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

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
HS Chen ◽  
C Jungen ◽  
Y Kimura ◽  
P Dibbets-Schneider ◽  
SRD Piers ◽  
...  
Keyword(s):  
Linear Relationship ◽  
Myocardial Fibrosis ◽  
Ischemic Cardiomyopathy ◽  
Sympathetic Innervation ◽  
Sympathetic Denervation ◽  
Cardiac Sympathetic Innervation ◽  
Funding Sources ◽  
Voltage Mapping ◽  
Heart To Mediastinum Ratio ◽  
Cardiac Sympathetic Denervation

Abstract 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.

scholarly journals Impact of cardiac sympathetic denervation on IH-induced ischemic cardiomyopathy aggravation

2020 ◽  
Vol 12 (2-4) ◽  
pp. 249
Author(s):  
M. Détrait ◽  
S. Bouyon ◽  
S. Brasseur ◽  
D. Godin-Ribuot ◽  
E. Belaidi ◽  
...  
Keyword(s):  
Ischemic Cardiomyopathy ◽  
Sympathetic Denervation ◽  
Cardiac Sympathetic Denervation

scholarly journals Cardiac sympathetic innervation via middle cervical and stellate ganglia and antiarrhythmic mechanism of bilateral stellectomy

2017 ◽  
Vol 312 (3) ◽  
pp. H392-H405 ◽  
Author(s):  
Tadanobu Irie ◽  
Kentaro Yamakawa ◽  
David Hamon ◽  
Keijiro Nakamura ◽  
Kalyanam Shivkumar ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Ventricular Fibrillation ◽  
Sympathetic Innervation ◽  
Sympathetic Activation ◽  
Hemodynamic Stability ◽  
Cardiac Sympathetic Innervation ◽  
Dispersion Of Repolarization ◽  
Stellate Ganglia ◽  
Cervical Ganglion ◽  
Cardiac Sympathetic Denervation

Cardiac sympathetic denervation (CSD) is reported to reduce the burden of ventricular tachyarrhythmias [ventricular tachycardia (VT)/ventricular fibrillation (VF)] in cardiomyopathy patients, but the mechanisms behind this benefit are unknown. In addition, the relative contribution to cardiac innervation of the middle cervical ganglion (MCG), which may contain cardiac neurons and is not removed during this procedure, is unclear. The purpose of this study was to compare sympathetic innervation of the heart via the MCG vs. stellate ganglia, assess effects of bilateral CSD on cardiac function and VT/VF, and determine changes in cardiac sympathetic innervation after CSD to elucidate mechanisms of benefit in 6 normal and 18 infarcted pigs. Electrophysiological and hemodynamic parameters were evaluated at baseline, during bilateral stellate stimulation, and during bilateral MCG stimulation in 6 normal and 12 infarcted animals. Bilateral CSD (removal of bilateral stellates and T2 ganglia) was then performed and MCG stimulation repeated. In addition, in 18 infarcted animals VT/VF inducibility was assessed before and after CSD. In infarcted hearts, MCG stimulation resulted in greater chronotropic and inotropic response than stellate ganglion stimulation. Bilateral CSD acutely reduced VT/VF inducibility by 50% in infarcted hearts and prolonged global activation recovery interval. CSD mitigated effects of MCG stimulation on dispersion of repolarization and T-peak to T-end interval in infarcted hearts, without causing hemodynamic compromise. These data demonstrate that the MCG provides significant cardiac sympathetic innervation before CSD and adequate sympathetic innervation after CSD, maintaining hemodynamic stability. Bilateral CSD reduces VT/VF inducibility by improving electrical stability in infarcted hearts in the setting of sympathetic activation. NEW & NOTEWORTHY Sympathetic activation in myocardial infarction leads to arrhythmias and worsens heart failure. Bilateral cardiac sympathetic denervation reduces ventricular tachycardia/ventricular fibrillation inducibility and mitigates effects of sympathetic activation on dispersion of repolarization and T-peak to T-end interval in infarcted hearts. Hemodynamic stability is maintained, as innervation via the middle cervical ganglion is not interrupted. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/anti-arrhythmic-mechanism-of-bilateral-stellectomy/ .

Impact of cardiac sympathetic denervation on IH-induced ischemic cardiomyopathy aggravation

2020 ◽  
Author(s):  
Maximin Détrait ◽  
Jonathan Gaucher ◽  
Sophie Bouyon ◽  
Jean-Louis Pepin ◽  
Elise Belaidi ◽  
...  
Keyword(s):  
Ischemic Cardiomyopathy ◽  
Sympathetic Denervation ◽  
Cardiac Sympathetic Denervation

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

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
C Jungen ◽  
HS Chen ◽  
Y Kimura ◽  
P Dibbets-Schneider ◽  
SRD Piers ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Catheter Ablation ◽  
Sympathetic Innervation ◽  
Sympathetic Denervation ◽  
Mibg Imaging ◽  
German Research Foundation ◽  
Cardiac Sympathetic Innervation ◽  
National Budget ◽  
Segment Model ◽  
Public Grant

Abstract 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.

scholarly journals The effect of bilateral cardiac sympathetic denervation for refractory ventricular tachycardia in ischemic cardiomyopathy

2020 ◽  
Vol 36 (3) ◽  
pp. 524-527 ◽  
Author(s):  
Yuko Miki ◽  
Takehito Sasaki ◽  
Yoshinori Okazaki ◽  
Mitsuho Inoue ◽  
Katsura Niijima ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Ischemic Cardiomyopathy ◽  
Sympathetic Denervation ◽  
Cardiac Sympathetic Denervation

scholarly journals Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Joachim Brumberg ◽  
Ganna Blazhenets ◽  
Nils Schröter ◽  
Lars Frings ◽  
Wolfgang H. Jost ◽  
...  
Keyword(s):  
Sympathetic Innervation ◽  
Cardiac Sympathetic Innervation ◽  
Linear Conversion ◽  
Heart To Mediastinum Ratio

scholarly journals Effects of Cardiac Sympathetic Neurodegeneration and PPARγ Activation on Rhesus Macaque Whole Blood miRNA and mRNA Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Jeanette M. Metzger ◽  
Mary S. Lopez ◽  
Jenna K. Schmidt ◽  
Megan E. Murphy ◽  
Raghu Vemuganti ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Rhesus Macaque ◽  
Whole Blood ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Sympathetic Innervation ◽  
Sympathetic Denervation ◽  
Primate Model ◽  
Expression Levels ◽  
Cardiac Sympathetic Denervation

Degeneration of sympathetic innervation of the heart occurs in numerous diseases, including diabetes, idiopathic REM sleep disorder, and Parkinson’s disease (PD). In PD, cardiac sympathetic denervation occurs in 80-90% of patients and can begin before the onset of motor symptoms. Today, there are no disease-modifying therapies for cardiac sympathetic neurodegeneration, and biomarkers are limited to radioimaging techniques. Analysis of expression levels of coding mRNA and noncoding RNAs, such as microRNAs (miRNAs), can uncover pathways involved in disease, leading to the discovery of biomarkers, pathological mechanisms, and potential drug targets. Whole blood in particular is a clinically relevant source of biomarkers, as blood sampling is inexpensive and simple to perform. Our research group has previously developed a nonhuman primate model of cardiac sympathetic denervation by intravenous administration of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA). In this rhesus macaque (Macaca mulatta) model, imaging with positron emission tomography showed that oral administration of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone (n=5; 5 mg/kg daily) significantly decreased cardiac inflammation and oxidative stress compared to placebo (n=5). Here, we report our analysis of miRNA and mRNA expression levels over time in the whole blood of these monkeys. Differential expression of three miRNAs was induced by 6-OHDA (mml-miR-16-2-3p, mml-miR-133d-3p, and mml-miR-1262-5p) and two miRNAs by pioglitazone (mml-miR-204-5p and mml-miR-146b-5p) at 12 weeks posttoxin, while expression of mRNAs involved in inflammatory cytokines and receptors was not significantly affected. Overall, this study contributes to the characterization of rhesus coding and noncoding RNA profiles in normal and disease-like conditions, which may facilitate the identification and clinical translation of biomarkers of cardiac neurodegeneration and neuroprotection.

scholarly journals Local sympathetic denervation attenuates myocardial inflammation and improves cardiac function after myocardial infarction in mice

2017 ◽  
Vol 114 (2) ◽  
pp. 291-299 ◽  
Author(s):  
Karin A Ziegler ◽  
Andrea Ahles ◽  
Timo Wille ◽  
Julia Kerler ◽  
Deepak Ramanujam ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Neural Control ◽  
Molecular Mechanisms ◽  
Sympathetic Innervation ◽  
Critical Role ◽  
Left Ventricular ◽  
Sympathetic Denervation ◽  
Myocardial Inflammation ◽  
Cardiac Inflammation ◽  
Cardiac Sympathetic Denervation

Abstract Aims Cardiac inflammation has been suggested to be regulated by the sympathetic nervous system (SNS). However, due to the lack of methodology to surgically eliminate the myocardial SNS in mice, neuronal control of cardiac inflammation remains ill-defined. Here, we report a procedure for local cardiac sympathetic denervation in mice and tested its effect in a mouse model of heart failure post-myocardial infarction. Methods and results Upon preparation of the carotid bifurcation, the right and the left superior cervical ganglia were localized and their pre- and postganglionic branches dissected before removal of the ganglion. Ganglionectomy led to an almost entire loss of myocardial sympathetic innervation in the left ventricular anterior wall. When applied at the time of myocardial infarction (MI), cardiac sympathetic denervation did not affect acute myocardial damage and infarct size. In contrast, cardiac sympathetic denervation significantly attenuated chronic consequences of MI, including myocardial inflammation, myocyte hypertrophy, and overall cardiac dysfunction. Conclusion These data suggest a critical role for local sympathetic control of cardiac inflammation. Our model of myocardial sympathetic denervation in mice should prove useful to further dissect the molecular mechanisms underlying cardiac neural control.

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