Cardiac Sympathetic Nerve Dysfunction Research Articles

Cardiac Sympathetic Nerve Function in Patients with Severe Aortic Stenosis Prior and After Transcatheter Aortic Valve Implantation

Background: While the non-invasive assessment of cardiac sympathetic nerve dysfunction is readily accessible, its applicability in invasive intervention for structural heart disease has received limited investigation. Our study aimed to clarify the cardiac sympathetic nerve function in patients with severe Aortic stenosis (AS) and its postoperative changes after transcatheter aortic valve implantation (TAVI) using 123I-metaiodobenzylguanidine scintigraphy (MIBG) in combination with 5-year mortality prediction model. Methods: Consecutive 26 patients (83±5ys, male 4) with severe AS who underwent MIBG prior TAVI procedures were retrospectively enrolled. Of those, 15 patients underwent postoperative-follow up MIBG. The early and delayed heart-to-mediastinum ratio (e- and d-H/M), and washout rate (WR) were obtained from MIBG planner imaging. The MIBG 5-year mortality prediction model was employed to compare pre and after TAVI. Cardiac function and wall thickness were evaluated with transthoracic echocardiography. Results: Preoperative e-H/M, d-H/M, and WR were 2.4±0.5, 2.3±0.4, and 29±14% respectively, and WR showed significant correlation to left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) (r=-0.4 and 0.6; p=0.03, and 0.001 for LVEF and BNP, respectively). 102±28 days after TAVI, either H/M or WR did not show significant improvement among enrolled patients (2.5±0.3, 2.3±0.4, and 30±11% for e-, d-H/M, and WR for after TAVI), while the BNP level was significantly reduced (128±691 and 94±194 pg/dl, for pre vs. after, p=0.008). Five patients showed a significant recovery in WR (37.0±13.8 and 28.8±8.5% for pre and post, p=0.04), and left ventricular wall thickness was significantly thinner compared to those who did not recover (15.2±3.2 vs 11.2±2.4, p=0.02; 14.2±2.9 vs 10.8±1.8, p=0.02 for intraventricular septum and posterior wall, respectively). In 5-year prediction risk model, 7 patients showed a significant reduction in mortality risk, and the patients who did not show risk reduction had significantly reduced renal function (eGFR 57.5±18.8 vs. 38.2±11.3 ml/min/1.73m2, p=0.03 for recovered vs. not recovered). Conclusion: After a 3-month follow-up after TAVI, diverse response in cardiac MIBG parameters were observed among patients with severe AS, despite successful valve replacement. Cardiac MIBG serves as a non-invasive tool that can comprehensively evaluate and surrogate the severity of heart failure resulting from a multi-factorial condition.

Abstract 17680: MIBG Myocardial Scintigraphy is Useful for Predicting CTRCD Caused by Trastuzumab

Introduction: Trastuzumab is known to reduce the mortality rate, recurrence rate, and metastasis rate in Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer patients, and it is recommended to administer it for 12 months to all early-stage HER2-positive breast cancer patients. However, trastuzumab administration can lead to Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). The guidelines suggest that regular echocardiography every 3 months is useful for early detection of CTRCD, but there are no tests available to predict it before its onset.The purpose of this study is to determine whether cardiac sympathetic nerve evaluation using MIBG myocardial scintigraphy before trastuzumab administration can predict the development of CTRCD three months after administration. Methods: MIBG myocardial scintigraphy was performed before trastuzumab administration in 35 HER2-positive breast cancer patients, and cardiac function assessment was conducted using echocardiography before administration, at 1 month, and at 3 months. Simultaneously, NT-proBNP and troponin levels were measured. CTRCD was defined as a decrease in global longitudinal strain (GLS) of 10% or more from before administration at the 3-month follow-up. Results: Anthracycline and trastuzumab regimens were used in 21 patients (60%). CTRCD occurred in 17 patients at the 3-month follow-up. There were no significant differences in age or previous medication between the CTRCD group and the non-CTRCD group, but the early H/M ratio in MIBG myocardial scintigraphy was significantly lower in the CTRCD group (2.77±0.36) compared to the non-CTRCD group (3.10±0.36) (p<0.01). There were no significant differences in the delay H/M ratio or washout rate. None of the echocardiographic parameters, NT-proBNP levels, or troponin levels showed significant differences and did not become predictive factors. Conclusions: MIBG myocardial scintigraphy is useful for predicting CTRCD caused by trastuzumab. Preclinical studies have suggested that HER2 transactivation from β-adrenergic receptors in the myocardium confers cardioprotection. Suppression of HER2 signaling during cardiac sympathetic nerve dysfunction potentially contributes to the development of CTRCD.

Prognostic Significance of Cardiac 123I-MIBG SPECT Imaging in Heart Failure Patients With Preserved Ejection Fraction

The authors sought to elucidate the prognostic value of cardiac sympathetic nerve dysfunction as evaluated using iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) single-photon emission computed tomography (SPECT) imaging in patients with heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). Cardiac sympathetic nerve dysfunction assessed by 123I-MIBG imaging is associated with poor outcomes in chronic HF patients with reduced left ventricular ejection fraction (HFrEF). However, no information is available on the prognostic vale of cardiac 123I-MIBG SPECT imaging in patients with HFpEF. We studied 148 patients admitted for acute decompensated HF (ADHF) with nonischemic HFpEF and who underwent cardiac 123I-MIBG imaging at discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (H/M) was measured on the delayed planar image (late H/M). SPECT analysis of the delayed image was conducted, and the tracer uptake in all 17 regions on the polar map was scored on a 5-point scale by comparison with a sex-matched normal control database. The total defect score (TDS) was calculated by summing the score of each of the 17 segments. The primary endpoint was the association between TDS and cardiac events (the composite of emergent HF hospitalization and cardiac death). During a mean follow-up period of 2.4 ± 1.6 years, 61 patients experienced cardiac events. TDS was significantly associated with cardiac events after multivariate Cox adjustment (P< 0.0001). Patients with high TDS levels had a significantly greater risk of cardiac events than those with middle or low TDS levels (63% vs 40% vs 20%, respectively; P< 0.0001; HR: 4.69; 95%CI: 2.29 to 9.61; and HR: 2.46; 95%CI: 1.14 to 5.29). C-statistic of TDS was 0.730 (95% CI:0.651 to 0.799), which was significantly higher than that of late H/M (0.607; 95%CI: 0.524 to 0.686; P = 0.0228). Cardiac 123I-MIBG SPECT imaging provided useful prognostic information in nonischemic ADHF patients with HFpEF. (Clinical Trial: Osaka Prefectural Acute Heart Failure Syndrome Registry [OPAR]: UMIN000015246).

Long-term serial changes of cardiac sympathetic nerve dysfunction in acute decompensated heart failure patients with reduced, mid-range and preserved left ventricular ejection fraction

Abstract Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with chronic heart failure (CHF). Serial evaluation of cardiac MIBG imaging was shown to be useful for predicting adverse outcome in CHF. However, there was no information available on long-term serial changes of cardiac sympathetic nerve dysfunction after discharge of acute decompensated heart failure (ADHF) hospitalization. Purpose We aimed to clarify the serial change of cardiac MIBG imaging parameter in long-term after discharge of heart failure hospitalization, especially relating to HFrEF (LVEF&amp;lt;40%), HFmrEF (40%≤LVEF&amp;lt;50%) and HFpEF (LVEF≥50%). Methods We studied 112 patients (HFrEF; n=44, HFmrEF; n=23 and HFpEF; n=45) who were admitted for ADHF, discharged with survival and without heart failure hospitalization during follow-up period. All patients underwent cardiac MIBG imaging at the timing of discharge, in 6–12 months and in 18–24 months after discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). The cardiac MIBG washout rate (WR) was calculated from the early and delayed planar images after taking radioactive decay of I-123 into consideration. Results In HFrEF patients, late H/M was significantly improved from discharge to 6–12 months data (1.60±0.24 vs 1.75±0.31, p&amp;lt;0.0001). Late H/M of HFmrEF patients was also significantly improved from discharge to 18–24 months data (1.71±0.27 vs 1.84±0.29 p=0.043). On the other hand, late H/M of HFpEF patients was not significantly changed. As for WR, WR in HFrEF and HFmrEF patients was significantly improved from discharge to 18–24 months data, although WR of HFpEF was not significantly changed. Conclusion The improvement in cardiac sympathetic nerve dysfunction was observed in patients with HFrEF and HFmrEF, not in HFpEF, after the discharge of acute heart failure hospitalization. Funding Acknowledgement Type of funding source: None

Prognostic significance of cardiac 123I-MIBG SPECT imaging in patients with acute decompensated heart failure with preserved left ventricular ejection fraction

Abstract Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with heart failure (HF). Most of the literature on the use of 123I-MIBG imaging is based on planar images in patients with chronic HF and reduced left ventricular ejection fraction (HFrEF), because It is technically challenging to conduct precise 123I-MIBG SPECT analysis in globally denervated heart, which is frequently observed in HFrEF patients. There was no information available on cardiac sympathetic nerve dysfunction evaluated by cardiac MIBG SPECT imaging in acute decompensated HF (ADHF) patients with preserved left ventricular ejection fraction (HFpEF). Purpose We aimed to clarify the prognostic significance of 123I-MIBG SPECT myocardial imaging in ADHF patients with HFpEF. Methods We enrolled 183 patients who were admitted for ADHF with HFpEF, discharged with survival. All patients underwent cardiac MIBG imaging at the timing of discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). We studied 156 patients after excluding 27 patients whose MIBG SPECT reconstruction was difficult due to too low MIBG uptake or extracardiac accumulation interference. SPECT analysis on the delayed image was conducted by using CardioBull, a fully automated software for the quantification of I-123 MIBG SPECT. All of 17 regional tracer uptake were compared with normal control database. A scoring algorithm for the evaluation of low uptake employs a 5-point scoring system as 0–4 for normal, mildly abnormal, moderately abnormal, severe abnormal, and perfusion defect, respectively. The summed severity (SSS) scores were obtained by summing the score for all segments. SSS could range from 0 to 68. The endpoint of this study is cardiac events defined as the composite of unplanned heart failure hospitalization and cardiac death. Results During a mean follow up period of 2.4±1.6 years, 60 patients reached cardiac events. SSS was significantly high in patients with than without cardiac events (20 [10–27] vs 7 [4–16], p&amp;lt;0.0001). SSS (p&amp;lt;0.0001) was significantly associated with cardiac events after multivariable Cox adjustment of age, sex, creatinine and log-transformed BNP level, although late H/M showed the significant association with the endpoint at the univariate Cox analysis. Kaplan-Meier analysis showed that patients with high SSS (&amp;gt;10, defined by median) had significantly greater risk of cardiac event (56% vs 21%, Hazard ratio: 3.56 (2.00–6.33, p&amp;lt;0.0001). ROC curve analysis showed that area under the curve (AUC) of SSS was 0.746 [95% CI:0.670, 0.812], which was significantly higher than that of late H/M (0.618 [95% CI:0.537, 0.695]) (p=0.0159). Conclusion Cardiac MIBG SPECT imaging was useful for risk stratification in ADHF patients with HFpEF. Funding Acknowledgement Type of funding source: None

The NADPH oxidase inhibitor apocynin improves cardiac sympathetic nerve terminal innervation and function in heart failure.

What is the central question of this study? Does NADPH oxidase activation mediate cardiac sympathetic nerve denervation and dysfunction in heart failure. What is the main findings and its importance? Cardiac sympathetic nerve terminal density and function were reduced in heart failure after myocardial infarction in rabbits. The NADPH oxidase inhibitor apocynin prevented the reduction in cardiac sympathetic nerve terminal density and function in heart failure. This suggest that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in heart failure. NADPH oxidase may be a potential therapeutic target for cardiac sympathetic denervation and dysfunction in heart failure. Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by decreased noradrenaline transporter (NAT) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits. Rabbits with MI or a sham operation were randomized to orally receive an NADPH oxidase inhibitor, apocynin (6mgkg-1 day-1 ), or placebo for 30days. MI rabbits exhibited left ventricular dilatation, systolic dysfunction, and increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by treatment with apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by apocynin treatment. NAT, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

Clinical and radiological diversity in genetically confirmed primary familial brain calcification

Primary familial brain calcification (PFBC) is a rare neuropsychiatric disorder with characteristic symmetrical brain calcifications. Patients with PFBC may have a variety of symptoms, although they also may be clinically asymptomatic. Parkinsonism is one of the most common movement disorders; however, the underlying mechanism remains unclear. This condition is typically transmitted in an autosomal dominant fashion. To date, mutations in SLC20A2, PDGFRB, PDGFB, and XPR1 have been reported to cause PFBC. The aim of the study was to identify the genetic cause of brain calcification in probands from three PFBC families and in 8 sporadic patients and to perform clinical and radiological assessments focusing on parkinsonism in mutation carriers. Three familial PFBC probands and their relatives and eight sporadic patients affected with brain calcifications were enrolled in this study. Whole-exome sequencing identified three novel mutations: c.269G > T, p.(Gly90Val) and c.516+1G > A in SLC20A2 in familial cases, and c.602-1G > T in PDGFB in a sporadic patient. The c.516+1G > A mutation resulted in exon 4 skipping in SLC20A2 (p.Val144Glyfs*85). Dopamine transporter single photon emission computed tomography using 123I-ioflupane and 123I-metaiodobenzylguanidine cardiac scintigraphy revealed pre-synaptic dopaminergic deficit and cardiac sympathetic nerve dysfunction in two SLC20A2-related PFBC patients with parkinsonism.

Abstract 11959: Cardiac Denervation Appears Before Becoming Myocardial Tissue Fibrosis in Patients With Cardiac Involvement Sarcoidosis and Active Inflammation Using C-11 Hydroxyephedine PET/CT and Cardiac Magnetic Resonance

Background: Cardiac involvement sarcoidosis (CS) has increased risk of arrhythmia linked to sudden death. Cardiac sympathetic nervous (SNS) dysfunction may play an important role for these events. However, the association between the SNS dysfunction and active inflammation or tissue fibrosis has not been studied. The aim of this study was to evaluate the left ventricle (LV) SNS dysfunction measured by C-11 hydroxyephedrine (HED) positron emission tomography (PET)/CT and its association with tissue fibrosis measured by cardiac magnetic resonance (CMR) in patients with CS and active inflammation. Methods: Eleven patients with CS based on the JMHW guidelines (1993) were enrolled. CS (age 59±16 y) and preserved LVEF (64±14 %) underwent HED PET, FDG PET, and CMR. Ten healthy controls underwent HED PET. LV wall was divided into 17 segments. Reduced HED uptake, focal FDG uptake, and late gadolinium enhancement (LGE) on CMR were defined as positive for the visual assessment. In addition, whole LV and regional HED uptake was quantitatively assessed by retention index (RI). Standard uptake value (SUV) was measured in the FDG positive segments. Results: CS had reduced global LV HED RI compared to control (0.09±0.04 vs. 0.15±0.03 %/min, P&lt;0.001). FDG positive group (n=7) had lower global HED RI than FDG negative group (n=4) (0.065±0.027 vs. 0.130±0.040 %/min, P=0.010). In contrast, there was no significant difference in LGE positive segments numbers between the two groups (3.14±2.79 vs. 1.25±0.96, P=0.46). In segmental analysis, the percentage of abnormal segments were trend to higher in HED than LGE (P=0.19). In addition, there was no correlation between regional FDG SUV and HED RI (n=42 segments, R=-0.11, P=0.50). Conclusions: Cardiac involvement sarcoidosis with active LV inflammation and preserved LVEF showed global LV cardiac sympathetic nervous dysfunction. Denervation area was tended to be larger than tissue fibrosis. Furthermore, no association was seen between FDG uptake and HED retention index in regional level. These findings may imply that multiple factors other than inflammatory process and tissue fibrosis may be involved in the cardiac sympathetic nervous dysfunction in cardiac involvement sarcoidosis.

Right ventricular dysfunction and inflammation are related to cardiac sympathetic nerve dysfunction in patients with chronic heart failure and left ventricular systolic dysfunction

Right ventricular dysfunction and inflammation are related to cardiac sympathetic nerve dysfunction in patients with chronic heart failure and left ventricular systolic dysfunction

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Cardiac 123I-MIBG scintigraphy and arrhythmic risk in left ventricular noncompaction

Left ventricular noncompaction is an unusual but increasingly recognized cardiomy-opathy, the etiology of which is still not definitely established. Clinical presentation includes a wide spectrum of scenarios, including heart failure, thromboembolism and malignant arrhyth-mias, with half of deaths occurring suddenly. Early detection of LVNC is therefore essential to prevent sudden cardiac death. To our knowledge, this is the first report of the presence of cardiac sympathetic nervous dysfunction, assessed by 123iodine-metaiodobenzylguanidine myocardial scintigraphy, in a patient with LVNC, preserved left ventricular systolic function and exercise-induced nonsustained ventricular tachycardia. This finding may be related to the increased arrhythmic risk observed in this cardiomyopathy, giving a new insight into the pathophysiology of LVNC. O miocárdio não-compactado (MNC) é uma miocardiopatia que, embora rara, tem sido gradualmente mais descrita. O espectro de apresentac, ão clínica é variável, incluindo insufi-ciência cardíaca, fenómenos tromboembólicos e arritmias, sendo que metade das mortes ocorre subitamente (MSC). Por conseguinte, o diagnóstico precoce e correto do MNC é fundamental para a prevenc¸ão da MSC. O presente artigo ilustra pela primeira vez a presenc¸a de disfunc¸ão neuronal simpática, avaliada por cintigrafia cardíaca com 123I-metaiodobenzilguinadina, num doente com MNC, func¸ão sistólica ventricular esquerda preservada e taquicardia não susten-tada induzida pelo esforc¸o. A presenc¸a de alterac¸ões na actividade adrenérgica cardíaca pode estar relacionada com o maior risco arrítmico característico desta miocardiopatia, podendo contribuir para o melhor esclarecimento da sua patofisiologia.

Cardiac 123I-MIBG scintigraphy and arrhythmic risk in left ventricular noncompaction

Left ventricular noncompaction is an unusual but increasingly recognized cardiomyopathy, the etiology of which is still not definitely established. Clinical presentation includes a wide spectrum of scenarios, including heart failure, thromboembolism and malignant arrhythmias, with half of deaths occurring suddenly. Early detection of LVNC is therefore essential to prevent sudden cardiac death. To our knowledge, this is the first report of the presence of cardiac sympathetic nervous dysfunction, assessed by 123iodine-metaiodobenzylguanidine myocardial scintigraphy, in a patient with LVNC, preserved left ventricular systolic function and exercise-induced nonsustained ventricular tachycardia. This finding may be related to the increased arrhythmic risk observed in this cardiomyopathy, giving a new insight into the pathophysiology of LVNC.

Effect of Cardiac Resynchronization Therapy on Cardiac Sympathetic Nervous Dysfunction and Serum C‐reactive Protein Level

Cardiac autonomic dysfunction is associated with a poor prognosis in patients with heart failure (HF). Systemic inflammation is elevated in patients with HF. We hypothesized that cardiac resynchronization therapy (CRT) improves cardiac sympathetic nervous dysfunction and systemic inflammation. To test our hypothesis, we evaluated cardiac sympathetic activity and serum levels of high sensitive C-reactive protein (hs-CRP) before and after CRT. Twenty-seven patients with chronic HF (19 men, eight women; mean age 67 ± 10 years) with nonischemic cardiomyopathy who underwent CRT were evaluated. Each patient was evaluated before and 6 months after CRT. Responders were defined as patients showing ≥15% absolute decrease in left ventricular end-systolic volume. Cardiac sympathetic activity was estimated with cardiac (123) I-metaiodobenzylguanidine (MIBG) scintigrams. Patients were categorized as responders (n = 19) and nonresponders (n = 8) according to echocardiographic findings. In responders, the mean heart-to-mediastinum (H/M) ratio at the delayed phase in cardiac (123) I-MIBG scintigraphic findings was significantly increased (P<0.05) and serum levels of hs-CRP were decreased (P <0.01). Such improvements were not observed in nonresponders. Stepwise multiple regression analysis showed that the reduction in hs-CRP level was independently associated with the increase in the H/M ratio at delayed phase. Our results demonstrated that cardiac sympathetic nervous dysfunction and systemic inflammation were improved in responder HF patients to CRT. Furthermore, the reduction in systemic inflammation was associated with the improvement in cardiac sympathetic nervous dysfunction.

Clinical Features of Myocardial Triglyceride in Different Types of Cardiomyopathy Assessed by Proton Magnetic Resonance Spectroscopy: Comparison With Myocardial Creatine

Myocardial lipid overstorage may produce cardiomyopathy, leading to dysfunction, but advanced heart failure may cause lipolysis via sympathetic nerve activation. In the failing heart, the creatine kinase system may also be impaired. The aims of this study were to assess myocardial triglyceride (TG) and creatine (CR) in different types of cardiomyopathy and to investigate whether they are related to the severity of cardiac dysfunction. In patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 12) or ischemic cardiomyopathy (ICM, n = 10), and normal subjects (NML, n = 22), myocardial TG and CR were evaluated using proton magnetic resonance spectroscopy. To assess cardiac sympathetic nerve activity, myocardial MIBG (a radioactive guanethidine analog) uptake was measured in DCM. Myocardial TG was significantly lower in hypertrophic cardiomyopathy (HCM) (1.92 ± 0.99 μmol/g), but higher in ICM (7.59 ± 4.36 μmol/g) than in NML hearts (4.05 ± 1.94 μmol/g). There was no significant difference in TG between DCM (4.84 ± 6.45 μmol/g) and NML. Myocardial CR in HCM (20.4 ± 8.4 μmol/g), DCM (14.8 ± 4.8 μmol/g), and ICM (19.4 ± 6.3 μmol/g) was significantly lower than that in NML hearts (27.1 ± 4.3 μmol/g). Overall, myocardial CR correlated positively with the severity of heart failure estimated by ejection fraction or myocardial BMIPP (a radioactive fatty acid analog) uptake, but TG did not. In DCM, myocardial TG correlated with body mass index, but not with MIBG uptake. Myocardial TG may be related to the specific cause of disease rather than the severity of cardiac dysfunction. In contrast, myocardial CR reflects the severity of heart failure despite different pathoetiologic mechanisms of dysfunction. In DCM, myocardial TG may be affected by an overweight state rather than cardiac sympathetic nerve dysfunction. Thus, myocardial CR has a closer relationship to heart failure severity than does myocardial TG.

11C-meta-hydroxyephedrine defects persist despite functional improvement in hibernating myocardium

Regional cardiac sympathetic nerve dysfunction develops in hibernating myocardium and may play a role in its association with sudden cardiac death. Interventions to improve cardiac function (i.e., revascularization) improve survival, but the potential reversibility of sympathetic nerve dysfunction remains unclear. Pigs (n = 11) were chronically instrumented with a proximal left anterior descending coronary artery (LAD) stenosis to produce hibernating myocardium. Prior to therapeutic interventions, there was LAD occlusion with collateral-dependent myocardium, reduced regional function (echocardiographic LAD wall-thickening 23% +/- 4% vs 83% +/- 6% in Remote, P < .001), and large defects in (11)C-meta-hydroxyephedrine (HED) PET (48% +/- 4% of LV area, 26% +/- 2% integrated reduction). Successful PCI or pravastatin therapy improved regional (LAD wall-thickening 23% +/- 4% to 42% +/- 6%, P < .05) and global LV function (fractional shortening 24% +/- 2% to 31% +/- 2%, P < .01), but did not alter regional HED uptake, retention, defect size, or defect severity. Despite significant functional improvement of hibernating myocardium as a result of PCI or pravastatin therapy, there were no changes in HED defect size or severity. Thus, inhomogeneity in myocardial sympathetic innervation persisted, and the lack of plasticity suggests that even in the absence of significant infarction, structural rather than functional defects are responsible for reduced myocardial norepinephrine uptake in chronic ischemic heart disease.

Serum heart-fatty acid binding protein levels in patients with Lewy body disease

In order to examine a possible role of serum heart-fatty acid binding protein (H-FABP) in patients with Lewy body disease, we measured serum levels of H-FABP in patients with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD). Serum levels of H-FABP were measured using a solid-phase enzyme-linked immunoassay. Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy was performed on each patient and the heart to mediastinum (H/M) ratio was calculated. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the H-FABP between DLB and AD patients. Independent predictive variables for serum H-FABP levels were analyzed using multivariate regression analysis. Serum levels of H-FABP were significantly higher in DLB patients and PD patients than in AD patients. H/M ratios of the DLB and PD patients were significantly lower than those of AD patients. The diagnostic value of the serum H-FABP levels between AD and DLB patients was inferior to that of the delayed H/M ratio of (123)I-MIBG cardiac scintigraphy. Multivariate regression analysis revealed that the delayed H/M ratio predicted serum H-FABP levels in the PD patients. Examination of serum H-FABP levels did not allow discrimination between DLB and AD patients. Cardiac sympathetic nerve dysfunction may be associated with elevation of serum H-FABP in Lewy body disease patients.

Association of visual hallucinations with reduction of MIBG cardiac uptake in Parkinson's disease

Postganglionic cardiac sympathetic denervation is evident in patients with Parkinson's disease (PD) and iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy has proven to be a useful tool for diagnosis of PD. To elucidate the factors associated with severity of cardiac sympathetic nerve dysfunction in PD patients. We investigated 95 PD patients hospitalized in the Department of Neurology at Tottori University Hospital. (123)I-MIBG cardiac scintigraphy was performed on each patient and the early and delayed heart to mediastinum (H/M) ratios and washout rate (WR) of (123)I-MIBG cardiac scintigraphy were calculated. Independent predictive variables for parameters of (123)I-MIBG cardiac scintigraphy were analyzed by multivariate regression analysis. Multivariate regression analysis revealed that the presence of visual hallucinations (VH) and the patient's age at the time of evaluation independently predicted the early or delayed H/M ratio. Analysis of covariance, adjusted for the age of the patients as covariates, revealed that the early and delayed H/M ratios of PD patients with VH but no dementia, as well as PD patients with dementia were significantly lower than the ratios in PD patients with no VH or dementia. Cardiac sympathetic dysfunction may be associated with the presence of VH in PD patients.

221 Comparison of cardiac sympathetic nerve dysfunction as predictors of prognosis in diabetic cardiomyopathy in both insulin and non-insulin diabetes

221 Comparison of cardiac sympathetic nerve dysfunction as predictors of prognosis in diabetic cardiomyopathy in both insulin and non-insulin diabetes

Effects of metabolic and myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic neuropathy in type 2 diabetes mellitus: A prospective study in Japanese patients

In diabetic patients, cardiac autonomic neuropathy is an important factor affecting prognosis. Whether this condition in diabetic patients is caused directly by neurovisceral metabolic disorder and/or indirectly by micro circulation remains to be clarified. The aim of this study was to determine whether cardiac sympathetic nerve dysfunction can be detected using adenosine triphosphate (ATP) testing, while also investigating the effects of metabolic and/or myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic nerve dysfunction in patients with type 2 diabetes mellitus (DM-2) in Japan. This prospective study was performed at the Division of Diabetology Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan. Patients aged ≥ 18 years with DM-2 with no abnormalities on electrocardiography (ECG) or echocardiography were enrolled. An ATP thallium (Tl)-201 myocardial scintigraphy test (ATP test) and iodine (I)-123 metaiodobenzylguanidine (MIBG) scintigraphy were performed. ATP was administered by continuous IV infusion over 6 minutes at 0.16 mg/kg · min. Five minutes after the ATP infusion was started, T1-201 111 MBq IV was administered. Single-photon emission computed tomography (SPECT) imaging was begun immediately after the end of ATP infusion and was completed 3 hours after stress to show washout from stress to rest. I-123 MIBG 111 MBq IV was administered. A planar image from the front side and a SPECT image (early phase) was obtained 15 to 30 minutes later. After 3 hours, a planar image from the front side and a SPECT image (late phase) were obtained to show washout from stress to rest. The mean TI washout rate (ATP-WR) and heart-to-mediastinum (H/M) ratio in the late-phase scintigraphic images and the washout rate of MIBG (MIBG-WR) in the left ventricle was determined. The correlations of these measurements with the mean values of glycosylated hemoglobin (HbA1c) and fasting plasma glucose obtained from monthly measurements over the previous 6 and 24 months were determined. A total of 25 patients were enrolled (13 men, 12 women; mean [SD] age, 59.86 [8.28] years). Significant negative correlations between both ATP-WR and MIBG-WR and HbA1c were found (r = -0.52 [P = 0.02] and -0.47 [P = 0.03], respectively). Although no correlation was found between ATP-WR values and the early phase H/M ratio, a significant positive correlation was observed between ATP-WR and H/M ratio (r = 0.54; P = 0.02). In the present study in Japanese diabetic patients without subjective signs of coronary artery disease and without abnormalities on ECG or echocardiography, ATP-WR, an indicator of myocardial blood flow, was correlated with myocardial sympathetic nerve dysfunction and 24-month glycemic control. However, sympathetic nerve dysfunction was not correlated with 24-month glycemic control.

Cardiac Sympathetic Nerve Activity Can Detect Congestive Heart Failure Sensitively in Patients With Hypertrophic Cardiomyopathy

Cardiac sympathetic nerve dysfunction is related to poor clinical outcome in patients with several different heart diseases. However, it is not clear whether cardiac sympathetic nerve activity is useful for predicting the onset of congestive heart failure (CHF) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to examine the prognostic value of performing (123)I-labeled metaiodobenzylguanidine (MIBG) scintigraphy in patients with HCM in comparison with other conventional prognostic variables. (123)I-labeled MIBG images were obtained from 84 HCM patients without prior CHF. After measurement of cardiac function, the patients were followed up for 9 to 86 months in our hospital. According to the cutoff values for the heart/mediastinum ratio (H/M) on delayed images of control subjects (ie, mean - 1 and 2 SDs), the patients were subdivided into the following three groups: group A (H/M, > 2.11; 34 patients); group B (H/M, < 1.86 to </= 2.11; 30 patients); and group C (H/M, </= 1.86; 20 patients). The prevalence of CHF was 0% in group A, 3.3% in group B, and 55.0% in group C. Kaplan-Meier analysis showed a significant difference in the prevalence of CHF among the three groups. Multivariate analysis using the Wald chi(2) test revealed that the delayed H/M was the most powerful predictor of CHF among the variables. Cardiac sympathetic nerve activity is useful for predicting the onset of CHF in patients with HCM.