Recurrent ventricular tachycardia after cardiac sympathetic denervation: Prolonged cycle length with improved hemodynamic tolerance and ablation outcomes.

INTRODUCTION: Cardiac 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. METHODS: We 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. RESULTS: Ninety-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. CONCLUSION: RFA 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.

Cryothermal energy demonstrates shorter ablation time and lower complication rates compared with radiofrequency in surgical hybrid ablation for recurrent ventricular tachycardia.

BACKGROUND: Recurrent ventricular tachycardia (VT) after prior endocardial catheter ablation(s) presents challenges in the setting of prior cardiac surgery where percutaneous epicardial access may not be feasible. OBJECTIVE: The purpose of this study was to compare the outcomes of cryothermal vs radiofrequency ablation in direct surgical epicardial access procedures. METHODS: We performed a retrospective study of consecutive surgical epicardial VT ablation cases. Surgical cases using cryothermal vs radiofrequency ablation were analyzed and outcomes were compared. RESULTS: Between 2009 and 2022, 43 patients underwent either a cryothermal (n = 17) or a radiofrequency (n = 26) hybrid epicardial ablation procedure with direct surgical access. Both groups were similarly matched for age, sex, etiology of VT, and comorbidities with a high burden of refractory VT despite previous endocardial and/or percutaneous epicardial ablation procedures. The surgical access site was lateral thoracotomy (76.5%) in the cryothermal ablation group compared with lateral thoracotomy (42.3%) and subxiphoid approach (38.5%) in the radiofrequency group, with the remainder in both groups performed via median sternotomy. The ablation time was significantly shorter in those undergoing cryothermal ablation vs radiofrequency ablation (11.54 ± 15.5 minutes vs 48.48 ± 23.6 minutes; P < .001). There were no complications in the cryothermal ablation group compared with 6 patients with complications in the radiofrequency group. Recurrent VT episodes and all-cause mortality were similar in both groups. CONCLUSION: Hybrid surgical VT ablation with cryothermal or radiofrequency energy demonstrated similar efficacy outcomes. Cryothermal ablation was more efficient and safer than radiofrequency in a surgical setting and should be considered when surgical access is required.

Sympathetic innervation of the supraclavicular brown adipose tissue: A detailed anatomical study.

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.

Cardiac sympathetic denervation and mental health.

BACKGROUND: Bilateral 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. METHODS: 10 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. RESULTS: A 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. CONCLUSION: The 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.

Arrhythmic Risk Profile and Outcomes of Patients Undergoing Cardiac Sympathetic Denervation for Recurrent Monomorphic Ventricular Tachycardia After Ablation.

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<0.0001). Conclusions Patients referred for CSD for refractory scar-mediated monomorphic VT are at a higher risk of VT recurrence after ablation as compared with those not requiring CSD, mostly because of their cardiac comorbidities. CSD significantly reduced both the expected risk of recurrences and VT burden.

Non-invasive stereotactic body radiation therapy for refractory ventricular arrhythmias: an institutional experience.

BACKGROUND: Initial studies have reported excellent safety and efficacy for stereotactic body radiation therapy (SBRT) in patients with refractory ventricular tachycardia (VT). METHODS: This is a single-center retrospective analysis of eight consecutive patients who underwent SBRT for refractory, scar-related VT. The anatomic target for radioablation was defined based on surface 12-lead ECG VT morphology, cardiac magnetic resonance imaging, and electroanatomic mapping data when available. The target volume treated and the prescribed radiation dose (15-25 Gy) was based on the combined clinical assessment of the cardiac electrophysiologist and radiation oncologist. Ventricular arrhythmias, radiation-related outcomes, and adverse events were monitored at follow-up. RESULTS: Eight patients underwent nine SBRT sessions. All patients were male with an average age of 75 ± 7.3 years and mean ejection fraction of 21 ± 7%. SBRT was performed with delivery of an average of 22.2 ± 3.6 Gy in a single session with a procedure time of 18.2 ± 6.0 min. All but one session was performed on an inpatient basis. No acute complications occurred. During a median follow-up of 7.8 months (IQR 4.8, 9.9), ICD therapies decreased from median 69.5 (43.5, 115.8) pre-SBRT to 13.3 (IQR 7.7, 35.8) post-SBRT (p = 0.036). There were three patient deaths in the follow-up period, unrelated to SBRT. Apparent clinical benefit occurred 33% of the time after SBRT. CONCLUSIONS: The patients experienced overall reduction in VT burden following SBRT, though not with the immediate effect seen in other patient series. Further studies (basic, translational, and clinical) are essential to determine the benefit of SBRT and if so, the optimal protocols and patient selection.

Cardiovascular autonomic reflex function after bilateral cardiac sympathetic denervation for ventricular arrhythmias.

BACKGROUND: Bilateral 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. OBJECTIVE: The purpose of this study was to assess ANS responses in patients with CMP before and after BCSD as compared with demographically matched healthy controls. METHODS: Patients 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. RESULTS: Eighteen 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. CONCLUSION: Patients with CMP and refractory VAs on optimal medical therapy have detectable but blunted adrenergic responses, which are not disrupted by BCSD.

Prognostic impact of atrial rhythm and dimension in patients with structural heart disease undergoing cardiac sympathetic denervation for ventricular arrhythmias.

BACKGROUND: Cardiac 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. OBJECTIVES: The 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. METHODS: Patients 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. RESULTS: Between 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. CONCLUSION: In 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.

Renal denervation as adjunctive therapy to cardiac sympathetic denervation for ablation refractory ventricular tachycardia.

BACKGROUND: Autonomic modulation is finding an increasing role in the treatment of ventricular arrhythmias. Renal denervation (RDN) has been described as a treatment modality for refractory ventricular tachycardia (VT) in case series. OBJECTIVE: The purpose of this study was to evaluate RDN as an adjunctive therapy to cardiac sympathetic denervation (CSD) for ablation refractory VT. METHODS: Patients who underwent RDN after radiofrequency ablation and CSD procedures at our center from 2012 to 2019 were evaluated. RESULTS: Ten patients underwent RDN after CSD (9 bilateral and 1 left-sided only) with a median follow-up of 23 months. The mean age was 59.9 ± 10.4 years, and 9/10 (90%) were men. All had cardiomyopathy with a mean ejection fraction of 33% ± 11% (20% ischemic). Four (40%) underwent CSD during the same hospitalization as that for RDN. Patients who underwent RDN as adjunctive therapy to CSD had a decrease in all implantable cardioverter-defibrillator therapies (shocks + antitachycardia pacing [ATP]) from 29.5 ± 25.2 to 7.1 ± 10.1 comparing 6 months pre-RDN to 6 months post-RDN (P = .028). Implantable cardioverter-defibrillator shocks were significantly decreased from 7.0 ± 6.1 to 1.7 ± 2.5 comparing 6 months pre-RDN to 6 months post-RDN (P = .026). This benefit was driven by a decrease in therapies for 6 patients who had a staged procedure, not performed during the same hospitalization (28.5 ± 24.3 to 1.0 ± 1.2; P = .043). CONCLUSION: RDN demonstrates the potential benefit when VT recurs after radiofrequency ablation and CSD. The benefit is seen in patients who undergo a staged procedure. The need for acute RDN after CSD portends a poor prognosis.

Liver Disease as a Predictor of New-Onset Atrial Fibrillation.

Background Impact of liver disease on development of atrial fibrillation ( AF ) is unclear. The purpose of the study was to evaluate prevalence of AF in the setting of liver disease and whether increasing severity of liver disease, using Model for End-Stage Liver Disease ( MELD ), is independently associated with increased risk of AF . Methods and Results Retrospective data analysis of 1727 patients with liver disease evaluated for liver transplantation between 2006 and 2015 was performed, and patient characteristics were analyzed from billing codes and review of medical records. Multivariable time-dependent Cox proportional hazards model was performed to determine effect of increasing MELD score on risk of developing AF . Prevalence of AF was 11.2%. Incidence of AF at median follow-up time of 1.04 years was 8.5%. Both prevalence and incidence of AF increased with increasing MELD scores. Prevalence of AF was 3.7%, 6.4%, 16.7%, and 20.2% corresponding with MELD quartiles 1 to 10, 11 to 20, 21 to 30, and >30, respectively. Compared with patients with MELD quartile 1 to 10, patients with MELD quartile of 11 to 20 had hazard ratio of 2.73 (confidence interval, 1.47-5.07), those in the MELD quartile of 21 to 30 had a hazard ratio of 5.17 (confidence interval, 2.65-10.09), and those with MELD values >30 had hazard ratio of 9.33 (confidence interval, 3.93-22.14) for development of new-onset AF . Other significant variables associated with new-onset AF were age, sleep apnea, valvular heart disease, hemodynamic instability, and reduced left ventricular ejection fraction <50% (hazard ratio, of 1.06, 2.17, 3.21, 2.00, and 2.44, respectively). Conclusions Prevalence and incidence of AF in patients with liver disease is high. Severity of liver disease, as measured by MELD , is an important predictor of new-onset AF . This novel finding suggests an interaction between inflammatory and neurohormonal changes in liver disease and pathogenesis of AF .

Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias.

BACKGROUND: Cardiac 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). OBJECTIVES: This study assessed the value of CSD and the characteristics associated with outcomes in this population. METHODS: Patients 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. RESULTS: Between 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. CONCLUSIONS: CSD 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.