The role of nuclear medicine technique in evaluating electrophysiology in diabetic hearts especially with 123I-MIBG cardiac SPECT imaging.

Diabetes mellitus is a risk factor for cardiovascular morbidity and death. Cardiac autonomic diabetic neuropathy (CADN) is a common and serious complication of diabetes mellitus, which consists of damage to the autonomic nerve fibres that innervate the heart and blood vessels, resulting in alterations in heart rate control and vascular dynamics, associated with disabling clinical manifestations and increased mortality and incidence of both silent myocardial ischaemia and infarction. In vivo non-invasive radionuclide assessment of cardiac sympathetic innervation is possible with the use of radioabelled analogues of norepinephrine, which are actively taken up by the postganglionic presynaptic sympathetic nerve fibres of the heart. The catecholamine analogue 123I-metaiodobenzylguanidine (123I-MIBG) is the most commonly used tracer for imaging myocardial presynaptic sympathetic innervation on a broad clinical basis. 123I-MIBG imaging provides unique insights into the effects of diabetes on cardiac sympathetic integrity and the pathophysiological consequences of cardiac sympathetic dysinnervation. It also allows the assessment of both glycemic control on the progression of autonomic neuropathy and the effects of the autonomic derangement on myocardial blood flow regulation, function and electrophysiology, showing even potential for the prediction of adverse outcome.

[Dementia with Lewy bodies and Alzheimer's disease: differential diagnosis by cardiac sympathetic innervation MIBG imaging]. / Demencia con cuerpos de Lewy y enfermedad de Alzheimer: diagnóstico diferencial mediante estudio de la inervación simpática cardíaca con MIBG.

UNLABELLED: Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease (AD). At present, pre-mortem diagnosis of DLB can only be made clinically using the International Consensus Criteria. However, an accurate differential diagnosis between these diseases could improve the therapeutic handling of patients with DLB, due to their supersensitivity to neuroleptic treatment and the difficult treatment of their psychotic symptoms. OBJECTIVE: To assess the utility of cardiac MIBG imaging as diagnostic study for DLB, to help in the differential diagnosis with AD. MATERIAL AND METHODS: Cardiac MIBG imaging was performed in 11 patients with clinical criteria of probable DLB (7 males, mean age 77 years [range 62-89 years], mean MMSE 17 [range 11-28], and in 9 patients with clinical criteria of probable AD (3 males, mean age 79 years [range 61-87 years], mean MMSE 17 [range 4-25]). Planar anterior images of the thorax were acquired at 15 minutes. (early study) and 4 hours (late study) after tracer injection. Myocardial MIBG activity was quantified by means of a heart-to-mediastinum ratio (HMR). A HMR > 1.8 was considered normal. RESULTS: Respect AD patients, patients with DLB showed decreased HMR in the early study (1.34 +/- 0.27 [range 1.03-1.98] vs. 1.84 +/- 0.22 [range 1.53-2.15], p<0.001) and in the late study (1.22 +/- 0.23 [range 0.95-1.75] vs. 1.73 +/- 0.08 [range 1.59-1.89], p<0.0001). CONCLUSIONS: Cardiac MIBG imaging could be a useful tool for differential diagnosis between DLB and AD.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation.

OBJECTIVES: The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND: Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS: In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS: Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS: The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

Towards new understanding of the heart structure and function.

Structure and function in any organ are inseparable categories, both in health and disease. Whether we are ready to accept, or not, many questions in cardiovascular medicine are still pending, due to our insufficient insight in the basic science. Even so, any new concept encounters difficulties, mainly arising from our inert attitude, which may result either in unjustified acceptance or denial. The ventricular myocardial band concept, developed over the last 50 years, has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium. After more than five centuries long debate on macroscopic structure of the ventricular myocardium, this concept has provided a promising ground for its final understanding. Recent validations of the ventricular myocardial band, reviewed here, as well as future research directions that are pointed out, should initiate much wider scientific interest, which would, in turn, lead to reconciliation of some exceeded concepts about developmental, electrical, mechanical and energetical events in human heart. The benefit of this, of course, would be the most evident in the clinical arena.

Sympathetic reinnervation of cardiac allografts evaluated by 123I-MIBG imaging.

UNLABELLED: Some heart-transplant patients present with improved heart rate response to exercise and anginal pain suggesting reinnervation of allografts. Studies performed up to 5 y post-transplantation have suggested that reinnervation is a slow process that occurs only after 1 y post-transplantation. The purpose of this study was to evaluate the extent of sympathetic reinnervation in heart-transplant patients and its relation to cardiac function. METHODS: We performed 123I-metaiodobenzylguanidine (MIBG) studies and rest/exercise radionuclide ventriculography in 31 heart-transplant patients 6 mo to 12 y post-transplantation. Intensity of myocardial MIBG uptake was quantified by a heart-to-mediastinum ratio (HMR), and the regional distribution of MIBG was determined by tomographic studies. RESULTS: HMR correlated positively with time after transplantation (r = 0.607, P < 0.001). Patients studied from 2 to 12 y post-transplantation had an HMR significantly higher than patients studied before 2 y post-transplantation (1.62 +/- 0.2 versus 1.34 +/- 0.2, P < 0.05). Myocardial MIBG uptake was anterolateral in 16 patients, anterior in 3 and anterolateral and septal in 3. Myocardial MIBG uptake was absent in 9 patients. Vasculopathy developed in 8 patients, and 5 of them (63%) had decreased myocardial MIBG uptake. Peak filling rate was higher in patients studied from 2 to 12 y post-transplantation (2.7 +/- 0.8 end-diastolic volume (EDV)/s versus 2.16 +/- 0.5 EDV/s, P = 0.02). CONCLUSION: Sympathetic reinnervation increases with time after heart transplantation and is seen more frequently after 2 y post-transplantation. Complete reinnervation of the transplanted heart does not occur even up to 12 y post-transplantation. Early vasculopathy may delay the process of sympathetic reinnervation.

Regional cerebral blood flow changes in chronic alcoholic patients induced by naltrexone challenge during detoxification.

UNLABELLED: The recent introduction of the opioid antagonist naltrexone for alcohol-dependence therapy has been mainly based on behavioral animal models that provide evidence of the involvement of the endogenous opioid system in alcohol drinking and dependence. However, the neurophysiological mechanisms of the effect of naltrexone in alcoholic patients remain unknown. This study investigates the effects of a naltrexone challenge on regional cerebral blood flow (rCBF) in chronic alcoholic patients during detoxification. METHODS: Sixteen alcoholic inpatients underwent two 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECTs: a basal SPECT on day 10 of abstinence and a second SPECT on day 12 of abstinence after oral administration of 150 mg naltrexone. Region-to-cerebellar ratios were obtained for the orbitary frontal, prefrontal, lateral temporal and mesial temporal regions, basal ganglia and thalamus in each hemisphere. A percentage of rCBF change between both SPECTs was calculated for each region as 100 x (naltrexone - baseline)/ baseline. Values from 13 brain SPECTs of age-matched normal volunteers including test-retest measurements were used for statistical comparison. RESULTS: In baseline conditions, alcoholics showed lower rCBF than controls in left orbitofrontal cortex (84.0+/-5.1 versus 89.8+/-5.0, P < 0.01) and prefrontal cortex (left hemisphere: 87.4+/-5.2 versus 96.2+/-3.6, P < 0.001; right hemisphere: 87.0+/-4.9 versus 95.8+/-4.2, P< 0.001). After naltrexone, a significant rCBF decrease was found versus test-retest values in left basal ganglia (-3.3%+/-4.0% versus 1.5%+/-4.1%, P< 0.05), right basal ganglia (-4.2%+/-4.9% versus 0.6%+/-2.7%, P < 0.01) and left mesial temporal region (-4.5%+/-6.8% versus 2.2%+/-2.9%, P < 0.01). CONCLUSION: The rCBF decrease detected by SPECT after naltrexone challenge in structures rich in opioid receptors, such as the basal ganglia and the left mesial temporal region, may reflect a naltrexone-induced decreased metabolic activity in these areas. These results support the involvement of the opioid system in alcohol dependence. Furthermore, the localization of naltrexone-induced rCBF changes in mesial temporal structures and in basal ganglia supports the implication of emotional memory and obsessive-compulsive phenomena in craving.

Systolic ventricular filling.

The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart. From the earliest Erasistratus' observations, principal mechanisms responsible for the ventricular filling have still remained obscured. Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities. The true origin and the precise time frame for generating such force are still controversial. Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction. Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling. The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart. Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling. Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction. Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis. Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intra-cavitary blood volume (hemoskeleton), explain the physical principles involved in this action. This contraction occurs during the last part of classical systole and the first part of diastole. Therefore, the most important part of ventricular diastole (i.e. the rapid filling phase), in which it receives >70% of the stroke volume, belongs to the active muscular contraction of the ascendent segment. We hope that these facts will give rise to new understanding of the principal mechanisms involved in normal and abnormal diastolic heart function.

Evaluation of renal graft haemodynamia by 51Cr-EDTA and o-[131I]iodohippurate: its use in the early diagnosis of glomerular hyperfiltration.

Chronic rejection is the most important cause of renal graft dysfunction. Non-immunological mechanisms have been suggested as a probable origin of chronic graft rejection, provoking a decrease in renal mass function, followed by glomerular hyperfiltration in the remnant nephrons, which could cause progressive glomerulosclerosis and functional loss. Early, or preclinical, identification of patients with glomerular hyperfiltration, defined as an increase in glomerular filtration fraction (GFF) and in glomerular capillary pressure (GCP), could prolong graft life. The objective of this study was to evaluate, non-invasively, stable renal graft haemodynamia and early glomerular hyperfiltration. We studied 116 renal transplant patients with stable renal function and five healthy living kidney donors with normal renal function. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined using 51Cr-EDTA and o-[131I]iodohippurate, respectively. GFF was obtained from the relation between GFR and ERPF, and GCP from a mathematical model (Hall-Gomez' formula). A simultaneous analysis of renal function was performed. In transplant patients, the GFR and ERPF were significantly lower than in healthy, living, kidney donors (P<0.02). The same trend was observed for GCP (P<0.01), while GFF was not significantly different. Twelve patients (10.3%) had criteria of glomerular hyperfiltration. In patients without criteria of glomerular hyperfiltration, plasma level and clearance of creatinine were 128+/-33 micromol.l-1 and 56+/-15 ml.min-1, respectively; and in those patients with glomerular hyperfiltration criteria were 108+/-18 micromol.l-1 (P=NS) and 83+/-24 ml.min-1 (P=0.002) respectively. It is concluded that determinations of GFR, ERPF, GFF and GCP allow non-invasive evaluation of renal graft haemodynamia and can be useful in the early detection of glomerular hyperfiltration.

[The effect of a race 4 hours in duration on the production of beta-endorphin and adrenocorticotropic hormone]. / Efecto de una carrera de cuatro horas de duración sobre la producción de betaendorfina y hormona adrenocorticotropa.

BACKGROUND: Physiological hormone adaptation to a prolonged and submaximum exercise is not well known. The present study was designed to evaluate changes in plasma levels of beta-endorphin and ACTH before and after a 4 hour pedestrian race. SUBJECTS AND METHOD: Fourteen amateur athletes enrolled in a 4-hour race were studied. Beta-endorphin and ACTH determinations were performed (double antibody IRMA) 10 minutes before and after the race. Simultaneously, heart rate and blood pressure were registered. RESULTS: After the race beta-endorphin level increased 2.8 times with respect to basal values (X [DE]) (42.2 [20,5] VS 14.9 [5.1] pM/I; p < 0.0001), and ACTH level increased 3.5 times (110.8 [72.9] vs 31.4 [14.2] pg/ml; p < 0.0001). There was a positive correlation between the increase of beta-endorphin and ACTH and the distance covered by each athlete (r = 0.617, p < 0.001 and r = 0.533, p < 0.05, respectively), and between the increase of basal and post-race values of both hormones (r = 0.935; p < 0.001). CONCLUSION: Prolonged and submaximum exercise provokes beta-endorphin and ACTH increase, and is related to the amount of performed exercise. There is a positive correlation between the increase of plasma levels of both hormones. Therefore, exercise amount could be one of the main modulator mechanism of beta-endorphin and ACTH release.

[67 Ga-citrate scintigraphy as a determiner in the diagnosis of a subacute thyroiditis]. / Gammagrafía con 67Ga-citrato determinante en el diagnóstico de una tiroiditis subaguda.

We present the case of a 41-year-old man admitted to the hospital with fever and toxic syndrome possibly having an oncological or infectious origin. A whole body scan with 67Ga-citrate showed an intense and diffuse radiotracer accumulation in the thyroid gland. The patient was re-evaluated and studied with other diagnostic tests including a thyroid 99mTc-pertechnetate scintigraphy and a thyroidal radioiodine uptake. A correct final diagnosis of painless subacute thyroiditis was made.

[Interpretation of thyroid incidentalomas in (18)F-FDG PET/CT studies]. / Interpretación de incidentalomas tiroideos en estudios PET/TC con (18)F-FDG.

OBJECTIVE: Thyroid findings or incidentalomas in (18)F-FDG PET/CT studies are relatively frequent, being its clinical significance subject of controversy. The aim of this study was to show our experience in the detection of thyroid incidentalomas by PET/CT studies as well as its follow up. MATERIAL AND METHODS: A retrospective and descriptive review was conducted on patients who had thyroid incidentalomas detected in (18)F-FDG PET/CT studies between June 2010 and March 2013. Patient's medical records were reviewed for age, genre, maximum standardized uptake value (SUVmax), thyroid diseases, TSH and antithyroid antibodies levels, ultrasound, fine-needle aspiration (FNA) and cytology. RESULTS: 4085 PET/CT studies for several purposes were performed. Eighty-three of these studies (2.03%) showed thyroid incidentalomas. Thirty-seven patients showed a diffuse increase of glucose metabolism in the thyroid gland and 46 showed a focal increase of glucose metabolism. Five out of 46 patients with focal uptake were diagnosed of a neoplastic disease by cytology (11%). The SUVmax of malignant pathology did not differ from that of benign thyroid diseases (Mean: 10,26 and 5,92 respectively). CONCLUSION: In our experience, focal thyroid incidentalomas detected in (18)F-FDG PET/CT studies are related to a significant risk of malignancy (11%). Therefore, in these situations, an ultrasound study with fine needle biopsy should be recommended. Moreover, a diffuse increase of glucose metabolism in the thyroid gland is often associated with benign thyroid pathology.

[Utility of early imaging of myocardial innervation scintigraphy in the diagnosis of Lewy Body Dementia]. / Utilidad de la imagen precoz de la gammagrafía de inervación miocárdica en el diagnóstico de la demencia con cuerpos de Lewy.

UNLABELLED: The importance of accurate and early diagnosis of dementia with Lewy bodies (DLB) lies in its pharmacological management. Delayed imaging of cardiac (123)I-MIBG scintigraphy allows differentiation between DLB and other neurodegenerative diseases with cognitive impairment. The aim of this study was to assess the utility of early imaging of cardiac (123)I-MIBG scintigraphy for differentiating DLB from others neurodegenerative disease with cognitive impairment. MATERIAL AND METHODS: We assess retrospectively 106 patients (51 men, mean age 78 years) with cognitive impairment that underwent a cardiac (123)I-MIBG study. Planar images were acquired in anterior view of the thorax 15min (early) and 4h (delayed) after tracer administration. The heart-to-mediastinum ratios (HMR) at 15m (HMR15m) and at 4h (HMR4h) were obtained. RESULTS: After four years, 52 patients were diagnosed of DLB.HMR15m and HMR4h were significantly inferior in DLB respect to the others neurodegenerative diseases (1,27±0,15 vs 1,76±0,15,p<0,05) and (1,14±0,13 vs 1,68±0,19,p<0.01), respectively. The ROC analysis showed a HMR15m cut off point of 1.56 to differentiated DLB from the other dementias with a sensitivity and a specificity of 98%. CONCLUSIONS: Early imaging of cardiac (123)I-MIBG scintigraphy can help to differentiate DLB from other neurodegenerative diseases with cognitive impairment.

Cardiac sympathetic impairment parallels nigrostriatal degeneration in Probable Dementia with Lewy Bodies.

AIM: Dementia with Lewy Bodies (DLB) must be distinguished from other types of dementia because of important differences in patient management and outcome. Both reduction in cardiac 123I-metaiodobenzilguanidine (MIBG) uptake and decreased 123I-FP-CIT binding in basal ganglia have been described in DLB. The aim of this study was to assess the relationship between cardiac sympathetic activity and nigrostriatal degeneration in patients with probable DLB. METHODS: Twenty-eight patients (15 males; mean age 77 years, range 64-88 years) with clinical international criteria of probable DLB were included in the study. All patients underwent a cardiac MIBG scintigraphy and a FP-CIT SPECT. Global cardiac MIBG uptake was semiquantified by means of heart-to-mediastinum ratio (HMR) (normal >1.56). FP-CIT binding in basal ganglia was calculated and compared with an age-matched control group. The relation between cardiac MIBG uptake and FP-CIT uptake in basal ganglia, and the relationship of these two techniques with distinctive symptoms of DLB, features of past medical history and data from the neuropsychological examination were assessed. RESULTS: Cardiac MIBG uptake was decreased in 23 of 28 patients (HMR=1.32, range 0.95-1.85). The FP-CIT binding in basal ganglia was significantly lower than in control group (2.01±0.5 vs 2.62±0.2, P<0.05). All patients with reduced cardiac HMR showed decreased FP-CIT binding in basal ganglia. There was a positive correlation between the HMR and specific binding ratio of striatum (P<0.01). A high correlation between FP-CIT SPECT and the presence of parkinsonism also was found. No correlation between cardiac MIBG uptake and demographic, clinical or neuropsychological data was found. CONCLUSION: In probable DLB cardiac MIBG uptake and FP-CIT binding in basal ganglia are reduced. The positive correlation between both measures suggests that cardiac sympathetic degeneration and nigrostriatal degeneration parallel similarly in patients with probable DLB.

Emerging role of nuclear cardiology in heart failure.

The management of patients with heart failure requires the integration of clinical skills and accurate complementary tests for the correct diagnosis, treatment and estimation of individual prognosis. Identification of those patients most at risk of death, and those most likely to benefit from currently available treatment technologies, remains a challenge. Although the basic characterization of patients with heart failure is supported primarily by the assessment of the left ventricular function, there are several nuclear cardiology techniques and tracers, either available or under development, which can provide important noninvasive imaging insights into the pathophysiology, prognosis and management of patients with heart failure. Nuclear techniques for molecular imaging of the myocardium such as those involved in the processes of myocardial perfusion, metabolism and viability, cellular injury, dyssynchrony, intersticial dysregulation and neurohormonal receptor function may facilitate better clinical outcomes for patients with heart failure. This review mainly focuses on cardiac sympathetic imaging, as other modalities of nuclear cardiology in the assessment of patients with HF are reviewed more extensively in other sections of this issue.