Injectable conductive hydrogel restores conduction through ablated myocardium.

INTRODUCTION: Therapies for substrate-related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization. METHODS: A nanocellulose carbon nanotube-conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue. RESULTS: The conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The direct current conductivity under aqueous conduction was 4.3 × 10-1 S/cm. In four canine hearts, when compared with the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of the conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation restored through the ablated tissue. Gross specimen examination demonstrated retention of the hydrogel within the tissue. CONCLUSIONS: This proof-of-concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long-term retention and biocompatibility of the hydrogel through in vivo experimentation.

Paced QRS morphology predicts incident left ventricular systolic dysfunction and atrial fibrillation.

BACKGROUND: The prognostic significance of paced QRS complex morphology on surface ECG remains unclear. This study aimed to assess long-term outcomes associated with variations in the paced QRS complex. METHODS: Adult patients who underwent dual-chamber pacemaker implantation with 20% or more ventricular pacing and a 12-lead ECG showing a paced complex were included. The paced QRS was analyzed in leads I and aVL. Long-term clinical and echocardiographic outcomes were compared at 5 years. RESULTS: The study included 844 patients (43.1% female; age 75.0 ±â€¯12.1). Patients with a longer paced QRS (pQRS) duration in lead I had a lower rate of atrial fibrillation (HR 0.80; p = 0.03) and higher rate of systolic dysfunction (HR 1.17; p < 0.001). Total pacing complex (TPC) duration was linked to higher rates of ICD implantation (HR 1.18; p = 0.04) and systolic dysfunction (HR 1.22, p < 0.001). Longer paced intrinsicoid deflection (pID) was associated with less atrial fibrillation (HR 0.75; p = 0.01), more systolic dysfunction (HR 1.17; p < 0.001), ICD implantation (HR 1.23; p = 0.04), and CRT upgrade (HR 1.23; p = 0.03). Exceeding thresholds for TPC, pQRS, and pID of 170, 146, and 112 ms in lead I, respectively, was associated with a substantial increase in systolic dysfunction over 5 years (p < 0.001). CONCLUSIONS: Longer durations of all tested parameters in lead I were associated with increased rates of left ventricular systolic dysfunction. ICD implantation and CRT upgrade were also linked to increased TPC and pID durations. Paradoxically, patients with longer pID and pQRS had less incident atrial fibrillation.

Single-site ventricular pacing via the coronary sinus in patients with tricuspid valve disease.

Aims: To evaluate coronary sinus single-site (CSSS) left ventricular pacing in adult patients with normal left ventricular ejection fraction (LVEF) when traditional right ventricular lead implantation is not feasible or is contraindicated. Methods and results: We performed a retrospective analysis of 23 patients with tricuspid valve surgery/disease who received a CSSS ventricular pacing lead to avoid crossing the tricuspid valve. Two matched control populations were obtained from patients receiving (i) conventional right ventricular single-site (RVSS) leads and (ii) coronary sinus leads for cardiac resynchronization therapy (CSCRT). Main outcomes of interest were lead stability, electrical lead parameters and change in LVEF during long-term follow-up. Successful CSSS pacing was accomplished in all 23 patients without any procedural complications. During the 5.3 ± 2.8-year follow-up 22/23 (95.7%) leads were functional with stable pacing and sensing parameters, and 1/23 (4.3%) was extracted for unrelated reasons. Compared to CSSS leads, the lead revision/abandonment was similar with RVSS leads (Hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.03, 22.0), but was higher with CSCRT leads (HR 7.41, 95% CI 1.30, 139.0). There was no difference in change in LVEF between CSSS and RVSS groups (-2.4 ± 11.0 vs. 1.5 ± 12.8, P = 0.76), but LVEF improved in CSCRT group (11.2 ± 16.5%, P = 0.002). Fluoroscopy times were longer during implantation of CSSS compared to RVSS leads (25.6 ± 24.6 min vs. 12.3 ± 18.6 min, P = 0.049). Conclusion: In patients with normal LVEF, single-site ventricular pacing via the coronary sinus is a feasible, safe and reliable alternative to right ventricular pacing.

Right ventricular pacemaker lead position is associated with differences in long-term outcomes and complications.

INTRODUCTION: Cardiac pacing from the right ventricular apex is associated with detrimental long-term effects and nonapical pacing locations may be associated with improved outcomes. There is little data regarding complications with nonapical lead positions. The aim of this study was to assess long-term outcomes and lead-related complications associated with differing ventricular lead tip position. METHODS AND RESULTS: All adult patients who underwent dual-chamber pacemaker implantation from 2004 to 2014 were included if they had postprocedure chest radiographs amenable to lead position determination. Long-term outcomes and lead-related complication rates were recorded. These were compared at 5 years between: (1) apical and septal leads, (2) apical and nonseptal nonapical (NSNA), and (3) apical and septal with >40% ventricular pacing. We retrospectively evaluated 3,450 patients, which included 238 with a septal position and 733 with NSNA lead positions. Septal lead position was associated with a lower mortality compared to apical leads (24% vs. 31%, P = 0.02). In patients with greater than 40% pacing, septal leads were associated with significantly higher rates of incident atrial fibrillation compared to apical leads (49% vs. 34%, P = 0.04). NSNA positions were associated with a significantly higher rate of lead dislodgement (4% vs. 2%, P = 0.005) and need for revision (8% vs. 5%, P = 0.005). CONCLUSIONS: Septal pacemaker lead position is associated with a lower mortality compared to apically placed leads, but a higher incidence of atrial fibrillation with higher percentage ventricular pacing. NSNA lead locations are associated with more complications and should be avoided.

Idiopathic Ventricular Tachycardia.

Idiopathic ventricular tachycardia (VT) is an important cause of morbidity and less commonly, mortality in patients with structurally normal hearts. Appropriate diagnosis and management are predicated on an understanding of the mechanism, relevant cardiac anatomy, and associated ECG signatures. Catheter ablation is a viable strategy to adequately treat and potentially provide a cure in patients that are intolerant to medications or when these are ineffective. In this review, we discuss special approaches and considerations for effective and safe ablation of VT arising from the right ventricular outflow tract, left ventricular outflow tract, left ventricular fascicles, papillary muscles, and moderator band.

Failure of Intrinsic Antitachycardia Pacing to Terminate Ventricular Tachycardia and Potential Proarrhythmic Effects.

Intrinsic antitachycardia pacing (iATP) is a novel, automated antitachycardia pacing (ATP) algorithm that provides individualized therapy to terminate ventricular tachycardia (VT). If the first ATP attempt is unsuccessful, the algorithm analyzes the tachycardia cycle length and the postpacing interval and adjusts the subsequent sequence to successfully terminate VT. This algorithm was effective in a single clinical study without a comparator arm. However, iATP failure has not been well-documented in the literature. This publication represents the first case series with episode analysis of iATP failure, including a demonstration of its proarrhythmic effect.

Cardioneuroablation Using Epicardial Pulsed Field Ablation for the Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people worldwide. The cardiac autonomic nervous system (ANS) is widely recognized as playing a key role in both the initiation and propagation of AF. This paper reviews the background and development of a unique cardioneuroablation technique for the modulation of the cardiac ANS as a potential treatment for AF. The treatment uses pulsed electric field energy to selectively electroporate ANS structures on the epicardial surface of the heart. Insights from in vitro studies and electric field models are presented as well as data from both pre-clinical and early clinical studies.

Epicardial Pulsed Field Ablation of Ganglionated Plexi: Computational and Pre-Clinical Evaluation of a Bipolar Sub-Xiphoid Catheter for the Treatment of Atrial Fibrillation.

Epicardial pulsed field ablation (PFA) of ganglionated plexi (GPs) is being explored as a potential treatment for atrial fibrillation. Initial work using open-chest access with a monopolar ablation device has been completed. This study describes the early development work for a device that can be used with subxiphoid access and deliver bipolar ablation pulses. Electric field computational models have been used for the initial guidance on pulse parameters. An in vivo assessment of these ablation parameters has been performed in an open-chest canine study, while subxiphoid access and navigation of the device has been demonstrated in a porcine model. Results from this acute study have demonstrated the promising potential of this approach.

Targeted ablation of epicardial ganglionated plexi during cardiac surgery with pulsed field electroporation (NEURAL AF).

BACKGROUND: Modulation of the cardiac autonomic nervous system (ANS) is a promising adjuvant therapy in the treatment of atrial fibrillation (AF). In pre-clinical models, pulsed field (PF) energy has the advantage of selectively ablating the epicardial ganglionated plexi (GP) that govern the ANS. This study aims to demonstrate the feasibility and safety of epicardial ablation of the GPs with PF during cardiac surgery with a primary efficacy outcome of prolongation of the atrial effective refractory period (AERP). METHODS: In a single-arm, prospective analysis, patients with or without a history of AF underwent epicardial GP ablation with PF during coronary artery bypass grafting (CABG). AERP was determined immediately pre- and post- GP ablation to assess cardiac ANS function. Holter monitors were performed to determine rhythm status and heart rate variability (HRV) at baseline and at 1-month post-procedure. RESULTS: Of 24 patients, 23 (96%) received the full ablation protocol. No device-related adverse effects were noted. GP ablation resulted in a 20.7 ± 19.9% extension in AERP (P < 0.001). Post-operative AF was observed in 7 (29%) patients. Holter monitoring demonstrated an increase in mean heart rate (74.0 ± 8.7 vs. 80.6 ± 12.3, P = 0.01). There were no significant changes in HRV. There were no study-related complications. CONCLUSIONS: This study demonstrates the safety and feasibility of epicardial ablation of the GP using PF to modulate the ANS during cardiac surgery. Large, randomized analyses are necessary to determine whether epicardial PF ablation can offer a meaningful impact on the cardiac ANS and reduce AF. TRIAL REGISTRATION: Clinical trial registration: NCT04775264.

Effect of catheter ablation on the hemodynamics of the left atrium : Hemodynamics of ablation.

BACKGROUND: This study aims to evaluate the impact of catheter ablation for atrial fibrillation (AF) on left atrial (LA) flow dynamics and geometrical changes. METHODS: This exploratory study included computational flow simulations from 10 patients who underwent catheter ablation for AF. Complete cardiac cycle dataset was simulated before and after ablation using computational fluid dynamics. The study main endpoints were the changes in LA volume, LA velocity, LA wall shear stress (WSS), circulation (Γ), vorticity, pulmonary vein (PV) ostia area, and LA vortices before and after ablation. RESULTS: There was an average decrease in LA volume (11.58 ± 15.17%) and PV ostia area (16.6 ± 21.41%) after ablation. A non-uniform trend of velocity and WSS changes were observed after ablation. Compared with pre-ablation, 4 patients exhibited lower velocities, WSS distributions, and a decreased Γ (> 8.5%), while 6 developed higher velocities and WSS distributions. These geometrical changes dictated different flow mixing in the LA and distinct vortex patterns, characterized by different spinning velocities, vorticities, and rotational directions. Regions with q-criterion > 0 were found to be dominant in the LA, indicating prevalent rotational vortex structures. CONCLUSION: Catheter ablation for AF induced different geometrical changes on the LA and the PVs, therefore influencing flow mixing and vortex patterns in the LA, in addition to overall velocity and WSS distribution. Further exploration of the impact of catheter ablation on intracardiac flow dynamics is warranted to discern patterns that may correlate with clinical outcomes.

Role of Multimodality Imaging and Preoperative Management in Intrapericardial Paragangliomas: Experience From a Case Series.

Intrapericardial paragangliomas are rare, highly vascular tumors that frequently adhere to adjacent structures and blood vessels, making surgical resection challenging. In this case series, we discuss the role of multimodality imaging and preoperative embolization in the management of 3 patients presenting with intrapericardial paragangliomas. (Level of Difficulty: Advanced.).

Open-chest Pulsed Electric Field Ablation of Cardiac Ganglionated Plexi in Acute Canine Models.

This study aimed to evaluate the safety and acute effect on markers of cardiac autonomic tone following pulsed electric fields (PEFs) delivered to epicardial ganglionated plexi (GP) during a cardiac surgical procedure. Ablation of GP as a treatment for atrial fibrillation (AF) has shown promise, but thermal ablation energy sources are limited by the risk of inadvertent collateral tissue injury. In acute canine experiments, median sternotomy was performed to facilitate the identification of 5 epicardial GP regions using an anatomy-guided approach. Each site was targeted with saline-irrigated PEF (1000 V, 100 µs, 10 electrocardiogram [ECG]-synchronized pulse sequences). Atrial effective refractory period (AERP) and local electrogram (EGM) amplitude were measured before and after each treatment. Histology was performed on samples from treatment-adjacent structures. In 5 animals, 30 (n = 2) and 60 (n = 3) pulses were successfully delivered to each of the 5 target sites. There was no difference in local atrial EGM amplitude before and after PEF application at each site (1.83 ± 0.41 vs. 1.92 ± 0.53 mV, P = .72). The mean AERP increased from 97 ± 15 ms at baseline to 115 ± 7 ms following treatment at all sites (18.6% increase; 95% confidence interval, 1.9-35.2; P = .037). There were no sustained ventricular arrhythmias or acute evidence of ischemia following delivery. Histology showed complete preservation of adjacent atrial myocardium, phrenic nerves, pericardium, and esophagus. Use of PEF to target regions rich in cardiac GP in open-chest canine experiments was feasible and effective at acutely altering markers of cardiac autonomic tone.

Effects of Pulsed Electric Fields on the Coronary Arteries in Swine.

BACKGROUND: Previous animal studies have shown no significant vascular injury from pulsed electrical field (PEF) ablation. We sought to assess the effect of PEF on swine coronary arteries. METHODS: We performed intracoronary and epicardial (near the coronary artery) PEF ablations in swine pretreated with dual antiplatelet and antiarrhythmic therapy. Intracoronary PEF was delivered using MapiT catheters (Biotronik, Berlin), whereas epicardial PEF was delivered using EPT catheters (Boston Scientific, MA). PEF pulse duration was microseconds (Nanoknife 3.0, Angio Dynamics, NY) or nanoseconds (CellFX, Pulse Biosciences, CA). RESULTS: We performed 39 intracoronary ablations in 10 swine and 20 epicardial-pericoronary ablations in 4 separate swine. Intracoronary PEF was delivered at higher energy compared with epicardial PEF (46 [interquartile range, IQR 20-85] J versus 10 [IQR 10-11] J, P < 0.01). Reversible coronary spasm occurred in 49% intracoronary ablations and 45% epicardial ablations (P=0.80). At the end study, fixed coronary stenosis was demonstrated in 44% intracoronary ablations (80% for microsecond PEF and 18% for nanosecond PEF) and 0% epicardial ablations. Visible hemorrhagic and/or fibrotic myocardial lesions were observed at necropsy with similar frequency between intracoronary and epicardial PEF (45% versus 50%, P=0.70). Nanosecond PEF (49 ablations in 11 swine), when compared with microsecond PEF (10 intracoronary ablations in 3 swine), resulted in lower energy delivery (21 [IQR 10-46] J versus 129 [IQR 24-143] J, P=0.03) and less incidence of fixed coronary stenosis (18% versus 80%, P=0.04). CONCLUSIONS: In the swine model, intracoronary PEF resulted both in significant coronary spasm and fixed coronary stenosis. Epicardial PEF, delivered at lower energy, resulted in reversible spasm but no fixed coronary stenosis.

Substrate Characterization and Outcomes of Catheter Ablation of Ventricular Arrhythmias in Patients With Mitral Annular Disjunction.

BACKGROUND: Mitral annular disjunction (MAD) has recently been recognized as an arrhythmogenic entity. Data on the electrophysiological substrate as well as the outcomes of catheter ablation of ventricular arrhythmias in patients with MAD is limited. METHODS: Forty patients with MAD (mean age 47±15 years; 70% female) underwent catheter ablation for ventricular arrhythmias. Detailed clinical, electrocardiographic, cardiac imaging, and procedural data were collected. Clinical outcomes were compared between patients who had substrate modification in the MAD area and those who did not. RESULTS: Twenty-three (57.5%) patients had ablation for premature ventricular contractions, 10 (25%) patients for sustained ventricular tachycardia, and 7 (17.5%) patients for premature ventricular contraction-triggered ventricular fibrillation. Mean end-systolic MAD length was 10.58±3.49 mm on transthoracic echocardiography. Seventeen (42.5%) patients had preprocedural cardiac magnetic resonance imaging, and 5 (29%) patients had late gadolinium enhancement. Among the 18 (45%) patients who had abnormal local electrograms (low voltage, long-duration, fractionated, isolated mid-diastolic potentials) during electroanatomical mapping, 10 (25%) patients had abnormal electrograms in the anterolateral mitral annulus and/or MAD area. Substrate modification was performed in 10 (25%) patients. Catheter ablation was acutely successful in 36 (90%) patients (elimination of premature ventricular contraction or noninducibility of ventricular tachycardia). After a median follow-up duration of 54.08 (interquartile range, 10.67-89.79) months, premature ventricular contraction burden decreased from a median of 9.75% (interquartile range, 3.25-14) before the ablation to a median of 4% (interquartile range, 1-7.75) after the ablation (P=0.03 [95% CI, 0.055-6.5]). Eight (20.5%) patients had repeat ablation for ventricular arrhythmias. Substrate modification of the MAD was associated with a trend toward lower rates of repeat ablation (0% versus 26.7%; P=0.16). CONCLUSIONS: Patients with MAD have a complex arrhythmogenic substrate, and catheter ablation is effective in reducing recurrence of ventricular arrhythmias. Substrate mapping and ablation may be considered in these patients.

Bipolar Electroporation Across the Interventricular Septum: Electrophysiological, Imaging, and Histopathological Characteristics.

BACKGROUND: Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined. OBJECTIVES: This study sought to evaluate the electrophysiological, imaging, and histological characteristics of bipolar direct-current PEF delivered across the interventricular septum. METHODS: PEF was applied between identical solid-tip ablation catheters positioned on either side of the septum in a chronic canine model. Intracardiac and surface electrophysiological data were recorded following delivery. In 4 animals, cardiac magnetic resonance (CMR) was performed early (6 ± 2 days) and late (30 ± 2 days) postablation. After 4 weeks of survival, cardiac specimens were sectioned for histopathological analysis. RESULTS: In 8 canines, PEF was delivered in 27 separate septal sites (45 ± 17 J/site) with either microsecond or nanosecond PEF. Acute complications included transient complete atrioventricular block in 5 animals (63%) after delivery at the anterobasal septum, with right bundle branch block persisting in 3 (38%). Ventricular fibrillation occurred in 1 animal during microsecond but not nanosecond PEF. Postprocedural CMR showed prominent edema and significant left ventricular systolic dysfunction, which recovered with late imaging. At 4 weeks, 36 individual well-demarcated lesions were demonstrated by CMR and histopathology. Lesion depth measured by histology was 2.6 ± 2.1 mm (maximum 10.9 mm and near transmural). CONCLUSIONS: Bipolar PEF ablation of the interventricular septum is feasible and can produce near transmural lesions. Myocardial stunning, edema, and conduction system injury may occur transiently. Further studies are required to optimize safe delivery and efficacious lesions.

Ventricular nanosecond pulsed electric field delivery using active fixation leads: a proof-of-concept preclinical study.

BACKGROUND: Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept. METHODS: In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration (n = 2) and between two leads (n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month. RESULTS: Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with < 5% residual cardiomyocytes. CONCLUSIONS: Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads.

Safety and Efficacy of Apixaban, Rivaroxaban, and Warfarin in End-Stage Renal Disease With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the role of direct oral anticoagulants (DOACs) in this population is limited. METHODS: Electronic databases were searched and articles comparing the safety and efficacy of warfarin with apixaban or rivaroxaban were identified. Pooled hazard ratios (HR) were computed using a random-effects model. RESULTS: A total of eight articles consisting of 30,806 patients; (rivaroxaban 2196, apixaban 2745 and warfarin 25,865) were identified. The pooled HR for major bleeding events favored apixaban over warfarin (0.53, 95% confidence interval (CI) 0.33-0.84, p = 0.008). Apixaban was similar to warfarin in terms of clinically relevant non-major bleeding (HR 1.08, 95% CI 0.64-1.84, p = 0.77) and stroke events (HR 1.09, 95% CI 0.85, 1.39, p = 0.99). There was no significant difference in the risk of major bleeding events (HR 0.95, 95% CI 0.50-1.81, p = 0.88) and stroke between rivaroxaban (HR 1.39, 95% CI, 0.59-3.29, p = 0.09) and warfarin. The combined results of major bleeding in the apixaban group were not affected by the sensitivity analysis. CONCLUSIONS: Apixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD.