Nilesh Mathuria

FREEDOM FROM RECURRENT VENTRICULAR TACHYCARDIA AFTER CATHETER ABLATION IS ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH STRUCTURAL HEART DISEASE: AN INTERNATIONAL VT ABLATION CENTER COLLABORATIVE GROUP STUDY

BACKGROUND The impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown. OBJECTIVE The purpose of this study was to examine the association between VT recurrence after ablation and survival in patients with scar-related VT. METHODS Analysis of 2061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality. RESULTS One-year freedom from VT recurrence was 70% (72% in ischemic and 68% in nonischemic cardiomyopathy). Fifty-seven patients (3%) underwent cardiac transplantation, and 216 (10%) died during follow-up. At 1 year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and nonischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence than in those with recurrence (90% vs 71%, P<.001). In multivariable analysis, recurrence of VT after ablation showed the highest risk for transplant and/or mortality [hazard ratio 6.9 (95% CI 5.3-9.0), P<.001]. In patients with ejection fraction <30% and across all New York Heart Association functional classes, improved transplant-free survival was seen in those without VT recurrence. CONCLUSION Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year. Freedom from VT recurrence is associated with improved transplant-free survival, independent of heart failure severity.

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.

Hybrid procedures for epicardial catheter ablation of ventricular tachycardia: Value of surgical access

BACKGROUND Prior chest surgery limits the ability to obtain epicardial access in patients referred for catheter ablation of ventricular tachycardia (VT). OBJECTIVE The purpose of this study was to describe the utility of different surgical approaches to access the epicardium for VT ablation. METHODS Clinical data of 14 patients with drug-refractory VT who underwent hybrid surgical epicardial access for catheter mapping and ablation in the electrophysiology lab were reviewed. Baseline patient and procedural characteristics including access, exposure, mapping techniques, and ablation were analyzed. RESULTS Of a total of 14 patients (age 63.2 ± 10.3 years), 11 had a subxiphoid window performed, and three patients underwent limited anterior thoracotomy to access the epicardium. The indication for surgical access was prior cardiac surgery (n = 12), previous failed epicardial access (n = 1), and ablation in close proximity to the coronary arteries and phrenic nerve (n = 1). Mapping in patients with subxiphoid surgical access was limited to the inferior and diaphragmatic surface of the heart extending posteriorly to the basal lateral wall. With limited anterior thoracotomy, access to the apex, anterior, and mid to apical anterolateral walls was obtained. In these regions, adhesions were more severe and repeat entry into the epicardial region at a different intercostal level was needed in two of three patients. CONCLUSION Surgical access with subxiphoid window and limited anterior thoracotomy in the electrophysiology lab is feasible and safe. The surgical approach can be tailored to the region of interest in the ventricle to be mapped and ablated.

Functional pace-mapping responses for identification of targets for catheter ablation of scar-mediated ventricular tachycardia.

Background— Myocardial scars harbor areas of slow conduction and display abnormal electrograms. Pace-mapping at these sites can generate a 12-lead ECG morphological match to a targeted ventricular tachycardia (VT), and in some instances, multiple exit morphologies can result. At times, this can also result in the initiation of VT, termed pace-mapped induction (PMI). We hypothesized that in patients undergoing catheter ablation of VT, scar substrates with multiple exit sites (MES) identified during pace-mapping have improved freedom from recurrent VT, and PMI of VT predicts successful sites of termination during ablation. Methods and Results— High-density mapping was performed in all subjects to delineate scar (0.5–1.5 mV). Sites with abnormal electrograms were tagged, stimulated (bipolar 10 mA at 2 ms), and targeted for ablation. MES was defined as >1 QRS morphology from a single pacing site. PMI was defined as initiation of VT during pace-mapping (400–600 ms). In a 2-year period, 44 consecutive patients with scar-mediated VT underwent mapping and ablation. MES were observed during pace-mapping in 25 patients (57%). At 9 months, 74% of patients who exhibited MES during pace-mapping had no recurrence of VT compared with 42% of those without MES observed (P=0.024), with an overall freedom from VT of 61%. Thirteen patients (30%) demonstrated PMI, and termination of VT was seen in 95% (18/19) of sites where ablation was performed. Conclusions— During pace-mapping, electrograms that exhibit MES and PMI may be specific for sites critical to reentry. These functional responses hold promise for identifying important sites for catheter ablation of VT.

Impact of local ablation on interconnected channels within ventricular scar: mechanistic implications for substrate modification.

Background— The extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping. Methods and Results— Analysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.6±14.7 mm (range, 2–50 mm). Among all patients, 9.7±7.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 23±12 LPs targeted. Conclusions— Ablation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the first mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs.Background—The extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping. Methods and Results—Analysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.6±14.7 mm (range, 2–50 mm). Among all patients, 9.7±7.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 23±12 LPs targeted. Conclusions—Ablation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the first mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs.

Ambulatory monitoring of congestive heart failure by multiple bioelectric impedance vectors.

OBJECTIVES This study was designed to investigate the properties of multiple bioelectric impedance signals recorded during congestive heart failure (CHF) by utilizing various electrode configurations of an implanted cardiac resynchronization therapy system. BACKGROUND The monitoring of CHF has relied mainly on right-side heart sensors. METHODS Fifteen normal dogs underwent implantation of cardiac resynchronization therapy systems using standard leads. An additional left atrial (LA) pressure lead sensor was implanted in 5 dogs. Continuous rapid right ventricular (RV) pacing was applied over several weeks. Left ventricular (LV) catheterization and echocardiography were performed biweekly. Six steady-state impedance signals, utilizing intrathoracic and intracardiac vectors, were measured through ring (r), coil (c), and device Can electrodes. RESULTS Congestive heart failure developed in all animals after 2 to 4 weeks of pacing. Impedance diminished gradually during CHF induction, but at varying rates for different vectors. Impedance during CHF decreased significantly in all measured vectors: LV(r)-Can, -17%; LV(r)-RV(r), -15%; LV(r)-RA(r), -11%; RV(r)-Can, -12%; RV(c)-Can, -7%; and RA(r)-Can, -5%. The LV(r)-Can vector reflected both the fastest and largest change in impedance in comparison with vectors employing only right-side heart electrodes, and was highly reflective of changes in LV end-diastolic volume and LA pressure. CONCLUSIONS Impedance, acquired by different lead electrodes, has variable responses to CHF. Impedance vectors employing an LV lead are highly responsive to physiologic changes during CHF. Measuring multiple impedance signals could be useful for optimizing ambulatory monitoring in heart failure patients.

Left Ventricular Twist Mechanics in a Canine Model of Reversible Congestive Heart Failure: A Pilot Study

BACKGROUND Left ventricular (LV) twist dynamics play an important role in LV systolic and diastolic function. The aim of this preliminary study was to investigate LV twist dynamics in a canine model of reversible congestive heart failure (CHF). METHODS Pacing systems were implanted in adult dogs, and continuous chronic right ventricular pacing (230-250 beats/min) was applied until CHF induction. Pacing was then stopped to allow the heart to recover. Echocardiography and LV catheterization were performed at baseline, during CHF while pacing was temporarily switched off, and during recovery. LV twist was computed as the difference between apical and basal rotation measured using 2-dimensional speckle tracking. Torsion was further calculated as LV twist divided by the LV long axis. The untwisting rate was computed as the peak diastolic time derivative of twist. RESULTS In 6 dogs that completed the study, we found that CHF developed after 2 to 4 weeks of pacing, with LV end-diastolic volume, end-systolic volume, end-diastolic pressure, and the time constant of relaxation during isovolumic relaxation period (tau) all increasing significantly compared with baseline and recovering to normal levels 2 to 4 weeks after pacing was stopped. LV twist, torsion, and untwisting rate decreased significantly with CHF compared with baseline and improved during recovery from CHF. CONCLUSION LV twist dynamics reflect pacing-induced CHF and its reversal as assessed by echocardiographic speckle tracking.

A novel SCN5A mutation V1340I in Brugada syndrome augmenting arrhythmias during febrile illness.

BACKGROUND Mutations in the SCN5A gene, which encodes the cardiac sodium channel, have been implicated in the pathogenesis of Brugada syndrome (BrS). Febrile illnesses have been recognized to unmask and/or trigger the BrS phenotype. However, the pathophysiological mechanism has not been fully elucidated. OBJECTIVE A novel SCN5A missense mutation, V1340I, was identified in a patient with BrS suffering from frequent episodes of polymorphic ventricular tachycardia (VT) and syncope associated with fever. The biophysical modifications of hNa(v)1.5 by V1340I were studied. METHODS The effects of the V1340I mutation were studied in the 2 splice variants, SCN5A and SCN5A-Q1077del (delQ), using patch-clamp techniques at various temperatures between 22 degrees C and 40 degrees C. RESULTS At 22 degrees C, V1340I-SCN5A generated markedly diminished sodium currents compared to the wild-type (WT) SCN5A. On the contrary, V1340I-delQ generated almost identical current density compared to the WT-delQ. However, V1340I-delQ significantly attenuated the peak current density compared to the WT-delQ at 32 degrees C, 37 degrees C and 40 degrees C. The voltage dependency of steady-state activation was leftward shifted both in WT-delQ and V1340I-delQ at 40 degrees C. In addition, the V1340I-delQ accelerated the recovery time course from fast inactivation compared to the WT-delQ at 40 degrees C. Immunohistochemical staining showed that both V1340I-SCN5A and V1340I-dQ were expressed in the plasma membrane. CONCLUSION Our study supports the concept that febrile illness predisposes individuals who carry a loss of function SCN5A mutation, such as V1340I, to fever-induced ventricular arrhythmias in BrS by significantly reducing the sodium currents in the hyperthermic state.

Advances in Ablation of Ventricular Tachycardia in Nonischemic Cardiomyopathy

Management of patients with nonischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) remains challenging. The role of catheter ablation for VT continues to evolve for these patients. Prior reports have described the location of the arrhythmogenic substrate for patients with NICM to be frequently located along the basal left ventricle, with an epicardial predilection. Furthermore, predictors for identifying whether mapping the endocardium or epicardial surface of the heart have been identified for improved success of VT ablation in this patient population. This chapter will review the latest advances in catheter ablation of ventricular tachycardia in patients with NICM.

Pleuropericardial Fistula Formation After Prior Epicardial Catheter Ablation for Ventricular Tachycardia

A 61-year-old man with nonischemic cardiomyopathy (left ventricular ejection fraction, 20%) underwent ventricular tachycardia (VT) ablation for recurrent implantable cardioverter-defibrillator shocks despite antiarrhythmic drugs. The patient had undergone a combined endocardial/epicardial VT ablation 3 years prior. During this index procedure, percutaneous epicardial access was obtained as previously described1 without complications and the pericardiogram was normal. Epicardial mapping revealed a large, dense scar covering the lateral wall of the left ventricle. Extensive ablation with an externally irrigated ablation catheter was performed on the epicardial surface, targeting late potentials and pace maps of induced VTs. Steroids were not administered in the pericardial space. The patient was free from VT for 3 years but then had recurrent …