Impact of Contact Force on Pulsed Field Ablation Outcomes Using Focal Point Catheter.

BACKGROUND: Conventional focal radiofrequency catheters may be modified to enable multiple energy modalities (radiofrequency or pulsed field [PF]) with the benefit of contact force (CF) feedback, providing greater flexibility in the treatment of arrhythmias. Information on the impact of CF on lesion formation in PF ablations remains limited. METHODS: An in vivo study was performed with 8 swine using an investigational dual-energy CF focal catheter with local impedance. Experiment I: To evaluate atrial lesion formation, contiguity, and width, a point-by-point approach was used to create an intercaval line. The distance between the points was prespecified at 4±1 mm. Half of the line was created with radiofrequency energy, whereas the other half utilized PF (single 2.0 kV application with a proprietary waveform). Experiment II: To evaluate single application lesion dimensions with a proprietary waveform, discrete ventricular lesions were performed with PFA (single 2.0 kV application) with targeted levels of CF: low, 5 to 15 g; medium, 20 to 30 g; and high, 35 to 45 g. Following 1 week of survival, animals underwent endocardial/epicardial remapping, and euthanasia to enable histopathologic examination. RESULTS: Experiment I: Both energy modalities resulted in a complete intercaval line of transmural ablation. PF resulted in significantly wider lines than radiofrequency: minimum width, 14.9±2.3 versus 5.0±1.6 mm; maximum width, 21.8±3.4 versus 7.3±2.1 mm, respectively; P<0.01 for each. Histology confirmed transmural lesions with both modalities. Experiment II: With PF, lesion depth, width, and volume were larger with higher degrees of CF (depth: r=0.82, P<0.001; width: r=0.26, P=0.052; and volume: r=0.55, P<0.001), with depth increasing at a faster rate than width. The mean depths were as follows: low (n=17), 4.3±1.0 mm; medium (n=26), 6.4±1.2 mm; and high (n=14), 9.1±1.4 mm. CONCLUSIONS: Using the same focal point CF-sensing catheter, a novel PF ablation waveform with a single application resulted in transmural atrial lesions that were significantly wider than radiofrequency. Lesion depth showed a significant positive correlation with CF with depths of 6.4 mm at moderate CF.

Cardiac Pressure Overload Decreases ETV1 Expression in the Left Atrium, Contributing to Atrial Electrical and Structural Remodeling.

BACKGROUND: Elevated intracardiac pressure attributable to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The purpose of this study is to characterize the response of the ETV1 (ETS translocation variant 1) signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling. METHODS: We performed gene expression profiling in 265 left atrial samples from patients who underwent cardiac surgery. Comparative gene expression profiling was performed between 2 murine models of cardiac pressure overload, transverse aortic constriction banding and angiotensin II infusion, and a genetic model of Etv1 cardiomyocyte-selective knockout (Etv1f/fMlc2aCre/+). RESULTS: Using the Cleveland Clinic biobank of human LA specimens, we found that ETV1 expression is decreased in patients with reduced ejection fraction. Consistent with its role as an important mediator of the NRG1 (Neuregulin 1) signaling pathway and activator of rapid conduction gene programming, we identified a direct correlation between ETV1 expression level and NRG1, ERBB4, SCN5A, and GJA5 levels in human LA samples. In a similar fashion to patients with heart failure, we showed that left atrial ETV1 expression is downregulated at the RNA and protein levels in murine pressure overload models. Comparative analysis of LA RNA sequencing datasets from transverse aortic constriction and angiotensin II-treated mice showed a high Pearson correlation, reflecting a highly ordered process by which the LA undergoes electrical and structural remodeling. Cardiac pressure overload produced a consistent downregulation of ErbB4, Etv1, Scn5a, and Gja5 and upregulation of profibrotic gene programming, which includes Tgfbr1/2, Igf1, and numerous collagen genes. Etv1f/fMlc2aCre/+ mice displayed atrial conduction disease and arrhythmias. Correspondingly, the LA from Etv1f/fMlc2aCre/+ mice showed downregulation of rapid conduction genes and upregulation of profibrotic gene programming, whereas analysis of a gain-of-function ETV1 RNA sequencing dataset from neonatal rat ventricular myocytes transduced with Etv1 showed reciprocal changes. CONCLUSIONS: ETV1 is downregulated in the LA during cardiac pressure overload, contributing to both electrical and structural remodeling.

Proarrhythmic effects from competitive atrial pacing and potential programming solutions.

BACKGROUND: Programmed long AV delays and intrinsic long first degree AV block may increase risk for competitive atrial pacing (CAP) in devices without CAP avoidance algorithms. METHODS: Patients identified with CAP-induced mode switch episodes were followed clinically from September 2013 to August 2019. Attempts to avoid CAP included shortening of postventricular atrial refractory period (PVARP) or postventricular atrial blanking period (PVAB), or change to AAI or DDI modes. After observing associations with sensor-driven pacing, rate response was inactivated in a subset. RESULTS: Among 23 patients identified with CAP (22 St Jude Medical [Abbott]; one Boston Scientific Corporation devices), atrial fibrillation (AF) was induced in 12 (52%), lasting 10 seconds to 28 hours and 32 minutes. In one patient with an ICD CAP-induced AF with rapid ventricular rates that triggered a shock, inducing ventricular fibrillation, syncope, and another shock. Changing AV delays and shortening of PVARP failed to resolve CAP. After noting that all had CAP during sensor-driven pacing, rate response was inactivated in seven, resolving further device-induced AF in the three of seven that had prior CAP-induced AF. In two patients with intact AV conduction, AAI(R) pacing resolved further documentation of CAP. CONCLUSIONS: CAP predominantly occurs during sensor-driven atrial pacing that competes with intrinsic atrial events falling in PVARP. Inactivation of the activity sensor or change to atrial-based pacing modes (AAI/R) appears to effectively prevent induction of device-induced atrial proarrhythmia. Ultimately, a corrective algorithm is needed to avoid CAP-induced proarrhythmia.