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.

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.

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.

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.

Feasibility of percutaneous epicardial mapping and ablation for refractory atrial fibrillation: Insights into substrate and lesion transmurality.

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.

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.

Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up.

BACKGROUND: Left and bilateral cardiac sympathetic denervation (CSD) have been shown to reduce burden of ventricular arrhythmias acutely in a small number of patients with ventricular tachyarrhythmia (VT) storm. The effects of this procedure beyond the acute setting are unknown. OBJECTIVE: The purpose of this study was to evaluate the intermediate and long-term effects of left and bilateral CSD in patients with cardiomyopathy and refractory VT or VT storm. METHODS: Retrospective analysis of medical records for patients who underwent either left or bilateral CSD for VT storm or refractory VT between April 2009 and December 2012 was performed. RESULTS: Forty-one patients underwent CSD (14 left CSD, 27 bilateral CSD). There was a significant reduction in the burden of implantable cardioverter-defibrillator (ICD) shocks during follow-up compared to the 12 months before the procedure. The number of ICD shocks was reduced from a mean of 19.6 ± 19 preprocedure to 2.3 ± 2.9 postprocedure (P < .001), with 90% of patients experiencing a reduction in ICD shocks. At mean follow-up of 367 ± 251 days postprocedure, survival free of ICD shock was 30% in the left CSD group and 48% in the bilateral CSD group. Shock-free survival was greater in the bilateral group than in the left CSD group (P = .04). CONCLUSION: In patients with VT storm, bilateral CSD is more beneficial than left CSD. The beneficial effects of bilateral CSD extend beyond the acute postsympathectomy period, with continued freedom from ICD shocks in 48% of patients and a significant reduction in ICD shocks in 90% of patients.

Device artifact reduction for magnetic resonance imaging of patients with implantable cardioverter-defibrillators and ventricular tachycardia: late gadolinium enhancement correlation with electroanatomic mapping.

BACKGROUND: Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) of ventricular scar has been shown to be accurate for detection and characterization of arrhythmia substrates. However, the majority of patients referred for ventricular tachycardia (VT) ablation have an implantable cardioverter-defibrillator (ICD), which obscures image integrity and the clinical utility of MRI. OBJECTIVE: The purpose of this study was to develop and validate a wideband LGE MRI technique for device artifact removal. METHODS: A novel wideband LGE MRI technique was developed to allow for improved scar evaluation on patients with ICDs. The wideband technique and the standard LGE MRI were tested on 18 patients with ICDs. VT ablation was performed in 13 of 18 patients with either endocardial and/or epicardial approach and the correlation between the scar identified on MRI and electroanatomic mapping (EAM) was analyzed. RESULTS: Hyperintensity artifact was present in 16 of 18 of patients using standard MRI, which was eliminated using the wideband LGE and allowed for MRI interpretation in 15 of 16 patients. All patients had ICD lead characteristics confirmed as unchanged post-MRI and had no adverse events. LGE scar was seen in 11 of 18 patients. Among the 15 patients in whom wideband LGE allowed visualization of myocardium, 10 had LGE scar and 5 had normal myocardium in the regions with image artifacts when using the standard LGE. The left ventricular scar size measurements using wideband MRI and EAM were correlated with R(2) = 0.83 and P = .00003. CONCLUSION: Wideband LGE MRI improves the ability to visualize myocardium for clinical interpretation, which correlated well with EAM findings during VT ablation.

Epicardial ablation of ventricular tachycardia: an institutional experience of safety and efficacy.

BACKGROUND: Epicardial ablation has been shown to be a useful adjunct for treatment of ventricular tachycardia (VT). OBJECTIVE: To report the trends, safety, and efficacy of epicardial mapping and ablation at a single center over an 8-year period. METHODS: Patients referred for VT ablation (June 2004 to July 2011) were divided into 3 groups: ischemic cardiomyopathy (ICM), nonischemic cardiomyopathy (NICM), and idiopathic ventricular arrhythmias (VA). Patients with scar-mediated VT who underwent combined epicardial and endocardial (epi-endo) mapping and ablation were compared with those who underwent endocardial-only (endo-only) ablation with regard to patient characteristics, acute procedural success, 6- and 12-month clinical outcomes. RESULTS: Among 144 patients referred for VT ablation, 95 patients underwent 109 epicardial procedures (94% access rate). Major complications were seen in 8 patients (8.8%) with pericardial bleeding (>80 cm(3)) in 6 cases (6.7%), although no tamponade, surgical intervention, or procedural mortality was seen. Patients with ICM who underwent a combined epi-endo ablation had improved freedom from VT compared with those who underwent endo-only ablation at 12 months (85% vs 56%; P = .03). In patients with NICM, no differences were seen between those who underwent epi-endo ablation and those who underwent endo-only ablation at 12 months (36% vs 33%; P = 1.0). In idiopathic VA, only 2 of 17 patients were successfully ablated from the epicardium. CONCLUSIONS: In this large tertiary single-center experience, complication rates are acceptably low and improved clinical outcomes were associated with epi-endo ablation in patients with ICM. Patients with NICM represent a growing referred population, although clinical recurrence remains high despite epicardial ablation. Epicardial ablation has a low yield in idiopathic VA.

Distribution of late potentials within infarct scars assessed by ultra high-density mapping.

BACKGROUND: Late potential (LP) electrograms represent areas of slow conduction and are often sites critical to reentrant tachycardia circuits. The distribution of LPs within infarct scar is not known. OBJECTIVE: The purpose of this study was to delineate infarct heterogeneity using ultra high-density mapping and to determine the location of LPs with respect to scar architecture. METHODS: Detailed endocardial (n = 21) and epicardial (n = 8) ultra high-density mapping was performed to delineate the substrate for ventricular tachycardia (VT) in 21 patients with ischemic cardiomyopathy. LP was defined as a low-voltage electrogram (< 1.5 mV) with distinct onset after the QRS. Very late potentials (vLPs) were classified as LPs with onset > 100 ms after the QRS. RESULTS: A mean of 787 ± 391 and 810 ± 375 points in the LV endocardium and epicardium were sampled. Multipolar mapping identified heterogeneous islets (HIs) with relatively preserved electrogram amplitudes (≥ 0.51 mv) within dense scar (8.5 ± 4.9/4.5 ± 2.6 HIs per endocardium/epicardium) in all patients. In maps on which putative VT isthmuses were identified (25/29), 57% of vLP were recorded in or adjacent to HI. An LP-targeted ablation strategy combined with pace mapping achieved acute success in all patients (complete success in 52% and partial success in 48%). After 15 ± 7 months, 65% of patients remained free of VT episodes. CONCLUSION: Ultra high-density mapping with a multipolar catheter facilitates the delineation of heterogeneous scar architecture at higher resolution. Electrograms within and adjacent to HIs have a higher incidence of vLP, and these sites are frequently critical to reentry. These findings have important implications for substrate-based ablation strategies.

Characterization of the arrhythmogenic substrate in ischemic and nonischemic cardiomyopathy implications for catheter ablation of hemodynamically unstable ventricular tachycardia.

OBJECTIVES: The purpose of this study was to compare the characteristics and prevalence of late potentials (LP) in patients with nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) etiologies and evaluate their value as targets for catheter ablation. BACKGROUND: LP are frequently found in post-myocardial infarction scars and are useful ablation targets. The relative prevalence and characteristics of LP in patients with NICM is not well understood. METHODS: Thirty-three patients with structural heart disease (NICM, n = 16; ICM, n = 17) referred for catheter ablation of ventricular tachycardia were studied. Electroanatomic mapping was performed endocardially (n = 33) and epicardially (n = 19). The LP were defined as low voltage electrograms (<1.5 mV) with onset after the QRS interval. Very late potentials (vLP) were defined as electrograms with onset >100 ms after the QRS. RESULTS: We sampled an average of 564 +/- 449 points and 726 +/- 483 points in the left ventricle endocardium and epicardium, respectively. Mean total low voltage area in patients with ICM was 101 +/- 55 cm(2) and 56 +/- 33 cm(2), endocardial and epicardial, respectively, compared with NICM of 55 +/- 41 cm(2) and 53 +/- 28 cm(2), respectively. Within the total low voltage area, vLP were observed more frequently in ICM than in NICM in endocardium (4.1% vs. 1.3%; p = 0.0003) and epicardium (4.3% vs. 2.1%, p = 0.035). An LP-targeted ablation strategy was effective in ICM patients (82% nonrecurrence at 12 +/- 10 months of follow-up), whereas NICM patients had less favorable outcomes (50% at 15 +/- 13 months of follow-up). CONCLUSIONS: The contribution of scar to the electrophysiological abnormalities targeted for ablation of unstable ventricular tachycardia differs between ICM and NICM. An approach incorporating LP ablation and pace-mapping had limited success in patients with NICM compared with ICM, and alternative ablation strategies should be considered.