Attempted salvage of infected cardiovascular implantable electronic devices: Are there clinical factors that predict success?

BACKGROUND: Published guidelines mandate complete device removal in cases of cardiovascular implantable electronic device (CIED) infection. Clinical predictors of successful salvage of infected CIEDs have not been defined. METHODS: Data from the Multicenter Electrophysiologic Device Infection Collaboration, a prospective, observational, multinational cohort study of CIED infection, were used to investigate whether clinical predictors of successful salvage of infected devices could be identified. RESULTS: Of 433 adult patients with CIED infections, 306 (71%) underwent immediate device explantation. Medical management with device retention and antimicrobial therapy was initially attempted in 127 patients (29%). "Early failure" of attempted salvage occurred in 74 patients (58%) who subsequently underwent device explantation during the index hospitalization. The remaining 53 patients (42%) in the attempted salvage group retained their CIED. Twenty-six (49%) had resolution of CIED infection (successful salvage group) whereas 27 patients (51%) experienced "late" salvage failure. Upon comparing the salvage failure group, early and late (N = 101), to the group experiencing successful salvage of an infected CIED (N = 26), no clinical or laboratory predictors of successful salvage were identified. However, by univariate analysis, coagulase-negative staphylococci as infecting pathogens (P = 0.0439) and the presence of a lead vegetation (P = 0.024) were associated with overall failed salvage. CONCLUSIONS: In patients with definite CIED infections, clinical and laboratory variables cannot predict successful device salvage. Until new data are forthcoming, device explantation should remain a mandatory and early management intervention in patients with CIED infection in keeping with existing expert guidelines unless medical contraindications exist or patients refuse device removal.

Prevention, Diagnosis, and Treatment of Cardiac Implantable Electronic Device Infections.

Cardiac implantable electronic device (CIED) infections are complex medical problems that are increasingly encountered. They are associated with significant morbidity and mortality with tremendous economic cost. The current review will emphasize the prevention, diagnosis, and treatment of this clinical entity using the relatively limited evidence that is currently available. Because there is a paucity of high quality evidence regarding prevention, diagnosis, and treatment of CIED infections, this review will attempt to summarize the best evidence as well as to suggest, when possible, paradigms for care. The topic of CIED infections is a dynamic one as the scope of CIED continues to widen. Furthermore, there are promising advancements in CIED technology which may help reduce its occurrence the future. Unfortunately, significant gaps in knowledge remain, and definitive recommendations regarding CIED infections and future studies should be directed at improving our ability to prevent infections.

Effect of the 2010 task force criteria on reclassification of cardiovascular magnetic resonance criteria for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: We sought to evaluate the effect of application of the revised 2010 Task Force Criteria (TFC) on the prevalence of major and minor Cardiovascular Magnetic Resonance (CMR) criteria for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) versus application of the original 1994 TFC. We also assessed the utility of MRI to identify alternative diagnoses for patients referred for ARVC evaluation. METHODS: 968 consecutive patients referred to our institution for CMR with clinical suspicion of ARVC from 1995 to 2010, were evaluated for the presence of major and minor CMR criteria per the 1994 and 2010 ARVC TFC. CMR criteria included right ventricle (RV) dilatation, reduced RV ejection fraction, RV aneurysm, or regional RV wall motion abnormalities. When quantitative measures of RV size and function were not available, and in whom abnormal size or function was reported, a repeat quantitative analysis by 2 qualified CMR physicians in consensus. RESULTS: Of 968 patients, 220 (22.7%) fulfilled either a major or a minor 1994 TFC, and 25 (2.6%) fulfilled any of the 2010 TFC criterion. Among patients meeting any 1994 criteria, only 25 (11.4%) met at least one 2010 criterion. All patients who fulfilled a 2010 criteria also satisfied at least one 1994 criterion. Per the 2010 TFC, 21 (2.2%) patients met major criteria and 4 (0.4%) patients fulfilled at least one minor criterion. Eight patients meeting 1994 minor criteria were reclassified as satisfying 2010 major criteria, while 4 patients fulfilling 1994 major criteria were reclassified to only minor or no criteria under the 2010 TFC.Eighty-nine (9.2%) patients had alternative cardiac diagnoses, including 43 (4.4%) with clinically significant potential ARVC mimics. These included cardiac sarcoidosis, RV volume overload conditions, and other cardiomyopathies. CONCLUSIONS: Application of the 2010 TFC resulted in reduction of total patients meeting any diagnostic CMR criteria for ARVC from 22.7% to 2.6% versus the 1994 TFC. CMR identified alternative cardiac diagnoses in 9.2% of patients, and 4.4% of the diagnoses were potential mimics of ARVC.

Navigated DENSE strain imaging for post-radiofrequency ablation lesion assessment in the swine left atria.

AIMS: Prior work has demonstrated that magnetic resonance imaging (MRI) strain can separate necrotic/stunned myocardium from healthy myocardium in the left ventricle (LV). We surmised that high-resolution MRI strain, using navigator-echo-triggered DENSE, could differentiate radiofrequency ablated tissue around the pulmonary vein (PV) from tissue that had not been damaged by radiofrequency energy, similarly to navigated 3D myocardial delayed enhancement (3D-MDE). METHODS AND RESULTS: A respiratory-navigated 2D-DENSE sequence was developed, providing strain encoding in two spatial directions with 1.2 × 1.0 × 4 mm(3) resolution. It was tested in the LV of infarcted sheep. In four swine, incomplete circumferential lesions were created around the right superior pulmonary vein (RSPV) using ablation catheters, recorded with electro-anatomic mapping, and imaged 1 h later using atrial-diastolic DENSE and 3D-MDE at the left atrium/RSPV junction. DENSE detected ablation gaps (regions with >12% strain) in similar positions to 3D-MDE (2D cross-correlation 0.89 ± 0.05). Low-strain (<8%) areas were, on average, 33% larger than equivalent MDE regions, so they include both injured and necrotic regions. Optimal DENSE orientation was perpendicular to the PV trunk, with high shear strain in adjacent viable tissue appearing as a sensitive marker of ablation lesions. CONCLUSIONS: Magnetic resonance imaging strain may be a non-contrast alternative to 3D-MDE in intra-procedural monitoring of atrial ablation lesions.

Variability in clinical features of early versus late cardiovascular implantable electronic device pocket infections.

BACKGROUND: Cardiovascular implantable electronic device (CIED) pocket infections are often related to recent CIED placement or manipulation, but these infections are not well characterized. The clinical presentation of CIED pocket infection, based on temporal onset related to last CIED procedure, deserves further study. METHODS: The MEDIC (Multicenter Electrophysiologic Device Infection Cohort) prospectively enrolled subjects with CIED infection. Subjects were stratified into those whose infection occurred <12 months (early) or ≥ 12 months (late) since their last CIED-related procedure. RESULTS: There were 132 subjects in the early group and 106 in the late group. There were more females (P = 0.009) and anticoagulation use (P = 0.039) in the early group. Subjects with early infections were more likely to have had a generator change or lead addition as their last procedure (P = 0.03) and had more prior CIED procedures (P = 0.023). Early infections were more likely to present with pocket erythema (P < 0.001), swelling (P < 0.001), and pain (P = 0.007). Late infections were more likely to have pocket erosion (P = 0.005) and valvular vegetations (P = 0.009). In bacteremic subjects, early infections were more likely healthcare-associated (P < 0.001). In-hospital and 6-month mortality were equivalent. CONCLUSION: A total of 45% of patients with CIED pocket infection presented >12 months following their last CIED-related procedure. Patients with early infection were more likely to be female, on anticoagulation, and present with localized inflammation, whereas those with late infection were more likely to have CIED erosion or valvular endocarditis.

Multi-sensor esophageal temperature probe used during radiofrequency ablation for atrial fibrillation is associated with increased intraluminal temperature detection and increased risk of esophageal injury compared to single-sensor probe.

BACKGROUND: Radiofrequency (RF) ablation in the posterior left atrium has risk of thermal injury to the adjacent esophagus. Increased intraluminal esophageal temperature has been correlated with risk of esophageal injury. The objective of this study was to compare esophageal temperature monitoring (ETM) using a multi-sensor temperature probe with 12 sensors to a single-sensor probe during catheter ablation for atrial fibrillation (AF). METHODS AND RESULTS: We compared the detection of intraluminal esophageal temperature rises in 543 patients undergoing RF ablation for AF with ETM. Esophageal endoscopy (EGD) was performed on all patients with maximum esophageal temperature ≥ 39°C. Esophageal lesions were classified by severity as mild or severe ulcerations. Four hundred fifty-five patients underwent RF ablation with single-sensor ETM and 88 patients with multi-sensor ETM. Thirty-nine percent of patients with single-sensor versus 75% with multi-sensor ETM reached a maximum detected esophageal temperature ≥ 39°C (P < 0.0001). Esophageal injury was detected by EGD in 29% of patients with maximum temperature ≥ 39°C by single-sensor versus 46% of patients with multi-sensor ETM (P = 0.021). Thirty-nine percent of patients with lesions in the single-sensor probe group had severe ulcerations compared to 33% of patients in the multi-sensor probe group (P = 0.641). CONCLUSIONS: Intraluminal esophageal temperature ≥ 39°C is detected more frequently by the multi-sensor temperature probe versus the single-sensor probe, with more frequent esophageal injury and with comparable severity of injury. Despite detecting esophageal temperature rises in more patients, the multi-sensor probe may not have any measurable benefit compared to a single-sensor probe.

Catheter ablation of scar-related atypical atrial flutter.

AIMS: The aim of the study was to assess the impact of isthmus location of atypical atrial flutters/atrial tachycardias (ATs) on outcomes of catheter ablation. Atrial tachycardias are clinically challenging arrhythmias that can occur in the presence of atrial scar--often due to either cardiac surgery or prior ablation for atrial fibrillation. We previously demonstrated a catheter ablation approach employing rapid multielectrode activation mapping with targeted entrainment manoeuvrs. However, the role that AT isthmus location plays in acute and long-term success of ablation remains uncertain. METHODS AND RESULTS: Retrospective multicenter analysis of 91 consecutive AT patients undergoing ablation using a systematic four-step approach: (i) high-density activation mapping; (ii) analysis of atrial activation to identify wavefronts of electrical propagation; (iii) targeted entrainment of putative channels; and (iv) irrigated radiofrequency ablation of constrained regions of the circuit. Clinical outcomes, procedural details, and clinical profiles were determined. A total of 171 ATs (1.9 ± 1.0 per patient, 26% septal ATs) were targeted for ablation. The acute success rates were 97 and 77% for patients with either non-septal ATs or septal ATs, respectively (P = 0.0023). Similarly, the long-term success rates were 82 and 67% for patients with either no septal ATs or at least one septal AT, respectively (P = 0.1057). The long-term success rates were 75, 88, and 57% for patients with ATs associated with prior catheter ablation, cardiac surgery or MAZE, and idiopathic atrial scar, respectively. CONCLUSION: Catheter ablation of AT can be successfully performed employing a strategy of combined high-density activation and entrainment mapping. Septal ATs are associated with higher rates of acute and long-term recurrences.

Efficacy and safety of implantable cardiac defibrillators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis.

AIMS: Implantable cardiac defibrillator (ICD) implantation is a class IIA recommendation for patients with cardiac sarcoidosis (CS). However, little is known about the efficacy and safety of ICDs in this population. The goal of this multicentre retrospective data review was to evaluate the efficacy and safety of ICDs in patients with CS. METHODS AND RESULTS: Electrophysiologists at academic medical centres were asked to identify consecutive patients with CS and an ICD. Clinical information, ICD therapy history, and device complications were collected for each patient. Data were collected on 235 patients from 13 institutions, 64.7% male with mean age 55.6 ± 11.1. Over a mean follow-up of 4.2 ± 4.0 years, 85 of 234 (36.2%) patients received an appropriate ICD therapy (shocks and/or anti-tachycardia pacing) and 67 of 226 (29.7%) received an appropriate shock. Fifty-seven of 235 patients (24.3%) received a total of 222 inappropriate shocks. Forty-six adverse events occurred in 41 of 235 patients (17.4%). Patients who received appropriate ICD therapies were more likely to be male (73.8 vs. 59.6%, P = 0.0330), have a history of syncope (40.5 vs. 22.5%, P = 0.0044), lower left ventricular ejection fraction (38.1 ± 15.2 vs. 48.8 ± 14.7%, P ≤ 0.0001), ventricular pacing on baseline electrocardiogram (16.1 vs. 2.1%, P = 0.0002), and a secondary prevention indication (60.7 vs. 24.5%, P < 0.0001) compared with those who did not receive appropriate ICD therapies. CONCLUSION: Patients with CS and ICDs are at high risk for ventricular arrhythmias. This population also has high rates of inappropriate shocks and device complications.

Comparison of electroanatomical mapping systems: accuracy in left atrial mapping.

BACKGROUND: Current 3D mapping systems have difficulty rendering complex cardiac structures. Different electroanatomical mapping software has been recently developed which uses a mathematical algorithm to improve interpolation between mapped points and delineation of closely spaced structures. This study tested the feasibility and accuracy of this software in comparison to traditional software. METHODS: In vivo 3D impedance-based mapping using a multielectrode catheter with a single geometry point cloud was performed in the left atria and pulmonary veins (PV) in 23 patients undergoing catheter ablation for atrial fibrillation. The maps were analyzed with traditional (NavX, St. Jude Medical, Minnetonka, MN, USA), either with or without multichamber mapping versus St. Jude OneModel™ software and dimensions of cardiac chambers in human studies were compared to preprocedural computed tomographic (CT) or magnetic resonance (MR) scans to determine the relative accuracy of the maps. RESULTS: Maps created by the OneModel software provided greater detail of complex cardiac structures compared to traditional software. Comparison of the left atrial/pulmonary vein electroanatomical maps with the CT and MR scans as reference standard demonstrated significantly less error in measurement of all PV ostial long- and short-axis dimensions, inter-PV distance, and ridge width (left PV to left atrial appendage) with the OneModel versus traditional software (P < 0.001 for all dimensions measured). CONCLUSIONS: The OneModel software produces maps that are more accurate in rendering complex cardiac structures compared to traditional software.

Ventricular tachycardia following trans-apical aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) is a relatively new procedure for high-risk patients with severe aortic stenosis. We report a case of a new left ventricular outflow tract ventricular tachycardia following TAVR.

Independent susceptibility markers for atrial fibrillation on chromosome 4q25.

BACKGROUND: Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus. METHODS AND RESULTS: Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5066 case and 30 661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk In Communities Study, Cleveland Clinic Lone AF Study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score composed of SNPs that tagged distinct AF susceptibility signals was constructed and tested for association with AF, and all results were subjected to meta-analysis. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95% confidence interval 1.50 to 2.15, P=1.2 x 10(-20)) in the discovery sample. Adjustment for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs that tagged these 3 susceptibility signals. CONCLUSIONS: We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with biological relevance in the pathogenesis of AF.

Direct visualization of epicardial structures and ablation utilizing a visually guided laser balloon catheter: preliminary findings.

BACKGROUND: Intrapericardial mapping and ablation can be utilized to target epicardial arrhythmic circuits. Current epicardial ablation strategies are associated with risk of damage to adjacent structures, including the coronary vasculature and phrenic nerves. OBJECTIVES: The purpose of this study was to evaluate the feasibility of an investigational, visually guided laser balloon catheter for manipulation within the pericardial space, visualization of epicardial structures, and delivery of laser ablation lesions to the ventricular myocardium. METHODS: Pericardial access was obtained in 4 anesthetized swine by subxyphoid puncture. The laser balloon catheter was introduced into the pericardial space via a deflectable sheath, and was manipulated to predefined regions in all animals. Visually guided laser ablation was performed on the ventricular myocardium, with post mortem examination of lesion size and depth. RESULTS: The laser ablation catheter could be manipulated to all targeted regions in all animals. Associated structures, including epicardial coronary arteries and veins as well as an endocardial catheter in the left atrial appendage, were easily visualized. A total of 9 laser energy applications at varying power/time settings were performed. Ablation utilizing moderate (7-8.5 W) power produced relatively uniform lesions (diameter 5-12 mm, depth 6-9 mm), while high (14 W) power produced a visible "steam pop" with a large, hemorrhagic lesion (22 × 11 × 11 mm). CONCLUSIONS: The investigational laser balloon catheter can be manipulated within the epicardial space, allowing for direct visualization of surrounding structures during ablation. Titration of laser power can be utilized to create moderate-sized ablation lesions while avoiding steam pops.

Visually-guided balloon catheter ablation of atrial fibrillation: experimental feasibility and first-in-human multicenter clinical outcome.

BACKGROUND: Electric isolation of the pulmonary veins (PVs) can successfully treat patients with paroxysmal atrial fibrillation. However, it remains technically challenging to identify the left atrial-PV junction and sequentially position the ablation catheter in a point-by-point contiguous fashion to isolate the PVs. In this study, a novel endoscopic ablation system was used to directly visualize and ablate tissue at the left atrial-PV junction with laser energy. METHODS AND RESULTS: This study consisted of 2 phases: a short-term (n=9) and long-term (n=11) canine experimental validation phase and a multicenter clinical feasibility phase (n=30 paroxysmal atrial fibrillation patients). After transseptal puncture, the balloon-based endoscopic ablation system was advanced to each PV ostium, and arcs of laser energy (90 degrees to 360 degrees ) were projected onto the target left atrial-PV junction. Electric PV isolation was defined with a circular multielectrode catheter. In the short-term preclinical experimental phase, 15 of 17 targeted PVs (88%) were successfully isolated. Pathological examination revealed well-demarcated circumferential lesions with minimal endothelial disruption. In the long-term experiments, 9 of 10 targeted veins (90%) remained persistently isolated (at 4 to 8 weeks). In the clinical phase, 105 of 116 PVs (91%) were successfully isolated. After a single procedure, the 12-month drug-free rate of freedom from atrial fibrillation was 60% (18 of 30 patients). There were no significant PV stenoses, but adverse events included 1 episode of cardiac tamponade, 1 stroke without residual defect, and 1 asymptomatic phrenic nerve palsy. CONCLUSIONS: This study establishes the feasibility of a novel paradigm for AF ablation: direct visualization to guide catheter ablation of the left atrial-PV junction.

Initial experience with a multielectrode catheter equipped with the single-axis sensor technology for high-density electroanatomical mapping in a swine model.

INTRODUCTION: magnetic-based electroanatomical mapping systems are widely used during catheter ablation. Currently, the size of the sensor incorporated in the catheter to allow its localization is large, prohibiting the placement of more than one sensor on any single catheter. As a result, multielectrode catheters cannot be tracked by the magnetic-based mapping systems. Single-axis sensors (SAS) are new generation sensors that are significantly smaller in size. The small size of these new sensors allows the placement of more than one sensor on each catheter, allowing the tracking of multielectrode catheters. The objective of this study is to test the feasibility of creating high-density magnetic electroanatomical maps using a new generation multielectrode catheter equipped with the SAS technology. METHODS AND RESULTS: anatomical reconstruction of cardiac chambers and the aorta, together with activation mapping of the right atrium during both sinus rhythm and pacing-induced premature atrial contractions (PACs), were performed in 5 swine using both a conventional mapping catheter and the novel multielectrode catheter equipped with SAS. The multielectrode mapping provided a detailed definition of cardiac anatomy while requiring shorter acquisition times. In addition, mapping of PACs origin was significantly faster using the multielectrode catheter. CONCLUSION: the novel multielectrode catheter equipped with the SAS technology can be used in combination with magnetic electroanatomical mapping systems to generate high-density anatomical reconstructions and activation maps.

Impact of tricuspid regurgitation and prior coronary bypass surgery on the geometry of the coronary sinus: a rotational coronary angiography study.

INTRODUCTION: The coronary sinus (CS) is often distorted in patients with advanced cardiomyopathy, making CS cannulation difficult. The objective of this study was to examine the impact of the underlying cardiac pathology on the variability of the CS anatomy, using rotational coronary venous angiography (RCVA). METHODS AND RESULTS: Seventy-nine patients undergoing RCVA for cardiac resynchronization therapy (CRT) were evaluated: age 63 +/- 15 years, 43% with prior coronary artery bypass grafting (CABG). Aspects of the CS anatomy which could impact cannulation were examined: the CS ostial angle, the posterior displacement of the CS away from the atrioventricular groove, a measure of CS curvature, and the presence of stenoses and aneurysmal dilatations. The CS ostial angle was variable (65-151 degrees, mean 119 +/- 19 degrees, <90 degrees in 8 patients) and decreased significantly (P = 0.0022) with increasing severity of tricuspid regurgitation (TR), reaching 94 +/- 18 degrees in patients with severe TR. The posterior displacement of the CS was significantly more accentuated in patients with prior CABG when compared with the patients without CABG (7.1 +/- 3.7 vs 4.5 +/- 2.8 mm; P = 0.0246). The decrease in luminal diameter at the CS-great cardiac vein (GCV) junction was 2.0 +/- 1.0 mm, being more pronounced in patients with prior CABG versus nonCABG (26 vs 20%; P = 0.042). Stenoses and aneurysmal dilatations of the CS-GCV were encountered in 4 (5%) and 6 (8%) of patients, respectively, all of them with prior CABG, representing 12% and 18% of the CABG group. CONCLUSION: The CS anatomy in patients undergoing CRT is variable, and is impacted by the severity of the underlying TR and history of a prior CABG.

Prevention of ventricular arrhythmias with sarcoplasmic reticulum Ca2+ ATPase pump overexpression in a porcine model of ischemia reperfusion.

BACKGROUND: Ventricular arrhythmias are life-threatening complications of heart failure and myocardial ischemia. Increased diastolic Ca2+ overload occurring in ischemia leads to afterdepolarizations and aftercontractions that are responsible for cellular electric instability. We inquired whether sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) overexpression could reduce ischemic ventricular arrhythmias by modulating Ca2+ overload. METHODS AND RESULTS: SERCA2a overexpression in pig hearts was achieved by intracoronary gene delivery of adenovirus in the 3 main coronary arteries. Homogeneous distribution of the gene was obtained through the left ventricle. After gene delivery, the left anterior descending coronary artery was occluded for 30 minutes to induce myocardial ischemia followed by reperfusion. We compared this model with a model of permanent coronary artery occlusion. Twenty-four-hour ECG Holter recordings showed that SERCA2a overexpression significantly reduced the number of episodes of ventricular tachycardia after reperfusion, whereas no significant difference was found in the occurrence of sustained or nonsustained ventricular tachycardia and ventricular fibrillation in pigs undergoing permanent occlusion. CONCLUSIONS: We show that Ca2+ cycling modulation using SERCA2a overexpression reduces ventricular arrhythmias after ischemia-reperfusion. Strategies that modulate postischemic Ca2+ overload may have clinical promise for the treatment of ventricular arrhythmias.

Electrical remodeling contributes to complex tachyarrhythmias in connexin43-deficient mouse hearts.

Loss of connexin43 (Cx43) gap junction channels in the heart results in a marked increase in the incidence of spontaneous and inducible polymorphic ventricular tachyarrhythmias (PVTs). The mechanisms resulting in this phenotype remain unclear. We hypothesized that uncoupling promotes regional ion channel remodeling, thereby increasing electrical heterogeneity and facilitating the development of PVT. In isolated-perfused control hearts, programmed electrical stimulation elicited infrequent monomorphic ventricular tachyarrhythmias (MVT), and dominant frequencies (DFs) during MVT were similar in the right ventricle (RV) and left ventricle (LV). Moreover, conduction properties, action potential durations (APDs), and repolarizing current densities were similar in RV and LV myocytes. In contrast, PVT was common in Cx43 conditional knockout (OCKO) hearts, and arrhythmias were characterized by significantly higher DFs in the RV compared to the LV. APDs in OCKO myocytes were significantly shorter than those from chamber-matched controls, with RV OCKO myocytes being most affected. APD shortening was associated with higher levels of sustained current in myocytes from both chambers as well as higher levels of the inward rectifier current only in RV myocytes. Thus, alterations in cell-cell coupling lead to regional changes in potassium current expression, which in this case facilitates the development of reentrant arrhythmias. We propose a new mechanistic link between electrical uncoupling and ion channel remodeling. These findings may be relevant not only in cardiac tissue but also to other organ systems where gap junction remodeling is known to occur.

Evaluation of catheter ablation of periatrial ganglionic plexi in patients with atrial fibrillation.

Recent data suggests that the cardiac autonomic nervous system has an important role in the initiation and maintenance of atrial fibrillation (AF). This study investigated (1) the feasibility of identifying and targeting these autonomic ganglia using endocardial radiofrequency stimulation and ablation, respectively; (2) the efficacy of endocardial ablation to completely eliminate the vagal response elicited from epicardial stimulation; and (3) the effect of autonomic ablation on the acute inducibility of AF. The study included 18 patients referred for catheter ablation of suspected vagal-mediated AF. The endocardial left atrial surface was stimulated at high frequency (20 to 50 Hz) to elicit a vagal response. In selected patients (n = 5), pericardial access was obtained using a subxyphoid puncture to permit epicardial stimulation. Catheter ablation of the putative autonomic ganglionic sites was performed from the left atrial endocardium using irrigated radiofrequency energy. After ablation of all identifiable autonomic ganglia, high-frequency pacing was repeated to induce AF. In all patients, stimulation at certain endocardial sites elicited a vagal response. Endocardial ablation abrogated this vagal responsiveness. Furthermore, for sites accessible from the pericardium, the vagal response elicited using epicardial stimulation was also eliminated. Despite successful ablation of these ganglia, AF was still inducible in 17 of 18 patients. In conclusion, successful ablation of autonomic ganglia from an endocardial approach can be reliably achieved using an irrigated catheter. In addition, ablation of these structures in patients with vagal-mediated AF is insufficient to prevent its acute reinduction with high-frequency atrial stimulation.