Incremental Benefit of Stepwise Nonpulmonary Vein Trigger Provocation During Catheter Ablation of Atrial Fibrillation.

BACKGROUND: The importance of nonpulmonary vein (PV) triggers for the initiation/recurrence of atrial fibrillation (AF) is well established. OBJECTIVES: This study sought to assess the incremental benefit of provocative maneuvers for identifying non-PV triggers. METHODS: We included consecutive patients undergoing first-time AF ablation between 2020 and 2022. The provocation protocol included step 1, identification of spontaneous non-PV triggers after cardioversion of AF and/or during sinus rhythm; step 2, isoproterenol infusion (3, 6, 12, and 20-30 µg/min); and step 3, atrial burst pacing to induce AF followed by cardioversion during residual or low-dose isoproterenol infusion or induce focal atrial tachycardia. Non-PV triggers were defined as non-PV ectopic beats triggering AF or sustained focal atrial tachycardia. RESULTS: Of 1,372 patients included, 883 (64.4%) underwent the complete stepwise provocation protocol with isoproterenol infusion and burst pacing, 334 (24.3%) isoproterenol infusion only, 77 (5.6%) burst pacing only, and 78 (5.7%) no provocative maneuvers (only step 1). Overall, 161 non-PV triggers were found in 135 (9.8%) patients. Of these, 51 (31.7%) non-PV triggers occurred spontaneously, and the remaining 110 (68.3%) required provocative maneuvers for induction. Among those receiving the complete stepwise provocation protocol, there was a 2.2-fold increase in the number of patients with non-PV triggers after isoproterenol infusion, and the addition of burst pacing after isoproterenol infusion led to a total increase of 3.6-fold with the complete stepwise provocation protocol. CONCLUSIONS: The majority of non-PV triggers require provocative maneuvers for induction. A stepwise provocation protocol consisting of isoproterenol infusion followed by burst pacing identifies a 3.6-fold higher number of patients with non-PV triggers.

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.

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.

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.

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.

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.

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.

Sinus rhythm QRS amplitude and fractionation in patients with nonischemic cardiomyopathy to identify ventricular tachycardia substrate and location.

BACKGROUND: Ventricular tachycardia (VT) substrate in left ventricular (LV) nonischemic cardiomyopathy (NICM) consists of fibrosis with surviving myocardium. OBJECTIVE: The purpose of this study was to determine whether, in patients with LV NICM and sustained VT, reduced QRS amplitude and QRSf during sinus rhythm can identify the presence and location of abnormal septal (S-NICM) and/or free-wall (FW-NICM) VT substrate. METHODS: We compared patients with NICM and VT (group 1) with electroanatomic mapping septal (S-NICM; n = 21) or free-wall (FW-NICM; n = 20) VT substrate to a 38-patient reference cohort (group 2) with cardiac magnetic resonance imaging (cMRI) and NICM but no VT referred for primary prevention implantable cardioverter-defibrillator (26 [68.4%] with late gadolinium enhancement). RESULTS: Group 1 had lower QRS amplitude in leads II (0.60 ± 0.22 vs 0.86 ± 0.35, P <.001), aVR (0.60 ± 0.24 vs 0.75 ± 0.31, P = .002), aVF (0.48 ± 0.20 vs 0.70 ± 0.28, P <.001), and V2 (1.09 ± 0.52 vs 1.38 ± 0.55, P = .001) than group 2. QRS <0.55 mV in lead aVF identified VT and accompanying substrate with sensitivity 70% and specificity 71%. Most group 1 and group 2 patients had 12-lead ECG QRS fractionation (QRSf) in ≥2 contiguous leads (78% vs 63.2%, P = .14). Sensitivity and specificity for ≥2 QRSf leads identifying respective regional electroanatomic or cMRI abnormalities were 76% and 50% for inferior, 44% and 87% for lateral, and 21% and 89% for anterior leads. CONCLUSION: In LV NICM, low frontal plane QRS (<0.55 mV in aVF) is associated with VT substrate. Although multilead QRS fractionation is associated with the presence and location of VT substrate, it is frequently identified in patients without VT with cMRI abnormalities.

Isolated critical epicardial arrhythmogenic substrate abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy and ventricular tachycardia.

BACKGROUND: Ventricular tachycardia (VT) substrate abnormalities in arrhythmogenic right ventricular cardiomyopathy (ARVC) typically involve both the right ventricular (RV) endocardium (ENDO) and epicardium (EPI). OBJECTIVE: The purpose of this study was to examine the prevalence, electrophysiological features, and outcomes of catheter ablation of VT in patients with isolated epicardial substrate (IES) abnormalities. METHODS: We studied 71 consecutive patients with VT who met Task Force criteria for ARVC and underwent detailed ENDO and EPI mapping. Patients with critical IES demonstrated (1) confluent EPI bipolar abnormal electrograms (EGMs) and (2) no or minor (<5.0 cm2) RV ENDO low bipolar voltage. Induced VTs were localized using activation mapping, entrainment mapping, and/or pacemapping. RESULTS: Twelve patients (17%) had IES. Extensive EPI bipolar low-voltage area (Bi-LVA; 74 ± 40 cm2) and EGM abnormalities were identified in all patients. Uni-ENDO LVA (<5.5 mV) was seen in 11 of 12 patients (92%) (41 ± 25 cm2) and corresponded to EPI RV bipolar abnormalities. A median of 2 VTs (range 1-7; cycle length 288 ± 68 ms) were induced and localized to the EPI. EPI ablation resulted in noninducibility of all targeted VTs. Preablation cardiac magnetic resonance (CMR) imaging was performed in 10 of 12 patients with RV dyskinesis and/or late gadolinium enhancement in only 4 of 10 patients. During follow-up of 56 ± 46 months, 9 of 12 patients (75%) remained VT-free. CONCLUSION: In patients with ARVC and VT, substrate abnormalities can uncommonly be isolated to the RV EPI. Detection of critical IES may be limited with CMR imaging but suggested by ENDO unipolar EGM abnormalities. EPI ablation eliminates VT in these patients and typically results in long-term VT-free survival.

Active esophageal cooling for the prevention of thermal injury during atrial fibrillation ablation: a randomized controlled pilot study.

BACKGROUND: Severe endoscopically detected esophageal thermal lesions (EDELs) have been associated with higher risk of progression to atrio-esophageal fistula (AEF) following radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We sought to evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs. OBJECTIVE: We sought To evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs METHODS: Consecutive patients undergoing first-time RFCA were randomized in a 1:1 fashion to esophageal cooling (device group) or standard temperature monitoring (control group). Ablation on the posterior wall was performed with a maximum power of 30W for up to 20s. All patients underwent EGD within 48 h. Endoscopy findings were classified as 1, erythema-mild injury; 2, superficial ulceration-moderate injury; 3, deep ulceration-significant injury; and 4, fistula/perforation. Severe EDELs were defined as grade 3 or 4 lesions. RESULTS: Forty-four patients completed the study (22 device group, 22 control group). Adjunctive posterior wall isolation was performed more frequently in the device group (11/22, 50% vs. 4/22, 18%). EDELs were detected in 5/22 (23%) control group patients, with mild or moderate injury in 2/5 patients (40%) and severe thermal injury in 3/5 patients (60%). In the device group, EDELs were detected in 8/22 (36%) patients, with mild or moderate injury in 7/8 (87%) patients and severe thermal injury in 1/8 (12%) patients. There was no acute perforation or AEF during follow-up. CONCLUSIONS: Active esophageal cooling may reduce the occurrence of severe EDELs. A larger randomized study is warranted to further evaluate the benefit of this strategy.

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.