     

Improvement in cardiac adrenergic function post biventricular pacing for heart failure.

AIMS: We investigated whether biventricular (BiV) pacing favourably affects cardiac sympathetic activity in heart failure (HF). METHODS AND RESULTS: In 10 HF patients treated with BiV pacing, we assessed cardiac sympathetic activity by metaiodobenzylguanidine ((123)I-MIBG) imaging. Patients were randomized in a double-blinded crossover fashion, for two weeks of either inactivation of BiV pacing or BiV pacing, with crossover to the alternate group for a further two weeks. After randomization blocks, cardiac (123)I-MIBG imaging and a 6 min walk test were performed. BiV pacing was associated with significant improvements in cardiac (123)I-MIBG uptake reflected by increases in early (BiV 1.71 +/- 0.09 vs. non-BiV 1.63 +/- 0.06, P = 0.03) and late (at 4 h) heart to mediastinal ratio of uptake (BiV 1.54 +/- 0.08 vs. non-BiV 1.45 +/- 0.06, P = 0.03). Additionally, pulmonary (123)I-MIBG uptake, measured as lung to mediastinal ratio, significantly improved (P = 0.009). Six-minute walk and systolic blood pressure tended to improve with BiV vs. non-BiV pacing (P = 0.09). CONCLUSION: In patients with stable HF, BiV pacing is associated with long-term improvements in cardiac sympathetic nerve activity, as reflected by improvements in cardiac (123)I-MIBG uptake. This is a potential mechanism for morbidity and mortality benefits observed in larger studies.     

Cardiac Metaiodobenzylguanidine Imaging and Heart Failure

The autonomic nervous system has pivotal roles in pathophysiology and prognosis in patients with heart failure. Cardiac ¹²³I-labeled metaiodobenzylguanidine (MIBG) imaging enables noninvasive and quantitative assessment of cardiac sympathetic innervation in cardiology practice. Several investigations have demonstrated independent and incremental prognostic values of this imaging technique in combination with clinical information in patients with heart failure. Cardiac MIBG imaging may help cardiologists evaluate cardiac sympathetic nerve function and predict lethal event risk in heart failure. It can contribute not only to the identification of low-risk or high-risk probability for lethal events but also to the selection of the appropriate therapeutic strategy, such as medical and device therapy in patients at greater risk for lethal outcomes due to pump failure or sudden arrhythmic events. Thus, precise risk stratification through cardiac MIBG imaging may contribute to more effective use of medical resources and more appropriate selection of therapeutic strategy in heart failure patients.     

Modulation of Ventricular Repolarization and R‐R Interval Is Altered in Patients with Globally Impaired Cardiac 123I‐MIBG Uptake

Background: Cardiac ¹²³l‐metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. Methods: Twenty‐nine patients with prior myocardial infarction were divided into two groups by a heart‐to‐mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M < 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holler recording and a standard 12‐lead electrocardiography were used for evaluation of HRV, QT‐RR relation, and QT dispersion. Results. Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT‐RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 ± 25 msec) than in group 11(43 ± 19 msec) and group III (28 ± 9 msec). Conclusion. These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.     

Impairment of cardiac sympathetic function in patients with acute myocardial infarction and unstable angina

AIM:To assess the state of sympathetic innervation of the heart in patients with acute coronary syndrome. MATERIAL: Patients with Q-myocardial infarction (MI, n=36), non-Q-MI (n=13), and unstable angina (UA, n=9). METHODS: Each subject underwent single-photon emission computed tomography (SPECT) and planar scintigraphy using iodine-123 metaiodobenzylguanidine ((123)I-MIBG) for assessment of cardiac sympathetic function. We analyzed early (15 minutes) and delayed (4 hours) images after (123)I-MIBG administration. Resting (99m)Tc-MIBI myocardial scintigraphy was performed for evaluation of myocardial perfusion. Location, extent (%) and severity (Un.) of defects were determined using program. (123)I-MIBG did not accumulate in myocardium of 3.5% patients. All other patients demonstrated (123)I-MIBG accumulation defects. These defects were colocolized with (99m)Tc-MIBI uptake abnormalities. However both extent and severity of sympathetic innervation defects exceeded those of perfusion defects in all patients. Mean extent and severity of sympathetic neuronal damage areas were the greatest in patients with Q-MI (41+/-8% and 1119+/-377 Un. respectively) and the least in patients with UA (22+/-12% and 602+/-353 Un., respectively). On the contrary the mean extent of areas with sympathetic endings dysfunction but normal perfusion was the largest in UA group and the least in Q-MI group (18+/-11 and 10+/-7%, respectively, p<0,05). CONCLUSION: Impairment of cardiac sympathetic function in patients with acute coronary syndrome could be detected by SPECT with (123)I-MIBG. Locations of (123)I-MIBG and (99m)Tc-MIBI defects were similar but sympathetic dysfunction areas were larger than areas with reduced perfusion. This result suggests higher sensitivity of sympathetic endings to ischemia compared with cardiomyocytes. Myocardial areas with sympathetic endings dysfunction but normal perfusion can be defined as myocardium at risk.     

Iodine-123 metaiodobenzylguanidine scintigraphic analysis of myocardial sympathetic innervation in patients with AL (primary) amyloidosis

Background Although a high incidence of myocardial adrenergic denervation has been reported in patients with familial amyloid polyneuropathy, assessment of cardiac sympathetic nerve function has not been available in patients with AL (primary) amyloidosis. Methods To test the hypothesis that myocardial sympathetic nerve innervation might be impaired and variable according to the presence or absence of clinical autonomic abnormalities and congestive heart failure in AL amyloidosis, we examined 25 patients by use of iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Results Ten of the 16 patients without autonomic symptoms and 5 of the 9 patients with autonomic neuropathy showed congestive heart failure. The heart/mediastinal activity (H/M) ratio (1.53 ± 0.06 vs 1.29 ± 0.05 at 3 hours, P < .001) and myocardial washout ratio (41.5% ± 4.8% vs 30.8% ± 4.0%, P < .001) of MIBG were significantly increased in patients without autonomic symptoms compared with patients showing autonomic neuropathy. In patient groups with and without autonomic dysfunction, patients demonstrating congestive heart failure exhibited a significantly decreased H/M ratio and increased washout compared with patients with no heart failure, and left ventricular fractional shortening was positively correlated with the H/M ratio and inversely correlated with the washout ratio. There were significant correlations between the low-frequency component of the heart rate variability and the H/M ratio and washout ratio in the entire patient population. Conclusions Patients with AL amyloidosis and no autonomic dysfunction showed variable degrees of enhanced cardiac adrenergic neuronal activity with presynaptic sympathetic dysfunction. In contrast, patients with AL amyloidosis and autonomic neuropathy exhibited prominent myocardial adrenergic denervation with normal or impaired sympathetic neural function of the heart. This study demonstrates that myocardial uptake and turnover of MIBG in patients with AL amyloidosis are heterogeneous and dependent on the presence or absence of congestive heart failure and cardiac autonomic dysfunction. (Am Heart J 2002;144:122-9.)     

Imaging cardiac neuronal function and dysfunction

In recent years, the importance of alterations of cardiac autonomic nerve function in the pathophysiology of heart diseases including heart failure, arrhythmia, ischemic heart disease, and diabetes has been increasingly recognized. Several radiolabeled compounds have been synthesized for noninvasive imaging, including single photon emission CT and positron emission tomography (PET). The catecholamine analogue I-123 metaiodobenzylguanidine (MIBG) is the most commonly used tracer for mapping of myocardial presynaptic sympathetic innervation on a broad clinical basis. In addition, radiolabeled catecholamines and catecholamine analogues are available for PET imaging, which allows absolute quantification and tracer kinetics modeling. Postsynaptic receptor PET imaging added new insights into mechanisms of heart disease. These advanced imaging techniques provide noninvasive, repeatable in vivo information of autonomic nerve function in the human heart and are promising for providing profound insights into molecular pathophysiology, monitoring of treatment, and determination of individual outcome.     

QT Interval Variability in Type 2 Diabetic Patients with Cardiac Sympathetic Dysinnervation Assessed by 123I‐Metaiodobenzylguanidine Scintigraphy

QT Variability and Sympathetic Dysinnervation . Introduction: The mechanism of adverse prognosis attributable to proarrhythmic cardiac sympathetic dysinnervation in patients with type 2 diabetes is incompletely understood. This study sought the association of cardiac sympathetic dysinnervation with temporal instability of ventricular repolarization assessed by beat‐to‐beat QT interval variability. Methods and Results: ¹²³I‐metaiodobenzylguanidine (¹²³I‐MIBG) scintigraphy was analyzed in 31 type 2 diabetic patients for cardiac sympathetic dysinnervation (4‐hour heart‐to‐mediastinum ratio <1.8) and regional sympathetic integrity and washout rate (from 15‐minute ¹²³I‐MIBG uptake). Relative QT variability was defined from a continuous 5‐minute ECG in the supine position (n = 31) and standing position (subgroup; n = 15) by the log ratio of absolute QT variability (QT variance divided by the mean QT interval squared) to heart rate (HR) variability (HR variance divided by the mean HR squared). Patients with (n = 16; 52%) versus without cardiac sympathetic dysinnervation demonstrated higher relative QT variability in the supine position (P < 0.001), owing to lower HR variability. However, on standing, absolute QT variability was significantly raised in these patients (P = 0.009) despite similar HR variability in the 2 groups. Correlations of heart‐to‐mediastinum ratio with standing QT variability (relative [r =?0.63, P = 0.013] and absolute [r =?0.79, P = 0.001]) were superior to corresponding supine measures (relative [r =?0.47, P = 0.008] and absolute [P = NS]). No associations of QT variability with washout rate or regional ¹²³I‐MIBG uptake were identified. Conclusion: Elevated QT variability is associated with cardiac sympathetic dysinnervation in type 2 diabetes and may contribute to adverse prognosis. Moreover, QT variability may be more specific for cardiac sympathetic innervation when measured in the context of sympathetic activation. (J Cardiovasc Electrophysiol, Vol. 24, pp. 305‐313, March 2013)     

Sympathetic nervous system function as measured by I-123 metaiodobenzylguanidine predicts transplant-free survival in heart failure patients with idiopathic dilated cardiomyopathy

BACKGROUND: Heightened activity of the sympathetic nervous system in heart failure patients is a major contributor to disease progression and death. I-123 metaiodobenzylguanidine (MIBG) provides an accurate, noninvasive method to assess cardiac sympathetic nerve activity. METHODS: Thirty-seven patients with New York Heart Association class II, III, or IV heart failure underwent baseline measurement of I-123 MIBG heart-to-mediastinum ratios, maximum oxygen consumption, radionuclide left ventricular ejection fraction, and plasma norepinephrine levels. Patients were followed 48.8+/-8.6 months to endpoints of cardiac death or transplantation. The heart-to-mediastinum ratio of I-123 MIBG activity measured 15 minutes after injection was the only independent predictor of transplant-free survival (P<.0001). I-123 MIBG imaging at 15 minutes identified patients with subsequent cardiac transplantation or death with a sensitivity of 92% and specificity of 72%, whereas the corresponding values for maximum oxygen consumption were 75% and 56%. By Kaplan-Meier survival analysis, the time to a cardiac endpoint was significantly shorter in patients with a 15-minute I-123 MIBG heart-to-mediastinum ratio below the group mean ratio of 1.536, compared with patients with a preserved I-123 MIBG ratio. Maximum oxygen consumption was not predictive of time to cardiac transplant or death. CONCLUSIONS: In this study of patients with congestive heart failure resulting from dilated cardiomyopathy, a 15-minute heart-to-mediastinum ratio of I-123 MIBG activity provided more accurate prediction of cardiac transplantation or death than other standard clinical tests.     

Metaiodobenzylguanidine [131I] scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [131I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [131I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [131I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [123I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.     

A new look at the heart in diabetes mellitus: from ailing to failing

This review discusses some of the mechanisms inherent in diabetes that predispose patients to increased cardiac morbidity and mortality. Single photon emission computerized tomography or photon emission tomography with radioactive labeled analogues of norepinephrine have shown that cardiac sympathetic dysfunction and incompetence are early and also late abnormalities in patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. Furthermore, myocardial blood flow assessment with photon emission tomography has shown that in patients without myocardial perfusion deficits, endothelial-dependent vasodilatation is severely reduced in relation to cardiac sympathetic dysfunction. In addition, signs of endothelial activation have also been found early in patients with Type I and Type II diabetes in whom vascular disease has not been clinically detected. This activation in conjunction with glycaemic control is important in determining macrovascular mortality. Cardiac sympathetic dysfunction is partially restored to normal with near normalisation of glycaemia. Interpretations. Recently unrecognized “subtle” changes predispose the heart to failure, after ischaemia-induced remodelling, and arteriosclerotic plaques to instability and rupture. These changes act in conjunction with effects, driven by hyperglycaemia and diabetes, on the endothelium of large blood vessels, e. g. on nitric oxide release or on protein kinase-C β activation. Meticulous glucose control early on and rapid recompensation of hyperglycaemia in patients with acute coronary syndrome are part of a successful intensive multifactorial approach to prevent the heart in diabetes converting from ailing to failing. [Diabetologia (2000) 43: 1455–1469]     

Risk stratification assessed by combined lung and heart iodine-123 metaiodobenzylguanidine uptake in patients with idiopathic dilated cardiomyopathy

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

Monitoring of therapeutic effect in heart failure patients: a clinical application of 123I MIBG imaging?

Labelling of metaiodobenzylguanidine (MIBG) with ¹²³I allowsscintigraphic visualization of the cardiac sympathetic nervoussystem and ¹²³I MIBG was the first radiopharmaceutical thatallowed imaging of cardiac neurotransmission by single photonemission computed tomography. Norepinephrine (NE) is the majorneurotransmitter of the sympathetic nervous system. ¹²³I MIBG,an analogue of NE, and NE have similar molecular structures,and use the same uptake and storage mechanisms in the pre-synapticsympathetic nerve ending. Uptake-1 is the most important uptakemechanism of MIBG in human, and is sodium- and energy-dependent.Other uptake mechanisms are the non-neuronal uptake-2 mechanism,which is sodium- and energy-independent, and diffusion. The cardiac sympathetic nervous system is mainly involved inpreserving circulatory homeostasis during environmental stress.Increase of sympathetic nervous activity or a rise in     

Long-term course and cardiac sympathetic nerve activity in patients with hypertrophic cardiomyopathy.

OBJECTIVE--To investigate the relation between regional myocardial sympathetic nerve activity and the electrocardiographic and cardiac functional changes in hypertrophic cardiomyopathy. DESIGN--A retrospective study to compare the findings of myocardial scintigraphy with iodine-123 metaiodobenzylguanidine (MIBG) and the serial electrocardiographic changes. SETTING--Myocardial scintigraphy was performed with iodine-123 MIBG and thallium-201 and single photon emission computed tomography (SPECT) in the division of nuclear medicine of Kanazawa University Hospital. Both SPECT studies were performed within a week. PATIENTS--22 patients with hypertrophic cardiomyopathy classified according to their serial electrocardiographic changes--namely, 15 patients with an increase in or the appearance of a negative T wave (group A) and seven patients with a conduction disturbance or a decrease in or disappearance of the negative T wave (group B). The mean follow up period was 45 (range 12-143) months. RESULTS--Group B showed a high rate of decreased activity or defects in MIBG uptake compared with group A (p less than 0.005). The areas of decreased activity or defects corresponded with the hypertrophied portion of the left ventricular wall. Although the early myocardial uptake (MIBG: thallium ratio) was similar in both groups, the mean (SD) MIBG clearance rate was significantly higher (p less than 0.05) in group B (0.25 (0.17)) than in group A (0.10 (0.15)). CONCLUSION--Abnormalities of regional myocardial sympathetic nerve activity may be important in patients with hypertrophic cardiomyopathy and suspected progression of myocardial damage.