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

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.

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00644.2016 ◽

2017 ◽

Vol 312 (3) ◽

pp. H392-H405 ◽

Cited By ~ 34

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/ .

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Impact of aging on cardiac sympathetic innervation measured by 123I-mIBG imaging in patients with systolic heart failure

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-016-3432-3 ◽

2016 ◽

Vol 43 (13) ◽

pp. 2392-2400 ◽

Cited By ~ 20

Author(s):

Giuseppe Rengo ◽

Gennaro Pagano ◽

Dino Franco Vitale ◽

Roberto Formisano ◽

Klara Komici ◽

...

Keyword(s):

Heart Failure ◽

Sympathetic Innervation ◽

Systolic Heart Failure ◽

Mibg Imaging ◽

Cardiac Sympathetic Innervation

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Reversible reduction of cardiac sympathetic innervation after coronary artery bypass graft surgery: An observational study using serial iodine 123–labeled meta-iodobenzyl-guanidine (MIBG) imaging

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2012.03.005 ◽

2012 ◽

Vol 144 (1) ◽

pp. 210-216.e1 ◽

Cited By ~ 5

Author(s):

Athanasios Katsikis ◽

George Ekonomopoulos ◽

Spyros Papaioannou ◽

Anna Kouzoumi ◽

Maria Koutelou

Keyword(s):

Coronary Artery ◽

Observational Study ◽

Artery Bypass ◽

Sympathetic Innervation ◽

Bypass Graft ◽

Mibg Imaging ◽

Artery Bypass Graft ◽

Cardiac Sympathetic Innervation ◽

Iodine 123 ◽

Reversible Reduction

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Cardiac Sympathetic Innervation and Ablation of Ventricular Tachycardia

Atlas of Cardiac Innervation ◽

10.1007/978-3-319-45800-7_8 ◽

2016 ◽

pp. 131-145

Author(s):

John T. Duell ◽

Thomas Klein ◽

Mark F. Smith ◽

Wengen Chen ◽

Vasken Dilsizian ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Sympathetic Innervation ◽

Cardiac Sympathetic Innervation

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Sirtuin 4 contributes to heart failure development by increasing mitochondrial oxidative stress

European Heart Journal ◽

10.1093/ehjci/ehaa946.3602 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Koentges ◽

E Khan ◽

S Birkle ◽

M Hoelscher ◽

K Pfeil ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Cardiac Function ◽

Funding Source ◽

Lipid Peroxidation Product ◽

German Research Foundation ◽

Mitochondrial Oxidative Stress ◽

Pronounced Increase ◽

National Budget ◽

Public Grant

Abstract Sirtuin 4 (SIRT4) is a mitochondrial NAD+-dependent deacylase which inhibits the oxidation of glucose and fatty acids, and has been implicated in the regulation of oxidative stress. Given the importance of cardiac energy depletion and ROS during heart failure development, we aimed to define the role of SIRT4 in the development of heart failure. Mice with deletion (SIRT4−/−) or overexpression (SIRT4 TG) of SIRT4 were subjected to transverse aortic constriction (TAC) for 12 weeks or underwent sham procedures. Using echocardiography, ejection fraction (EF) was not different between SIRT4 TG and WT mice subjected to sham operations. In contrast, TAC induced a more pronounced decrease in EF (35% vs. 51%; p<0.05), and a more pronounced increase in LV endsystolic diameter (4.5mm vs. 3.6mm; p<0.05) and myocardial fibrosis (2.2-fold; p<0.05) in SIRT4 TG mice compared to WT mice. Myocardial levels of the lipid peroxidation product 4-hydroxynonenal were increased in WT mice following TAC and were synergistically increased in SIRT4 TG mice following TAC (+66% vs. WT TAC; p<0.05). Administration of the mitochondria-targeted antioxidant MitoQ normalized 4-hydroxynonenal levels, markedly attenuated the decline in EF and almost normalized endsystolic LV diameter in SIRT4 TG mice following TAC. Cardiac function and morphology were unaffected in SIRT4−/− mice during normal or increased workload conditions. Thus, while SIRT4 is not required to maintain cardiac function even in response to increased energy demands, increased expression of SIRT4 accelerates the development of heart failure following TAC, at least in part due to increased mitochondrial oxidative stress. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Research Foundation

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Time-efficient three-dimensional transmural scar assessment provides relevant substrate characterization for ventricular tachycardia features and long-term recurrences in ischemic cardiomyopathy

EP Europace ◽

10.1093/europace/euab116.344 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

L K Gutierrez ◽

S Merino-Caviedes ◽

JM Alfonso-Almazan ◽

S Sanz-Estebanez ◽

L Cordero-Grande ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Ischemic Cardiomyopathy ◽

Three Dimensional ◽

Correlation Coefficients ◽

Translational Study ◽

National Budget ◽

Funding Sources ◽

Scar Assessment ◽

Public Grant ◽

Lge Cmr

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): - Ministerio de Ciencia e Innovación and the ProCNIC Foundation - Grant TEC2017-82408-R Background We aimed to validate a 3D methodology for transmural scar assessment using time-efficient upsampled models from 2D delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) sequences and determine the clinical implications in ischemic cardiomyopathy-related ventricular tachycardia (VT) episodes. Methods Translational study including 10 pigs with myocardial infarction and 15 patients with spontaneous VT episodes and underlying infarct-related scar. Pigs underwent 3D LGE-CMR sequences to test 3D transmural-based scar assessment using several downsampled resolutions from the original images. Validation in patients included 3D and 2D LGE-CMR studies performed within the same protocol. Transmural-based scar areas were used for correlation analyses with the cycle length (CL) of VT episodes. Scar volumes were used as a benchmark comparison. Results In pigs, 3D transmural-based scar areas showed interclass correlation coefficients >0.94 between original 3D high-resolution- and downsampled-derived models. In patients, scar area quantification in myocardial regions with 3D transmurality <0.2 (for upsampled 2D-derived models) and <0.1 (for 3D-derived models) showed direct correlation with the CL of spontaneous VT episodes (r = 0.69; p < 0.01 and r = 0.79; p < 0.01, respectively) (See Abstract Figure). After ablation, patients with VT recurrences showed lower scar areas on 3D and upsampled 2D models using <0.1 and <0.2 transmurality criteria, respectively, than patients without VT recurrences (48.5 [37.7, 67.5] vs. 91.5 [84.3, 117.3] cm2, respectively, for 3D-derived models; p = 0.004, and 64.0 [43.5, 69.5] vs. 83.0 [70.2, 99.7] cm2, respectively, for upsampled 2D models; p = 0.04). Conversely, time-consuming scar volume reconstructions from 2D or 3D LGE-CMR sequences did not show significant differences between patients with and without VT recurrences. Conclusions Three-dimensional transmural scar assessment in upsampled 2D-LGE-CMR-derived models provides time-efficient characterization of infarct-related myocardial substrates associated with the CL of spontaneous VT episodes and VT recurrences after ablation. Abstract Figure

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Cardiac sympathetic innervation in a patient with catecholaminergic polymorphic ventricular tachycardia

Heart Rhythm ◽

10.1016/j.hrthm.2013.10.037 ◽

2014 ◽

Vol 11 (8) ◽

pp. 1490-1491 ◽

Cited By ~ 1

Author(s):

Matthias Paul ◽

Peter Kies ◽

Michael Schäfers ◽

Eric Schulze-Bahr

Keyword(s):

Ventricular Tachycardia ◽

Sympathetic Innervation ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Cardiac Sympathetic Innervation

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Bilateral cardiac sympathetic denervation of a recurrent refractory ventricular tachycardia occurring after catheter ablation of atrial fibrillation and outflow tract premature ventricular contractions

Journal of Arrhythmia ◽

10.1002/joa3.12159 ◽

2019 ◽

Vol 35 (2) ◽

pp. 287-289 ◽

Cited By ~ 1

Author(s):

Atsuhiko Yagishita ◽

Masahiko Goya ◽

Yoshihide Takahashi ◽

Hironori Ishibashi ◽

Kikou Akiyoshi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ventricular Tachycardia ◽

Catheter Ablation ◽

Outflow Tract ◽

Sympathetic Denervation ◽

Premature Ventricular Contractions ◽

Cardiac Sympathetic Denervation

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The effects of sympathetic denervation on spontaneous ventricular defibrillation in the rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-119 ◽

1992 ◽

Vol 70 (6) ◽

pp. 890-896

Author(s):

Menashe B. Waxman ◽

Arjun D. Sharma ◽

John Asta ◽

Laszlo Endrenyi

Keyword(s):

Ventricular Tachycardia ◽

Ventricular Fibrillation ◽

Refractory Period ◽

Sympathetic Innervation ◽

Sympathetic Denervation ◽

Spontaneous Reversion ◽

Group 2 ◽

6 Hydroxydopamine ◽

Spontaneous Defibrillation ◽

Group 1

Ventricular tachycardia or ventricular fibrillation was electrically induced in 38 normal rats (group 1) and 24 sympathetically denervated rats (6-hydroxydopamine) (group 2). The time for spontaneous reversion to sinus rhythm was measured during (1) control, (2) isoproterenol, and (3) the combination of isoproterenol and phenylephrine. The time for spontaneous reversion was the same in both groups in the three states. The reversion time was prolonged threefold by isoproterenol, and restored to control values when phenylephrine was added to the infusion of isoproterenol. The tachycardia duration and the refractory period were inversely related: log10 (tachycardia duration) = 3.466 – 0.091 (refractory period). Ventricular tachycardia/fibrillation induction was examined as follows: (i) Ventricular tachycardia/fibrillation was induced in 100% of normal rats (group 1), but only 42% of the denervated rats (group 2, p < 0.001); (ii) during isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of rats of both groups; and (iii) when phenylephrine was added to isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of group 1 rats versus 82% of group 2 rats, (p = NS). These observations suggest (1) the induction of ventricular tachycardia/fibrillation is highly dependent on intact sympathetic innervation, and (2) exogenous adrenergic agonists modulate the duration of ventricular fibrillation through their effects on ventricular refractory period, independent of sympathetic innervation.Key words: spontaneous defibrillation, sympathetic denervation.

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