Mechanisms of persistent atrial fibrillation and recurrences within 12 months post-ablation: Non-invasive mapping with electrocardiographic imaging.

Introduction: Catheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient. Methods: Seventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 months of ablation and underwent a follow-up ECGI. Driver locations and movies were compared for pre- and post-ablation AF. Results: A total of 243 focal drivers were mapped during pre-ablation AF. 62% of the drivers were mapped in the left atrium (LA). The pulmonary vein region harbored most of the drivers (43%). 35% of the drivers were mapped in the right atrium (RA). 59% (10/17) and 53% (9/17) of patients had repetitive sources in the left pulmonary veins (LPV) and left atrial appendage (LAA), and the lower half of RA, respectively. All patients had focal drivers. 29% (5/17) of patients had macro-reentry waves. 24% (4/17) of patients had rotors. Activation patterns during persistent AF varied from single macro-reentry to complex activity with multiple simultaneous wavefronts in both atria, resulting in frequent wave collisions. A total of 76 focal driver activities were mapped in 7/8 patients during recurrence. 59% of the post-ablation AF drivers were mapped in the LA. The pulmonary vein region harbored 50% of total drivers. 39% of sources were mapped in the RA. AF complexity remained similar post-ablation. 58% (44/76) of pre-ablation sources persisted during recurrence. 38% (3/8) of patients had macro-reentry and one patient had rotors. Conclusion: ECGI provides patient-specific information on mechanisms of persistent AF and recurrent arrhythmia. More than half pre-ablation sources repeated during post-ablation recurrence. This study provides direct evidence for drivers that persist days and months after the ablation procedure. Patient-tailored bi-atrial ablation is needed to successfully target persistent AF and prevent recurrence. ECGI can potentially predict recurrence and assist in choice of therapy.

Ablation using 3D maps adjusted for spatial displacement of premature ventricular complexes relative to sinus beats: Improving precision by correcting for the shift.

INTRODUCTION: Point-by-point 3-dimensional (3D) electroanatomic mapping (EAM) is used to guide catheter ablation of premature ventricular complexes (PVCs). Due to the differences in the spatial excursion of the cardiac chambers during cardiac cycles in PVCs vs sinus rhythm, the 3D location registration during PVCs is shifted relative to sinus rhythm. In this study, we describe our strategy to adjust for this displacement in real-time during PVC mapping. METHODS AND RESULTS: We report 21 patients who underwent catheter ablation of 23 unique PVCs using Carto 3. After mapping the earliest site for each PVC, we reregistered its 3D location to a sinus rhythm beat in real-time, and used this to guide ablation lesion delivery. The PVC earliest location was spatially displaced from the successful ablation lesion in sinus rhythm by average 6.7 (range 3.3-13.0) mm. Offline, we subsequently analyzed 25 unique chamber maps and 606 PVC points. For each point, we reregistered the 3D location to a preceding sinus beat. The PVC points were displaced from sinus rhythm location by average 4.4 (0.3-13.7) mm. The maximally displaced point for each chamber was 7.7 (4.7-13.7) mm. The general direction of shift during PVC was leftward and inferior relative to sinus rhythm. CONCLUSIONS: During electroanatomic mapping of PVCs using the Carto 3 system, points mapped during PVCs are spatially displaced relative to their location in sinus rhythm. Electrophysiologists should recognize this phenomenon and account for the shift to guide accurate delivery of ablation lesions.

Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

BACKGROUND: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking. METHODS: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire. RESULTS: Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months. CONCLUSIONS: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia.

BACKGROUND: Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia. METHODS: We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter-defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. RESULTS: From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation "blanking period" (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. CONCLUSIONS: In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes-Jewish Hospital Foundation and others.).

Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias.

BACKGROUND: Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping. METHODS AND RESULTS: Seven subjects were enrolled. We generated phase maps and activation maps from electrocardiographic imaging-reconstructed epicardial unipolar electrograms. For ventricular signals, phase was computed with (1) pseudoempirical mode decomposition detrending and (2) a novel Moving Average (MVG) detrending approach. For atrial fibrillation signals, MVG was modified to incorporate dynamic cycle length (DCL) changes (MVG-DCL). Phase maps were visually analyzed to study phase singularity points and rotors. Results show that phase is sensitive to cycle length choice, a limitation that was addressed by the MVG-DCL algorithm. MVG-DCL was optimal for atrial fibrillation analysis. Phase maps helped to highlight high-curvature wavefronts and rotors. However, for some activation patterns, phase generated nonrotational singularity points and false rotors. CONCLUSIONS: Phase mapping computes singularity points and visually highlights rotors. As such, it can help to provide a clearer picture of the spatiotemporal activation characteristics during atrial fibrillation. However, it is advisable to incorporate electrogram characteristics and the time-domain activation sequence in the analysis, to prevent misinterpretation and false rotor detection. Therefore, for mapping complex arrhythmias, a combined time-domain activation and phase mapping with variable cycle length seems to be the most reliable method.

Implementation of a Screening Program for Patients at Risk for Posttraumatic Stress Disorder.

INTRODUCTION: Implantable cardioverter defibrillator (ICD) recipients who suffer from posttraumatic stress disorder (PTSD) are known to be associated with significant cardiac-specific mortality. Clinical observations suggest that PTSD is frequently undetected in ICD recipients followed up at electrophysiology (EP) outpatient clinics. Early recognition of PTSD is important to reduce the risk of serious manifestations on patient outcomes. METHODS: All ICD recipients aged 19 years or older at the Washington University School of Medicine (WASHU) EP clinic, a large urban EP clinic, were invited to participate in the project. An informed consent letter with an attached primary care: posttraumatic stress disorder (PC: PTSD) survey was offered to the participants who met the inclusion criteria. Those who completed the survey were included in the project. Individuals with positive survey result were offered a referral to mental health services. Comparisons between PTSD and non-PTSD patients were done using a two-sample t-test for continuous variables. Using Fisher's exact test, PTSD prevalence was compared to the study by Ladwig et al in which prevalence was determined as the proportion of patients with positive findings of PTSD (n = 38/147). All analyses were conducted using SAS v9.4. The proportion of patients having PTSD was determined and an exact 95% confidence interval was evaluated based on the binomial distribution. RESULTS: Using a convenience sample, 50 ICD recipients (33 males and 17 females) were enrolled. The project had a 30-day outcome period. Nine (18%) of the 50 participants had positive PC: PTSD findings and all these nine participants were referred to a mental health specialist. The current project demonstrated an 18% (9/50) PTSD prevalence rate when compared to a 26% (38/147) prevalence rate in the study by Ladwig et al (P = 0.34). Although this project did not demonstrate 20% PTSD prevalence rate, as hypothesized, the 18% PTSD prevalence rate is consistent with previous research. CONCLUSION: The prevalence of PTSD noted in the current project is consistent with previous research and validates underrecognition of PTSD in ICD patients. Offering a referral to all ICD recipients at EP clinic visits with a positive PC: PTSD screening to a mental health specialist is an important step in reducing the risk of serious manifestations on patient outcomes.

Cardiac electrophysiological substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients.

BACKGROUND: Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ill-defined. METHODS AND RESULTS: Using noninvasive ECG imaging, we studied 25 BrS patients to characterize the electrophysiological substrate and 6 patients with right bundle-branch block for comparison. Seven healthy subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract with the following properties (in comparison with healthy controls; P<0.005): (1) ST-segment elevation and inverted T wave of unipolar electrograms (2.21±0.67 versus 0 mV); (2) delayed right ventricular outflow tract activation (82±18 versus 37±11 ms); (3) low-amplitude (0.47±0.16 versus 3.74±1.60 mV) and fractionated electrograms, suggesting slow discontinuous conduction; (4) prolonged recovery time (381±30 versus 311±34 ms) and activation-recovery intervals (318±32 versus 241±27 ms), indicating delayed repolarization; (5) steep repolarization gradients (Δrecovery time/Δx=96±28 versus 7±6 ms/cm, Δactivation-recovery interval/Δx=105±24 versus 7±5 ms/cm) at right ventricular outflow tract borders. With increased heart rate in 6 BrS patients, reduced ST-segment elevation and increased fractionation were observed. Unlike BrS, right bundle-branch block had delayed activation in the entire right ventricle, without ST-segment elevation, fractionation, or repolarization abnormalities on electrograms. CONCLUSIONS: The results indicate that both slow discontinuous conduction and steep dispersion of repolarization are present in the right ventricular outflow tract of BrS patients. ECG imaging could differentiate between BrS and right bundle-branch block.

Repolarization changes underlying long-term cardiac memory due to right ventricular pacing: noninvasive mapping with electrocardiographic imaging.

BACKGROUND: Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. METHODS AND RESULTS: Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. CONCLUSIONS: These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker-induced cardiac memory.

Noninvasive electroanatomic mapping of human ventricular arrhythmias with electrocardiographic imaging.

The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.

Catheter ablation of atrial fibrillation: long-term outcomes.

Atrial fibrillation is the most common arrhythmia faced in clinical practice with a substantial impact on morbidity, mortality, and heathcare expenditures. Patients with atrial fibrillation in which a rhythm control strategy is desired to improve quality of life have had limited options. The discovery of the role of pulmonary vein triggers has led to the development of catheter ablation techniques that have shown promising short-term success rates. Long-term outcomes were until recently, lacking. These results confirm the inherently recurrent nature of atrial fibrillation and the need for multiple procedures to achieve reasonable long-term successful maintenance of sinus rhythm.

Noninvasive characterization of epicardial activation in humans with diverse atrial fibrillation patterns.

BACKGROUND: Various mechanisms of atrial fibrillation (AF) have been demonstrated experimentally. Invasive methods to study these mechanisms in humans have limitations, precluding continuous mapping of both atria with sufficient resolution. In this article, we present continuous biatrial epicardial activation sequences of AF in humans using noninvasive electrocardiographic imaging (ECGI). METHODS AND RESULTS: In the testing phase, ECGI accuracy was evaluated by comparing ECGI with co-registered CARTO images during atrial pacing in 6 patients. Additionally, correlative observations from catheter mapping and ablation were compared with ECGI in 3 patients. In the study phase, ECGI maps during AF in 26 patients were analyzed for mechanisms and complexity. ECGI noninvasively imaged the low-amplitude signals of AF in a wide range of patients (97 procedural success). Spatial accuracy for determining initiation sites from pacing was 6 mm. Locations critical to maintenance of AF identified during catheter ablation were identified by ECGI; ablation near these sites restored sinus rhythm. In the study phase, the most common patterns of AF were multiple wavelets (92), with pulmonary vein (69) and non-pulmonary vein (62) focal sites. Rotor activity was seen rarely (15). AF complexity increased with longer clinical history of AF, although the degree of complexity of nonparoxysmal AF varied widely. CONCLUSIONS: ECGI offers a noninvasive way to map epicardial activation patterns of AF in a patient-specific manner. The results highlight the coexistence of a variety of mechanisms and variable complexity among patients. Overall, complexity generally increased with duration of AF.

Accurate ECG diagnosis of atrial tachyarrhythmias using quantitative analysis: a prospective diagnostic and cost-effectiveness study.

UNLABELLED: Quantitative ECG Analysis. INTRODUCTION: Optimal atrial tachyarrhythmia management is facilitated by accurate electrocardiogram interpretation, yet typical atrial flutter (AFl) may present without sawtooth F-waves or RR regularity, and atrial fibrillation (AF) may be difficult to separate from atypical AFl or rapid focal atrial tachycardia (AT). We analyzed whether improved diagnostic accuracy using a validated analysis tool significantly impacts costs and patient care. METHODS AND RESULTS: We performed a prospective, blinded, multicenter study using a novel quantitative computerized algorithm to identify atrial tachyarrhythmia mechanism from the surface ECG in patients referred for electrophysiology study (EPS). In 122 consecutive patients (age 60 ± 12 years) referred for EPS, 91 sustained atrial tachyarrhythmias were studied. ECGs were also interpreted by 9 physicians from 3 specialties for comparison and to allow healthcare system modeling. Diagnostic accuracy was compared to the diagnosis at EPS. A Markov model was used to estimate the impact of improved arrhythmia diagnosis. We found 13% of typical AFl ECGs had neither sawtooth flutter waves nor RR regularity, and were misdiagnosed by the majority of clinicians (0/6 correctly diagnosed by consensus visual interpretation) but correctly by quantitative analysis in 83% (5/6, P = 0.03). AF diagnosis was also improved through use of the algorithm (92%) versus visual interpretation (primary care: 76%, P < 0.01). Economically, we found that these improvements in diagnostic accuracy resulted in an average cost-savings of $1,303 and 0.007 quality-adjusted-life-years per patient. CONCLUSIONS: Typical AFl and AF are frequently misdiagnosed using visual criteria. Quantitative analysis improves diagnostic accuracy and results in improved healthcare costs and patient outcomes.

Transient local injury current in right ventricular electrogram after implantable cardioverter-defibrillator shock predicts heart failure progression.

OBJECTIVES: This study aimed to identify an early marker of functional impairment after an implantable cardioverter-defibrillator (ICD) shock as a predictor of heart failure progression. BACKGROUND: The ICD population has substantial risk of death due to progressive pump failure. METHODS: Near-field (NF) bipolar right ventricular (RV) electrograms (EGMs) during induced ventricular fibrillation (VF) and 10 s after rescue ICD shock were analyzed in 310 patients (mean age 59 +/- 14.5 years, 219 men [71%]) with structural heart disease, New York Heart Association functional class I to III, and implanted with a single- or dual-chamber Medtronic (Minneapolis, Minnesota) ICD for primary (245 patients, 79%) or secondary prevention of sudden cardiac arrest. A local injury current (LIC) on NF RV EGM was defined as a deviation of EGM potential > or =1 mV or > or =15% of the preceding R-wave peak-to-peak amplitude. RESULTS: During mean follow-up of 29.3 +/- 15.0 months, the combined end point of death or hospitalization due to congestive heart failure (CHF) exacerbation was documented in 40 patients (12.9%, or 5.3% per person-year of follow-up). LIC was observed in 106 patients. In multivariate risk analysis, after adjustment for baseline prognostic factors (ejection fraction, history of atrial fibrillation, diabetes mellitus) and appropriate ICD shocks during follow-up, patients with observed LIC after induced VF rescue ICD shock at ICD implantation were more likely to die or to be hospitalized (hazard ratio: 2.69; 95% confidence interval: 1.41 to 5.14; p = 0.003). CONCLUSIONS: Transient LIC on bipolar NF RV EGM after induced VF rescue ICD shock is associated with increased risk of CHF progression, future hospitalizations due to CHF exacerbation, and subsequent heart failure death.