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BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

BackgroundBilateral cardiac sympathetic denervation (BCSD) is a surgical treatment for refractory ventricular arrhythmias. Although the procedure has shown efficacy at reducing cardiac arrhythmias, its impact on mental health is unknown. In the current study we examined associations between the BCSD procedure and mental health.Methods10 ventricular arrhythmia patients undergoing BCSD completed assessments of anxiety, depression, and posttraumatic stress symptoms at pre- and post-BCSD time points. Wilcoxon signed rank and Mann-Whitney U tests were used to examine differences in mental health symptoms in the pre- and post-BSCD states. Point biserial correlations were used to explore associations between BCSD response and mental health symptoms.ResultsA significant reduction of anxiety symptoms was observed from pre- to post-BCSD. At the post-BCSD assessment, participants who successfully responded to the BCSD procedure exhibited lower anxiety symptoms compared to non-responders. However, no significant relationships were identified for depressive or PTSD symptoms.ConclusionThe BCSD procedure is associated with reduced anxiety shortly after successful treatment for refractory ventricular arrhythmias in a small sample. Longitudinal surveillance of mental health symptoms after BCSD may be warranted to monitor the impact of this procedure on mental health.

Background Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar-related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population. Methods and Results Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter-defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter-defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar-mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person-months, P=0.01) and the sustained VT/implantable cardioverter-defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person-months, P=0.03). The median number of sustained VT/implantable cardioverter-defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1, P

IntroductionCardiac sympathetic denervation (CSD) is utilized for the management of ventricular tachycardia (VT) in structural heart disease when refractory to radiofrequency ablation (RFA) or when patient/VT characteristics are not conducive to RFA.MethodsWe studied consecutive patients who underwent CSD at our institution from 2009 to 2018 with VT requiring repeat RFA post-CSD. Patient demographics, VT/procedural characteristics, and outcomes were assessed.ResultsNinety-six patients had CSD, 16 patients underwent RFA for VT post-CSD. There were 15 male and 1 female patients with mean age of 54.2 ± 13.2 years. Fourteen patients had nonischemic cardiomyopathy. A mean of 2.0 ± 0.8 RFAs for VT was unsuccessful before the patient undergoing CSD. The median time between CSD and RFA was 104 days (interquartile range [IQR] = 15-241). The clinical VT cycle length was significantly increased after CSD both spontaneously on ECG and/or ICD interrogation (355 ± 73 ms pre-CSD vs. 422 ± 94 ms post-CSD, p = .001) and intraprocedurally (406 ± 86 ms pre-CSD vs. 457 ± 88 ms post-CSD, p = .03). Two patients had polymorphic and 14 had monomorphic VT (MMVT) pre-CSD, and all patients had MMVT post-CSD. The proportion of mappable, hemodynamically stable VTs increased from 35% during pre-CSD RFA to 58% during post-CSD RFA (p = .038). At median follow-up of 413 days (IQR = 43-1840) after RFA, eight patients had no further VT.ConclusionRFA for recurrent MMVT post-CSD is a reasonable treatment option with intermediate-term clinical success in 50% of patients. Clinical VT cycle length was significantly increased after CSD with associated improvement in mappable, hemodynamically tolerated VT during RFA.

BackgroundBilateral cardiac sympathetic denervation (BCSD) is an effective therapy for ventricular arrhythmias (VAs) in cardiomyopathies (CMPs). After BCSD, residual autonomic nervous system (ANS) function is unknown.ObjectiveThe purpose of this study was to assess ANS responses in patients with CMP before and after BCSD as compared with demographically matched healthy controls.MethodsPatients with CMP undergoing BCSD and matched healthy controls were recruited. Noninvasive measures-finger cuff beat-to-beat blood pressure (BP), electrocardiography, palmar electrodermal activity (EDA), and finger pulse volume (FPV)-were obtained at rest and during autonomic stressors-posture change, handgrip, and mental stress. Maximal as well as specific responses to stressors were compared.ResultsEighteen patients with CMP (mean age 54 ± 14 years; 16 men, 89%; left ventricular ejection fraction 36% ± 14%) with refractory VAs and 8 matched healthy controls were studied; 9 patients with CMP underwent testing before and after (median 28 days) BCSD, with comparable ongoing medication. Before BCSD, patients with CMP (n = 13) had lower resting systolic BP and FPV than did healthy controls (P < .01). Maximal FPV and systolic BP reflex responses, expressed as percent change were similar, while diastolic BP, mean BP, and EDA responses were blunted. After BCSD, resting measurements were unchanged relative to presurgical baseline (n = 9). EDA responses to stressors were abolished, confirming BCSD, while maximal FPV and BP responses were preserved. Diastolic BP, mean BP, and FPV responses to orthostatic challenge pointed toward a better tolerance of active standing after BCSD as compared with before. Responses to other stressors remained unchanged.ConclusionPatients with CMP and refractory VAs on optimal medical therapy have detectable but blunted adrenergic responses, which are not disrupted by BCSD.

BackgroundCardiac sympathetic denervation (CSD) is a promising treatment for patients with structural heart disease (SHD) and refractory ventricular tachyarrhythmias (VTs). The effect of CSD on atrial rhythm as well as the prognostic impact of atrial arrhythmias (AAs) or left atrial volume index (LAVI) on CSD outcome are unknown.ObjectivesThe goals of this study were to evaluate the impact of AAs and LAVI on CSD outcome and to assess changes in AAs burden and in atrial pacing after CSD.MethodsPatients with SHD undergoing CSD for VTs were analyzed. Hazards models were built to assess predictors of sustained VT/implantable cardioverter-defibrillator (ICD) shock recurrences and death/orthotopic heart transplant (OHT). Changes before vs after CSD were assessed using ICD, clinical, and echocardiographic data. A drug index was devised to correct for medication use.ResultsBetween 2009 and 2018, 91 patients (mean age 56 ± 13 years; mean left ventricular ejection fraction 34% ± 14%; 47% with a history of AAs) underwent left CSD (16%) or bilateral CSD (BCSD). The median follow-up was 14 months (interquartile range 4-37 months). Using multivariable analysis, neither LAVI nor AAs were associated with recurrences; LAVI was an independent predictor of death/OHT. AAs burden did not change after BCSD, but atrial pacing increased from a median of 28% to 72% (P < .01). Left ventricular end-diastolic diameter slightly increased; however, sustained VT/ICD shocks were reduced.ConclusionIn patients with SHD undergoing CSD, LAVI predicts death/OHT. AAs burden, already low at baseline, was unchanged after BCSD, while the need for atrial pacing increased, suggesting an impact of BCSD on sinus node chronotropism.

BackgroundCardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart disease (SHD) and recurrent ventricular tachyarrhythmias (VT).ObjectivesThis study assessed the value of CSD and the characteristics associated with outcomes in this population.MethodsPatients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD.ResultsBetween 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided-only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up.ConclusionsCSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided-only procedure.