Cardiac 123I-MIBG Scintigraphy Research Articles

Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder

Abstract Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson’s disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43–87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1–3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson’s disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio < 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson’s disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson’s disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson’s disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.

Optimal Protocol and Clinical Usefulness of 123I-MIBG Cardiac Scintigraphy for Differentiation of Parkinson's Disease and Dementia with Lewy Body from Non-Parkinson's Diseases.

123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy was a useful imaging modality for the diagnosis of Parkinson's disease, but its diagnostic performances were variably reported. This retrospective study compared the diagnostic performances and investigated the optimal imaging protocol of 123I-MIBG cardiac scintigraphy at various imaging time points in patients suspected of Parkinson's disease in clinical practice. In patients suspected of Parkinson's disease, clinical records, autonomic function tests, and 123I-MIBG cardiac scintigraphy were retrospectively reviewed. Semi-quantitative parameters such as heart-to-mediastinum ratio (HMR) and washout rate (WR) were calculated and compared at 15 min, 1 h, 2 h, 3 h, and 4 h post-injection (p.i.). of 123I-MIBG cardiac scintigraphy. Group A consisted of Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy body (DLB), and group B consisted of non-Parkinson's diseases such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), drug-induced parkinsonism (DIP), essential tremor (ET), Parkinson-plus syndrome (PPS), and unspecified secondary parkinsonism (NA). The diagnostic performances of HMR and WR were compared for differentiation of group A from group B, and their clinical usefulness and optimal imaging time points were explored. Seventy-eight patients were included in group A (67 PD, 7 PDD, 4 DLB), and 18 patients were included in group B (5 MSA, 3 PSP, 2 DIP, 2 ET, 1 PPS, and 1 NA). Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value of HMR and WR were maximized at 4 h p.i., (82.1%, 85.7%, 82.6%, 97.0%, and 46.2%; cutoff threshold < 1.717; area under curve 0.8086) and at the time interval between 1 and 4 h p.i. (65.4%, 85.7%, 68.5%, 96.2%, and 30.8%; cutoff threshold > 24.1%; area under curve 0.8246), respectively, and PPVs of both HMR and WR persistently showed greater than 92.7% at earlier time points and shortertime intervals. This study reassured that 4-h-delayed imaging is recommended for the best diagnostic performances in 123I-MIBG cardiac scintigraphy. Although it showed suboptimal diagnostic performances to differentiate PD, PDD, and DLB from non-Parkinson's diseases, it can be useful as an auxiliary measure for the differential diagnosis in usual clinical practice. The online version contains supplementary material available at 10.1007/s13139-023-00790-w.

Cardiac 123I-mIBG scintigraphy for prediction of catheter ablation outcome in patients with atrial fibrillation

BackgroundPrevious studies show inconsistent results on the role of innervation imaging (with 123I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post-CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF. Methods123I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patient was followed for 12 months. ResultsMultivariable analysis demonstrated that late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/Mlate <1.6 (sensitivity 73.53%, specificity 81.3%, AUC 0.792, P < .001) and WR > 25.11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0.712, P < .001) indicate high probability of AF relapses during 12 months after CA. ConclusionPre-CA parameters of global cardiac sympathetic activity estimated by 123I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients with normal LVEF and absence of significant CAD.

The value of cardiac sympathetic activity and mechanical dyssynchrony as cardiac resynchronization therapy response predictors: comparison between patients with ischemic and non-ischemic heart failure

BackgroundImpaired cardiac sympathetic activity and mechanical dyssynchrony (MD) are associated with poor prognosis in patients with heart failure (HF) after cardiac resynchronization therapy (CRT). The study aims to assess the significance of scintigraphic evaluation of cardiac sympathetic innervation and contractility in predicting response to CRT in patients with ischemic and non-ischemic chronic HF. Methods and resultsThe study includes 58 HF patients, who were referred for CRT. Prior to CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging and gated myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) SPECT/CT device. At a one-year follow-up post-CRT, the delayed heart-to-mediastinum 123I-MIBG uptake ratio was an independent predictor of CRT response in non-ischemic HF patients (OR 1.469; 95% CI 1.076-2.007, p = .003). In ischemic HF patients the MD index histogram bandwidth (HBW) obtained by CZT-gated MPI had a predictive value (OR 1.06, 95% CI 1.001-1.112, p = .005) to CRT response. ConclusionCRT response can be predicted by cardiac 123I-MIBG scintigraphy, specifically by the heart-to-mediastinum ratio in non-ischemic HF and by the MD index HBW in ischemic HF. These results suggest the value of a potentially useful algorithm to improve outcomes in HF patients who are candidates for CRT.

Cardiac 123I-mIBG Imaging in Heart Failure.

Cardiac sympathetic upregulation is one of the neurohormonal compensation mechanisms that play an important role in the pathogenesis of chronic heart failure (CHF). In the past decades, cardiac 123I-mIBG scintigraphy has been established as a feasible technique to evaluate the global and regional cardiac sympathetic innervation. Although cardiac 123I-mIBG imaging has been studied in many cardiac and neurological diseases, it has extensively been studied in ischemic and non-ischemic CHF. Therefore, this review will focus on the role of 123I-mIBG imaging in CHF. This non-invasive, widely available technique has been established to evaluate the prognosis in CHF. Standardization, especially among various combinations of gamma camera and collimator, is important for identifying appropriate thresholds for adequate risk stratification. Interestingly, in contrast to the linear relationship between 123I-mIBG-derived parameters and overall prognosis, there seems to be a “bell-shape” curve for 123I-mIBG-derived parameters in relation to ventricular arrhythmia or appropriate implantable cardioverter defibrillator (ICD) therapy in patients with ischemic CHF. In addition, there is a potential clinical role for cardiac 123I-mIBG imaging in optimizing patient selection for implantation of expensive devices such as ICD and cardiac resynchronization therapy (CRT). Based on cardiac 123I-mIBG data risk models and machine learning, models have been developed for appropriate risk assessment in CHF.

Myocardial innervation imaging: MIBG in clinical practice

Abstract 123I-metaiodobenzylguanidine (MIBG) is a radiolabeled norepinephrine analog that can be used to investigate myocardial sympathetic innervation. 123I MIBG scintigraphy has been investigated with interest in many disease settings. In patients with systolic heart failure (HF), 123I MIBG scintigraphy can capture functional impairment and rarefaction of sympathetic terminals (which manifest as reduced early and late heart-to-mediastinum [H/M] ratio on planar scintigraphy), and increased sympathetic outflow (which can be visualized as high washout rate). These findings have been consistently associated with a worse outcome: most notably, a phase 3 trial found that patients with a late H/M 1.60 have a higher incidence of all-cause and cardiovascular mortality and life-threatening arrhythmias over a follow-up of less than 2 years. Despite these promising findings, 123I MIBG scintigraphy has not yet been recommended by major HF guidelines as a tool for additive risk stratification, and has then never entered the stage of widespread adoption into current clinical practice. 123I MIBG scintigraphy has been evaluated also in patients with myocardial infarction, genetic disorders characterized by an increased susceptibility to ventricular arrhythmias, and several other conditions characterized by impaired sympathetic myocardial innervation. In the present chapter we will summarize the state-of-the-art on cardiac 123I MIBG scintigraphy, the current unresolved issues, and the possible directions of future research.

Association of plasma α-synuclein with cardiac 123I-MIBG scintigraphy in early Parkinson’s disease

Cardiac 123I-metaiodobenzylguanidine (MIBG) uptake correlates with the extent of cardiac sympathetic denervation found in disease with Lewy pathology, such as Parkinson’s disease (PD). Protein α-synuclein, the main component of Lewy body, is a candidate biomarker of PD, but its relationship with cardiac MIBG uptake has never been explored. Plasma α-synuclein levels were measured in 37 patients with early PD. Cardiac 123I-MIBG scintigraphy and 18F-FP-CIT brain PET were performed, and striatal dopamine transporter (DAT) uptake was quantified using automated segmentation. The relationships of plasma α-synuclein levels with cardiac MIBG and striatal DAT uptake were investigated. The plasma α-synuclein level correlated with early (R = 0.38, P = 0.033) and delayed (R = 0.49, P = 0.0055) MIBG heart-to-mediastinum (H/M) ratios, and its correlation with delayed H/M ratio remained significant after adjustment with age, disease duration, motor severity, and striatal DAT uptake (P = 0.016). The regional SUVRs of any subregions of caudate and putamen did not correlate with plasma α-synuclein level. In the patients with early PD, the plasma α-synuclein level correlated with cardiac sympathetic denervation, but not with nigrostriatal degeneration. This may suggest that plasma α-synuclein levels more readily reflect the peripheral deposition of Lewy bodies than their central deposition.

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

Abstract 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 &amp;lt; 0.001) and at follow-up (P &amp;lt; 0.001) in those with hyperglycaemia. Patients with hyperglycaemia had higher rates of HF (P &amp;lt; 0.001) and death events (P &amp;lt; 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.

Relationship between heart rate response and cardiac innervation in patients with suspected or known coronary artery disease

BackgroundChronotropic response to pharmacological stress test is blunted in patients with autonomic neuropathy. The relationship between heart rate (HR) changes during pharmacological stress test and cardiac autonomic dysfunction has not been fully investigated. We assessed the potential interplay between HR response (HRR) and myocardial innervation in patients with suspected or known coronary artery disease (CAD). Methods and ResultsWe studied 71 patients with suspected or known CAD referred to pharmacological stress myocardial perfusion imaging and 123I metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy. HRR was calculated as the maximum percent change from baseline according to the formula: (peak HR − rest HR)/rest HR × 100. 123I-MIBG heart-to-mediastinum (H/M) ratio was calculated and a late H/M ratio < 1.6 was considered abnormal. HRR progressively decreased with decreasing late H/M ratio (P for trend = 0.02) and a significant correlation between HRR and late H/M ratio (P = 0.03) was observed. The addition of HRR to a model including age, diabetes, known CAD, left ventricular ejection fraction, and stress-induced ischemia added incremental value in predicting an abnormal late H/M ratio, increasing the global chi-square from 8.09 to 13.8 (P = 0.02). ConclusionsThe relationship between HRR and cardiac sympathetic innervation in patients with suspected or known CAD confirms a strong interplay between cardiac response to stress tests and cardiac autonomic activation. This finding suggests that HRR may be used as a surrogate for assessing cardiac sympathetic function.

Abstract 9177: Prognostic Value of Chronic Kidney Disease and Cardiac Sympathetic Dysfunction Assessed by 123 I-metaiodobenzylguanidine Scintigraphy for Lethal Arrhythmic Events in Chronic Heart Failure

Introduction: Clinical implication of chronic kidney disease (CKD) and cardiac sympathetic nerve activity (CSNA) for lethal arrhythmic events has not been fully elucidated in patients with chronic heart failure (CHF). Hypothesis: The combination of CKD and abnormal CSNA, assessed by 123 I-metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy, may provide useful prognostic information for the incidence of lethal arrhythmic events. Methods: We studied 165 consecutive hospitalized CHF patients without dialysis. In a clinically stable condition, cardiac 123 I-MIBG scintigraphy was performed. CKD was defined as estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m 2 , and abnormal CSNA was defined as late heart to mediastinum ratio &lt;1.6. We then investigated the incidence of lethal arrhythmic events (sustained ventricular arrhythmia, appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death). Results: During a median follow-up of 5.3 years, lethal arrhythmic events were observed in 40 patients (24.2%). The patients were divided into 4 groups according to the presence of CKD and CSNA abnormality: non-CKD/ normal CSNA ( n = 52), CKD/ normal CSNA ( n = 39), non-CKD/ abnormal CSNA ( n = 33), and CKD/ abnormal CSNA ( n = 41).The Kaplan-Meier analysis showed that CKD/ abnormal CSNA had the highest event rate (log-rank p = 0.004). In addition, the multivariable Cox proportional hazard analysis after the adjustment of multiple confounders showed that CKD/ abnormal CSNA was an independent predictor for lethal arrhythmic events compared to non-CKD/ normal CSNA (HR, 4.667, p = 0.006). However, the other two groups did not show significant differences compared to non-CKD/ normal CSNA. Conclusions: The combination of CKD and abnormal CSNA, assessed by cardiac 123 I-MIBG scintigraphy, had a significant prognostic value for the incidence of lethal arrhythmic events in patients with CHF.

Intrasubject relationship between striatal 18F-FP-CIT uptake and cardiac 123I-MIBG uptake differs by motor subtype in early Parkinson disease.

Parkinson disease (PD) is a heterogeneous neurodegenerative disorder. Dopamine transporter imaging using 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (FP-CIT) and noradrenergic cardiac imaging using 123I-meta-iodobenzylguanidine (MIBG) have been used in combination or separately to study PD patients. Published results regarding uptake of the 2 tracers in each motor subtype are fairly abundant and mostly in agreement. However, data on the intrasubject association between dopaminergic and noradrenergic systems in PD patients are relatively scant and vary. We aimed to assess the intrasubject relationship between striatal dopamine transporter density using a PET tracer and cardiac sympathetic innervation in tremor-dominant subtype (TD) and akinetic-rigid subtype (AR) of PD.This study has a cross-sectional design. Thirty-one patients with early PD (17 TD/14 AR) who underwent both 123I-MIBG cardiac scintigraphy and 18F-FP-CIT PET/CT were retrospectively selected. We assessed the relationship between heart-to-mediastinum ratio (H/M) of 123I-MIBG and specific (striatal)-to-nonspecific (cerebellar) dopamine transporter binding ratio (S/N) measured from 4 separate regions-of-interest (bilateral caudate nuclei and lentiform nuclei) of 18F-FP-CIT in each motor subtype.S/N of all 4 striatal regions were significantly lower in the AR subgroup than in the TD subgroup. H/M was not significantly different. There was a significant intrasubject correlation between H/M and S/N of the lentiform nucleus in AR-PD but no correlation between H/M and any of 4 S/N in TD-PD.Our data suggest a coupled degeneration of nigrostriatal dopaminergic and myocardial sympathetic denervation in AR subtype, but not in TD subtype, of early PD patients. These different results between the 2 motor subtypes likely reflects the heterogeneous pathophysiology of PD.

Sympathetic modulation by antihypertensive drugs.

Sympathetic modulation by antihypertensive drugs.

Value of cardiac 123I-mIBG scintigraphy in prognosis of catheter ablation outcome in patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Science Foundation Background. Previous studies show inconsistent results on the role of innervation imaging (with 123I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF. Thus, the goal of the present study was to estimate the utility of pre-procedural cardiac 123I-mIBG scintigraphy to identify patients at risk for AF recurrence after CA. Methods. 123I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patients were followed for 12 months. A blanking period of 3 months was applied. The primary endpoint of the study was AF recurrence between 3 and 12 months after ablation. Results. Multivariable analysis demonstrated that late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/Mlate &amp;lt;1.6 (sensitivity 73.53 %, specificity 81.3%, AUC 0,792 , p &amp;lt; 0.001) and WR &amp;gt; 25,11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0,712 , p &amp;lt; 0.001) indicate high probability of AF relapses during 12 months after CA. Kaplan-Meier analysis showed that the H/Mlate &amp;lt; 1.6, WR &amp;gt; 25,11 and LAD &amp;gt; 45 mm significantly increase the risk of AF recurrence after CA (p &amp;lt; 0.001, p &amp;lt; 0.001, p &amp;lt; 0.025 respectively). Conclusion. Pre CA parameters of global cardiac sympathetic activity estimated by 123I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients.

Impact of Admission Hyperglycemia on Heart Failure Events and Mortality in Patients With Takotsubo Syndrome at Long-term Follow-up: Data From HIGH-GLUCOTAKO Investigators.

To investigate admission hyperglycemia effects on the sympathetic system and long-term prognosis in Takotsubo syndrome (TTS). In patients with TTS and hyperglycemia (n = 28) versus normoglycemia (n = 48), serum norepinephrine and 123I-labeled metaiodobenzylguanidine (MIBG) cardiac scintigraphy were assessed. Heart failure (HF) occurrence and death events over 2 years were evaluated. At hospitalization, those with hyperglycemia versus normoglycemia had higher levels of inflammatory markers and B-type natriuretic peptide and lower left ventricular ejection fraction. Glucose values correlated with norepinephrine levels (R 2 = 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 hyperglycemia. Patients with hyperglycemia had higher rates of HF (P < 0.001) and death events (P < 0.05) after 24 months. In multivariate Cox regression analysis, hyperglycemia (P = 0.008), tumor necrosis factor-α (P = 0.001), and norepinephrine (P = 0.035) were independent predictors of HF events. Patients with TTS and hyperglycemia exhibit sympathetic overactivity with a hyperglycemia-mediated proinflammatory pathway, which could cause worse prognosis during follow-up.

The prognostic significance of cardiac sympathetic activity and dyssynchrony in cardiac resynchronization therapy in ischemic and non-ischemic heart failure patients

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Foundation for Basic Research Introduction Impaired cardiac sympathetic activity and contractility are associated with poor prognosis in patients with heart failure after cardiac resynchronization therapy (CRT). There are few prognostic data of the cardiac sympathetic activity and dyssynchrony in patients with chronic heart failure of various etiologies. Purpose To examine the prognostic significance of scintigraphic cardiac sympathetic activity and contractility in predicting the response to CRT and to assess the differences between patients with ischemic (IHF) and non-ischemic (NIHF) heart failure. Methods This study included 38 heart failure patients (24 male; mean age of 56 ± 11 years; 16 patients with ischemic etiology), who were submitted to CRT. Before CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging for cardiac sympathetic activity evaluating: early and delay heart to mediastinum ratio (eH/M and dH/M), summed MIBG Score (eSMS and dSMS). Moreover all patients underwent gated SPECT with the assessments of left ventricle dyssynchrony indexes: standard deviation (SD) and histogram bandwidth (HBW). In addition, all patients underwent gated blood-pool SPECT (GBPS) to assessed ejection fraction (EF) and stroke volume (SV) of both ventricles. Results One year after CRT response defined as LV ESV decreased by≥15% and/or LV EF increase by≥5%. Baseline cardiac sympathetic activity parameters showed significant differences between responders and non-responders only in NIHF patients: eH/M: 2.27 (2.02–2.41) vs. 1.64 (1.32–2.16); dH/M: 2.18 (2.11–2.19) vs. 1.45 (1.23 – 1.61); eSMS: 7 (5-7) vs. 15.5 (10–28.5); dSMS: 10 (10–13) vs. 16.5 (15.5–29). Significant differences in baseline LV dyssynchrony indexes between responders and non-responders were in patients of both group: in NIHF patients - SD: 54.3 (43–58) degree vs. 65 (62–66) degree; HBW: 179.5 (140–198) degree vs. 211 (208-213) degree, p &amp;lt; 0.054 in IHF patients - HBW: 162 (115.2–180) degree vs. 115.2 (79.2–136.8) degree. Contractility of RV was significantly differed between responders and non-responders in IHF patients: RV EF: 54.5 (41-56) % vs. 44.5 (37–49.5) %; RV SV: 80 (69-101) ml vs. 55.5 (50–72.5) ml. According to univariate logistic regression analyses in IHF patients LV dyssynchrony indexes – SD (OR = 1.55; 95% CI 1.09-2.2; p &amp;lt; 0.5) and HBW (OR = 1.13; 95% CI 1.02-1.24; p &amp;lt; 0.5), as well as RV indexes – RV EF (OR = 1.11; 95% CI 1.001-1.23; p &amp;lt; 0.5), RV SV (OR = 1.07; 95% CI 1.003-1.138; p &amp;lt; 0.5) were predictors of CRT response. In the group of NIHF patients, dH/M (OR = 1.47; 95% CI 1.08-2; p &amp;lt; 0.5), SD (OR = 0.83; 95% CI 0.73-0.95; p &amp;lt; 0.5), HBW (OR = 0.96; 95% CI 0.93-0.99; p &amp;lt; 0.5) showed the predictive value in terms of CRT response. Conclusion Scintigraphic methods can be used to select patients for CRT. Cardiac 123I-MIBG scintigraphy and gated SPECT may be used for predicting CRT response in NIHF patients. Whereas in IHF patients ECG-gated SPECT and GBPS may be valuable for predicting the response to CRT.

Clinical and neuroendocrinological characteristics of delayed orthostatic hypotension in Parkinson's disease.

Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and neuroendocrinological characteristics of DOH in patients with Parkinson's disease (PD). A total of 132 patients with newly diagnosed PD were enrolled. Baseline clinical characteristics, including olfactory function, and changes in norepinephrine (NE) and vasopressin (ADH) concentrations during the head-up tilt test (HUT), were examined. Fifty-five patients (42%) had classical orthostatic hypotension (COH), and 19 patients (14%) had DOH. Patients with COH and DOH tended to have more severe hyposmia than patients without OH. A multivariate linear regression model showed that hyposmia was associated with DOH and COH. The increase of heart rate against the fall in blood pressure was significantly lower in patients with COH and DOH than those without OH. The NE levels at supine rest and after upright tilting were lower in the COH group than in the PD without OH and DOH groups. The levels of ADH were higher in the DOH group than in the COH group at supine rest and higher than in the PD without OH group after upright tilting. There was no significant difference in the cardiac 123I-MIBG scintigraphy between the COH and DOH groups. Compared with patients without OH, patients with DOH had severe hyposmia. Relatively preserved peripheral sympathetic nervous system function in patients with DOH suggests that DOH might be an early and milder form of OH in PD.

Impact of the number of comorbidities on cardiac sympathetic derangement in patients with reduced ejection fraction heart failure

IntroductionHeart failure (HF) is frequently associated with comorbidities. 123I-metaiodobenzylguanidine (123I-mIBG) imaging constitutes an effective tool to measure cardiac adrenergic innervation and to improve prognostic stratification in HF patients, including the risk of major arrhythmic events. Although comorbidities have been individually associated with reduced cardiac adrenergic innervation, thus suggesting increased arrhythmic risk, very comorbid HF patients seem to be less likely to experience fatal arrhythmias. We evaluated the impact of the number of comorbidities on cardiac adrenergic innervation, assessed through 123I-mIBG imaging, in patients with systolic HF. MethodsPatients with systolic HF underwent clinical examination, transthoracic echocardiography and cardiac 123I-mIBG scintigraphy. The presence of 7 comorbidities/conditions (smoking, chronic obstructive pulmonary disease, diabetes mellitus, peripheral artery disease, atrial fibrillation, chronic ischemic heart disease and chronic kidney disease) was documented in the overall study population. ResultsThe study population consisted of 269 HF patients with a mean age of 66±11 years, a left ventricular ejection fraction (LVEF) of 31±7%, and 153 (57%) patients presented ≥3 comorbidities. Highly comorbid patients presented a reduced late heart to mediastinum (H/M) ratio, while no significant differences emerged in terms of early H/M ratio and washout rate. Multiple regression analysis revealed that the number of comorbidities was not associated with mIBG parameters of cardiac denervation, which were correlated with age, body mass index and LVEF. ConclusionIn systolic HF patients, the number of comorbidities is not associated with alterations in cardiac adrenergic innervation. These results are consistent with the observation that very comorbid HF patients suffer lower risk of sudden cardiac death.

Reduced Cardiac 123I-MIBG Scintigraphy and Olfactory Impairment in Idiopathic REM Sleep Behavior Disorder

Cardiac 123I-MIBG scintigraphy (cMIBG) and an olfactory function test using the Odor Stick Identification Test for Japanese (OSIT-J) were performed for 46 patients with idiopathic REM behavior disorder (iRBD). The H/M ratio on cMIBG of iRBD patients was classified according to the Hoehn-Yahr's (H-Y) stages of Parkinson's disease (PD) as follows: early images, normal range, 11(23.9%); H-YI, 3 (6.5%); H-YII, 5 (10.9%); ≥ H-YIII, 27 (58.7%); and delayed images, normal range, 9 (19.6%); H-YI, 3 (6.5%); H-YII, 1 (2.2%); ≥ H-YIII, 33 (71.7%). The OSIT-J scores decreased in 76.2% of iRBD patients, and 20.5% of Normal subjects. The OSIT-J scores in iRBD patients were strongly correlated with the H/M ratio on early and delayed cMIBG images (p<0.001, Pearson correlation coefficient). PD progresses from H-Y stage I to V, with the H/M ratio on cMIBG decreasing as the H-Y stage progresses.The H/M ratio in iRBD patients decreased to PD H-Y III/IV or dementia with Lewy bodies (DLB) levels in 71.7% of patients.Thus, in many cases, iRBDs is a precursor of DLBs but not of PDs. Although olfactory dysfunction has no disease specificity, it is a simple and useful screening test that can be applied before cMIBG for patients with iRBD.

P542Cardiac autonomic dysfunction and inflammatory response in heart failure - markers for cardiac resynchronization therapy response?

Abstract Funding Acknowledgements FCP Introduction Cardiac sympathetic activation and inflammatory response are involved in chronic heart failure (HF) pathophysiology. The severity of autonomic dysfunction and inflammation might be responsible for different responses to HF treatment. Aim To evaluate the impact of cardiac autonomic dysfunction, and it´s association with systemic inflammation, on cardiac resynchronization therapy (CRT) response in severe HF patients. Methods Single centre, prospective, longitudinal study, including consecutive patients, referred to CRT. Demographic data, HF aetiology and NYHA class were evaluated. Left ventricular (LV) function data (LV ejection fraction - LVEF) by echocardiography, heart to mediastinum early ratio (HMRe) by 123I-MIBG cardiac scintigraphy, and plasmatic TNF-α levels (pg/mL) were determined, at baseline and 4 months after CRT implantation. CRT response was defined by an absolute increase of at least 5% in LVEF at 4 months evaluation after CRT. Patients were divided in 4 groups according to HMRe and TNF-α cut-points: Group I (TNF-α &amp;gt; 2.0 pg/ml + HMRe ≥ 1.6), Group II (TNF-α &amp;gt; 2.0 pg/ml + HMRe &amp;lt; 1.6), Group III (TNF-α ≤ 2.0 pg/ml + HMRe ≥ 1.6) and Group IV (TNF-α ≤ 2.0 pg/ml + HMRe &amp;lt; 1.6). Data was analyzed using descriptive statistics and groups were compared by Fisher"s exact test. Results A total of 95 patients were included (age 68.6 ± 10.2 years), 67.4% male and 32.6% female, 40% with diabetes mellitus, 30.5% with ischemic cardiomyopathy, 23.2% in NYHA III/IV, baseline LVEF - 26 ± 7%. At 4 months, LVEF was 40 ± 11%. In total, 73.7% were responders and 26.3% were non-responders to CRT. There were 28 patients (29.5%) with HMRe ≥ 1.6, with 25 responders (89.3%) and 48 patients (50.5%) with TNF-α ≤ 2.0 pg/ml, with 38 responders (79.2%). Group I had 16 patients (16.8%), with 81.2% responders; Group II had 31 patients (32.7%), with 61.3% responders; Group III had 12 patients (12.6%), with 100% responders, and Group IV had 36 patients (37.9%), with 72.2% responders. Conclusion: In patients with severe HF submitted to CRT, combining cardiac autonomic dysfunction and inflammation, associated to high rate of CRT non response. Contrarily, those with preserved cardiac autonomic function and no increased levels of inflammation identified most significantly CRT responders. CRT response according to HMRe and TNFα HMRe ≥ 1.6 (n = 28) HMRe &amp;lt; 1.6 (n = 67) Responders NO Respondersn (%) Responders NO Respondersn (%) TNF α &amp;gt; 2 pg/mL (n = 47) G I: 13 (81.2%) 3 (18.8%) GII: 19 (61.3%) 12 (38.7%) * TNF α ≤ 2 pg/mL (n = 48) G III: 12 (100%) 0 (0%)* G IV: 26 (72.2%) 10 (27.8%)

The relation between cardiac 123I-mIBG scintigraphy and functional response 1 year after CRT implantation.

Aims Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection.Methods and results A total of 78 stable CHF subjects (age 66.8 ± 9.6 years, 73% male, LVEF 25.2 ± 6.7%, QRS duration 153 ± 23 ms, NYHA 2.2 ± 0.7) referred for CRT implantation were enrolled. Subjects underwent 123I-mIBG scintigraphy prior to implantation. Early and late heart-to-mediastinum (H/M) ratio and 123I-mIBG washout were calculated. CRT response was defined as either an increase of LVEF to >35%, any improvement in LVEF of >10%, QRS shortening to <150 ms, or improvement in NYHA class of >1 class. In 33 patients LVEF increased to >35%, QRS decreased <150 ms in 36 patients, and NYHA class decreased in 33 patients. Late H/M ratio and hypertension were independent predictors of LVEF improvement to >35% (P = 0.0014 and P = 0.0149, respectively). In addition, early H/M ratio, LVEF, and absence of diabetes mellitus (DM) were independent predictors for LVEF improvement by >10%. No independent predictors were found for QRS shortening to <150 ms or improvement in NYHA class.Conclusion Early and late H/M ratio were independent predictors of CRT response when improvement of LVEF was used as measure of response. Therefore, cardiac 123I-mIBG scintigraphy may be used as a tool to optimize selection of subjects that might benefit from CRT.