Pilot study to evaluate left-to-right ventricular offset in biventricular pacing-comparison of electrocardiographic imaging and ECG.

INTRODUCTION: Biventricular pacing (BiVp) improves outcomes in systolic heart failure patients with electrical dyssynchrony. BiVp is delivered from epicardial left ventricular (LV) and endocardial right ventricular (RV) electrodes. Acute electrical activation changes with different LV-RV stimulation offsets can help guide individually optimized BiVp programming. We sought to study the BiVp ventricular activation with different LV-RV offsets and compare with 12-lead ECG. METHODS: In five patients with BiVp (63 ± 17-year-old, 80% male, LV ejection fraction 27 ± 6%), we evaluated acute ventricular epicardial activation, varying LV-RV offsets in 20 ms increments from -40 to 80 ms, using electrocardiographic imaging (ECGI) to obtain absolute ventricular electrical uncoupling (VEUabs, absolute difference in average LV and average RV activation time) and total activation time (TAT). For each patient, we calculated the correlation between ECGI and corresponding ECG (3D-QRS-area and QRS duration) with different LV-RV offsets. RESULTS: The LV-RV offset to attain minimum VEUabs in individual patients ranged 20-60 ms. In all patients, a larger LV-RV offset was required to achieve minimum VEUabs (36 ± 17 ms) or 3D-QRS-area (40 ± 14 ms) than that for minimum TAT (-4 ± 9 ms) or QRS duration (-8 ± 11 ms). In individual patients, 3D-QRS-area correlated with VEUabs (r 0.65 ± 0.24) and QRS duration correlated with TAT (r 0.95 ± 0.02). Minimum VEUabs and minimum 3D-QRS-area were obtained by LV-RV offset within 20 ms of each other in all five patients. CONCLUSIONS: LV-RV electrical uncoupling, as assessed by ECGI, can be minimized by optimizing LV-RV stimulation offset. 3D-QRS-area is a surrogate to identify LV-RV offset that minimizes LV-RV uncoupling.

Technical note: Minimizing CIED artifacts on a 0.35 T MRI-Linac using deep learning.

BACKGROUND: Artifacts from implantable cardioverter defibrillators (ICDs) are a challenge to magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT). PURPOSE: This study tested an unsupervised generative adversarial network to mitigate ICD artifacts in balanced steady-state free precession (bSSFP) cine MRIs and improve image quality and tracking performance for MRgRT. METHODS: Fourteen healthy volunteers (Group A) were scanned on a 0.35 T MRI-Linac with and without an MR conditional ICD taped to their left pectoral to simulate an implanted ICD. bSSFP MRI data from 12 of the volunteers were used to train a CycleGAN model to reduce ICD artifacts. The data from the remaining two volunteers were used for testing. In addition, the dataset was reorganized three times using a Leave-One-Out scheme. Tracking metrics [Dice similarity coefficient (DSC), target registration error (TRE), and 95 percentile Hausdorff distance (95% HD)] were evaluated for whole-heart contours. Image quality metrics [normalized root mean square error (nRMSE), peak signal-to-noise ratio (PSNR), and multiscale structural similarity (MS-SSIM) scores] were evaluated. The technique was also tested qualitatively on three additional ICD datasets (Group B) including a patient with an implanted ICD. RESULTS: For the whole-heart contour with CycleGAN reconstruction: 1) Mean DSC rose from 0.910 to 0.935; 2) Mean TRE dropped from 4.488 to 2.877 mm; and 3) Mean 95% HD dropped from 10.236 to 7.700 mm. For the whole-body slice with CycleGAN reconstruction: 1) Mean nRMSE dropped from 0.644 to 0.420; 2) Mean MS-SSIM rose from 0.779 to 0.819; and 3) Mean PSNR rose from 18.744 to 22.368. The three Group B datasets evaluated qualitatively displayed a reduction in ICD artifacts in the heart. CONCLUSION: CycleGAN-generated reconstructions significantly improved both tracking and image quality metrics when used to mitigate artifacts from ICDs.

Computerized electrocardiogram data transformation enables effective algorithmic differentiation of wide QRS complex tachycardias.

BACKGROUND: Accurate automated wide QRS complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) can be accomplished using calculations derived from computerized electrocardiogram (ECG) data of paired WCT and baseline ECGs. OBJECTIVE: Develop and trial novel WCT differentiation approaches for patients with and without a corresponding baseline ECG. METHODS: We developed and trialed WCT differentiation models comprised of novel and previously described parameters derived from WCT and baseline ECG data. In Part 1, a derivation cohort was used to evaluate five different classification models: logistic regression (LR), artificial neural network (ANN), Random Forests [RF], support vector machine (SVM), and ensemble learning (EL). In Part 2, a separate validation cohort was used to prospectively evaluate the performance of two LR models using parameters generated from the WCT ECG alone (Solo Model) and paired WCT and baseline ECGs (Paired Model). RESULTS: Of the 421 patients of the derivation cohort (Part 1), a favorable area under the receiver operating characteristic curve (AUC) by all modeling subtypes: LR (0.96), ANN (0.96), RF (0.96), SVM (0.96), and EL (0.97). Of the 235 patients of the validation cohort (Part 2), the Solo Model and Paired Model achieved a favorable AUC for 103 patients with (Solo Model 0.87; Paired Model 0.95) and 132 patients without (Solo Model 0.84; Paired Model 0.95) a corroborating electrophysiology procedure or intracardiac device recording. CONCLUSION: Accurate WCT differentiation may be accomplished using computerized data of (i) the WCT ECG alone and (ii) paired WCT and baseline ECGs.

Automatic wide complex tachycardia differentiation using mathematically synthesized vectorcardiogram signals.

BACKGROUND: Automated wide complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) may be accomplished using novel calculations that quantify the extent of mean electrical vector changes between the WCT and baseline electrocardiogram (ECG). At present, it is unknown whether quantifying mean electrical vector changes within three orthogonal vectorcardiogram (VCG) leads (X, Y, and Z leads) can improve automated VT and SWCT classification. METHODS: A derivation cohort of paired WCT and baseline ECGs was used to derive five logistic regression models: (i) one novel WCT differentiation model (i.e., VCG Model), (ii) three previously developed WCT differentiation models (i.e., WCT Formula, VT Prediction Model, and WCT Formula II), and (iii) one "all-inclusive" model (i.e., Hybrid Model). A separate validation cohort of paired WCT and baseline ECGs was used to trial and compare each model's performance. RESULTS: The VCG Model, composed of WCT QRS duration, baseline QRS duration, absolute change in QRS duration, X-lead QRS amplitude change, Y-lead QRS amplitude change, and Z-lead QRS amplitude change, demonstrated effective WCT differentiation (area under the curve [AUC] 0.94) for the derivation cohort. For the validation cohort, the diagnostic performance of the VCG Model (AUC 0.94) was similar to that achieved by the WCT Formula (AUC 0.95), VT Prediction Model (AUC 0.91), WCT Formula II (AUC 0.94), and Hybrid Model (AUC 0.95). CONCLUSION: Custom calculations derived from mathematically synthesized VCG signals may be used to formulate an effective means to differentiate WCTs automatically.

Conceptual and literature basis for wide complex tachycardia and baseline ECG comparison.

Accurate wide QRS complex tachycardia (WCT) differentiation into either ventricular tachycardia or supraventricular wide complex tachycardia using 12­lead electrocardiogram (ECG) interpretation is essential for diagnostic, therapeutic, and prognostic reasons. There is an ever-expanding variety of WCT differentiation methods and criteria available to clinicians. However, only a few make use of the diagnostic value of comparing the ECG during WCT to that of the patient's baseline ECG. Therefore, we highlight the conceptual rationale and scientific literature supporting the diagnostic value of WCT and baseline ECG comparison.

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.).

The WCT Formula II: An effective means to automatically differentiate wide complex tachycardias.

BACKGROUND: Differentiation of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) or supraventricular wide complex tachycardia (SWCT) using conventional manually-operated electrocardiogram (ECG) interpretation methods is difficult. Recent research has shown that accurate WCT differentiation may be accomplished by automated approaches (e.g., WCT Formula) implemented by computerized ECG interpretation software. OBJECTIVE: We sought to develop a new automated means to differentiate WCTs. METHODS: First, a derivation cohort of paired WCT and baseline ECGs was examined to secure independent VT predictors to be incorporated into a logistic regression model (i.e., WCT Formula II). Second, the WCT Formula II was trialed against a separate validation cohort of paired WCT and baseline ECGs. RESULTS: The derivation cohort comprised 317 paired WCT (157 VT, 160 SWCT) and baseline ECGs. The WCT Formula II was composed of baseline QRS duration (p = 0.02), WCT QRS duration (p < 0.001), frontal percent time-voltage area change (p < 0.001), and horizontal percent time-voltage area change (p < 0.001). The area under the curve (AUC) for VT and SWCT differentiation was 0.96 (95% CI 0.94-0.98) for the derivation cohort. The validation cohort consisted of 284 paired WCT (116 VT, 168 SWCT) and baseline ECGs. WCT Formula II implementation on the validation cohort yielded effective WCT differentiation (AUC 0.96; 95% CI 0.94-0.98). CONCLUSION: The WCT Formula II is an example of how contemporary ECG interpretation software could be used to differentiate WCTs successfully.

Heparin reversal with protamine sulfate is not required in atrial fibrillation ablation with suture hemostasis.

BACKGROUND: The utility of protamine sulfate for heparin reversal in catheter-based atrial fibrillation (AF) ablation is unclear when using the suture closure technique for vascular hemostasis. OBJECTIVE: This study sought to address if protamine sulfate use for heparin reversal reduces vascular access complications in AF catheter ablation when suture techniques are used for postprocedural vascular hemostasis. METHODS: This is a retrospective multicenter observational study of 294 consecutive patients who underwent catheter ablation for AF with subsequent vascular access hemostasis by means of a figure-of-eight suture or stopcock technique. A total of 156 patients received protamine for heparin reversal before sheath removal while 138 patients did not receive protamine. The two groups were compared for procedural activated clotting time (ACT), access site complications, and duration of hospital stay. RESULTS: Baseline demographic characteristics were comparable in both groups. Despite higher ACT before venous sheath removal in patients not receiving protamine (288.0 ± 44.3 vs 153.9 ± 32.0 seconds; P < .001), there was no significant difference in groin complications, postoperative thromboembolic events, or duration of hospital stay between the two groups. Suture failure requiring manual compression was rarely observed in this cohort (0.34%). CONCLUSION: With modern vascular access and sheath management techniques, for patients undergoing catheter ablation for AF, simple suture closure techniques can obviate the need for protamine administration to safely achieve hemostasis after removal of vascular sheaths.

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.

Interaction of cardiac implantable electronic device and patent foramen ovale in ischemic stroke: A case-only study.

BACKGROUND: Cardiovascular implantable electronic device (CIED) leads are a nidus for right atrial thrombi. Right-to-left thromboembolism across a patent foramen ovale (PFO) is a putative mechanism for ischemic stroke and PFO has been associated with stroke. We used a novel unbiased case-only study design to assess the effect modification of PFO-associated ischemic stroke risk by presence of CIED. We hypothesized that presence of CIED, as a nidus for right atrial thrombus formation, magnifies the PFO-ischemic stroke relationship; therefore, among hospitalized ischemic stroke patients we would find a higher prevalence of CIED in patients with PFO. METHODS: We included consecutive first ischemic stroke patients admitted to our hospital from 2006 to 2015, who were enrolled in a prospectively maintained stroke registry. PFO was ascertained from documentation on echocardiography, and presence of CIED at time of stroke was determined from chest radiography reports at or prior to hospitalization. We measured distributions of CIED within PFO and control groups and used Fisher's exact test to evaluate the PFO-CIED association among ischemic stroke patients. RESULTS: We included 7089 patients (age: 64.5 ± 14.9 years, 51% female). Echocardiography diagnosed PFO in 760 (10.7%) patients and CIED was reported on chest radiography in 752 (10.6%) patients. Prevalence of CIED was lower in the PFO (61/760, 8.0%) compared to control group (691/6329, 10.9%), P = 0.015. CONCLUSION: Among admitted ischemic stroke patients, we did not find a higher prevalence of CIED in patients with PFO compared to controls. Therefore, in the underlying source population, the presence of CIED did not increase the PFO-associated ischemic stroke risk.

Electrophysiologic Scar Substrate in Relation to VT: Noninvasive High-Resolution Mapping and Risk Assessment with ECGI.

BACKGROUND: Ischemic cardiomyopathy (ICM) can provide the substrate for ventricular tachycardia (VT). OBJECTIVE: To map noninvasively with high resolution the electrophysiologic (EP) scar substrate, identify its relationship to reentry circuits during VT, and stratify VT risk in ICM patients. METHODS: Noninvasive high-resolution epicardial mapping with electrocardiographic imaging (ECGI) was performed in 32 ICM patients (17 with clinical VT, 15 without VT). Abnormal scar EP substrate was determined based on electrogram (EGM) amplitude (as percentage of maximal peak-to-peak voltage over the entire ventricular epicardium; total scar [TS] < 30%; dense scar [DS] < 15%), fractionation, and presence of late potentials (LPs). Scar burden was defined as the ratio of the scar size to the total epicardial surface area. The VT activation pattern was mapped and correlated with the EP substrate to identify components of the reentry circuit. RESULTS: Patients with VT had higher scar burden (TS: 51.0 ± 9.3% vs 36.5 ± 5.4%, P < 0.05; DS: 29.5 ± 7.3% vs 16.8 ± 6.8%, P < 0.05) with lower normalized unipolar EGM voltage (TS: 0.107 ± 0.027 vs 0.153 ± 0.031, P < 0.05; DS: 0.073 ± 0.023 vs 0.098 ± 0.026, P < 0.05), greater prevalence of fractionated EGMs (TS: 44.1 ± 10.6% vs 26.8 ± 6.3%, P < 0.05; DS: 50.8 ± 10.8% vs 30.9 ± 7.0%, P < 0.05), and LPs (TS: 26.8 ± 10.7% vs 15.8 ± 5.3, P < 0.05). VTs were mapped in eight patients; the reentry circuits were closely related to the EP substrate. CONCLUSIONS: ECGI noninvasively identified scar EP substrate that underlies abnormal conduction in ICM patients. It identified regions within the scar that aligned with critical elements of the reentry circuit during VT. ECGI can potentially be used for VT risk stratification in ICM patients.

Noninvasive mapping of ventricular activation in patients with transplanted hearts.

This is the first reported study of ventricular activation patterns after cardiac transplantation, using electrocardiographic imaging (ECGI), a noninvasive method for electrophysiologic mapping. This study of ten patients reveals that transplanted hearts have unique ventricular activation patterns in sinus rhythm, activating early in the epicardial aspect of the anterior or inferior septum, with intact right and left bundle branch conduction. They have late activation with slowing of conduction near the right ventricular (RV) basal free wall, causing a mild QRS prolongation and an rSr' pattern in lead V1 of the ECG. PVCs arise from both endocardial and epicardial locations in both ventricles.

Short-term and long-term effects of noninvasive cardiac radioablation for ventricular tachycardia: A single-center case series.

Background: Noninvasive cardiac radioablation is reported to be effective and safe for the treatment of ventricular tachycardia (VT). Objective: This study aimed to analyze the acute and long-term effects of VT radioablation. Methods: Patients with intractable VT or premature ventricular contraction (PVC)-induced cardiomyopathy were included in this study and treated using a single-fraction 25-Gy dose of cardiac radioablation. To quantitatively analyze the acute response after treatment, continuous electrocardiography monitoring was performed from 24 hours before to 48 hours after irradiation and at the 1-month follow-up. Long-term clinical safety and efficacy were assessed 1-year follow-up. Results: From 2019 to 2020, 6 patients were treated with radioablation for ischemic VT (n = 3), nonischemic VT (n = 2), or PVC-induced cardiomyopathy (n = 1). In the short-term assessment, the total burden of ventricular beats decreased by 49% within 24 hours after radioablation and further decreased by 70% at 1 month. The VT component decreased earlier and more dramatically than the PVC component (decreased by 91% and 57% at 1 month, respectively). In the long-term assessment, 5 patients showed complete (n = 3) or partial (n = 2) remission of ventricular arrhythmias. One patient showed recurrence at 10 months, which was successfully suppressed with medical treatment. The posttreatment PVC coupling interval was prolonged (+38 ms at 1 month). Ischemic VT burden decreased more markedly than nonischemic VT burden after radioablation. Conclusion: In this small case series of 6 patients, without a comparison group, cardiac radioablation appeared to decrease the intractable VT burden. A therapeutic effect was apparent within 1-2 days after treatment but was variable by etiology of cardiomyopathy.

Interobserver variability in target definition for stereotactic arrhythmia radioablation.

Background: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR. Methods: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated three predefined segments from the 17-segment model. Interobserver variability was evaluated by assessing volumes, variation in distance to the median volume expressed by the root-mean-square of the standard deviation (RMS-SD) over the target volume, and the Dice-coefficient. Results: Ten electrophysiologists completed the study. For the first phase interobserver variability was low as indicated by low variation in distance to the median volume (RMS-SD range: 0.02-0.02 cm) and high Dice-coefficients (mean: 0.97 ± 0.01). In the second phase distance to the median volume was large (RMS-SD range: 0.52-1.02 cm) and the Dice-coefficients low (mean: 0.40 ± 0.15). In the third phase, similar results were observed (RMS-SD range: 0.51-1.55 cm, Dice-coefficient mean: 0.31 ± 0.21). Conclusions: Interobserver variability is high for manual delineation of the VT-target and ventricular segments. This evaluation of the baseline observer variation shows that there is a need for methods and tools to improve variability and allows for future comparison of interventions aiming to reduce observer variation, for STAR but possibly also for catheter ablation.

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

BACKGROUND: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. METHODS: In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. FINDINGS: In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. CONCLUSIONS: These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. FUNDING: NIH, ASTRO, AHA, Longer Life Foundation.

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.