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Background: Data on relative safety, efficacy, and role of different percutaneous left ventricular assist devices for hemodynamic support during the ventricular tachycardia (VT) ablation procedure are limited., Methods and Results: We performed a multicenter, observational study from a prospective registry including all consecutive patients (N=66) undergoing VT ablation with a percutaneous left ventricular assist devices in 6 centers in the United States. Patients with intra-aortic balloon pump (IABP group; N=22) were compared with patients with either an Impella or a TandemHeart device (non-IABP group; N=44). There were no significant differences in the baseline characteristics between both the groups. In non-IABP group (1) more patients could undergo entrainment/activation mapping (82% versus 59%; P=0.046), (2) more number of unstable VTs could be mapped and ablated per patient (1.05±0.78 versus 0.32±0.48; P<0.001), (3) more number of VTs could be terminated by ablation (1.59±1.0 versus 0.91±0.81; P=0.007), and (4) fewer VTs were terminated with rescue shocks (1.9±2.2 versus 3.0±1.5; P=0.049) when compared with IABP group. Complications of the procedure trended to be more in the non-IABP group when compared with those in the IABP group (32% versus 14%; P=0.143). Intermediate term outcomes (mortality and VT recurrence) during 12±5-month follow-up were not different between both groups. Left ventricular ejection fraction ≤15% was a strong and independent predictor of in-hospital mortality (53% versus 4%; P<0.001)., Conclusions: Impella and TandemHeart use in VT ablation facilitates extensive activation mapping of several unstable VTs and requires fewer rescue shocks during the procedure when compared with using IABP.

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., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)

Objective: The aim of this study was to determine the pertinent anesthetic considerations for patients undergoing surgical sympathectomy for electrical storm (incessant ventricular tachycardia (VT) refractory to traditional therapies)., Design: This is a retrospective review of a prospective database., Setting: This single-center study took place in a university hospital setting., Participants: Twenty-six patients were enrolled., Interventions: Fifteen patients underwent left-sided sympathectomy, whereas 11 patients underwent bilateral sympathectomy., Measurements and Main Results: Anesthetic management of these patients was quite complex, requiring invasive monitoring, transesophageal echocardiography, one-lung ventilation, programming of cardiac rhythm management devices, and titration of vasoactive medications. Paired t test of hemodynamic data before, during, and after surgery showed no significant difference between preoperative and postoperative blood pressure values, regardless of whether the patient underwent unilateral or bilateral sympathectomy. Eight patients remained free of VT, three patients responded well to titration of oral medications, and one patient required 2 radiofrequency ablations after sympathectomy to control his VT. Three patients continued to have VT episodes, although reduced in frequency compared with before the procedure. Four patients were lost to followup. Overall, five patients within the cohort died within 30 days of the procedure. No patients developed any anesthetic complications or Horner's syndrome. The overall perioperative mortality (within the first 7 days of the procedure) was 2 of 26, or 7.7%., Conclusions: The anesthetic management of patients undergoing surgical sympathectomy for electrical storm can be quite complex, because these patients often present in a moribund and emergent state and cannot be optimized using current ACC/AHA guidelines. Expertise in invasive monitoring, transesophageal echocardiography, one-lung ventilation, cardiac rhythm device management, and pressor management is crucial for optimal anesthetic care., (© 2013 Elsevier Inc. All rights reserved.)

Purpose: To propose and test a modified wideband late gadolinium enhancement (LGE) magnetic resonance (MR) imaging technique to overcome hyperintensity image artifacts caused by implanted cardiac devices., Materials and Methods: Written informed consent was obtained from all participants, and the HIPAA-compliant study protocol was approved by the institutional review board. Studies in phantoms and in a healthy volunteer were performed to test the hypothesis that the hyperintensity artifacts that are typically observed on LGE images in patients with implanted cardiac devices are caused by insufficient inversion of the affected myocardial signal. The conventional LGE MR imaging pulse sequence was modified by replacing the nonselective inversion pulse with a wideband inversion pulse. The modified LGE sequence, along with the conventional LGE sequence, was evaluated in 12 patients with implantable cardioverter defibrillators (ICDs) who were referred for cardiac MR imaging., Results: The ICD causes 2-6 kHz in frequency shift at locations 5-10 cm away from the device. This off-resonance falls outside the typical spectral bandwidth of the nonselective inversion pulse used in conventional LGE, which results in the hyperintensity artifact. In 10 of the 12 patients, the conventional LGE technique produced severe, uninterpretable hyperintensity artifacts in the anterior and lateral portions of the left ventricular wall. These artifacts were eliminated with use of the wideband LGE sequence, thereby enabling confident evaluation of myocardial viability., Conclusion: The modified wideband LGE MR imaging technique eliminates the hyperintensity artifacts seen in patients with cardiac devices. The technique may enable LGE MR imaging in patients with cardiac devices, in whom LGE MR imaging otherwise could not be used for diagnosis., (© RSNA, 2013.)

Advances in the treatment of myocardial infarction (MI) have improved survival after ischemic cardiac injury. Post-infarct structural and functional remodeling results in electrophysiologic substrates at risk for monomorphic ventricular tachycardia (MMVT). Characterization of this substrate using a variety of clinical and investigative tools has improved our understanding of MMVT circuits, and has accelerated the development of device and catheter-based therapies aimed at identification and elimination of this arrhythmia. This review will discuss the central role of the ischemic heart disease substrate in the development MMVT. Electrophysiologic characterization of the post-infarct myocardium using bipolar electrogram amplitudes to delineate scar border zones will be reviewed. Functional electrogram determinants of reentrant circuits such as isolated late potentials will be discussed. Strategies for catheter ablation of reentrant ventricular tachycardia, including structural and functional targets will also be examined, as will the role of the epicardial mapping and ablation in the management of recurrent MMVT., (Copyright © 2013 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

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.

We describe a scar-related reentrant ventricular tachycardia circuit with a proximal segment in an endocardial basal septal scar and an exit in a region of slow conduction in a non-overlapping region of epicardial basal lateral scar. The 12-lead EKG demonstrates criteria for a basal lateral epicardial VT, however the same morphology could be produced with a longer stim-latency with pace mapping or VT induction from the endocardial septal region of scar. A significant segment of myocardium demonstrated no endocardial or epicardial scar on electroanatomic mapping, suggesting the presence of a mid-myocardial isthmus. Further evidence was provided by assessment of unipolar settings. The epicardial VT that initially appeared to originate from the basal lateral epicardial region, was successfully treated with radiofrequency ablation of the lateral aspect of the endocardial septal scar.

Background: The precise localization of the site of origin of a premature ventricular contractions (PVC) prior to ablation would facilitate the planning and execution of the electrophysiological procedure. Current electrocardiographic imaging (ECGI) techniques require body surface maps, a costly and complex procedure, that requires as many as 256 leads to localize the PVC origin. We developed and tested a novel myocardial activation based ECGI technique utilizing the readily available 12-lead ECG to localize the PVC origin., Methods: The major components of the 12-lead ECGI method are: the source model, proximity effect and spatial orientation, volume conductor, and patient specific model of the heart, lungs, and thorax as derived from magnetic resonance imaging (MRI). For the PVC origin localization, the fastest route algorithm is used on patient specific models created by newly developed morphing software. PVC localization by the 12-lead ECGI was correlated to the site of successful ablation., Results: Seven patients that underwent electrophysiological mapping and ablation of PVCs were studied. All patients (7/7) had accurate prediction of the PVC origin. However in two patients, no specific MRI was used for localization that resulted in an incorrect switch between the RV free wall and septum of the RVOT. With patient-specific models, these latter two cases would likely be localized correctly., Conclusions: This feasibility study of a novel myocardial activation-based ECGI using only the standard 12-lead ECG shows promise to localize the origin of PVC. This ECGI method yields activation estimates of isochrones on both ventricles from which the PVC origin location is derived. This method has the capability to localize the PVC from any part of the ventricular endocardium, intra-myocardium or epicardium., (© 2013.)

Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine (n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms(2), P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P = 0.0001), whereas left stellate ganglion stimulation showed the reverse (P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced.

Left stellate or right stellate ganglion stimulation (LGSG or RSGS, respectively) is associated with ventricular tachyarrhythmias; however, the electrophysiological mechanisms remain unclear. We assessed 1) regional dispersion of myocardial repolarization during RSGS and LSGS and 2) regional electrophysiological mechanisms underlying T-wave changes, including T-peak to T-end (Tp-e) interval, which are associated with ventricular tachyarrhythmia/ventricular fibrillation. In 10 pigs, a 56-electrode sock was placed around the heart, and both stellate ganglia were exposed. Unipolar electrograms, to asses activation recovery interval (ARI) and repolarization time (RT), and 12-lead ECG were recorded before and during RSGS and LSGS. Both LSGS and RSGS increased dispersion of repolarization; with LSGS, the greatest regional dispersion occurred on the left ventricular (LV) anterior wall and LV apex, whereas with RSGS, the greatest regional dispersion occurred on the right ventricular posterior wall. Baseline, LSGS, and RSGS dispersion correlated with Tp-e. The increase in RT dispersion, which was due to an increase in ARI dispersion, correlated with the increase in Tp-e intervals (R(2) = 0.92 LSGS; and R(2) = 0.96 RSGS). During LSGS, the ARIs and RTs on the lateral and posterior walls were shorter than the anterior LV wall (P < 0.01) and on the apex versus base (P < 0.05), explaining the T-wave vector shift posteriorly/inferiorly. RSGS caused greater ARI and RT shortening on anterior versus lateral or posterior walls (P < 0.01) and on base versus apex (P < 0.05), explaining the T-wave vector shift anteriorly/superiorly. LSGS and RSGS cause differential effects on regional myocardial repolarization, explaining the ECG T-wave morphology. Sympathetic stimulation, in line with its proarrhythmic effects, increases Tp-e interval, which correlates with increases in myocardial dispersion of repolarization.

Background: Radiofrequency ablation for ventricular tachycardia is an established therapy. Use of chemical agents for scar homogenization represents an alternative approach. The purpose of this study was to characterize the efficacy of collagenase (CLG) application on epicardial ventricular scar homogenization., Methods and Results: Myocardial infarcts were created in Yorkshire pigs (n=6) by intracoronary microsphere injection. After 46.6±4.3 days, CLG type 2, type 4, and purified CLG were applied in vitro (n=1) to myocardial tissue blocks containing normal myocardium, border zone, and dense scar. Histopathologic studies were performed to identify the optimal CLG subtype. In vivo high-density electroanatomic mapping of the epicardium was also performed, and border zone and dense scar surface area and late potentials were quantified before and after CLG-4 application (n=5). Of the CLG subtypes tested in vitro, CLG-4 provided the best scar modification and least damage to normal myocardium. During in vivo testing, CLG-4 application decreased border zone area (21.3±14.3 to 17.1±11.1 mm(2), P=0.043) and increased dense scar area (9.1±10.3 to 22.0±20.6 mm(2), P=0.043). The total scar area before and after CLG application was 30.4±23.4 and 39.2±29.5 mm(2), respectively (P=0.08). Late potentials were reduced by CLG-4 application (28.8±21.8 to 13.8±13.1, P=0.043). During CLG-4 application (50.0±15.5 minutes), systolic blood pressure and heart rate were not significantly changed (68.0±7.7 versus 61.8±5.3 mmHg, P=0.08; 77.4±7.3 versus 78.8±6.0 beats per minute, P=0.50, respectively)., Conclusions: Ventricular epicardial scar homogenization by CLG-4 application is feasible and effective. This represents the first report on bioenzymatic ablation of arrhythmogenic tissue as an alternative strategy for lesion formation.

Objectives: This study sought to determine whether ablation of recently described stable atrial fibrillation (AF) sources, either directly by Focal Impulse and Rotor Modulation (FIRM) or coincidentally when anatomic ablation passes through AF sources, may explain long-term freedom from AF., Background: It is unclear why conventional anatomic AF ablation can be effective in some patients yet ineffective in others with similar profiles., Methods: The CONFIRM (Conventional Ablation for AF With or Without Focal Impulse and Rotor Modulation) trial prospectively revealed stable AF rotors or focal sources in 98 of 101 subjects with AF at 107 consecutive ablation cases. In 1:2 fashion, subjects received targeted source ablation (FIRM) followed by conventional ablation, or conventional ablation alone. We determined whether ablation lesions on electroanatomic maps passed through AF sources on FIRM maps., Results: Subjects who completed follow-up (n = 94; 71.2% with persistent AF) showed 2.3 ± 1.1 concurrent AF rotors or focal sources that lay near pulmonary veins (22.8%), left atrial roof (16.0%), and elsewhere in the left (28.2%) and right (33.0%) atria. AF sources were ablated directly in 100% of FIRM cases and coincidentally (e.g., left atrial roof) in 45% of conventional cases (p < 0.05). During a median (interquartile range) of 273 days (138 to 636 days) after one procedure, AF was absent in 80.3% of patients if sources were ablated but in only 18.2% of patients if sources were missed (p < 0.001). Freedom from AF was highest if all sources were ablated, intermediate if some sources were ablated, and lowest if no sources were ablated (p < 0.001)., Conclusions: Elimination of stable AF rotors and focal sources may explain freedom from AF after diverse approaches to ablation. Patient-specific AF source distributions are consistent with the reported success of specific anatomic lesion sets and of widespread ablation. These results support targeting AF sources to reduce unnecessary ablation, and motivate studies on FIRM-only ablation., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine the availability of quinidine throughout the world., Background: Quinidine is the only oral medication that is effective for preventing life-threatening ventricular arrhythmias due to Brugada syndrome and idiopathic ventricular fibrillation. However, because of its low price and restricted indication, this medication is not marketed in many countries., Methods: We conducted a survey of the availability of quinidine by contacting professional medical societies and arrhythmia specialists worldwide. Physicians were e-mailed questionnaires requesting information concerning the quinidine preparation available at their hospital. We also requested information concerning cases of adverse arrhythmic events resulting from unavailability of quinidine., Results: A total of 273 physicians from 131 countries provided information regarding the availability of quinidine. Quinidine was readily available in 19 countries (14%), not accessible in 99 countries (76%), and available only through specific regulatory processes that require 4 to 90 days for completion in 13 countries (10%). We were able to gather information concerning 22 patients who had serious arrhythmias probably related (10 cases) or possibility related (12 cases) to the absence of quinidine, including 2 fatalities possibly attributable to the unavailability of quinidine., Conclusions: The lack of accessibility of quinidine is a serious medical hazard at the global level., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Electroanatomic mapping systems are an important tool to identify cardiac chamber voltage and assess channels of slow conduction., Objective: To assess the correlation between electroanatomic mapping voltage maps obtained during macroreentrant tachycardia compared to sinus rhythm (SR) with a contact mapping system., Methods: We retrospectively evaluated patients with atrial flutter (AFL) referred for radiofrequency ablation with electroanatomic voltage maps obtained during AFL and SR. The atrium was divided into predetermined segments. Overall atrial and segmental peak-to-peak bipolar voltages in AFL and SR were assessed. To directly compare a region within the same patient, tissue voltage differences during AFL and SR were assessed on the basis of mean voltage difference., Results: Sixteen patients (87% men) had available voltage maps. Eighty-one percent had typical cavotricuspid isthmus-dependent right AFL. A mean of 441.7±153.9 vs 398.1±125.4 total points (P = .22) were sampled during AFL and SR, with a mean of 99.5±58.9 vs 91.2±60.4 points (P = .45) sampled per region. Overall right atrial mean voltage was significantly higher during AFL than SR (0.554±0.092mV vs 0.473±0.079mV; P≤.001), with the lateral wall (0.707±0.120mV vs 0.573±0.097mV; P = .0004) and the cavotricuspid isthmus (0.559±0.100mV vs 0.356±0.066mV; P<.0001) also showing higher mean voltage during AFL. When compared within an individual patient, 19% (14 of 75) of the patient regions had a>0.5mV mean voltage difference and 40% (30 of 75) had a>0.25mV mean voltage difference., Conclusions: These data suggest that voltage maps performed during macroreentrant atrial arrhythmias often vary significantly from maps obtained during SR., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Epicardial mapping and ablation is increasingly being performed for the treatment of complex arrhythmias. Right ventricular (RV) puncture remains the most common complication, with damage to surrounding non-cardiac structures also a concern. We describe the standard techniques used in our lab essential for safe epicardial access, as well as a novel technique incorporating electroanatomic mapping (EAM) guidance. In a series of 8 patients referred for ventricular tachycardia ablation, an RV endocardial voltage map was created using EAM systems. EAM images were fused with preprocedure CT scans when available. A 17G Tuohy needle was integrated with the EAM system by attaching the needle to sterile electrode clamps. EAM location points were used in conjunction with standard access techniques until epicardial access was obtained. Epicardial access was successfully obtained in 8/8 (100%) patients. Successful access without RV puncture was achieved in 7/8 (88%) cases. This proof of concept study demonstrates that EAM systems can be used as an adjunct to standard access techniques to visualize and facilitate pericardial access., (© 2012 Wiley Periodicals, Inc.)

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., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Left ventricular (LV) twist mechanics and regional strain during cardiac sympathetic efferent activation are poorly understood. The purpose of this study was to compare the effects of left stellate ganglia (LSG) and right stellate ganglia (RSG) stimulation on cardiac twist/untiwst mechanics and regional strain. In nine pigs, echocardiographic imaging and LV pressure-volume measurements were performed before and during unilateral and bilateral stellate ganglion stimulation. LSG and RSG stimulation significantly augmented LV end-systolic pressure by 24% and 22% (P < 0.01), maximal rate of LV pressure change by 167% and 165% (P < 0.01), and time constant of LV relaxation by 20% and 12% (P < 0.01), respectively. RSG stimulation resulted in a greater chronotropic response than LSG stimulation (RSG: 68% vs. LSG: 12%, P < 0.01). Both LSG and RSG stimulation significantly increased global epicardial and endocardial LV rotation and diastolic untwisting rate and reduced the time to peak rotation (P < 0.05). However, LSG stimulation predominantly increased radial and circumferential strain in the LV inferoseptal, inferior, posterior, and lateral regions, whereas RSG stimulation primarily increased radial and circumferential strain in the anteroseptal, anterior, and lateral LV regions. Stimulation of both stellate ganglia led to a uniform increase in all LV segments. Our data suggest that LSG and RSG stimulation lead to a global increase in LV twist, driven by distinct regional strain heterogeneity that may result from myocardial innervation from the LSG and RSG. These findings provide a better understanding of the global and regional functional consequences of regional myocardial innervation from the LSG and RSG.

Increased cardiac sympathetic activation worsens dispersion of repolarization and is proarrhythmic. The functional differences between intrinsic nerve stimulation and adrenergic receptor activation remain incompletely understood. This study was undertaken to determine the functional differences between efferent cardiac sympathetic nerve stimulation and direct adrenergic receptor activation in porcine ventricles. Female Yorkshire pigs (n = 13) underwent surgical exposure of the heart and stellate ganglia. A 56-electrode sock was placed over the ventricles to record epicardial electrograms. Animals underwent bilateral sympathetic stimulation (BSS) (n = 8) or norepinephrine (NE) administration (n = 5). Activation recovery intervals (ARIs) were measured at each electrode before and during BSS or NE. The degree of ARI shortening during BSS or NE administration was used as a measure of functional nerve or adrenergic receptor density. During BSS, ARI shortening was nonuniform across the epicardium (F value 9.62, P = 0.003), with ARI shortening greatest in the mid-basal lateral right ventricle and least in the midposterior left ventricle (LV) (mean normalized values: 0.9 ± 0.08 vs. 0.56 ± 0.08; P = 0.03). NE administration resulted in greater ARI shortening in the LV apex than basal segments [0.91 ± 0.04 vs. 0.63 ± 0.05 (averaged basal segments); P = 0.003]. Dispersion of ARIs increased in 50% and 60% of the subjects undergoing BSS and NE, respectively, but decreased in the others. There is nonuniform response to cardiac sympathetic activation of both porcine ventricles, which is not fully explained by adrenergic receptor density. Different pools of adrenergic receptors may mediate the cardiac electrophysiological effects of efferent sympathetic nerve activity and circulating catecholamines.

Background: The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE)., Methods and Results: Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0-3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm(2); P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67)., Conclusions: Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm(2), with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF.

Introduction: Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets., Methods: We prospectively enrolled the first (n = 14, 11 males) consecutive patients undergoing FIRM-guided ablation for persistent (n = 11) and paroxysmal AF at 5 centers. A 64-pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10% cycle length prolongation). Conventional ablation was performed only after FIRM-guided ablation., Results: Twelve out of 14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9 ± 0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM-guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n = 8 (4.9 ± 3.9 minutes at the primary source), and organization in n = 4. Total FIRM time for all patients was 12.3 ± 8.6 minutes., Conclusions: FIRM-guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM-guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation., (© 2012 Wiley Periodicals, Inc.)

Background: Radiofrequency ablation is first-line therapy for atrial flutter (AFL). There are no studies of ablation in patients with severe pulmonary arterial hypertension (PAH)., Methods: Consecutive patients with severe PAH (systolic pulmonary artery pressure >60 mmHg) and AFL referred for ablation were evaluated. Patients with complex congenital heart disease were excluded., Results: A total of 14 AFL ablation procedures were undertaken in 12 patients. A total of 75% of patients were female; mean age 49 ± 12 years. SPAP prior to ablation was 99 ± 35 mmHg. Baseline 6-minute walk distance was 295 ± 118 m. ECG demonstrated a typical AFL pattern in only 42% of cases. Baseline AFL cycle length was longer in PAH patients compared to controls (295 ± 53 ms vs 252 ± 35 ms, P = 0.006). Cavotricuspid isthmus dependence was verified in 86% of cases. Acute success was obtained in 86% of procedures. SPAP decreased from 114 ± 44 mmHg to 82 ± 38 mmHg after ablation (P = 0.004). BNP levels were lower postablation (787 ± 832 pg/mL vs 522 ± 745 pg/mL, P = 0.02). Complications were seen in 14%. A total of 80% (8/10) of patients were free of AFL at 3 months; 75% (6/8) at 1 year., Conclusion: Ablation of AFL in severe PAH patients is feasible, with good short- and intermediate-term success rates. The ECG pattern is not a reliable marker of isthmus dependence. The SPAP and BNP levels may decrease postablation. AFL may be a marker of poor outcomes in patients with PAH with a 1-year mortality rate of 42% in this study. This rate is higher than expected in the general PAH population., (© 2012 Wiley Periodicals, Inc.)

Background: Intramyocardial nerve sprouting after myocardial infarction is associated with ventricular arrhythmias. Whether human stellate ganglia remodel in association with cardiac pathology is unknown. The purpose of this study was to determine whether cardiac pathology is associated with remodeling of the stellate ganglia in humans., Methods and Results: Left stellate ganglia were collected from patients undergoing sympathetic denervation for intractable ventricular arrhythmias and from cadavers, along with intact hearts. Clinical data on patients and cadaveric subjects were reviewed. We classified ganglia from normal, scarred, and nonischemic cardiomyopathic hearts without scar as NL (n=3), SCAR (n=24), and NICM (n=7), respectively. Within left stellate ganglia, neuronal size, density, fibrosis, synaptic density, and nerve sprouting were determined. Nerve density and sprouting were also quantified in cadaveric hearts. Mean neuronal size in normal, scarred, and nonischemic cardiomyopathic hearts without scar groups were 320 ± 4 μm(2), 372 ± 10 μm(2), and 435 ± 10 μm(2) (P=0.002), respectively. No significant differences in neuronal density and fibrosis were present between the groups. Synaptic density in ganglia from SCAR and NICM groups were 57.8 ± 11.2 μm(2)/mm(2) (P=0.084) and 44.5 ± 7.9 μm(2)/mm(2) (P=0.039), respectively, compared with the normal group, 17.8 ± 7 μm(2)/mm(2) (overall P=0.162). There were no significant differences in left stellate ganglia nerve sprouting or myocardial nerve density between the groups., Conclusions: Neuronal hypertrophy within left stellate ganglia is associated with chronic cardiomyopathy in humans. Ganglionic and myocardial nerve sprouting and nerve density were not significantly different. These changes may be related to increased cardiac sympathetic signaling and ventricular arrhythmias. Further studies are needed to determine the electrophysiological consequences of extracardiac neuronal remodeling in humans.

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.

Purpose of Review: Implantable cardioverter-defibrillator (ICD) implantation is the standard of care for secondary prevention in patients with previous cardiac arrest and for primary prevention in appropriately selected patients with cardiomyopathy. However, ICD therapies and the arrhythmias that trigger these therapies cause decreased quality of life as well as increased morbidity and mortality. In this review, we summarize the recent evidence for interventions that may prevent ICD therapies., Recent Findings: Pharmacologic therapy remains central to prevent ICD shocks, but there is limited new evidence for drug therapies. Programming techniques continue to evolve which decrease the risk of inappropriate shocks. Cardiac resynchronization therapy (CRT) improves quality of life and decreases mortality, at least in part because of decreased arrhythmia burden. Procedures such as catheter ablation of ventricular tachycardia and procedures to modulate the autonomic nervous system can help minimize ICD therapy., Summary: Pharmacologic therapy and appropriate device programming remain essential to the overall care of ICD patients. The role of CRT continues to grow as we gain a better understanding of its benefits. Advancements in the fields of catheter ablation and new understanding of the autonomic nervous system's effects on ventricular arrhythmias allow interventions to decrease the frequency of ICD shocks.

Ablation of cavotricuspid ishtmus flutter and atrial tachycardia in a complex substrate has never been reported using remote navigation via superior approach. Venous access was obtained via right internal jugular for ablation and left subclavian for duodecapolar catheter placement into the coronary sinus. In a posttransplant patient presenting with both regular and irregular tachycardia, both cavotricuspid isthmus flutter in the donor and atrial tachycardia in the recipient was mapped using a two catheter approach. Successful ablation of typical atrial flutter and anastomotic block was achieved. This is the first report of successful ablation of cavotricuspid isthmus flutter and posttransplant atrial tachycardia using magnetic navigation via superior approach. Using only two catheters, this approach is logical and feasible in complex substrates with interrupted inferior venous access.

Atrial fibrillation is the most common human arrhythmia, causing significant mortality and morbidity. Because of the potential for complications, it is important that procedures be made as safe and effective as possible by combining safe procedural planning with effective therapy delivery. To change the current approach, large randomized studies are needed to guide the selection of patients who may safely undergo ablation without transesophageal echocardiography to exclude thrombus. For institutions routinely using computed tomography and magnetic resonance imaging to assess pulmonary vein anatomy before procedures, the possibility of excluding intracardiac thrombi using these imaging modalities should be considered., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Sosa and colleagues first described a percutaneous approach (via the subxiphoid area) to access the pericardial space in 1996. Epicardial mapping and ablation is increasingly used for the treatment of supraventricular and ventricular arrhythmias and represents an adjunctive approach for challenging arrhythmias to improve procedural success rates. Epicardial ablation should be considered not only after the failure of an endocardial ablation but often as a first-line approach. Complications may occur during percutaneous access and epicardial ablation, and these might be reduced or avoided by improved operator skills and experience. New tools to access the epicardial space are being evaluated., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: We hypothesized that human atrial fibrillation (AF) may be sustained by localized sources (electrical rotors and focal impulses), whose elimination (focal impulse and rotor modulation [FIRM]) may improve outcome from AF ablation., Background: Catheter ablation for AF is a promising therapy, whose success is limited in part by uncertainty in the mechanisms that sustain AF. We developed a computational approach to map whether AF is sustained by several meandering waves (the prevailing hypothesis) or localized sources, then prospectively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome., Methods: We recruited 92 subjects during 107 consecutive ablation procedures for paroxysmal or persistent (72%) AF. Cases were prospectively treated, in a 2-arm 1:2 design, by ablation at sources (FIRM-guided) followed by conventional ablation (n = 36), or conventional ablation alone (n = 71; FIRM-blinded)., Results: Localized rotors or focal impulses were detected in 98 (97%) of 101 cases with sustained AF, each exhibiting 2.1 ± 1.0 sources. The acute endpoint (AF termination or consistent slowing) was achieved in 86% of FIRM-guided cases versus 20% of FIRM-blinded cases (p < 0.001). FIRM ablation alone at the primary source terminated AF in a median 2.5 min (interquartile range: 1.0 to 3.1 min). Total ablation time did not differ between groups (57.8 ± 22.8 min vs. 52.1 ± 17.8 min, p = 0.16). During a median 273 days (interquartile range: 132 to 681 days) after a single procedure, FIRM-guided cases had higher freedom from AF (82.4% vs. 44.9%; p < 0.001) after a single procedure than FIRM-blinded cases with rigorous, often implanted, electrocardiography monitoring. Adverse events did not differ between groups., Conclusions: Localized electrical rotors and focal impulse sources are prevalent sustaining mechanisms for human AF. FIRM ablation at patient-specific sources acutely terminated or slowed AF, and improved outcome. These results offer a novel mechanistic framework and treatment paradigm for AF. (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation [CONFIRM]; NCT01008722)., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The utilization of the NIOBE™ magnetic navigation system (MNS, Stereotaxis, St. Louis, MO, USA) has increased significantly since the first published report in 2002. There has been much enthusiasm for this technology as a means to reduce radiation exposure to the patient and physician alike, and potentially decrease risks associated with catheter manipulation by less experienced operators. However, there are limited data regarding the acute, intermediate, and long-term results and procedural characteristics from ablation procedures utilizing this system. We present a review of the outcomes and procedural data available to date., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Background: The sympathetic nervous system is thought to play a role in the genesis of ventricular tachyarrhythmias (VT). Left and added right cardiac sympathectomy have been shown to reduce the burden of arrhythmias in the setting of a VT storm. However, the contribution of the right stellate ganglion (RSG) and the left stellate ganglion (LSG) to the innervation of the anterior left ventricular (LV) wall is not well understood., Objective: To evaluate the innervation of the anterior LV wall by the LSG and the RSG., Methods: The heart and stellate ganglia were exposed via sternotomy in pigs with normal hearts (n = 8). A 20-electrode catheter was placed on the anterior LV wall to record activation recovery interval (ARI), a surrogate measure of action potential duration. A microdialysis catheter was inserted in a similar location to sample interstitial norepinephrine (NE) content. ARI and NE measurements were recorded at baseline and during LSG and RSG stimulation., Results: LSG stimulation shortened ARI by 17.1% ± 10.5% (mean ± standard error), while RSG stimulation shortened ARI by 42.1% ± 15.7%, P = .04 (LSG vs RSG). LSG stimulation increased interstitial NE levels by 200% ± 65%, while RSG stimulation increased the NE content by 260% ± 40% (P = .012). LSG stimulation increased dispersion in ARI from 376.0 ± 83.7 ms(2) to 1242.5 ± 566 ms(2) (P = .03) and caused ventricular fibrillation in 2 pigs. During RSG stimulation, dispersion increased from 419 ± 65.8 to 474.8 ± 81 ms(2) (P = .4)., Conclusions: Both the LSG and the RSG provide significant innervation to the anterior LV wall as demonstrated by both ARI shortening and NE concentrations. LSG stimulation significantly increases ARI dispersion. This study provides mechanistic insight into the beneficial effects of left sympathectomy and the additional role of right sympathectomy in reducing arrhythmias in patients with anterior myocardial scars and VT storm., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The sympathetic nervous system is thought to play a key role in genesis and maintenance of ventricular arrhythmias. The myocardial effect of sympathetic stimulation on myocardial repolarization in humans is poorly understood. The purpose of this study was to evaluate the effects of direct and reflex sympathetic stimulation on ventricular repolarization in patients with postinfarct cardiomyopathy (ICM). The effects of direct sympathetic stimulation were assessed using isoproterenol, while those of reflex sympathetic stimulation were assessed with nitroprusside infusion in ICM patients (n = 5). Five patients without cardiomyopathy were also studied. Local repolarization was measured from intracardiac electrograms that were used to calculate the activation recovery interval (ARI), a surrogate of action potential duration. Isoproterenol significantly increased heterogeneity in repolarization in patients with ICM; the decrease in ARI from baseline was 72.9 ± 9.1 ms in more viable regions, 64.5 ± 8.9 ms in the scar, and 54.9 ± 9.1 ms in border zones (P = 0.0002 and 0.014 comparing normal and scar to border zones, respectively). In response to nitroprusside, the ARI at the border zones decreased significantly more than either scar or surrounding viable myocardium, which showed an increase in ARI (P = 0.014 and 0.08 comparing normal tissue and scar to border zones, respectively). Furthermore, isoproterenol increased ARI dispersion by 70%, while nitroprusside increased ARI dispersion by 230% when ICM patients were compared to those with structurally normal hearts (P = 0.0015 and P < 0.001, respectively). In humans, both direct and reflex sympathetic stimulations increase regional differences in repolarization. The normal tissue surrounding the scar appears denervated. Dispersion of ARI in response to sympathetic stimulation is significantly increased in patients with ICM.

Ventricular tachycardia as a late complication of blunt chest trauma has never been reported. We present a case of combined endocardial and epicardial delineation of the right ventricular arrhythmogenic substrate, where other causes of cardiomyopathy were excluded. The epicardial scar was more extensive than endocardial scar, and the central isthmus was likely intramural. A history of blunt chest trauma should be considered in patients with right ventricular cardiomyopathy., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

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.

The role of cardiac resynchronization therapy in mild heart failure has become a focus of attention with the publication of recent clinical trials. We present a review of the data supporting implantation of cardiac resynchronization devices in early stage heart failure. In addition, we present evidence that may suggest patients are often implanted too late for clinical benefit, potentially contributing to the relatively high nonresponder rate seen in randomized trials and clinical practice.