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Ablation for atrial fibrillation (AF) frequently requires multiple procedures to achieve durable restoration of sinus rhythm. Early studies have suggested that delayed enhancement magnetic resonance imaging (DE-MRI) of the left atrium (LA) can assist in performing repeat ablation procedures.The purpose of this study was to investigate the utility of DE-MRI in delineating regions of LA low voltage and PV reconnection sites in patients undergoing repeat PV isolation for recurrent AF.We enrolled 10 patients undergoing repeat ablation for AF recurrence to undergo preprocedural DE-MRI of the LA in conjunction with high-density voltage mapping (100 sites) of the LA during the ablation procedure. LA wall regions with hyperenhancement were segmented from DE-MRI images and retrospectively co-registered with the electroanatomic LA map. The association between scar on DE-MRI images and low-voltage regions of the LA was assessed, as was the association between scar gaps and electrogram-determined PV reconnection sites.Ten patients underwent successful DE-MRI imaging and repeat AF ablation without complication. In all 10 patients, the majority of PVs were found to have regained electrical continuity with the LA (30/37 PVs electrically active); all patients underwent successful reisolation of all PVs using standard ablation techniques. There was a significant association between scar identified by DE-MRI and low-voltage regions of the LA (-0.7±0.1 mV in scar regions; generalized estimating equations model clustered by patient, P.001). However, there was no association between scar gaps and PV reconnection sites.We demonstrate the co-registration of DE-MRI scar imaging and electroanatomic LA mapping, with agreement between regions of scar on DE-MRI and low voltage by mapping. However, at our center, this technique did not provide accurate information on the location of PV reconnection sites in patients undergoing repeat ablation for AF.

Laughter-Induced LBBB. We present the case of a patient with ischemic heart disease and intermittent left bundle branch block, reproducibly induced by laughter. Following treatment of ischemia with successful deployment of a drug-eluting stent, no further episodes of inducible LBBB were seen. Transient ischemia, exacerbated by elevated intrathoracic pressure during laughter, may have contributed to onset of this phenomenon. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1136-1138, October 2012)

Background The benefits of cardiac resynchronization in inducing reverse ventricular remodeling in patients with left ventricular (LV) systolic dysfunction have been well established. Still, up to 30% of the patients fail to derive significant improvement from this therapy. A subset of "nonresponders" experience deterioration in LV function following cardiac resynchronization therapy (CRT). Characteristics of this patient population, however, have not been studied. Objective To determine characteristics of patients who experience deterioration in LV function following CRT. Methods Clinical, electrocardiographic, and echocardiographic data were collected in 856 consecutive patients presenting for a new CRT device. For inclusion, all patients had an LV ejection fraction '40%, a QRS duration '120 ms, and available baseline and follow-up echocardiograms and electrocardiograms. Deterioration in LV function was defined as an absolute decrease of 5% or greater in ejection fraction from baseline. Multivariate models were constructed to identify variables significantly associated with deterioration. Results A total of 507 patients met inclusion criteria, of which 60 (11.8%) met criteria for deterioration. Patients with deterioration were more likely to be men (86.7% vs 66.9%; P = .002), have a non–left bundle branch block morphology (41.7% vs 23.7%; P = .001), and a history of atrial fibrillation (66.7% vs 51.7%; P = .03). On comparing the pre-CRT QRS duration with the first biventricular-paced QRS duration post-CRT implant, it was found that patients with LV deterioration had significant QRS widening than did those without deterioration (ms) (+3.9 ± 34.1 vs −9.0 ± 27.4, P = .007, respectively). In multivariate analysis, QRS widening indexed to the baseline QRS duration was significantly associated with LV deterioration (odds ratio 1.14 [1.06–1.23]; P = .001). Conclusion QRS widening is associated with deterioration in LV function following CRT.

Systolic heart failure is a progressive syndrome marked by contractile dysfunction of the myocardium, activation of neurohormonal response systems including adrenergic and renin–angiotensin–aldosterone signaling, as well as cardiac and systemic metabolic abnormalities. Despite major advances in medical therapy, predominantly targeting pharmacologic blockade of neurohormonal systems, the end-result is often progressive pump failure or sudden cardiac death due to malignant ventricular arrhythmias. The implantation of devices for systolic heart failure, including automatic internal cardiac defibrillators (AICD), cardiac resynchronization therapy (CRT), and long-term ventricular assist devices (VADs) has led to a further improvement in functional capacity and survival beyond optimal medical therapy. In this chapter, we will present the biological mechanisms that drive changes in myocardial structure and function, often improving as is the case with myocardial “reverse remodeling” after implantation of cardiac assist devices and cardiac resynchronizing pacemaker/defibrillator therapies.

This editorial refers to ‘Persistent iatrogenic atrial septal defect after pulmonary vein isolation by cryoballoon: an under-recognized complication’ by N-Y. Chan et al. , on page 1406. [T]here are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don't know we don't know. -Former US Secretary of Defense Donald Rumsfeld Atrial fibrillation (AF) remains a therapeutic challenge for millions of patients and their treating physicians. Advances in pharmacotherapy, including the development of novel antiarrhythmics1 and anticoagulants,2 have provided clinicians newer—but not necessarily better—treatment options for AF patients. There has been a concurrent evolution in catheter ablation for AF; novel ablation techniques have come, and in some cases gone,3 over the last several years. Whether these novel techniques will translate into improved safety and efficacy of AF ablation remains to be seen. While ablation modalities used in catheter-based therapy for AF are evolving, the physical introduction of those catheters into the left atrium (LA) remains a nearly universal constant. This is true for standard radiofrequency ablation approaches [i.e. wide, circumferential lesion sets to isolate the pulmonary veins (PV)], for more targeted LA ablation (of complex fractionated atrial electrograms, sympathetic ganglia, or putative rotors, for example), and for newer methods of achieving PV isolation (cryoablation, cyroballoon ablation, laser, microwave, robotically assisted catheter ablation, and so on). Each of these approaches relies on the delivery of one (and frequently more than one) catheter into the LA. …

Esophageal injury is a potential complication with radiofrequency ablation in the posterior wall of the left atrium (LA). The "box isolation" method isolates the posterior LA wall including the pulmonary veins without ablation on the posterior LA wall. This study compares the acute and long-term efficacy of the box isolation method with conventional circumferential pulmonary vein isolation (PVI) for catheter ablation of AF.Twenty-nine patients (age 60 ± 9 years, 62% male, 79% paroxysmal) with drug refractory AF underwent catheter ablation. Sixteen of the 29 patients (55%) underwent box isolation. Recurrence of AF was detected by checking the daily recorded rhythm strip on a portable home ECG monitor, irrespective of the symptoms. Mean follow-up duration was 10 ± 2 months.Complete isolation of the posterior LA using box isolation lesions was achieved in three of 16 (19%) patients. The other 13 patients underwent creation of additional lesions until all PVs were isolated. Of the 16 patients who underwent box isolation, four patients (25%) had complete success, six patients (38%) had improvement, and the remaining six patients (37%) had failure. Of the 13 patients who underwent the standard PV isolation, two patients (15%) had complete success, eight patients (62%) had improvement, and the remaining three patients (23%) had failure (p = 0.44).In this pilot study, the efficacy of box isolation is similar to the circumferential PVI for catheter ablation of AF. Few patients achieved PVI with box method alone. Based on these results, we do not recommend the box isolation strategy.

Bradycardia and transient asystole are well-described sequelae of a myriad of neurologic insults, ranging from focal to generalized injuries. Increased vagal tone also predisposes many individuals, particularly adolescents, to transient neurally mediated bradyarrhythmia. However, prolonged periods of sinus arrest without junctional or ventricular escape are quite rare, even after significant neurologic injury. We describe the case of a 17-year-old man who presented with anoxic brain injury secondary to hemorrhagic shock from a stab wound to the neck. His recovery was complicated by prolonged periods of sinus arrest and asystole, lasting over 60 seconds per episode. This case illustrates that sustained asystolic episodes may occur following significant neurologic injury, and may continue to recur even months after an initial insult. Pacemaker implantation for such patients should be strongly considered.

Aims To assess the utility of transoesophageal echocardiography (TEE) parameters such as spontaneous echo contrast (SEC), left atrial (LA) appendage velocities, and aortic plaque in predicting periprocedural cerebrovascular accidents (CVAs) in patients undergoing catheter ablation of atrial fibrillation (AF). Methods and results Five hundred and seventy-nine consecutive patients underwent catheter ablation of AF with pre-procedural TEE, 94% of whom also received pre-procedural warfarin and enoxaparin bridging. Of the 579 patients, 10 patients (cases) who developed periprocedural CVA (1.7%) and 40 randomly selected patients who did not develop CVA (controls) were included (50 study patients, age 58 ± 11 years, 82% male, 54% persistent AF). Periprocedural CVA was defined as a new neurological deficit that occurred anytime between the start of the procedure and 30 days after AF ablation. Demographic, clinical, and TEE variables of cases and controls were compared using standard statistical analyses. Patients with CVA more often had coronary artery disease [odds ratio (OR) 6.0, P = 0.03], previous history of CVA (OR 8.2, P = 0.02), and CHADS2 score ≥2 (OR 5.4, P = 0.03) than patients without CVA. There was no difference in any of the TEE parameters (SEC, LA appendage velocity and area, patent foramen ovale, atrial septal aneurysm, valve abnormality, and aortic plaque). When these TEE parameters were adjusted for coronary artery disease, prior CVA and CHADS2 ≥ 2, none emerged as an independent predictor of CVA. Conclusion Transoesophageal echocardiographic variables (other than LA thrombus) were not associated with the occurrence of periprocedural CVA in our patients undergoing catheter ablation of AF who generally received pre-procedural anticoagulation. Despite serving as markers of a thrombogenic milieu, the presence of SEC, low LA appendage velocities, and aortic plaque may not increase the risk of periprocedural CVA after AF ablation.

Background Methodological difficulties associated with QT measurements prompt the search for new electrocardiographic markers of repolarization heterogeneity. Objective We hypothesized that beat-to-beat 3-dimensional vectorcardiogram variability predicts ventricular arrhythmia (VA) in patients with structural heart disease, left ventricular systolic dysfunction, and implanted implantable cardioverter-defibrillators (ICDs). Methods Baseline orthogonal electrocardiograms were recorded in 414 patients with structural heart disease (mean age 59.4 ± 12.0; 280 white [68%] and 134 black [32%]) at rest before implantation of ICD for primary prevention of sudden cardiac death. R and T peaks of 30 consecutive sinus beats were plotted in 3 dimensions to form an R peaks cloud and a T peaks cloud. The volume of the peaks cloud was calculated as the volume within the convex hull. Patients were followed up for at least 6 months; sustained VA with appropriate ICD therapies served as an end point. Results During a mean follow-up time of 18.4 ± 12.5 months, 61 of the 414 patients (14.73% or 9.6% per person-year of follow-up) experienced sustained VA with appropriate ICD therapies: 41 of them were white and 20 were black. In the multivariate Cox model that included inducibility of VA and use of beta-blockers, the highest tertile of T/R peaks cloud volume ratio significantly predicted VA (hazard ratio 1.68, 95% confidence interval 1.01 to 2.80; P = .046) in all patients. T peaks cloud volume and T/R peaks cloud volume ratio were significantly smaller in black subjects (median 0.09 [interquartile range 0.04 to 0.15] vs. median 0.11 [interquartile range 0.06 to 0.22], P = .002). Conclusion A relatively large T peaks cloud volume is associated with increased risk of VA in patients with structural heart disease and systolic dysfunction.

Cardiac resynchronization therapy (CRT) has become an established treatment for patients with left ventricular (LV) systolic failure, congestive heart failure symptoms, and electrical evidence of ventricular dyssynchrony. 1 CRT reduces both morbidity and mortality in appropriate patients, with durable benefits demonstrated in multiple large, prospective, randomized trials. 2-4 However, one of the frustratingly persistent limitations of CRT is the significant nonresponder rate. Defining “response” admittedly is difficult because disease nonprogression or retardation may represent some form of salutary CRT effect. Nevertheless, it is generally accepted that the CRT nonresponder rate is somewhere between 20% and 50%, depending on the metrics used for assessment. 5 Given the up-front cost and invasive nature of CRT device implantation, investigators have been searching for better ways to screen CRT candidates and target device therapy more precisely in terms of both the recipient population and LV lead placement for a given patient. The promise of echocardiography to assist in maximizing CRT response at both the population and the patient levels is great, since echocardiography is relatively inexpensive, harmless, fast, and informative. Unfortunately, echocardiography has been largely unsuccessful as a screening tool. Initial single-center studies of tissue Doppler imaging as a technique for identifying patients with and those without dyssynchrony were promising and laid the foundation for larger, prospective randomized trials. The most noteworthy trial, PROSPECT (Predictors of Response to CRT), revealed the multiple limitations of tissue Doppler imaging. 6 Despite a rigorous education process for the echocardiographic core team, reproducibility of echocardiographic dyssynchrony indices was poor. In addition, when consensus was reached on whether tissue Doppler imaging suggested the presence or absence of LV dyssynchrony, the echocardiographic data correlated imperfectly with CRT response rates. In the post-PROSPECT era, many echocardiographers and electrophysiologists have become appropriately leery of echocardiography as a tool for guiding the application of CRT. A comparatively new echocardiographic modality, twodimensional speckle tracking, has been developed and applied to (among other things) screening patients for CRT. Speckle tracking involves the identification and tracking of unique acoustic signatures (speckles) throughout the cardiac cycle. By tracking these signatures, operators can determine tissue strain in different myocardial regions. Typically this includes evaluation of radial strain (myocardial thickening in short-axis LV views) and circumferential strain (myocardial shortening in the short-axis view). Advantages of speckle tracking compared to tissue Doppler imaging include the ability to use standard echocardiographic imaging modalities and the lack of dependence on beam angle during acquisition. At the same time, though, it must be noted that for all of the reported ease of data acquisition, deriving meaningful data from speckle tracking requires considerable expertise. Operators must manually select regions of interest, ensure that images are of adequate quality for interpretation, and interpret data in a meaningful and useful way.

Background There is a controversy regarding the association between QRS width and ventricular arrhythmias (VAs). We hypothesized that predictive value of the QRS width could be improved if QRS width were considered in the context of the sum magnitude of the absolute QRST integral in 3 orthogonal leads sum absolute QRST integral (SAI QRST). We explored correlations between QRS width, SAI QRST, and VA in primary prevention implantable cardioverter-defibrillator (ICD) patients with structural heart disease. Methods Baseline orthogonal electrocardiograms were recorded at rest in 355 patients with implanted primary prevention ICDs (mean age, 59.5 ± 12.4 years; 279 male [79%]). Patients were observed prospectively at least 6 months; appropriate ICD therapies because of sustained VA served as end points. The sum magnitude of the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated. Results During a mean follow-up of 18 months, 48 patients had sustained VA and received appropriate ICD therapies. There was no difference in baseline QRS width between patients with and those without arrhythmia (114.9 ± 32.8 vs 108.9 ± 24.7 milliseconds; P = .230). SAI QRST was significantly lower in patients with VA at follow-up than in patients without VA (102.6 ± 27.6 vs 112.0 ± 31.9 mV·ms; P = 0.034). Patients with SAI QRST (≤145 mV·ms) had a 3-fold higher risk of ventricular tachycardia (VT)/ventricular fibrillation (VF) (hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.59-6.75; P = .001). In the univariate analysis, QRS width did not predict VT/VF. In the bivariate Cox regression model, every 1 millisecond of incremental QRS widening with a simultaneous 1 mV·ms SAI QRST decrease raised the risk of VT/VF by 2% (HR, 1.02; 95% CI, 1.01-1.03; P = .005). Conclusion QRS widening is associated with ventricular tachyarrhythmia only if accompanied by low SAI QRST.

Methods: 180 consecutive patients who underwent their first catheter ablation of AF at our center were studied. This population was divided into two cohorts: those on AA at the time of ablation (127 patients, mean follow up 24.6 months) and those off AA at the time of ablation (53 patients, mean follow up 20.3 months). Off AA was defined as no AA in the previous week, or in the case of amiodarone, none in the last 90 days. All ablations were done using a wide area circumferential radiofrequency ablation of the pulmonary veins, followed by lasso guided segmental isolation. Only single procedure results are presented. Recurrent AF was defined as patient reported palpitations, or ECG and/or holter identified AF. Patients who underwent redo procedures were counted as failures.

Effect of Obesity and OSA on Outcomes Post AF Ablation. Background: Obesity and obstructive sleep apnea (OSA) have a strong association with atrial fibrillation (AF). The purpose of this study was to prospectively determine the effects of obesity, assessed by the body mass index (BMI) and OSA on the efficacy of catheter ablation of AF. Methods: The patient population consisted of 109 patients (mean age: 60 ± 10 years, 79% male, 67% paroxysmal, mean BMI 28 ± 5 kg/m2) who underwent catheter ablation of AF. Based on BMI, patients were classified as normal (

Introduction: Ibutilide has been shown to prolong repolarization times and increase the risk of ventricular tachyarrhythmias particularly in patients with structural heart disease. The mechanisms underlying its proarrhythmic effects remain incompletely understood. We sought to define the effects of ibutilide on the temporal lability of ventricular repolarization in patients with and without structural heart disease. Methods: Twenty-four patients referred for electrophysiology study underwent monophasic action potential (MAP) recordings in the right ventricle during sinus rhythm and random interval right atrial pacing (RIAP). Ibutilide was subsequently administered and the recordings repeated both in sinus rhythm and with RIAP. Digitized recordings were analyzed offline for calculation of the QT variability index (QTVI) based on surface ECG, and the MAP duration variability index (MAPDVI) based on the intracardiac MAP signal. Results: Of 24 patients enrolled, analyses were performed in 21 patients (mean age 59 ± 15 years, 38% women). In three patients, the data were not analyzed due to frequent premature ventricular complexes. Ibutilide resulted in significant changes in heart rate (mean difference: −7.4 ± 0.91 bpm, P < 0.0001) and the surface QT interval (mean difference: 59.6 ± 12.2 ms, P = 0.0001) during sinus rhythm. After ibutilide, QTVI remained unchanged from baseline during sinus rhythm but was significantly different in the setting of RIAP (mean difference: 0.345 ± 0.098, P = 0.0022). With subgroup analyses, these differences remained significant regardless of the presence or absence of heart disease. Conclusion: Ibutilide results in overall prolongation of ventricular repolarization and reductions in baseline sinus rates. Ibutilide increases temporal lability of repolarization only with enriched fluctuations in heart rate.

Aims Obstructive sleep apnoea (OSA) is a risk factor for atrial fibrillation (AF) recurrence after catheter ablation. The purpose of this study is to determine whether OSA assessed by the simple tool, the Berlin Questionnaire (BQ), is useful in predicting the efficacy of catheter ablation of AF. Methods and results The patient population consisted of 210 consecutive patients [mean age 58 +/- 10 years, 167 (80%) male, 119 (57%) paroxysmal] who underwent catheter ablation of AF and completed the BQ. Clinical success was defined as at least 90% reduction in AF burden after 3-month blanking period. Mean duration of follow-up was 25 +/- 12 months. One hundred and one of the 118 (85%) patients at low risk for OSA had clinical success as opposed to 64 of the 92 (70%) patients at high risk for OSA on BQ (P = 0.005). On multivariate analysis, only high-risk for OSA on BQ emerged as an independent predictor of procedural failure (OR 4.53, CI: 1.21-16.87, P = 0.02). Conclusion High risk of OSA on BQ predicts procedural failure after catheter ablation of AF. We recommend the use of BQ for risk-stratifying patients for OSA prior to AF ablation procedures and to identify patients for formal sleep study assessment.

Introduction: Pulmonary vein (PV) isolation by catheter ablation is an increasingly used strategy to treat atrial fibrillation (AF). Complication rates from AF ablation reported in different case series vary widely. We conducted a retrospective analysis of 641 consecutive ablation procedures to assess complication rates, temporal trends, and clinical predictors of adverse outcomes. Methods: All patients (n = 517) undergoing catheter ablation for AF at Johns Hopkins Hospital between February, 2001 and June, 2007 were prospectively enrolled in a database. Data from 641 consecutive procedures were analyzed and complications considered if they occurred within 30 days of ablation. Major complications were defined as those that required intervention, resulted in long-term disability, or prolonged hospitalization. Results: Thirty-two major complications occurred in 641 procedures (5%). Among the patients with major complications, seven had cerebrovascular accident (CVA), eight had tamponade, one had PV occlusion with hemoptysis, and 11 had vascular injury requiring surgical repair and/or transfusion. No periprocedural deaths occurred, and no instances of esophageal injury were seen. Complication rates were higher during the first 100 cases (9.0%) than during the subsequent 541 (4.3%). Major adverse clinical events were associated with age > 70 years (P = 0.007; odds ratio 3.7, 95% confidence interval 1.4–9.6) and female gender (P = 0.014; odds ratio 3.0, 95% confidence interval 1.3–7.2). No other clinical or procedural predictors of complication were identified. Conclusions: Complication rates from AF ablation remain significant, despite improved techniques and increased awareness of procedural risks. Both advanced age and female gender predict major adverse events, suggesting careful consideration of the risk/benefit profile in these patients prior to ablation.

Current ambulatory ECG monitoring systems are limited in their ability to diagnose patients with palpitations. The aim of this prospective study was to compare a new "leadless" ambulatory monitor with a standard event monitor in the evaluation of patients with palpitations.Eighteen consecutive patients (11 female, 56 +/- 16 years) referred for evaluation of palpitations were provided with both a standard event monitor and a "leadless" monitor for 30 days. They were asked to record episodes of palpitations with both monitoring devices.All 18 individuals were compliant with the "leadless" monitor for the 30-day period while only 14 (78%) patients were compliant with the standard event monitor (p = 0.10). During a combined monitoring period of 563 days, 159 symptomatic episodes were recorded with the "leadless" ECG monitor (8.8 +/- 9.7 per patient, range 1-35) and 169 symptomatic episodes were recorded with the event monitor (12 +/- 8.3 per patient, range 1-33) (p = NS). The "leadless" ECG monitor recorded arrhythmias in 13 of 18 patients (72%) and the standard event monitor recorded arrhythmias in 8 of 14 patients (57%) (p = NS).The "leadless" ECG monitor is associated with high patient compliance and results in high quality ECG recordings. The diagnostic yield of this monitoring system is equivalent to a standard event monitor.

Obtaining venous access for pacemaker or defibrillator implantation can be complicated by vascular injury and/or pneumothorax. In the current case presentation, we describe a pneumothorax related to venous access that occurred due to acute, intraprocedural occlusion of the ipsilateral axillary and subclavian vein.

Background: Although it is well recognized that recovery of pulmonary vein (PV) conduction is common among patients who fail atrial fibrillation (AF) ablation, little is known about the precise time course of recurrence. Objective: To determine the incidence and time course of early recurrence of conduction after PV isolation during AF ablation. Methods: The patient population was composed of 14 consecutive patients (9 men [64%]; age 56 ± 7 years) with AF who underwent radiofrequency catheter ablation via circumferential ablation with PV isolation, determined by a circular mapping catheter. After successful isolation of the PVs, repeat circular electrode recordings from each PV were obtained at 30 and 60 minutes. Results: After complete isolation of all PVs, early PV recurrence was observed in 13 (93%) patients and 26 veins (50%). Seventeen veins (33%) showed a first recurrence at 30 minutes, while nine veins (17%) showed a first recurrence at 60 minutes. Conclusion: The results reveal an extremely high rate of early recurrence of PV conduction following AF ablation. It is particularly notable that about one-fifth of the veins remained isolated at 30 minutes, but subsequently developed recurrence between 30 and 60 minutes. Of the veins that showed early recurrence, one-third developed a first recurrence at 60 minutes. These findings suggest that AF ablation procedures should incorporate a 60-minute waiting period after initial isolation in order to detect early recurrence of conduction.

Complex fractionated atrial electrograms (CFAEs) have been reported as ablative targets for the treatment of atrial fibrillation (AF). However, the process of CFAE identification is highly dependent on the operator's judgment.It is the aim of the study to report our initial experience with a novel software algorithm designed to automatically detect CFAEs.Nineteen patients (6 female, 58 +/- 8 years) who underwent catheter ablation of paroxysmal (n = 11) or persistent (n = 8) AF were included in the study. During ongoing AF, 100 +/- 15 left atrial (LA) endocardial locations were sampled under the guidance of integrated electroanatomical mapping with computed tomographic images. Bipolar electrograms recorded throughout the LA were analyzed using custom software that allows for automated detection of CFAEs. Interval confidence level (ICL), defined as the number of intervals between consecutive CFAE complexes during 2.5-second recordings, was used to characterize CFAEs. The CFAE sites with an ICL/=5 were considered as sites with highly repetitive CFAEs, which are thought to be potential ablation targets. For purposes of analysis, the LA was divided into 6 areas: pulmonary vein (PV) ostia, posterior wall, interatrial septum, roof, mitral annulus area, and appendage.Among a total of 1,904 LA locations sampled in 19 patients, 1,644 (86%) were categorized as CFAE sites, whereas 260 (14%) were categorized as as non-CFAE sites. Thirty-four percent of all CFAE sites were identified as sites with highly repetitive CFAEs. Of these, 24% were located at the interatrial septum, 22% on the posterior wall, 20% at the PV ostia, 18% at the mitral annulus area, 14% on the roof, and 2.7% at the LA appendage. In all patients, highly repetitive CFAE sites were distributed in 4 or more areas of the LA. Persistent AF patients had more highly repetitive CFAE sites on the posterior wall than paroxysmal AF patients (30% +/- 7.3% vs 14% +/- 8.2%, P.001). There was a strong trend toward more highly repetitive CFAE sites located at the PV ostia in patients with paroxysmal AF compared with persistent AF patients (24% +/- 13% vs 13% +/- 7.7%, P = .05).With the use of custom software, CFAE complexes were identified in more than 80% of the LA endocardial locations. LA sites with highly repetitive CFAE sites were located predominately in the septum, posterior wall, and PV ostia. Patients with persistent AF had a different anatomical distribution pattern of highly repetitive CFAE sites from those with paroxysmal AF, with a greater prevalence of highly repetitive CFAEs located on the posterior wall. Further studies are warranted to determine the clinical significance of these findings.

Two important limitations of the data regarding the outcomes of catheter ablation of atrial fibrillation (AF) are the short-term follow-up used in most published studies and the lack of single-procedure outcomes. The objective was to report the long-term single-procedure outcomes at our center. The patient population was comprised of 200 consecutive patients who underwent ablation (133 men; age 56 ± 11 years). Atrial fibrillation was paroxysmal in 92 (46%). Success was defined as absence of symptomatic AF, off antiarrhythmic drug (AAD) after a single procedure. After a follow-up of 26 ± 11 months, the single-procedure long-term success rate was 28% with an additional 7% of patients demonstrating improvement. After including repeat procedures in 64 patients, the overall long-term success rate was 41% with 11% demonstrating improvement. Further subgroup analysis of 48 paroxysmal AF patients considered to be optimal candidates for the procedure, revealed a long-term success rate of 69% with an additional 4% demonstrating improvement. A major complication occurred in 7.9% of patients. The results reveal that the long-term single-procedure success rate of catheter ablation of AF in a cohort of patients with predominantly non-paroxysmal AF is less than 40%. The inclusion of redo procedures resulted in an improvement in outcomes. A much higher success rate of 69% was achieved in patients with paroxysmal AF considered to be optimal candidates for this procedure. These results make it clear that further advances in the technique of catheter ablation of AF are needed to improve the safety and efficacy of this procedure. In order to be able to compare outcomes of various techniques in differing patient populations, we urge investigators to report long-term single procedure outcomes.

See related article, pages 558–566 Effective myocardial contraction depends in part on the efficient propagation of electrical signals through the tissue. The principal structure allowing for such rapid myocardial depolarization is the gap junction plaque, a collection of intercellular pores located primarily at intercalated discs. There, at myocyte poles, gap junctions function in close proximity to the complexes responsible for cell–cell tethering—desmosomes and fascia adherens junctions. Thus, the intercalated disc is the site of both intercellular coupling and adhesion. Gap junctions are formed by clusters of paired hexamers, one from each cell, which bridge to form a low-resistance intercellular channel facilitating the transmission of ions and small molecules (

Heart Failure (HF) is associated with an increased risk of sudden death caused by ventricular tachyarrhythmias. Recent studies have implicated repolarization abnormalities and, in particular, exaggerated heterogeneity of transmural repolarization in the genesis of polymorphic ventricular tachycardia in a canine model of nonischemic dilated cardiomyopathy. The presence and degree to which conduction abnormalities play a role in arrhythmogenesis in this model are uncertain. HF was produced in dogs by rapid RV-pacing for 3 to 4 weeks. High-resolution optical action potentials were recorded from epicardial and endocardial surfaces of arterially perfused canine wedge preparations isolated from LV and RV of normal and failing dogs. Cellular and molecular determinants of conduction were investigated using patch-clamp recordings, Western blot analysis, and immunocytochemistry. HF was associated with marked prolongation (by 33%) of the QRS duration of the volume conducted electrocardiogram and significant (>20%) slowing of epicardial and endocardial conduction velocities (CV) in both LV and RV. Cx43 expression was reduced by >40% in epicardial and endocardial layers of the LV, but was unchanged in the RV of failing hearts. Despite greater epicardial than endocardial Cx43 expression, epicardial CV was consistently slower ( P P P =0.8, not significant), and Masson trichrome staining revealed no significant change in fibrosis content in HF. Nonischemic dilated cardiomyopathy is associated with significant slowing of CV that was not directly related to reduced Cx43 expression. Changes in phosphorylation and localization of Cx43 may contribute to gap-junction dysfunction, CV slowing, and arrhythmias in HF.

Background Recurrence of atrial fibrillation (AF) after catheter ablation has been associated with left atrial (LA) fibrosis. However, arbitrary units of measure limit the interpatient comparison of delayed enhancement intensity. We sought to quantify LA fibrosis using a novel normalized measure: the image intensity ratio (IIR) of late-gadolinium enhanced magnetic resonance imaging (LGE-MRI). Methods LGE-MRI images (1.5 Tesla) were obtained in 30 patients (37% female, mean age 62 ± 8) prior to first (60%), second (23%), or third (17%) ablation procedure for AF. Multiplanar reformatted images were reconstructed from the stack of 3-D axial image data. Epicardial and endocardial contours were manually drawn around LA myocardium. The IIR, defined as local LA myocardial signal intensity divided by the mean LA blood pool image intensity, was measured for each of 20 sectors created on contiguous axial planes through the LA. Electroanatomic map (EAM) points were registered to the corresponding LGE-MRI images using custom software. Results A total of 2569 EAM points were analyzed. The average bipolar voltage was 0.9 ± 1.0 mV (0.5 between and 0.9 within patient standard deviation). Local IIR was strongly associated with bipolar voltage (Figure, P P Conclusions Higher IIR values were observed in areas with lower bipolar voltage on EAM. The IIR obtained from LGE-MRI may improve the quantification of LA fibrosis

The use of catheter-based techniques for the treatment of atrial fibrillation (AF) has grown rapidly over the last decade. Once-novel strategies, focusing principally on circumferential ablation to isolate pulmonary vein (PV) ostia, have become commonplace. As ablative therapy for AF has gained wider acceptance, the indications and target patient populations referred for AF ablation have expanded accordingly. The role of ablation for patients with drug-refractory, symptomatic paroxysmal AF is generally agreed upon. Less is known, though, about the long-term success of catheter ablation in patients with persistent (and particularly long-standing persistent) AF. Large trials which have included patients with longstanding persistent AF suggest that the rate of atrial arrhythmia recurrence in this group is high. Identifying predictors of recurrence in this patient population—particularly those that pinpoint patients for whom AF ablation is truly futile—is of obvious clinical importance. McCready et al. 1 provide data on predictors of AF recurrence following ablation in patients with persistent AF. The focus of the study was long-standing persistent AF, since the large majority of the patients studied (88%) had a continuous AF duration of .1 year leading up to ablation. The authors collected data in 191 patients undergoing a total of 292 procedures. The ablation strategy used was left to the discretion of the ablating physician; typically, circumferential PV isolation was performed (100% of patients) in conjunction with a roof line (71%), and occasionally with a mitral isthmus line (44%) and complex fractionated electrogram ablation (42%). It is important to note that ablation until return of sinus rhythm was not the endpoint of the procedure; restoration of sinus rhythm during ablation was only observed in 12% of the patients. Patients were followed for an average of 13 months, with a variety of types of follow-up monitoring including clinical assessment, electrocardiograms, Holter monitoring, and device interrogation. Procedural failure was defined as recurrent AF or atrial tachycardia (AT) .30 s duration, after a 3 m blanking period on or off an antiarrhythmic medication. Sixty-seven patients underwent two or more procedures. The results presented by McCready et al. are a stark reminder of the difficulties posed by patients with long-standing persistent AF. Although PVs were isolated in 100% of the cases, operators did not succeed in terminating AF during ablation in 88% of the patients; rather, patients with AF or AT at the conclusion of the case were cardioverted. During the follow-up period, singleprocedure success occurred in 32% of the patients over 13 months. Among patients who were categorized as having a successful outcome, 30% were still taking antiarrhythmic medications. Thus, the antiarrhythmic-free single-procedure success rate in this patient population can be predicted to be ,32%. Overall success (i.e. after up to four ablation procedures and on or off antiarrhythmic drug therapy) was 64% over the same period. Importantly, the incidence of major complications was 6.2%, including cardiac tamponade in 2.4% (two patients requiring surgical repair), stroke in 1%, phrenic nerve paralysis in 0.7%, and one patient with restrictive pericarditis requiring a surgical pericardectomy. The authors found that left atrial (LA) size, measured by transthoracic echocardiography, was the sole univariate and multivariate predictor of single-procedure success. Left atrial size was also the principal predictor of overall success. Atrial fibrillation duration, procedural strategy, and other variables that one might expect to predict outcome did not do so in this series of patients. On the basis of these findings, the authors performed receiver operator characteristic analysis and found that an LA size of ,43 mm gave greatest accuracy in predicting outcome.

Endothelial-selective delivery of therapeutic agents, such as drugs or genes, would provide a useful tool for modifying vascular function in various disease states. A potential molecular target for such delivery is E-selectin, an endothelial-specific cell surface molecule expressed at sites of activationin vivoand inducible in cultured human umbilical vein endothelial cells (HUVEC) by treatment with cytokines such as recombinant human interleukin 1β (IL-1β). Liposomes of various types (classical, sterically stabilized, cationic, pH-sensitive), each conjugated with mAb H18/7, a murine monoclonal antibody that recognizes the extracellular domain of E-selectin, bound selectively and specifically to IL-1β-activated HUVEC at levels up to 275-fold higher than to unactivated HUVEC. E-selectin-targeted immunoliposomes appeared in acidic, perinuclear vesicles 2–4 hr after binding to the cell surface, consistent with internalization via the endosome/lysosome pathway. Activated HUVEC incubated with E-selectin-targeted immunoliposomes, loaded with the cytotoxic agent doxorubicin, exhibited significantly decreased cell survival, whereas unactivated HUVEC were unaffected by such treatment. These results demonstrate the feasibility of exploiting cell surface activation markers for the endothelial-selective delivery of biologically active agents via immunoliposomes. Application of this targeting approachin vivomay lead to novel therapeutic strategies in the treatment of cardiovascular disease.

Background Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with the common –1306C/T matrix metalloproteinase-2 single nucleotide polymorphism (MMP2 SNP), which reduces the synthesis of matrix metalloproteinase-2 enzyme. Understanding the factors that mediate this association may improve current preventive and therapeutic strategies for AF. Methods To test the hypothesis that MMP2 SNP is associated with atrial fibrosis, the study was designed as a single center, observational, cross-sectional study. One hundred consecutive patients with symptomatic drug-resistant AF who underwent catheter ablation between September 2009 and February 2011 were enrolled. The endocardial bipolar electrogram voltage was measured point by point in the left atrium as panel data clustered by patient and compared with the result of genetic testing for MMP2 SNP. Results MMP2 SNP was present in at least 1 copy in 43% of patients, the minor allele frequency was 0.27, and genotype frequencies were in Hardy-Weinberg equilibrium (Χ2 = 2.34, P = .126). The overall mean atrial voltage for the 4878 measures in 87 patients was 0.89 ± 1.10 mV. MMP2 SNP was significantly associated with reduced bipolar voltage in codominant (–0.11 mV per T copy, P = .003) and dominant (–0.18 mV if CT or TT, P Conclusions We report a strong association between a common MMP2 promoter polymorphism and atrial scar fibrosis. Impaired tissue remodeling may mediate the previously reported association between the –1306C/T MMP2 polymorphism and AF.

face potentials were recorded using 120-lead system in a patient with ischemic cardiomyopathy and a left bundle branch block (LBBB) during sinus rhythm. A patient-specific heart-torso model derived from MRI with 291 heart-surface nodes was used to perform ECGI inverse solution. Onset of Q or R wave and end of Twave were detected by custom Matlab software on an averaged beat. Absolute QRST integral

A 78-year-old right-handed woman with a history of atrial fibrillation, prior transient ischemic attacks, and cerebrovascular disease developed expressive aphasia. She immediately began writing a note to a companion. Her first 2 attempts (Figure, A and B) demonstrated expressive aphasia …

Background: Among heart transplant candidates, atrial fibrillation (AF) is a common comorbidity; however, little is known about the impact of pre-transplant AF on incidence of post-transplant AF or other transplant outcomes., Methods: Adult heart transplant recipients transplanted from 07/01/2012 to 07/01/2021 with data available in both the Scientific Registry of Transplant Recipients and Symphony Health pharmacy databases were included. Recipients were categorized by presence of pre-transplant AF using prescription fill data. Perioperative outcomes and survival out to 5 years post-transplant were compared between those with and without pre-transplant AF., Results: Of the 11,789 heart transplant recipients, 2,477 (21.0%) had pre-transplant AF. Pre-transplant AF was associated with an increased likelihood of pre-discharge stroke (aOR 2.13 [95%CI: 1.07-4.26], p=0.03) and dialysis (aOR 1.45 [1.05-2.00], p=0.02), as well as of post-transplant AF at 6 months (aOR 2.42 [1.44-1.48], p=0.001) and 1 year (aOR 2.81 [1.72-4.56], p<0.001). Pre-transplant AF was associated with increased post-transplant mortality at 30 days (aHR 2.39 [1.29-4.44], p=0.006) and 1 year (aHR 1.46 [95% CI: 1.01-2.13], p=0.04), but similar mortality at 5 years (aHR 1.23 [0.96-1.58], p=0.11)., Conclusion: Heart transplant recipients with pre-transplant AF had worse short-term outcomes and increased risk of developing post-transplant AF but comparable survival at 5 years post-transplant. Our findings emphasize the importance of increased monitoring for perioperative complications and highlight the long-term safety of heart transplantation in this population., What Is New?: Patients with atrial fibrillation who undergo heart transplantation have worse short term survival (30-days and 1-year) but similar long term survival (5-years) compared to recipients without pre-transplant atrial fibrillation.Pre-transplant atrial fibrillation increases the risk of clinically significant post-transplant atrial fibrillation and peri-operative stroke.Rate vs rhythm control pharmacotherapy for atrial fibrillation is not associated with differences in survival in heart transplant recipients with pre-transplant atrial fibrillation., What Are the Clinical Implications?: Atrial fibrillation should not deter heart transplantation in appropriate candidates, though cardiovascular and stroke risk adjustment may be warranted.Use of amiodarone at doses ≤ 200 mg/day is not associated with reduced survival in heart transplant recipients with pre-transplant atrial fibrillation.