Sympathetic innervation pattern in NICM patients with ventricular tachycardia -anteroseptal versus inferolateral substrates-

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation - Projektnummer 447558597) Background Among patients with non-ischemic cardiomyopathy (NICM) two dominant ventricular tachycardia (VT) substrate locations, namely anteroseptal (AS) and inferolateral (IL), have been identified. The poor outcome after catheter ablation of AS substrates (ASS) compared to IL substrates (ILS) has been attributed to its deep intramural location. However, region specific tissue charateristics, including sympathetic innervation, as important determinant of arrhythmogeneity, may also contribute to the outcome disparity. Aim To evaluate the association between regional sympathetic denervation, myocardial fibrosis and VT substrates according to two dominant VT substrate locations. Methods Twenty-nine patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent electroanatomical substrate mapping and radiofrequency catheter ablation (RFCA), LGE-CMR and 123-I-MIBG imaging between 2011-2018 were included. The 16-segment model was used to describe the distribution of endocardial low unipolar voltage (UV <25th IQR) (=electroanatomical surrogate for fibrosis), the location of abnormal local electrograms and VT related sites (= surrogate for VT substrate) and the presence of LGE. Regional cardiac sympathetic innervation was determined by 123-I-MIBG imaging and analyzed according to the 16-segment model. Regions with sympathetic denervation were correlated with low UV areas, VT substrate location and LGE. Patients were categorized according to the dominant VT substrate location in ASS or ILS. Results Ten patients had a dominant ASS, 12 patients a dominant ILS and 1 patient had ASS and ILS; 6 patients had other VT substrate locations. All but one patient with ASS and one with ILS also showed corresponding low UV (=surrogate for fibrosis) in segments with VT substrates. Eight patients with IL VT substrates but only 4 with AS substrates showed corresponding LGE in the VT related segments. All patients with inferolateral VT substrates showed sympathetic denervation in IL segments (100% matching segments), but only 3/11 (27%) with anteroseptal substrates had sympathetic denervation in AS segments (P = 0.0002). UV was not significantly different between matching (VT substrate and denervation) and not matching ASS segments (5.74 ± 2.69 mV vs. 4.64 ± 1.85 mV, P = 0.78) and between matching ASS and ILS segments (5.74 ± 2.69 mV vs. 7.61 ± 2.91, P = 0.43). LGE location was matching with sympathetic denervation in all patients with ILS but only in 33% of patients with ASS. Conclusion Despite low endocardial UV (=surrogate for fibrosis) for AS and IL segments harboring VT substrates, regional sympathetic denervation coincided with fibrosis only for IL VT substrates. The mismatch between regional fibrosis and preserved innervation for AS VT substrates may contribute to a VT substrate difficult to control by RFCA.

40 Years Anniversary of Cardiac 123I-mIBG Imaging: State of the Heart

Purpose of Review This narrative review reflects on the body of evidence on cardiac 123I-mIBG imaging that has accumulated since the introduction in the late 1970s and focusses on to what extent cardiac 123I-mIBG imaging has fulfilled its potential in cardiology especially. Recent Findings In contrast to the linear relationship between 123I-mIBG-derived parameters and overall prognosis in heart failure, there seems a “bell-shape” curve for 123I-mIBG-derived parameters and arrhythmic events. In addition, there is a potential clinical role for cardiac 123I-mIBG in optimizing patient selection for expensive devices (i.e., ICD and CRT). This needs of course to be established in future trials. Summary Cardiac 123I-mIBG imaging is, despite the numerous of studies, sometimes mistakenly seen as a nice to have technique rather than a must have imaging modality. Although cardiac 123I-mIBG imaging has grown and matured over the years, its full clinical potential has still not been tested to the maximum.

Using Multimodal Functional Imaging in the Management of SDHx-Related Pheochromocytoma and Paraganglioma

Background: Succinate Dehydrogenase (SDH) subunit pathogenic variants predispose to Pheochromocytoma and Paraganglioma (PPGL). Functional imaging harnesses the innate receptor expression and the aberrant cellular pathways in PPGLs to improve diagnostic accuracy & guide treatments, including nuclear medicine therapies. Currently commonly available functional imaging modalities include 18F-FDG PET, 123I-MIBG and 68Ga-DOTATATE. Aims: To analyze the use of 123I-MIBG, 18F-FDG PET and 68Ga-DOTATATE in patients harboring SDHB & SDHD pathogenic variants and determine the detection rates for both primary tumors and metastatic sites of disease. Methods: Retrospective review of patient records and imaging reports allowed tumor characteristics and imaging features of 21 patients with SDH-related PPGL to be recorded. Contrast enhanced CT/MRI were used as control to calculate the sensitivity of each functional imaging modality. Avidity of the primary lesion and metastatic deposits were used to calculate detection rates. 123I-MIBG imaging was available for 22 primary tumors (8 SDHB, 14 SDHD), 18FDG-PET for 24 (9 SDHB, 15 SDHD) and 68Ga-DOTATATE for 6 (2 SDHB, 4 SDHD) respectively. Results: 29 PPGLs (primary and metastases, 13 SDHB, 16 SDHD) were identified in 21 patients. 123I-MIBG detected 14/22 (64%) primary tumors; 5/8 (63%) SDHB and 9/14 (64%) SDHD-related PPGL. According to tumor location, 3/3 PCCs, 6/8 HNPGLs and 4/11 non-HNPGLs demonstrated 123I-MIBG avidity. Both18F-FDG PET and 68Ga-DOTATATE detected all PPGLs imaged; 24 (9 SDHB, 15 SDHD) and 6 (2 SDHB, 4 SDHD) respectively, demonstrating 100% sensitivity in the detection of the primary PPGL in all the above locations. 6 metastatic deposits (located in bone, lungs, liver and local lymph nodes) in 4 patients were imaged using all 3 modalities (3 SDHB, 1 SDHD), all of which were avid on 18F-FDG PET and 68Ga-DOTATATE whereas only 50% demonstrated avidity on 123I-MIBG imaging. Discussion: Recent guidelines promote preferential use of 68Ga-DOTATATE and 18F-FDG PET as initial functional imaging modalities in SDHx-related disease over 123I-MIBG. The results from our patient cohort indicate superior sensitivity (100%) for detection of SDHx-related disease with FDG and Dotatate compared with MIBG. In contrast to the current literature, a high proportion (75%) of HNPGLs in our series demonstrated MIBG avidity. Further prospective studies are needed to further evaluate these and various other novel tracers to inform diagnostic and therapeutic strategy in PPGLs arising from SDHx and various other germline and somatic pathogenic variants.

Serial Changes in Cardiac Sympathetic Nervous Function After Transcatheter Aortic Valve Replacement: A Prospective Observational Study Using 123I-meta-iodobenzylguanidine Imaging

Purpose:Transcatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, it remains unclear whether such short-term improvements will be sustained thereafter. The present study aimed to investigate the mid-term (i.e., 6–12 months) effects of TAVR on CSNF in patients with severe AS using 123I-meta-iodobenzylguanidine (MIBG) imaging.Methods:Patients with severe AS who were scheduled to undergo TAVR between October 2017 and June 2019 were enrolled in this single-centre, prospective, observational study. MIBG imaging was performed at baseline, within 2 weeks after TAVR, and at 6–12 months post-TAVR to evaluate the heart–mediastinum ratio (H/M) and washout rate (WR). Differences between each MIBG parameter at three time points were analysed, and factors involved in the long-term improvement in the late H/M were investigated. Results:Of 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P=0.041) and further improved over 6–12 months after TAVR (P=0.041). The WR rapidly improved immediately after TAVR (P=0.003) but remained unchanged at 6–12 months (P=0.827). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (>0.1) (adjusted odds ratio: 0.035; 95% confidence interval: 0.004–0.070; P=0.037). Patients with a high baseline mPG (≥58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (<42 mmHg) (0.24 vs. 0.01; P=0.029).Conclusions:CSNF, as denoted by the late H/M, demonstrated sustained improvement from within 2 weeks after TAVR until 6–12 months later. Such improvement was related to baseline hemodynamic AS severity.

False iodine-131 MIBG scintigraphy findings in adrenal tumors: correlation with MR imaging

In this study, we report our experience regarding the occurrence of false radionuclide findings in adrenal iodine-131 MIBG scintigraphy. We present a total of five patients in which nuclear images were false negative or positive in three and two cases, respectively, according to the standard radionuclide established criteria. In particular, the three cases of false-negative MIBG images consisted of two patients with necrotic or cystic pheochromocytomas (Cases 1 and 3) and a patient with a small pheochromocytoma (Case 2); the two cases of false-positive MIBG imaging consisted of a patient with an adenoma showing intense tracer uptake and of a large primary necrotic carcinoma with heterogeneous tracer concentration.

Abstract 12941: Long-term Prognostic Value of Cardiac Metaiodobenzylguanidine Imaging and Non-sustained Ventricular Tachycardia in Patients With Implantable Cardioverter Defibrillator

Background: Cardiac MIBG imaging provides prognostic information in patients with chronic heart failure (CHF). Recent studies showed that the highest occurrence of severe arrhythmic events (SAE) was seen in CHF patients with an intermediate decrease in MIBG uptake rather than the lowest values. On the other hand, non-sustained ventricular tachycardia (NSVT) has been shown to be associated with SAE in CHF patients. However, there is little information available on long-term prognostic value of intermediate decrease in MIBG up take and NSVT for the prediction of severe ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) patients. Methods and Results: We prospectively enrolled 201 consecutive outpatients with ICD (age: 64±14 years, male: 81%, NYHA class:1.7±0.7, LVEF: 49±17%). At entry, all patients underwent cardiac MIBG imaging and 24-hour Holter electrocardiogram monitoring. An intermediate decrease in heart-to-mediastinum ratio on delayed planar image (H/M) was defined as 1.40-1.89. NSVT was defined as consecutive 3 or more beats and more than 100 bpm. During a follow-up period of 4.0±2.5 years, 59 patients had appropriate ICD discharge for severe ventricular tachyarrhythmias. At multivariate Cox regression analysis, intermediate decrease in H/M and NSVT were significantly and independently associated with appropriate ICD discharge after adjustment with age, sex and low left ventricular ejection fraction (≤35%). Appropriate ICD discharge was significantly more frequently observed in patients with both intermediate decrease in H/M and NSVT and with either intermediate decrease in H/M or NSVT than with none of them (47% vs 36% vs 14%, p<0.0001). Conclusions: Combination of cardiac MIBG imaging and NSVT would be more strongly associated with an increased risk for severe ventricular tachyarrhythmias in ICD patients.

Abstract 14945: Prognostic Value of Cardiac 123 I-MIBG Imaging for Predicting Cardiac Events After Transcatheter Aortic Valve Replacement

Introduction: In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported; however, the prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123 I-metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR. Hypothesis: We hypothesized that the improvement in MIBG parameter with TAVR treatment can be an indicator of better prognosis. Methods: This single-center prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and after TAVR to evaluate the delayed heart-mediastinum ratio (d-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR d-H/M (≥2.0 or <2.0) and on the presence of TAVR-related improvement in d-H/M (i.e. Δ d-H/M [post-TAVR – baseline] >0 or ≤0). The study endpoint was the occurrence of major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and hospitalization due to heart failure. Results: Among the 187 consecutive patients who underwent TAVR, 107 (27 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 15 (14.0%) patients had MACE. The incidence of MACE was significantly low in patients with d-H/M improvement and/or high post-TAVR d-H/M (≥2.0). Baseline d-H/M and frailty were associated with poor response of d-H/M to TAVR treatment. Moreover, post-TAVR d-H/M had significant effects on MACE, with an adjusted hazard ratio of 1.264 (95% confidence interval, 0.034-2.480; p=0.04). Conclusions: Both d-H/M improvement and high post-TAVR d-H/M were associated with better prognosis in patients who underwent TAVR. Cardiac MIBG imaging is useful for predicting cardiac events after TAVR.

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

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&lt;40%), HFmrEF (40%≤LVEF&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&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

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&lt;0.0001). SSS (p&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 (&gt;10, defined by median) had significantly greater risk of cardiac event (56% vs 21%, Hazard ratio: 3.56 (2.00–6.33, p&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