Utility of noninvasive electrocardiographic imaging in the localization of nonpulmonary vein triggers of atrial fibrillation determined by pacing common trigger sites.

INTRODUCTION: Identifying the origin of nonpulmonary vein atrial fibrillation (AF) triggers (NPVTs) after pulmonary vein isolation (PVI) can be challenging. We aimed to determine if noninvasive electrocardiographic imaging (ECGi) could localize pacing from common NPVT sites. ECGi combines measured body surface potentials with heart-torso geometry acquired from computed tomography (CT) to generate an activation map. METHODS: In 12 patients with AF undergoing first time ablation, the ECGi vest was fitted for preprocedural CT scan and worn during the procedure. After PVI, we performed steady-state pacing from 15 typical anatomic NPVT sites at a cycle length of 700-800 ms. We co-registered the invasive anatomic map with the CT-based ECGi epicardial activation map to compare ECGi predicted to true pacing origin. RESULTS: In the study cohort (67% male, 58% persistent AF, and 67% with left atrial dilation), 148 (82%) pacing sites had both capture and adequate anatomy acquired from the three-dimensional mapping system to co-register with ECGi activation map. Median distance between true pacing sites and point of earliest epicardial activation derived from the ECGi maps for all sites was 17 mm (interquartile range, 10-22 mm). Assuming paced sites treated as regions with a radius of 2.5 cm, the earliest activation site on ECGi map falls within the region with 94% accuracy. CONCLUSION: ECGi can approximate the origin of paced beats from common NPVT sites to within a median distance of 17 mm. A rapidly identified region may then be the focus of more detailed catheter-based mapping techniques to facilitate successful localization and ablation of NPVTs.

Long-Term Freedom From Ventricular Arrhythmias in ARVC With Endocardial Only Ablation: Predictors of Success.

BACKGROUND: Although the epicardial predominance of substrate abnormalities has been well demonstrated in early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC), endocardial (ENDO) ablation may suffice to eliminate ventricular tachycardia (VT) in some patients. OBJECTIVES: This study aimed to report the long-term outcomes of ENDO-only ablation in ARVC patients and factors that predict VT-free survival. METHODS: We included consecutive patients with Task Force Criteria diagnosis of ARVC undergoing a first ENDO-only VT ablation between 1998 and 2020. Ablation was predominantly guided by activation/entrainment mapping for mappable VTs and pace mapping/targeting abnormal electrograms for unmappable VTs. The primary endpoint was freedom from any recurrent sustained VT after the last ENDO-only ablation. RESULTS: Seventy-four ARVC patients underwent ENDO-only VT ablation. VT noninducibility was achieved in 49 (66%) patients. During median follow-up of 6.6 years (Q1-Q3: 3.4-11.2 years), 40 (54.1%) patients remained free from any VT recurrence with rare VT ≤2 episodes in additional 12.2%. Among patients with noninducibility, VT-free survival was 75.5% during long-term follow-up. In multivariable analysis, >45 y of age at diagnosis (HR: 0.41; 95% CI: 0.17-0.98) and VT noninducibility (HR: 0.36; 95% CI: 0.16-0.80) were predictors of VT-free survival. CONCLUSIONS: Long-term VT-free survival can be achieved in over half of ARVC patients following ENDO-only VT ablation, increasing to over 75% if VT noninducibility is achieved. Our results support consideration of a stepwise ENDO-only approach before proceeding to epicardial ablation if VT noninducibility can be achieved particularly in older patients.

Predictors of nonpulmonary vein triggers for atrial fibrillation: A clinical risk score.

BACKGROUND: Targeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation may reduce atrial fibrillation (AF) recurrence. Isoproterenol infusion and cardioversion of spontaneous or induced AF can provoke NPVTs but typically require vasopressor support and increased procedural time. OBJECTIVE: The purpose of this study was to identify risk factors for the presence of NPVTs and create a risk score to identify higher-risk subgroups. METHODS: Using the AF ablation registry at the Hospital of the University of Pennsylvania, we included consecutive patients who underwent AF ablation between January 2021 and December 2022. We excluded patients who did not receive NPVT provocation testing after failing to demonstrate spontaneous NPVTs. NPVTs were defined as non-pulmonary vein ectopic beats triggering AF or focal atrial tachycardia. We used risk factors associated with NPVTs with P <.1 in multivariable logistic regression model to create a risk score in a randomly split derivation set (80%) and tested its predictive accuracy in the validation set (20%). RESULTS: In 1530 AF ablations included, NPVTs were observed in 235 (15.4%). In the derivation set, female sex (odds ratio [OR] 1.40; 95% confidence interval [CI] 0.96-2.03; P = .080), sinus node dysfunction (OR 1.67; 95% CI 0.98-2.87; P = .060), previous AF ablation (OR 2.50; 95% CI 1.70-3.65; P <.001), and left atrial scar (OR 2.90; 95% CI 1.94-4.36; P <.001) were risk factors associated with NPVTs. The risk score created from these risk factors (PRE2SSS2 score; [PRE]vious ablation: 2 points, female [S]ex: 1 point, [S]inus node dysfunction: 1 point, left atrial [S]car: 2 points) had good predictive accuracy in the validation cohort (area under the receiver operating characteristic curve 0.728; 95% CI 0.648-0.807). CONCLUSION: A risk score incorporating predictors for NPVTs may allow provocation of triggers to be performed in patients with greatest expected yield.

Risk of atrial arrhythmias in patients with ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: In arrhythmogenic right ventricular cardiomyopathy (ARVC), risk of atrial arrhythmias (AAs) persists after ventricular tachycardia (VT) ablation. OBJECTIVE: The purpose of this study was to determine the type, prevalence, outcome, and risk correlates of AA in ARVC in patients undergoing VT ablation. METHODS: Prospectively collected procedural and clinical data on ARVC patients undergoing VT ablation were analyzed. Risk score for typical atrial flutter was determined from univariate logistic regression analysis. RESULTS: Of 119 consecutive patients with ARVC and VT ablation, 40 (34%) had AA: atrial fibrillation (AF) in 31, typical isthmus-dependent atrial flutter (AFL) in 27, and atrial tachycardia/atypical flutter (AT) in 10. Seventeen patients (43%) with AA experienced inappropriate defibrillator therapy, with 15 patients experiencing shocks. Ablation was performed for typical AFL in 21 (53%), AT in 5 (13%), and pulmonary vein isolation for AF in 4 (10%) patients and prevented AA in 78% and all AFL during additional mean follow-up of 65 months. Risk score for typical flutter included age >40 years (1 point), ≥moderate right ventricular dysfunction (2 points), ≥moderate tricuspid regurgitation (2 points), ≥moderate right atrial dilation (2 points), and right ventricular volume >250 cc (3points), with score >4 identifying 50% prevalence of typical flutter. CONCLUSION: AAs are common in patients with ARVC and VT, can result in inappropriate implantable cardioverter-defibrillator shocks, and typically are controlled with atrial ablation. A risk score can be used to identify patients at high risk for typical AFL who may be considered for isthmus ablation at the time of VT ablation.

Utility of Very High-Output Pacing to Identify VT Circuits in Patients Manifesting Traditionally Inexcitable Scar.

BACKGROUND: Entrainment and pace mapping are used to identify critical components (CCs) of ventricular tachycardia (VT) circuits. In patients with dense myocardial scarring, VT circuits may elude capture at standard high pacing outputs (up to 10 mA at a 2-millisecond pulse width). OBJECTIVES: The purpose of this study was to assess the utility of very high-output pacing (V-HOP, 50 mA at 2 milliseconds) for identifying CCs of VT circuits after standard high pacing output failed to elicit capture in densely scarred myocardial tissue. METHODS: Our standard VT ablation approach included electroanatomic mapping for substrate characterization and entrainment and/or pace mapping to identify CCs of VT circuits. Patients that required V-HOP to capture sites of interest comprised the study cohort. Ablation endpoints were VT termination and noninducibility. RESULTS: Twenty-five patients (71 ± 10 years of age, all males) undergoing 26 VT ablations met the inclusion criteria. The mean left ventricular ejection fraction was 30% ± 14%, and 85% had ischemic cardiomyopathy. V-HOP was used to successfully entrain VT in 17 patients, yielding central isthmus sites in 10 and entrance/exit sites in 4. VT terminated with radiofrequency ablation at these sites in 15 patients. In 9 patients, V-HOP identified scar locations with a delayed exit. Acute procedural success was achieved in 24 patients without any adverse events. Over a follow-up period of 16 ± 21 months, 2 patients experienced VT recurrence requiring repeat ablation during which the same location was targeted successfully in 1 patient. CONCLUSIONS: In VT patients with a dense scar that is traditionally inexcitable, V-HOP can identify CCs of the re-entrant circuit and guide successful ablation.

Identifying Origin of Nonpulmonary Vein Triggers Using 2 Stationary Linear Decapolar Catheters: A Novel Algorithm.

BACKGROUND: Targeting nonpulmonary vein triggers (NPVTs) of atrial fibrillation (AF) after pulmonary vein isolation can be challenging. NPVTs are often single ectopic beats with a surface P-wave obscured by a QRS or T-wave. OBJECTIVES: The goal of this study was to construct an algorithm to regionalize the site of origin of NPVTs using only intracardiac bipolar electrograms from 2 linear decapolar catheters positioned in the posterolateral right atrium (along the crista terminalis with the distal bipole pair in the superior vena cava) and in the proximal coronary sinus (CS). METHODS: After pulmonary vein isolation in 42 patients with AF, pacing from 15 typical anatomic NPVT sites was conducted. For each pacing site, the electrogram activation sequence was analyzed from the CS catheter (simultaneous/chevron/inverse chevron/distal-proximal/proximal-distal) and activation time (ie, CSCTAT) between the earliest electrograms from the 2 decapolar catheters was measured referencing the earliest CS electrogram; a negative CSCTAT value indicates the crista terminalis catheter electrogram was earlier, and a positive CSCTAT value indicates the CS catheter electrogram was earlier. A regionalization algorithm with high predictive value was defined and tested in a validation cohort with AF NPVTs localized with electroanatomic mapping. RESULTS: In the study patient cohort (71% male; 43% with persistent AF, 52% with left atrial dilation), the algorithm grouped with high precision (positive predictive value 81%-99%, specificity 94%-100%, and sensitivity 30%-94%) the 15 distinct pacing sites into 9 clinically useful regions. Algorithm testing in a 98 patient validation cohort showed predictive accuracy of 91%. CONCLUSIONS: An algorithm defined by the activation sequence and timing of electrograms from 2 linear multipolar catheters provided accurate regionalization of AF NPVTs to guide focused detailed mapping.

Creating Stretchable Electronics from Dual Layer Flex-PCB for Soft Robotic Cardiac Mapping Catheters.

The authors present in this study the development of a novel method for creating stretchable electronics from dual-layer flex printed circuit boards (flex-PCBs) as a platform for soft robotic sensor arrays (SRSAs) for cardiac voltage mapping applications. There is a crucial need for devices that utilize multiple sensors and provide high performance signal acquisition for cardiac mapping. Previously, our group demonstrated how single-layer flex-PCB can be postprocessed to create a stretchable electronic sensing array. In this work, a detailed fabrication process for creating a dual-layer multielectrode flex-PCB SRSA is presented, along with relevant parameters to achieve optimal postprocessing with a laser cutter. The dual-layer flex-PCB SRSA's ability to acquire electrical signals is demonstrated both in vitro as well as in vivo on a Leporine cardiac surface. These SRSAs could be extended into full-chamber cardiac mapping catheter applications. Our results show a significant contribution towards the scalable use of dual-layer flex-PCB for stretchable electronics.

Longitudinal electrocardiographic assessment in Brugada syndrome.

Background: The type 1 electrocardiographic (ECG) pattern diagnostic of Brugada syndrome (BrS) can be dynamic. Limited studies have rigorously evaluated the temporal stability of the Brugada ECG pattern. Objective: We sought to evaluate fluctuations of the Brugada pattern in serial resting ECGs from BrS patients managed within a large health care system. Methods: In our cohort of BrS patients with at least 2 standard, resting ECGs recorded on separate clinical encounters, we evaluated serial changes in the Brugada pattern and categorized patients into 1 of 3 groups: dynamic was defined as the presence of both type 1 and non-type 1 patterns in available ECGs; the provoked-only group was defined as having a non-type 1 Brugada pattern across resting ECGs; and the persistent group was defined as having a type 1 pattern on all ECGs. We also evaluated the clinical risk in this cohort according to the Shanghai risk score. Results: In 72 patients with BrS (mean age 46 ± 15 years, 69% male), 828 standard, resting ECGs were recorded over a median duration of 30.2 (interquartile range 6.3-68.1) months. The dynamic group comprised 50 (69% of the cohort) patients, the provoked-only group consisted of 17 patients (24% of the cohort), and the persistent group included 5 patients. No significant differences were detected in the total number of ECGs evaluated during the follow-up period between any of the groups. Only sinus node dysfunction and a prior cardiac arrest were associated with the persistent type 1 group. The majority of patients had a low annualized risk of lethal arrhythmic events. Conclusion: Most BrS patients have a dynamic Brugada pattern noted on longitudinal, resting ECGs. Expert consensus statements should provide clarity on the frequency of obtaining resting ECGs in patients suspected of having BrS during follow-up.

Stent-based delivery of AAV2 vectors encoding oxidation-resistant apoA1.

In-stent restenosis (ISR) complicates revascularization in the coronary and peripheral arteries. Apolipoprotein A1 (apoA1), the principal protein component of HDL possesses inherent anti-atherosclerotic and anti-restenotic properties. These beneficial traits are lost when wild type apoA1(WT) is subjected to oxidative modifications. We investigated whether local delivery of adeno-associated viral (AAV) vectors expressing oxidation-resistant apoA1(4WF) preserves apoA1 functionality. The efflux of 3H-cholesterol from macrophages to the media conditioned by endogenously produced apoA1(4WF) was 2.1-fold higher than for apoA1(WT) conditioned media in the presence of hypochlorous acid emulating conditions of oxidative stress. The proliferation of apoA1(WT)- and apoA1(4FW)-transduced rat aortic smooth muscle cells (SMC) was inhibited by 66% ± 10% and 65% ± 11%, respectively, in comparison with non-transduced SMC (p < 0.001). Conversely, the proliferation of apoA1(4FW)-transduced, but not apoA1(WT)-transduced rat blood outgrowth endothelial cells (BOEC) was increased 41% ± 5% (p < 0.001). Both apoA1 transduction conditions similarly inhibited basal and TNFα-induced reactive oxygen species in rat aortic endothelial cells (RAEC) and resulted in the reduced rat monocyte attachment to the TNFα-activated endothelium. AAV2-eGFP vectors immobilized reversibly on stainless steel mesh surfaces through the protein G/anti-AAV2 antibody coupling, efficiently transduced cells in culture modeling stent-based delivery. In vivo studies in normal pigs, deploying AAV2 gene delivery stents (GDS) preloaded with AAV2-eGFP in the coronary arteries demonstrated transduction of the stented arteries. However, implantation of GDS formulated with AAV2-apoA1(4WF) failed to prevent in-stent restenosis in the atherosclerotic vasculature of hypercholesterolemic diabetic pigs. It is concluded that stent delivery of AAV2-4WF while feasible, is not effective for mitigation of restenosis in the presence of severe atherosclerotic disease.

Characterization of the right ventricular substrate participating in postinfarction ventricular tachycardia.

BACKGROUND: The right ventricle (RV) is uncommonly implicated in postinfarction ventricular tachycardia (VT). The prevalence and features of the RV substrate participating in postinfarction VT are undefined. OBJECTIVES: The purpose of this study was to characterize critical right ventricular substrate (CRVS) involvement in patients with postinfarction VT. METHODS: We retrospectively reviewed 1279 patients with postinfarction VT undergoing catheter ablation at our center from January 2000 through May 2020. Cases with CRVS defined by conclusive demonstration of participation in VT with activation, entrainment, and/or pacemapping during sinus rhythm were identified. RESULTS: CRVS was identified in 27 of 1279 patients (2.1%): age 65 ± 13 years, 96% male, median left ventricular (LV) ejection fraction 25%, and 93% with left bundle branch block (LBBB) morphology VT. CRVS was identified by RV activation and/or entrainment mapping (n = 19) or by the presence of low-voltage abnormal electrograms with excellent pacemap for the targeted VT and noninducibility after ablation (n = 8). VT termination during RV ablation occurred in 15 patients. After median follow-up of 20 months (interquartile range 9-53 months) and median of 2 procedures (interquartile range 1-3), 22 of 27 patients (80%) had no VT recurrence and 11 (41%) died. CONCLUSION: The RV contains critical substrate elements of postinfarction VT in at least 2.1% of cases. RV mapping should be considered in cases in which LV mapping fails to demonstrate adequate targets, particularly in patients with LBBB morphology VT.

Feasibility of electroanatomic mapping and radiofrequency catheter ablation in Boxer dogs with symptomatic ventricular tachycardia.

BACKGROUND: Treatment for Boxers with ventricular tachycardia (VT) is limited. Electroanatomic mapping (EAM) facilitates identification of arrhythmogenic substrate for radiofrequency catheter ablation (RFCA). OBJECTIVE: Describe the use of EAM to guide RFCA in Boxers with VT. ANIMALS: Five client-owned Boxers with symptomatic VT or persistent VT despite antiarrhythmic medications. METHODS: Case series evaluating clinical, EAM, and before and after RFCA Holter data. RESULTS: Sustained VT was inducible in 3 dogs, but required aggressive stimulation protocols. Low-voltage areas consistent with electroanatomic scar were found in 2 dogs, located at the right ventricular (RV) outflow tract and cranial RV. Two dogs had a focal activation pattern of VT and 1 dog had a reentrant mechanism. After RFCA, all dogs no longer collapsed and had fewer runs of VT, 3 of which had 0 runs of VT. Number of ventricular premature beats increased in 3 dogs and decreased in 2 dogs, 1 of which had nearly complete resolution of all arrhythmias. Procedural complications included ventricular fibrillation (n = 2) with successful defibrillation, bruising or hemorrhage at the vascular access site (n = 4), retroperitoneal hemorrhage (n = 1), aortic and mitral regurgitation (n = 1), onset of frequent supraventricular tachycardia (n = 1), and persistent right pelvic limb lameness (n = 1). CONCLUSIONS AND CLINICAL IMPORTANCE: Electroanatomic mapping and RFCA are feasible in Boxers with VT. Based on this small cohort, RFCA may help decrease runs of VT and improve clinical signs. The anatomic substrate and electrophysiologic mechanisms are variable and require further study.

Magnetic susceptibility and R2* of myocardial reperfusion injury at 3T and 7T.

PURPOSE: Magnetic susceptibility (Δχ) alterations have shown association with myocardial infarction (MI) iron deposition, yet there remains limited understanding of the relationship between relaxation rates and susceptibility or the effect of magnetic field strength. Hence, Δχ and R2∗ in MI were compared at 3T and 7T. METHODS: Subacute MI was induced by coronary artery ligation in male Yorkshire swine. 3D multiecho gradient echo imaging was performed at 1-week postinfarction at 3T and 7T. Quantitative susceptibility mapping images were reconstructed using a morphology-enabled dipole inversion. R2∗ maps and quantitative susceptibility mapping were generated to assess the relationship between R2∗ , Δχ, and field strength. Infarct histopathology was investigated. RESULTS: Magnetic susceptibility was not significantly different across field strengths (7T: 126.8 ± 41.7 ppb; 3T: 110.2 ± 21.0 ppb, P = NS), unlike R2∗ (7T: 247.0 ± 14.8 Hz; 3T: 106.1 ± 6.5 Hz, P < .001). Additionally, infarct Δχ and R2∗ were significantly higher than remote myocardium. Magnetic susceptibility at 7T versus 3T had a significant association (ß = 1.02, R2 = 0.82, P < .001), as did R2∗ (ß = 2.35, R2 = 0.98, P < .001). Infarct pathophysiology and iron deposition were detected through histology and compared with imaging findings. CONCLUSION: R2∗ showed dependence and Δχ showed independence of field strength. Histology validated the presence of iron and supported imaging findings.