373 Utility of the early phase of DPD scintigraphy in the diagnosis of correlated TT-R cardiac amyloidosis

Aims The importance of cardiac scan with phosphonate-based radiotracers in the diagnosis of cardiac amyloidosis is now well established. Standard imaging is performed 3 h after tracer injection with a planar view on the cardiac region. This study sought to evaluate the predictive role of early-phase myocardial uptake (10 min after injection) of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) compared compared with standard late acquisition, in patients with suspected hereditary transthyretin-related cardiac amyloidosis (TTR-CA). Methods and results Fifty five patients with suspected of TTR-CA with typical aspects of the relative apical sparing at two-dimensional speckle-tracking echocardiography, reported as a specific pattern for cardiac amyloidosis, were enrolled after having signed informed written consent. They have been subjected to a 99mTc-DPD cardiac scintigraphy with planar acquisition at 10 min and 3 h after tracer injection (13 Mbq/Kg). Patients with cardiac uptake on the planar images concluded the examination with a SPECT-CT (cardiac protocol) to assess the affected myocardial segments. On planar images the heart-to-mediastinum-ratio was measured. Subsequently, the diagnosis of amyloidosis has to be confirmed with morphologic examinations such as biopsy and genetic tests. Of the enrolled patients with clinical and echocardiographic aspect of TTR-CA, 22 were positive for cardiac amyloidosis. All of them showed tracer uptake in both early and late images. In patients with positive results, the early-phase showed a Heart-to-mediastinum-ratio >1.2. SPECT/CT showed involvement of almost two myocardial segments: in all patients the ventricular septum showed significant tracer uptake. Conclusions Our small group of patients showed that 99mTc-DPD myocardial uptake intensity on early-phase scintigraphy can be used to anticipate the results of late images in diagnosis of TTR cardiac amyloidosis.

594 Impact of admission hyperglycaemia on heart failure events and mortality in patients with Takotsubo syndrome at long-term follow-up: data from the high-Glucotako investigators

Aims As known, Takotsubo Syndrome (TTS) can occur during stressful events that result in sympathetic overactivity. No studies have investigated the sympathetic activity and long-term prognosis in patients with TTS and admission hyperglycaemia vs. normoglycaemia. Moreover, whether hyperglycaemia may serve as a metabolic trigger to unbalance the sympathetic system axis as well as through over-inflammation is not fully understood. To investigate admission hyperglycaemia effects on the sympathetic system and long-term prognosis in Takotsubo syndrome (TTS). Methods and results In this multicentre study, we screened 4783 patients undergoing coronary angiography within the first 72 h of hospitalization for suspected acute coronary syndrome between January 2015 and January 2018. All enrolled patients met the InterTAK diagnostic criteria proposed in the European Society of Cardiology position statement for the diagnosis of TTS. Exclusion criteria encompassed patients with previous myocardial infarction, TTS events, or chronic kidney or liver disease. Patients with TTS were divided into those with hyperglycaemia vs. those with normoglycaemia according to a cutoff admission blood glucose value of 140 mg/dl. Sympathetic activity was assayed by blood values of norepinephrine and 123I-labelled metaiodobenzylguanidine (MIBG) cardiac scintigraphy with late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR), performed in 30 patients who did not present any contraindication to the examination, evaluated at baseline and at follow-up. Similarly, systemic inflammatory markers [C-reactive protein (CRP), white blood cell count (leukocytes and neutrophils), tumour necrosis factor-alpha (TNF-a)] and B-type natriuretic peptide (BNP) were assessed. Prespecified endpoints [heart failure (HF) and all-cause deaths] were assessed at long-term follow-up (12 and 24 months). At hospitalization, TTS patients with hyperglycaemia (N = 28) vs. those with normoglycaemia (M = 48) had significantly higher levels of inflammatory markers and B-type natriuretic peptide and lower left ventricular ejection fraction. Admission glucose values were correlated with norepinephrine levels (R2 = 0.39; P = 0.001). In 30 patients with TTS, 123I-MIBG cardiac scintigraphy showed lower late heart-to-mediastinum ratio values in the acute phase (P < 0.001) and at follow-up (P < 0.001) in those with hyperglycaemia. Patients with hyperglycaemia had higher rates of HF (P < 0.001) and death events (P < 0.05) after 24 months. In multivariate Cox regression analysis, hyperglycaemia (P = 0.008), tumour necrosis factor-alpha (P = 0.001), and norepinephrine (P = 0.035) were independent predictors of HF events. Conclusions Patients with TTS and hyperglycaemia exhibit sympathetic overactivity with a hyperglycaemia-mediated proinflammatory pathway, which could determine a worse prognosis during follow-up.

PARK2 Patient Presenting with Dopa-Responsive Dystonia

We report a 34-year-old female PARK2 patient presenting with dopa-responsive dystonia (DRD). She noticed difficulty in raising her foot while walking at the age of 24. Her lower limb symptoms were identified as dystonia later, and she was started on Menesit, which resulted in improvement of her symptoms. She was diagnosed as DRD and has been on continuous treatment since then. The specific binding ratio (SBR) of ¹²³I FP-CIT SPECT was significantly lower than those of controls of the same age, but ¹²³I-meta-iodobenzylguanidine myocardial scintigraphy showed a normal heart to mediastinum ratio. The Montreal Cognitive Assessment, Japanese version, was normal for her age. DRD is an inherited dystonia that typically begins during childhood and may be caused by mutations of the GCH1 (GTP cyclohydrolase), SPR (sepiapterin reductase), or TH (tyrosine hydroxylase) genes. Our patient was diagnosed as PARK2, known as autosomal-recessive juvenile Parkinson’s disease, based on genetic analysis. Although there was no family history of the disease, the decrease in SBR of ¹²³I FP-CIT SPECT enabled us to diagnose PARK2 and to differentiate this from DRD due to other genetic disorders.

Cardiac Autonomic Dysfunction Is Associated with Severity of REM Sleep without Atonia in Isolated REM Sleep Behavior Disorder

123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy was performed to assess cardiac autonomic dysfunction and demonstrate its correlation with clinical and polysomnographic characteristics in patients with isolated rapid eye movement (REM) sleep behavior disorder. All subjects including 39 patients with isolated REM sleep behavior disorder and 17 healthy controls underwent MIBG cardiac scintigraphy for cardiac autonomic dysfunction assessment. The isolated REM sleep behavior disorder was confirmed by in-lab overnight polysomnography. A receiver operating curve was constructed to determine the cut-off value of the early and delayed heart-to-mediastinum ratio in patients with isolated REM sleep behavior disorder. Based on each cut-off value, a comparison analysis of REM sleep without atonia was performed by dividing isolated REM sleep behavior disorder patients into two groups. MIBG uptake below the cut-off value was associated with higher REM sleep without atonia. The lower heart-to-mediastinum ratio had significantly higher REM sleep without atonia (%), both with cut-off values of early (11.0 ± 5.6 vs. 29.3 ± 23.2%, p = 0.018) and delayed heart-to-mediastinum ratio (9.1 ± 4.3 vs. 30.0 ± 22.9%, p = 0.011). These findings indicate that reduced MIBG uptake is associated with higher REM sleep without atonia in isolated REM sleep behavior disorder.

Global cardiac sympathetic denervation is associated with diffuse myocardial fibrosis in non-ischemic cardiomyopathy

Funding Acknowledgements Type of funding sources: None. Background Occurrence of ventricular tachycardias (VT) has been related to changes in sympathetic innervation and myocardial tissue in ischemic cardiomyopathy. In non-ischemic cardiomyopathy (NICM) patients with VT, the relation between global cardiac sympathetic innervation and non-ischemic fibrosis is less clear. The current gold standard in electrophysiology to identify non-ischemic fibrosis relies on unipolar endocardial voltage mapping. Objective To establish the relationship between global cardiac sympathetic innervation and global fibrosis. Methods 29 patients (93% male, 58 ± 14 years, mean LVEF 38%±13) from the ‘Leiden Nonischemic Cardiomyopathy Study’ undergoing VT ablation between 2011-2018 were included. Endocardial voltage mapping was performed and the mean endocardial unipolar voltage (UV) was taken as a surrogate for global fibrosis. Global cardiac sympathetic innervation was analyzed by 123-I-MIBG imaging using heart-to-mediastinum ratio (HMR). A cut-off of 1.8 was used to delineate between normal (>1.8) and denervated (<1.8). HMR was correlated with mean UV. Results For patients with global cardiac sympathetic denervation a linear relationship was present between HMR and mean UV (R = 0.5278, P = 0.0431. There was no significant linear relationship for patients with normal cardiac sympathetic innervation between HMR and mean UV (R=-0.1696, P = 0.5795). Conclusion Global cardiac sympathetic denervation is related to myocardial fibrosis in patients with NICM and VT. The data support an interplay between denervation and fibrosis which may contribute to arrhythmogeneity, as observed in ICM. Abstract Figure.

MIBG Cardiac Scintigraphy as a Potential Biomarker That Reflects Severity in Idiopathic REM Sleep Behavior Disorder

Study Objectives: 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy was performed to demonstrate the correlation with clinical characteristics of patients with idiopathic REM sleep behavior disorder (iRBD) and we found the factors that are associated with neurodegenerative diseases. Methods: All subjects including 39 patients with iRBD and 17 healthy controls underwent MIBG cardiac scintigraphy to assess cardiac autonomic dysfunction. The iRBDs were confirmed by in-lab overnight polysomnography. Receiver operating curve was performed to determine cut-off value of early and delayed heart to mediastinum ratio (HMR) in patients with iRBD. Based on each cut-off value, comparison analysis about RWA was performed by dividing into two groups within iRBD patients.Results: MIBG uptake below the cut-off value is associated with higher REM sleep without atonia (RWA). The lower HMR had significantly higher RWA (%) both with the cut-off value of early (11.0±5.6 VS 29.3±23.2, p=0.018) and delayed HMR (9.1±4.3 VS 30.0±22.9, p=0.011).Conclusion: This study suggests that MIBG uptake is a potential biomarker of the severity of RWA in iRBD.

Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy

Abstract[18F]fluorodeoxyglucose (FDG) PET and [123I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 ± 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson’s disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.