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Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health grants OT2OD023848 and P01 HL164311 to Dr Shivkumar and from the UCLA Amara-Yad Project. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Calcitonin gene-related peptide (CGRP) is widely used as a marker for nociceptive afferent axons. However, the distribution of CGRP-IR axons has not been fully determined in the whole rat heart. Immunohistochemically labeled flat-mounts of the right and left atria and ventricles, and the interventricular septum (IVS) in rats for CGRP were assessed with a Zeiss imager to generate complete montages of the entire atria, ventricles, and septum, and a confocal microscope was used to acquire detailed images of selected regions. We found that 1) CGRP-IR axons extensively innervated all regions of the atrial walls including the sinoatrial node region, auricles, atrioventricular node region, superior/inferior vena cava, left pre-caval vein, and pulmonary veins. 2) CGRP-IR axons formed varicose terminals around individual neurons in some cardiac ganglia but passed through other ganglia without making appositions with cardiac neurons. 3) Varicose CGRP-IR axons innervated the walls of blood vessels. 4) CGRP-IR axons extensively innervated the right/left ventricular walls and IVS. Our data shows the rather ubiquitous distribution of CGRP-IR axons in the whole rat heart at single-cell/axon/varicosity resolution for the first time. This study lays the foundation for future studies to quantify the differences in CGRP-IR axon innervation between sexes, disease models, and species., Competing Interests: Declaration of competing interest No potential conflicts of interest were disclosed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 Heart Rhythm Society. All rights reserved.)

Background: Patients with repaired tetralogy of Fallot (TOF) are at risk for ventricular tachycardia (VT) related to well-described anatomical isthmuses., Objective: The purpose of this study was to explore QRS morphology as an indicator of anatomical isthmus conduction., Methods: Patients with repaired TOF and complete right bundle branch block referred for transcatheter pulmonary valve replacement (PVR) or presenting with sustained VT underwent comprehensive 3-dimensional mapping in sinus rhythm. Electrocardiographic characteristics were compared to right ventricular (RV) activation and anatomical isthmus conduction properties., Results: Twenty-two patients (19 pre-pulmonary valve replacement and 3 clinical VT) underwent comprehensive 3-dimensional mapping (median 39 years; interquartile range [IQR] 27-48 years; 12 [55%] male). Septal RV activation (median 40 ms; IQR 34-46 ms) corresponded to the nadir in lead V 1 and free wall activation (median 71 ms; IQR 64-81 ms) to the transition point in the upstroke of the R' wave. Patients with isthmus block between the pulmonary annulus and the ventricular septal defect patch and between the ventricular septal defect patch and the tricuspid annulus (when present), were more likely to demonstrate lower amplitude R' waves in lead V 1 (5.8 mV vs 9.4 mV; P = .005), QRS fragmentation in lead V 1 (15 [94%] vs 2 [13%]; P < .001), and terminal S waves in lead aVF (15 [94%] vs 6 [40%]; P < .001) than those with intact conduction. During catheter ablation, these QRS changes developed during isthmus block., Conclusion: For patients with repaired TOF, the status of septal isthmus conduction was evident from sinus rhythm QRS morphology. Low-amplitude, fragmented R' waves in lead V 1 and terminal S waves in the inferior leads were related to septal isthmus conduction abnormalities, providing a mechanistic link between RV activation and common electrocardiographic findings., (Published by Elsevier Inc.)

Background: Cardioneuroablation (CNA) is an attractive treatment of vasovagal syncope. Its long-term efficacy and safety remain unknown., Objective: The purpose of this study was to develop a chronic porcine model of CNA to examine the susceptibility to ventricular tachyarrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) and cardiac autonomic function after CNA., Methods: A percutaneous CNA model was developed by ablation of left- and right-sided ganglionated plexi (n = 5), confirmed by histology. Reproducible bilateral vagal denervation was confirmed after CNA by extracardiac vagal nerve stimulation (VNS) and histology. Chronic studies included 16 pigs randomized to CNA (n = 8) and sham ablation (n = 8, Control). After 6 weeks, animals underwent hemodynamic studies, assessment of cardiac sympathetic and parasympathetic function using sympathetic chain stimulation and direct VNS, respectively, and proarrhythmic potential after left anterior descending (LAD) coronary artery ligation., Results: After CNA, extracardiac VNS responses remained abolished for 6 weeks despite ganglia remaining in ablated ganglionated plexi. In the CNA group, direct VNS resulted in paradoxical increases in blood pressure, but not in sham-ablated animals (CNA group vs sham group: 8.36% ± 7.0% vs -4.83% ± 8.7%, respectively; P = .009). Left sympathetic chain stimulation (8 Hz) induced significant corrected QT interval prolongation in the CNA group vs the sham group (11.23% ± 4.0% vs 1.49% ± 4.0%, respectively; P < .001). VT/VF after LAD ligation was more prevalent and occurred earlier in the CNA group than in the control group (61.44 ± 73.7 seconds vs 245.11 ± 104.0 seconds, respectively; P = .002)., Conclusion: Cardiac vagal denervation is maintained long-term after CNA in a porcine model. However, chronic CNA was associated with cardiovascular dysreflexia, diminished cardioprotective effects of cardiac vagal tone, and increased susceptibility to VT/VF in ischemia. These potential long-term negative effects of CNA suggest the need for rigorous clinical studies on CNA., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Right ventricular perforation is a catastrophic complication of catheter-based intracardiac interventions. In this context, appreciation of 5 attachments of the right ventricle to the aortoventricular unit is essential to recognize extent of right ventricular free wall. We herein present progressive dissection and virtual and photographic endoscopic images of the hearts without distortion. Real dissection images show us how and where to avoid this complication by indicating the true muscular component of the ventricular septum. Both virtual and photographic endoscopic images, when combined with transillumination, beautifully shows the thin wall regions and trabeculations with unprecedented clarity. We believe recognition of these anatomical nuances can reduce the likelihood of right ventricular perforation., Competing Interests: Funding Support and Author Disclosures This work was made possible by support from NIH grants OT2OD023848 to Dr Shivkumar and from the UCLA Amara-Yad Project. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures This work was made possible by support from National Institutes of Health SPARC Program grant OT2OD023848 to Dr Shivkumar and from the Tawara-McAlpine Festschrift (a component of the UCLA Amara-Yad Project). All other authors have reported that they have no relationship relevant to the contents of this paper to disclose.

Background: Mapping techniques to identify diseased myocardial substrate during ventricular tachycardia ablation procedures remain limited., Objective: We hypothesized that tissue derivative of the voltage with respect to time (dV/dt), the slope of the unipolar ventricular electrogram registered by local ventricular activation, represents a unique parameter for identifying potential arrhythmogenic tissue in the ischemic scar border zone., Methods: Using high-resolution electrical mapping, we examined dV/dt characteristics in the border zone of animals after chronic myocardial infarction (MI)., Results: Minimum dV/dt (dV/dt min ) in MI animals was less than that in control animals (-344.7 ± 68.7 in controls vs -174.2 ± 104.5 in MI; P < .001) and related to ventricular fibrosis. In MI animals, dV/dt min values were divided into high (≤-200 μV/ms) and low (>-200 μV/ms) dV/dt min . Low dV/dt min regions harbored arrhythmogenic substrates that were characterized by (1) high responsiveness to sympathetic stimulation, (2) presence of late potentials, and (3) lower unipolar and bipolar voltage amplitudes., Conclusion: Our data indicate that dV/dt min is a unique parameter for identifying arrhythmogenic myocardium and may add a useful metric to conventional mapping strategies., (Copyright © 2022. Published by Elsevier Inc.)

The autonomic nervous system functions in a fine-tuned manner to dynamically modulate cardiac function during normal physiological state. Autonomic dysregulation in cardiac disease states such as myocardial infarction and heart failure alters this fine balance, which in turn promotes disease progression and arrhythmogenesis. Neuromodulatory interventions that aim to restore this balance at distinct levels of the cardiac neuraxis thus have been shown to be effective in the treatment of arrhythmias. This review first describes the anatomy of the cardiac autonomic nervous system and the pathological changes that occur with neural remodeling in the setting of scar and cardiomyopathy, followed by therapeutic interventions for neuraxial modulation of arrhythmias such as atrial fibrillation and ventricular tachyarrhythmias., (Copyright © 2022. Published by Elsevier B.V.)

Background: The use of cardiac positron emission tomography-computed tomography (PET-CT) is increasingly used for the detection of underlying inflammation in patients with ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]), but the role of PET-CT remains undefined, particularly for patients who do not meet Task Force criteria for sarcoidosis., Objective: The purpose of this study was to determine the utility of PET-CT for clinical evaluation of VT/VF in patients with nonischemic cardiomyopathy., Methods: Consecutive patients with nonischemic cardiomyopathy and VT/VF who underwent cardiac PET-CT to detect inflammation between 2012 and 2019 were analyzed for baseline demographic characteristics, imaging results, and outcomes. Patients with known sarcoidosis or other conditions requiring immunosuppressive therapy were excluded., Results: PET-CT was performed in 133 patients with mean age 56.3 ± 13.5 years and left ventricular ejection fraction 43% ± 16.1%, with evidence of myocardial inflammation detected in 32 (23.5%). Patients with myocardial inflammation were managed conservatively with medical therapy including immunosuppressive agents. Ten patients with myocardial inflammation ultimately required catheter ablation for ongoing arrhythmias. There was no significant difference in arrhythmia recurrence between PET-positive and PET-negative groups (37.5% vs 32.4%; P = .43) or in time to recurrence (P = .26), in spite of the disparate management strategies. Gadolinium-enhanced cardiac magnetic resonance imaging was performed in 96 patients (72%); however, magnetic resonance imaging did not detect 31% of cases with active inflammation that were otherwise detected on PET-CT., Conclusion: The use of PET-CT significantly improves the detection of underlying myocardial inflammation contributing to ventricular arrhythmias. Management of these patients with immunosuppressive medical therapy is effective for arrhythmia control and may obviate the need for invasive ablation procedures in some patients., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Cerebral vasospasm is a complex disease resulting in reversible narrowing of blood vessels, stroke, and poor patient outcomes. Sympathetic perivascular nerve fibers originate from the superior cervical ganglion (SCG) to innervate the cerebral vasculature, with activation resulting in vasoconstriction. Sympathetic pathways are thought to be a significant contributor to cerebral vasospasm., Objective: We sought to demonstrate that stimulation of SCG in swine can cause ipsilateral cerebral perfusion deficit similar to that of significant human cerebral vasospasm. Furthermore, we aimed to show that inhibition of SCG can block the effects of sympathetic-mediated cerebral hypoperfusion., Methods: SCG were surgically identified in 15 swine and were electrically stimulated to achieve sympathetic activation. CT perfusion scans were performed to assess for changes in cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time-to-maximum (TMax). Syngo.via software was used to determine regions of interest and quantify perfusion measures., Results: SCG stimulation resulted in 20-30% reduction in mean ipsilateral CBF compared to its contralateral unaffected side (p < 0.001). Similar results of hypoperfusion were seen with CBV, MTT and TMax with SCG stimulation. Prior injection of lidocaine to SCG inhibited the effects of SCG stimulation and restored perfusion comparable to baseline (p > 0.05)., Conclusion: In swine, SCG stimulation resulted in significant cerebral perfusion deficit, and this was inhibited by prior local anesthetic injection into the SCG. Inhibiting sympathetic activation by targeting the SCG may be an effective treatment for sympathetic mediated cerebral hypoperfusion., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Mapping the structure/function organization of the cardiac nervous system is foundational for implementation of targeted neuromodulation-based therapeutics for the treatment of cardiac disease., Objective: The purpose of this study was to define the spatial organization of intrathoracic parasympathetic and sympathetic efferent projections to the heart., Methods: Yucatan mini-pigs (N = 11) were anesthetized and the thoracic cavity exposed. Electrical stimulation of the cervical vagi and stellate ganglia was performed individually, and hemodynamic responses were assessed in the intact state and after progressive debranching of each thoracic vagosympathetic trunk (VST). Subsequently, residual cardiac efferent projections arising from paravertebral chain ganglia (T1-T4) were evaluated by stimulation before and after individual ganglionic debranching., Results: Stimulation of the cervical vagi decreased heart rate and contractility while prolonging the activation-recovery interval (ARI). Stimulation of the stellate ganglia increased heart rate and contractility and decreased ARI. The majority of parasympathetic and sympathetic cardiac-evoked responses were mitigated after debranching of the right VST rostral to heart, whereas the left VST demonstrated a distribution with greater dispersion and caudal intrathoracic shift compared to the right. After complete thoracic VST debranching, stimulation of the T4 paravertebral chain ganglia demonstrated residual cardiac sympathetic efferent innervation to the heart in ∼50% of animals. That response was mitigated by transecting medial ganglionic branches., Conclusion: The nexus point for optimum neuromodulation engagement of parasympathetic efferent projections to the heart is the cervical vagus and the T1-T2 paravertebral chain ganglia for sympathetic control. Removal of principal sympathetic efferent projections to heart requires targeting the T1-T4 regions of the paravertebral chain., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures This work was made possible by support from National Institutes of Health grant OT2OD023848 to Dr Shivkumar. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cardiac sympathetic denervation (CSD) for refractory ventricular tachycardia (VT) has been shown to decrease VT recurrence and defibrillator shocks in patients with ischemic and nonischemic cardiomyopathy. Here and in the accompanying Video, we demonstrate the technique for minimally invasive CSD, highlight important technical points, and report surgical outcomes. CSD is accomplished through bilateral resection of the inferior one-third to one-half of the stellate ganglion en bloc with T2-T4 sympathectomy. Despite the high potential for perioperative risk, most patients do not have serious complications. We find that surgical CSD can be performed safely in an attempt to liberate patients from refractory VT., (Copyright © 2021 The Society of Thoracic Surgeons and the American College of Cardiology Foundation Published by Elsevier Inc. All rights reserved. Published by Elsevier Inc. All rights reserved.)

Managing arrhythmias from the left ventricular summit and interventricular septum is a major challenge for the clinical electrophysiologist requiring intimate knowledge of cardiac anatomy, advanced training and expertise. Novel mapping and ablation strategies are needed to treat arrhythmias originating from these regions given the current suboptimal long-term success rates with standard techniques. Herein, we describe innovative approaches to improve acute and long-term clinical outcomes such as mapping and ablation using the septal coronary venous system and the septal coronary arteries, alcohol ablation, coil embolization, and ablation of all early sites among others., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to develop a risk score (LGE Based Prediction of SCD Risk in Nonischemic Dilated Cardiomyopathy [ESTIMATED]) based on late gadolinium enhancement (LGE) cardiac magnetic resonance to predict sudden cardiac death (SCD) in patients with nonischemic dilated cardiomyopathy (NIDCM) and left ventricular ejection fraction ≤ 35%., Methods: We recruited 395 consecutive middle-aged patients with NIDCM and performed 3-year follow-up for SCD events. The score was developed and verified in 295 primary prevention patients, and the predictive value was confirmed by comparing the SCD events between the high-risk patients stratified by the score and 100 secondary prevention patients., Results: The ESTIMATED score (constructed by the LGE extent > 14%, syncope, atrial flutter/fibrillation, nonsustained ventricular tachycardia, advanced atrioventricular block, and age ≤ 20 or > 50 years) showed good calibrations for SCD prediction in the derivation (C-statistic: 0.80, 95% confidence interval: 0.74-0.86) and validation set (C-statistic: 0.80, 95% confidence interval: 0.71-0.87). By the score, 20.3% of primary prevention patients were categorized as high risk (≥ 3 points), 28.1% as intermediate risk (2 points), and 51.6% as low risk (0-1 points) for 3-year SCD events (45.9% vs 20.1% vs 5.1%, P < 0.0001). The 3-year SCD events were also well in agreement with the score stratification in patients without implantable cardioverter-defibrillator. High-risk primary prevention patients selected by the score in the derivation and validation sets had 3-year SCD events comparable with that in secondary prevention patients (47.6% vs 40.6% vs 38.7%, P = 0.81)., Conclusions: Our study derived and validated an LGE-based (ESTIMATED) risk score providing refined SCD prediction. The score may help to identify candidates for primary prevention implantable cardioverter-defibrillator in patients with NIDCM., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Dispersion in ventricular repolarization is relevant for arrhythmogenesis., Objective: The purpose of this study was to determine the spatiotemporal effects of sympathetic stimulation on ventricular repolarization., Methods: In 5 anesthetized female open-chest pigs, ventricular repolarization was measured from the anterior, lateral, and posterior walls of the left ventricle (LV) and right ventricle using up to 40 transmural plunge needles (4 electrodes each) before and after left stellate ganglion stimulation (LSGS) and right stellate ganglion stimulation. In addition, LSGS was performed in 3 pigs (2 male, 1 female) before and after verapamil (5-10 mg/h) administration., Results: LSGS yielded a biphasic response in repolarization in the lateral and posterior walls of the LV, with prolongation at ∼5 seconds (10 ± 1.5 ms) and shortening at 20-30 seconds of stimulation (-28.9 ± 4.4 ms) during a monotonic pressure increase. While the initial prolongation was abolished by verapamil, late shortening was augmented. Sequential transections of the vagal nerve and stellate ganglia augmented repolarization dispersion responses to LSGS in 2 of 5 hearts. An equal pressure increase by aortic occlusion resulted in a homogeneous shortening of repolarization in the LV, and the effects were smaller than those during LSGS. Right stellate stimulation shortened repolarization mainly in the anterior LV wall, but the effects were smaller than those of LSGS., Conclusion: LSGS first prolongs (through the L-type calcium current) and then shortens repolarization. The effect of LSGS was prominent in the posterior and lateral, not the anterior, LV walls., (Copyright © 2020. Published by Elsevier Inc.)

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., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Access to the epicardial space is fundamental to several cardiac procedures. While traditional indications include catheter ablation of ventricular arrhythmias and accessory pathways, novel indications include left atrial appendage occlusion, esophageal protection, mapping and ablation during atrial fibrillation procedures, implantation of epicardial pacing leads, and phrenic nerve displacement to facilitate safe ablation of atrial and ventricular arrhythmias. Accessing the epicardial space safely is a major challenge requiring intimate knowledge of cardiac anatomy, extensive training, and expertise. Over the past years, multiple technological advances have led to significant improvements in epicardial access success and safety. Important examples of such advances include CO 2 insufflation through the coronary sinus or the right atrial appendage, pressure sensor needle, computed tomography, cardiac magnetic resonance, and electroanatomic mapping-guided epicardial access. In addition, we provide special maneuvers to minimize inadvertent right ventricular perforation., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac sympathetic denervation (CSD) is an important adjunctive option for patients with refractory ventricular arrhythmias (VAs). Reports of efficacy of CSD in patients with structural heart disease (SHD) and refractory VA vary widely in literature., Objective: The purpose of this study was to conduct a systematic review of arrhythmic outcomes and complications in patients with SHD who underwent CSD due to recurrent VAs., Methods: Electronic databases (Google Scholar and PubMed) were searched to identify reports on CSD in SHD using appropriate medical subject terms. No sample size restriction was applied. All patients with known channelopathies were excluded. Baseline demographic and surgical data, arrhythmic outcomes, and procedural complications were evaluated., Results: A total of 13 studies and 173 patients were included. Of the 173 patients (121 [70%] male); pooled mean age 54.6 [95% confidence interval 52.6-56.7] years), 48 (28%) had ischemic cardiomyopathy, and 141 (82%) underwent bilateral CSD. Overall freedom from events ranged from 58% to 100%. Complications were reported in 49 patients(28%). Transient hypotension (9%), pneumothorax (5%), neuropathic pain (skin sensitivity) (4%), Horner syndrome (3%), sweating pattern changes (3%), and hemothorax (2%) were the most common complications. No procedure-related deaths were reported., Conclusion: CSD reduced the number of VA events in patients with SHD, and the benefit from the intervention seemed to be independent of the underlying SHD. Although overall rate of postprocedural complications was high, most of the complications were temporary. Major postprocedural complications after CSD were infrequent., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Recurrences of atrial fibrillation (AF) after ablation have been attributed to conduction gaps and nontransmural ablation lesions., Objective: The purpose of this study was to assess the feasibility of adjunctive percutaneous mapping of the epicardial regions of the left atrium to characterize the transmural extent of substrate and ablation lesions., Methods: Between 2014 and 2018, combined epicardial and endocardial mapping of AF was performed in 18 patients via an inferior subxiphoid percutaneous approach (16 with previously failed ablation procedures and 2 patients with long-standing persistent AF) at 2 centers. Epicardial substrate mapping was compared with endocardial mapping to assess transmural uniformity., Results: Of 18 patients, 4 (22%) demonstrated nontransmural atrial low-voltage regions with relative epicardial sparing in the left atrial posterior wall. Transmural isolation of the posterior wall was achieved after an endocardial "box" lesion set in 6/9 (67%), guided by epicardial voltage data, while epicardial and endocardial dissociation during AF was observed in 1 patient. In 3 patients, epicardial capture along the endocardial pulmonary vein lesion set despite endocardial capture loss and bidirectional block was observed. Two cases of mitral flutter were terminated from the epicardium. A balloon was positioned in the pericardial space in 6 patients for esophageal protection during ablation., Conclusion: A percutaneous epicardial approach for mapping and ablation of the left atrium is feasible in the electrophysiology laboratory during endocardial catheter ablation for AF and may be useful as an adjunctive approach in refractory cases. High-density epicardial mapping can provide direct evidence of nonuniform lesion and substrate transmurality of the human left atrium before and after ablation., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic ventricular ectopy (VE) shows predilection to sites within the left ventricular (LV) base such as the outflow tract/aortic sinuses, LV summit, and areas adjacent to the aortomitral continuity. We characterize VE arising from the inferior septum of the LV base that was successfully managed by LV endocardial ablation from the inferoseptal recess of the LV., Objective: The purpose of this study was to determine the incidence, electrocardiographic (ECG) findings, electrophysiological findings, and anatomical features associated with VE arising from the basal inferoseptal process of the LV (ISP-LV) ablated using an LV endocardial approach via the inferoseptal recess of the LV., Methods: A total of 425 consecutive patients undergoing VE ablation between January 1, 2012 and December 31, 2016 at 3 centers were evaluated. Demographic characteristics, ECG findings, and procedural data were analyzed for patients with ISP-LV VEs., Results: Seven (1.5%) had a site of origin from the ISP-LV. Common ECG findings were a right bundle branch block concordant pattern or an atypical left bundle branch block early transition pattern, suggestive of a basal origin with a left superior axis, a biphasic QRS complex in lead aVR, and a small s wave in lead V 6 . Earliest activation was seen in an area below the outflow tract accessed from the inferoseptal recess inferior to the His bundle. In 3 cases, transient junctional rhythm was seen during ablation. All cases were ablated successfully with no complications., Conclusion: VE arising from the ISP-LV represents a distinct subset of idiopathic arrhythmia and can be successfully treated by endocardial catheter ablation from the inferoseptal recess. They share common surface ECG and electrophysiological findings with special anatomical features that need recognition for successful catheter ablation., (Copyright © 2018 Heart Rhythm Society. All rights reserved.)

Ventricular arrhythmias are responsible for hundreds of thousands of deaths every year. Catheter ablation of ventricular tachycardia (VT) is an essential component of the management of these life-threatening arrhythmias. However, in many patients, despite medical and interventional therapy, VT recurs. Furthermore, some VT substrates (mid-myocardial, left ventricular summit, and intraseptal) are not easily targeted because of limitations of currently available technology. In certain clinical settings, ventricular fibrillation (VF) episodes that have premature ventricular contraction triggers can also be targeted with catheter ablation. However, in most patients there is no clear VF trigger to target, and therefore polymorphic VT or VF cannot be adequately treated with catheter ablation. The autonomic nervous system plays a crucial role in all aspects of ventricular arrhythmias, yet interventions specific to the cardiac neuronal axis have been largely underutilized. This underutilization has been most pronounced in patients with structural heart disease. However, there is a growing body of literature on the physiology and pathophysiology of cardiac neural control and the benefits of neuromodulation to treat refractory ventricular arrhythmias in these patients. We present case-based examples of neuromodulatory interventions currently available and a review of the literature supporting their use., (Copyright © 2018 Heart Rhythm Society. All rights reserved.)

Background: There is limited experience of surgical epicardial access in the contemporary era of ventricular tachycardia ablation after cardiac surgery., Objectives: The purpose of this study was to describe our institutional experience with surgical epicardial access and the influence of surgical approach and compare outcomes with those of a propensity-matched percutaneous epicardial access control group., Methods: We performed a retrospective study of consecutive surgical epicardial ventricular tachycardia (VT) ablation cases from a single center. Surgical cases were propensity-matched to percutaneous epicardial ablation controls and short-term and long-term outcomes were compared., Results: Between 2004 and 2016, 38 patients underwent 40 surgical epicardial access procedures (subxiphoid, n = 22; thoracotomy, n = 18). The commonest indication was prior coronary artery bypass grafting (45%), valve surgery (22%), or ventricular assist device (VAD) (10%). The mean procedure time was 444 minutes (standard deviation, 107 minutes). Mapped epicardial geometry area was 149 cm 2 (interquartile range 182 cm 2 ), which comprised 36% of the mapped epicardial geometric area of a percutaneous control group. Subxiphoid access gave preferential access to the inferior and inferolateral left ventricular segments and was less frequently able to access the anterior, anterolateral, and apical segments compared with a thoracotomy approach. When compared with results from a propensity-matched percutaneous-access group, short-term outcomes, complication rates, and 1-year survival free from a combined end point of VT recurrence, death, or transplantation were not statistically different., Conclusions: Surgical epicardial access after cardiac surgery for ablation of VT in patients with careful preprocedure evaluation can be performed with acceptable safety with no statistical difference in long-term outcomes compared with a propensity-matched percutaneous epicardial cohort. The region of left ventricular epicardium that can be mapped is limited compared with that of percutaneous cases and is determined by the surgical approach., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Magnetic resonance imaging (MRI) has been performed safely in patients without MRI-conditional cardiac implantable electronic devices (CIEDs), but experience specifically with cardiac magnetic resonance imaging (CMR) is limited in this patient population., Objective: Evaluate the safety of CMR in non-MRI-conditional CIEDs and the interpretability of images using wideband sequences., Methods: We performed 114 consecutive CMR studies in 111 patients (mean age 59 ± 14 years, with 12 pacemakers, 73 implantable cardioverter defibrillators, 29 biventricular defibrillators) using a wideband pulse sequence for late gadolinium enhancement (LGE) imaging. A standardized protocol for device management and patient monitoring was followed. Patients were evaluated for major clinical adverse events and device parameter changes immediately after CMR and at clinical follow-up., Results: In total, 111 CMR studies were completed successfully. There were no patient deaths, new arrhythmias, immediate generator or lead failures, electrical resets, or pacing capture failures in dependent patients. Right atrial, right ventricular, and left ventricular lead impedances were significantly lower post CMR, with median differences -7 Ω (interquartile range [IQR] -20 to 0 Ω; P < .0001), 0 Ω (IQR -19 to 0 Ω; P = .0001), and -10 Ω (IQR -30 to 0 Ω; P = .023), respectively. These changes persisted through the follow-up period, with median differences -18.5 Ω (IQR -41 to -66 Ω; P = .007), -19 Ω (IQR -44 to -7 Ω; P = .006), and -30 Ω (IQR -130 to 0 Ω; P = .003), respectively. Ninety-seven studies (87%) had no artifact limiting interpretation., Conclusions: CMR can be performed safely in non-MRI-conditional CIEDs using a standardized protocol. Use of a wideband pulse sequence for LGE imaging yields a high rate of studies unaffected by artifact., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Infrequent intraprocedural premature ventricular complexes (PVCs) may impede radiofrequency catheter ablation (RFA) outcome, and pharmacologic induction is unpredictable., Objective: The purpose of this study was to determine whether PVC circadian variation could help predict drug response., Methods: Consecutive patients referred for RFA with detailed Holter monitoring and frequent monomorphic PVCs were included. Patients were divided into 3 groups based on hourly PVC count relationship to corresponding mean heart rate (HR) during each of the 24 hours on Holter: fast-HR-dependent PVC (F-HR-PVC) type for a positive correlation (Pearson, P <.05), slow-HR-dependent PVC (S-HR-PVC) type for a negative correlation, and independent-HR-PVC (I-HR-PVC) when no correlation was found., Results: Fifty-one of the 101 patients (50.5%) had F-HR-PVC, 39.6% I-HR-PVC, and 9.9% S-HR-PVC; 30.7% had infrequent intraprocedural PVC requiring drug infusion. The best predictor of infrequent PVC was number of hours with PVC count <120/h on Holter (area under the curve 0.80, sensitivity 83.9%, specificity 74.3%, for ≥2 h). Only F-HR-PVC patients responded to isoproterenol. Isoproterenol washout or phenylephrine infusion was successful for the 3 S-HR-PVC patients, and no drug could increase PVC frequency in the 12 I-HR-PVC patients. Long-term RFA success rate in patients with frequent PVCs at baseline (82.9%) was similar to those with infrequent PVC who responded to a drug (77.8%; P = .732) but significantly higher than for those who did not respond to any drug (15.4%; P <.0001)., Conclusion: A simple analysis of Holter PVC circadian variability provides incremental value to guide pharmacologic induction of PVCs during RFA and predict outcome. Patients with infrequent I-HR-PVC had the least successful outcomes from RF ablation., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Pericardial adhesions can prevent epicardial access and restrict catheter movement during mapping and ablation of ventricular tachycardia (VT). The incidence of adhesions in patients without prior cardiac surgery or clinically evident pericarditis is not known., Objective: To describe the incidence of pericardial adhesions and explore their impact in patients without prior cardiac surgery or pericarditis., Methods: A retrospective search of our ablation database containing patients who underwent epicardial ablation for VT was undertaken. Adhesions were diagnosed with routine contrast pericardiography after pericardial entry. Demographics and long-term outcomes were compared between patients with and without adhesions., Results: Between 2004 and 2016, successful epicardial entry was achieved in 188 of 192 attempts (98%). In 155 first-time epicardial access attempts, pericardial adhesions were diagnosed in 13 (8%). When comparing baseline demographics, there was no significant difference. However, adhesions tended to occur more frequently with severe renal impairment (2% of patients without adhesions vs 15% of patients with adhesions, P = .07). No patient with a structurally normal heart had adhesions present. Adhesions were associated with limited epicardial mapping (3% of patients without adhesions vs 85% of patients with adhesions, P < .001) and lower short-term procedural success (68% of patients without adhesions vs 46% of patients with adhesions, P = .02), but complication rates were similar. The presence of adhesions did not translate into lower VT-free survival (P = .64) or freedom from a combined end point of VT recurrence, death, or transplant at 1 year (P = .93)., Conclusion: Adhesions may be unexpectedly encountered in patients without prior cardiac surgery or pericarditis. When present, they can limit mapping and may be associated with lower short-term success. Larger studies are required to determine their impact on long-term outcomes., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate the characteristics and outcome of patients undergoing ablation after electrical storm (ES)., Methods: Clinical and procedural characteristics, ventricular tachycardia (VT) recurrence, and mortality rates from 1940 patients undergoing VT ablation were compared between patients with and without ES., Results: The group of 677 patients with ES (34.9%) were older, were more frequently men, and had a lower ejection fraction, more advanced heart failure, and a higher prevalence of cardiovascular comorbidities as compared with those without ES (86.1% patients with ES had ≥2 comorbidities vs 71.4%; P < .001). Patients with ES had more inducible VTs (2.5 ± 1.8 vs 1.9 ± 1.9; P < .001), required longer procedures (296.1 ± 119.1 minutes vs 265.7 ± 110.3 minutes; P < .001), and had a higher in-hospital mortality (42 deaths [6.2%] vs 18 deaths [1.4%]; P < .001). At 1-year follow-up, patients with ES experienced a higher risk of VT recurrence and mortality (32.1% vs 22.6% and 20.1% vs 8.5%; long-rank, P < .001 for both). Among patients with ES, those without any inducible VT after ablation had a higher survival rate (86.3%) than did those with nonclinical VTs only (72.9%), those with clinical VTs inducible at programmed electrical stimulation (51.2%), and not-tested patients (65.0%) (long-rank, P < .001 for all). In multivariate analysis, ES remained an independent predictor of in-hospital mortality, VT recurrence, and 1-year mortality (P < .001)., Conclusion: Patients with ES have a high risk of VT recurrence and mortality. Patient and procedure characteristics are consistent with advanced cardiac disease and longer and more complex procedures. In patients with ES, acute procedural success is associated with a significant reduction in VT recurrence and improved 1-year survival., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Autonomic dysfunction contributes to induction of ventricular tachyarrhythmia (VT)., Objective: To determine the efficacy of charge-balanced direct current (CBDC), applied to the T1-T2 segment of the paravertebral sympathetic chain, on VT inducibility post-myocardial infarction (MI)., Methods: In a porcine model, CBDC was applied in acute animals (n = 7) to optimize stimulation parameters for sympathetic blockade and in chronic MI animals (n = 7) to evaluate the potential for VTs. Chronic MI was induced by microsphere embolization of the left anterior descending coronary artery. At termination, in anesthetized animals and following thoracotomy, an epicardial sock array was placed over both ventricles and a quadripolar carousel electrode positioned underlying the right T1-T2 paravertebral chain. In acute animals, the efficacy of CBDC carousel (CBDCC) block was assessed by evaluating cardiac function during T2 paravertebral ganglion stimulation with and without CBDCC. In chronic MI animals, VT inducibility was assessed by extrasystolic (S1-S2) stimulations at baseline and under >66% CBDCC blockade of T2-evoked sympathoexcitation., Results: CBDCC demonstrated a current-dependent and reversible block without impacting basal cardiac function. VT was induced at baseline in all chronic MI animals. One animal died after baseline induction. Of the 6 remaining animals, only 1 was reinducible with simultaneous CBDCC application (P < .002 from baseline). The ventricular effective refractory period (VERP) was prolonged with CBDCC (323 ± 26 ms) compared to baseline (271 ± 32 ms) (P < .05)., Conclusions: Axonal block of the T1-T2 paravertebral chain with CBDCC reduced VT in a chronic MI model. CBDCC prolonged VERP, without altering baseline cardiac function, resulting in improved electrical stability., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The autonomic nervous system regulates normal cardiovascular function and plays a critical role in the pathophysiology of cardiovascular disease. Further understanding of the interplay between the autonomic nervous system and cardiovascular system holds promise for the development of neuroscience-based cardiovascular therapeutics. To this end, techniques to image myocardial innervation will help provide a basis for understanding the fundamental underpinnings of cardiac neural control. In this review, we detail the evolution of gross and microscopic anatomical studies for functional mapping of cardiac neuroanatomy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Permanent His-bundle pacing (HBP) has the potential to physiologically normalize wide QRS duration in patients with bundle branch block and cardiomyopathy., Objective: The purpose of this study was to assess the feasibility of incorporating a His-bundle lead for cardiac resynchronization therapy (CRT) in lieu of a coronary sinus lead., Methods: Patients with an indication for CRT (n = 21) underwent attempted implantation of an HBP placed into the left ventricular (LV) lead port. Intracardiac intervals, QRS duration, New York Heart Association functional class, ejection fraction (EF), echocardiography, and lead characteristics were measured at baseline and at follow-up., Results: Of the 21 patients in whom implantation was attempted, HBP was successfully implanted in 16 (age 62 ± 18 years, 4 females, EF 25 ± 8). A significant reduction in mean QRS was observed, with narrowing from 180 ± 23 ms to 129 ± 13 ms (P <.0001). During the follow-up period, median New York Heart Association functional class improved from III to II (P <.001), and mean LV EF and left ventricular internal dimension in diastole (LVIDd) improved from 27% ± 10% to 41% ± 13% (P <.001) and from 5.4 ± 0.4 cm to 4.5 ± 0.3 cm (P <.001), respectively. At median 12-month follow-up, no dislodgments were observed, and only one patient lost nonselective capture that resolved with increased pacing output., Conclusion: Permanent HBP is feasible for patients with an indication for CRT using the LV port in lieu of a coronary sinus lead. In this initial experience, narrowing of QRS duration was achieved in 76% of patients with bundle branch block, and improvements in clinical and echocardiographic measures were observed with HBP. Future prospective comparative studies with HBP to achieve CRT are justifiable., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Neuromodulation of the paravertebral ganglia by using symmetric voltage controlled kilohertz frequency alternating current (KHFAC) has the potential to be a reversible alternative to surgical intervention in patients with refractory ventricular arrhythmias. KHFAC creates scalable focal inhibition of action potential conduction., Objective: The purpose of this article was to evaluate the efficacy of KHFAC when applied to the T1-T2 paravertebral chain to mitigate sympathetic outflow to the heart., Methods: In anesthetized, vagotomized, porcine subjects, the heart was exposed via a midline sternotomy along with paravertebral chain ganglia. The T3 paravertebral ganglion was electrically stimulated, and activation recovery intervals (ARIs) were obtained from a 56-electrode sock placed over both ventricles. A bipolar Ag electrode was wrapped around the paravertebral chain between T1 and T2 and connected to a symmetric voltage controlled KHFAC generator. A comparison of cardiac indices during T3 stimulation conditions, with and without KHFAC, provided a measure of block efficacy., Results: Right-sided T3 stimulation (at 4 Hz) was titrated to produce reproducible ARI changes from baseline (52 ± 30 ms). KHFAC resulted in a 67% mitigation of T3 electrical stimulation effects on ARI (18.5 ± 22 ms; P < .005). T3 stimulation repeated after KHFAC produced equivalent ARI changes as control. KHFAC evoked a transient functional sympathoexcitation at onset that was inversely related to frequency and directly related to intensity. The optimum block threshold was 15 kHz and 15 V., Conclusion: KHFAC applied to nexus (convergence) points of the cardiac nervous system produces a graded and reversible block of underlying axons. As such, KHFAC has the therapeutic potential for on-demand and reversible mitigation of sympathoexcitation., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Data evaluating repeat radiofrequency ablation (>1RFA) of ventricular tachycardia (VT) are limited., Objective: The purpose of this study was to determine the safety and outcomes of VT >1RFA in patients with structural heart disease., Methods: Patients with structural heart disease undergoing VT RFA at 12 centers with data on prior RFA history were included. Characteristics and outcomes were compared between first-time (1RFA) and >1RFA patients., Results: Of 1990 patients, 740 had >1RFA (mean 1.4 ± 0.9, range 1-10). >1RFA vs 1RFA patients did not differ with regard to age (62 ± 13 years vs 62 ± 13 years), left ventricular ejection fraction (33% ± 13% vs 34% ± 13%), or sex (88% vs 87% men), but they more often were nonischemic (53% vs 41%), had implantable cardioverter-defibrillator shocks (70% vs 63%) or VT storm (38% vs 33%), and had been treated with amiodarone (55% vs 48%) or ≥2 antiarrhythmic drugs (22% vs 14%). >1RFA procedures were longer (300 ± 122 minutes vs 266 ± 110 minutes), involved more epicardial access (41% vs 21%), induced VTs (2.4 ± 2.2 vs 1.9 ± 1.6) and only unmappable VTs (15% vs 9%), and VT was more often inducible after RFA (42% vs 33%, all P <.03). Total complications were higher for >1RFA vs 1RFA (8% vs 5%, P <.01), mostly related to pericardial effusion (2.4% vs 1.3%, P = .07) and venous thrombosis (0.8% vs 0.2%, P = .06). VT recurrence was higher for >1RFA vs 1RFA (29% vs 24%, P <.001). Survival was worse for >1RFA vs 1RFA if VT recurred (67% vs 78%, P = .003) but was equivalent if successful (93% vs 92%, P = .96)., Conclusion: Patients requiring repeat VT ablation differ significantly from those undergoing first-time ablation. Despite more challenging ablation characteristics, VT-free survival after repeat ablations is encouraging. Mortality is comparable if VT does not recur after RFA at specialized centers., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)