Effect of early catheter ablation of atrial fibrillation in patients with heart failure.

INTRODUCTION: According to current guidelines, pulmonary vein isolation as first-line therapy should be considered for patients with atrial fibrillation (AF), however, optimal timing of the procedure is still unknown in patients with heart failure (HF). We aimed to evaluate the effect of early catheter ablation (CA) in patients with HF and left ventricular ejection fraction (LVEF) below 50%. METHODS: We analyzed data from a structured registry comprising 227 patients with paroxysmal or persistent AF and HF with LVEF < 50% who underwent radiofrequency CA between 2015 and 2022. Early CA was defined as a procedure performed within 12 months of AF diagnosis. The median follow-up duration was 1748 (1176.3-2353.5) days, with a minimum follow-up of 365 days. Our endpoints were AF recurrence after a 3-months blanking period and all-cause mortality. RESULTS: Among the 227 patients with a median age of 64.3 years, 97 (42.7%) experienced AF recurrence and 55 (24.2%) died during the follow-up period. The median LVEF was 40% for early CA and 38% for delayed CA (p = .053). Early CA significantly reduced AF recurrence (HR = 0.25 [0.15-0.42], p < .001), however, the timing of procedure did not affect all-cause mortality (p = .16). These findings were consistent regardless of AF subtype or the burden of comorbidities, as assessed by the CHA2DS2-VASc score. CONCLUSION: The timing of CA of AF appears to be an important factor in patients with HF. Early CA reduced AF recurrence, although it does not impact all-cause mortality. We found similar results regardless of AF subtype or burden of comorbidities.

Adherence to the CLOSE Protocol and Low Baseline Generator Impedance Are Independent Predictors of Durable Pulmonary Vein Isolation.

Background: Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is predominantly attributed to pulmonary vein reconnection (PVR). Predictors of AF recurrence have been widely studied; however, data are scarce on procedural parameters that predict chronic PVR. We aimed to study PVR rates and predictors of PVR. Methods: We retrospectively included 100 patients who underwent repeated ablation due to AF recurrence after initial PVI with the CARTO system. PVR was determined during the repeated procedure by electrophysiological evaluation, and initial procedural characteristics predicting PVR were studied, including adherence to the CLOSE protocol, use of high power, first-pass isolation (FPI), and baseline generator impedance (BGI). Results: Thirty-eight patients underwent initial CLOSE-guided PVI, and sixty-two underwent initial non-CLOSE PVI. A repeat procedure was performed 23 ± 16 months after the initial procedure. In total, PVR was found in 192 of 373 PVs (51.5%), and all PVs were isolated in 17/100 (17%) patients. Factors associated with all PVs being isolated were adherence to the CLOSE protocol, a higher power setting, the presence of bilateral FPI, and lower BGI (88% vs. 28%, p < 0.0001; 37.5 W vs. 30 W, p = 0.0276; 88.2% vs. 40.4%, p = 0.0007; and 127.6 Ω vs. 136.6 Ω, p = 0.0027, respectively). In initial procedures with adherence to the CLOSE protocol, the FPI rate was significantly higher (73.7% vs. 25%, p < 0.0001), while there were no significant differences in terms of procedure time and left atrial dwell time (81 vs. 85 min, p = 0.83; and 60 vs. 58 min, p = 0.08, respectively). BGI ≥ 130 Ω (AUC = 0.7403, sensitivity: 77.1%, specificity: 68.8%, p = 0.0032) was associated with a significantly higher probability of PVR (OR = 6.757; p < 0.0001). In multivariable analysis, independent predictors for PVR were non-adherence to the CLOSE protocol and BGI ≥ 130 Ω. Conclusions: Our findings indicate that adherence to the CLOSE protocol and baseline generator impedance < 130 Ω during AF ablation are independent predictors of PVI durability.

Long-Term Durability of High- and Very High-Power Short-Duration PVI by Invasive Remapping: The HPSD Remap Study.

BACKGROUND: High-power short-duration ablation has shown impressive efficacy and safety for pulmonary vein isolation (PVI); however, initial efficacy results with very high power short-duration ablation were discouraging. This study compared the long-term durability of PVI performed with a 90- versus 50-W power setting. METHODS: Patients were randomized 1:1 to undergo PVI with the QDOT catheter using a power setting of 90 or 50 W. Three months after the index procedure, patients underwent a repeat electrophysiology study to identify pulmonary vein reconnections. Patients were followed for 12 months to detect AF recurrences. RESULTS: We included 46 patients (mean age, 64 years; women, 48%). Procedure (76 versus 84 minutes; P =0.02), left atrial dwell (63 versus 71 minutes; P =0.01), and radiofrequency (303 versus 1040 seconds; P <0.0001) times were shorter with 90- versus 50-W procedures, while the number of radiofrequency applications was higher with 90 versus 50 W (77 versus 67; P =0.01). There was no difference in first-pass isolation (83% versus 82%; P =1.0) or acute reconnection (4% versus 14%; P =0.3) rates between 90 and 50 W. Forty patients underwent a repeat electrophysiology study. Durable PVI on a per PV basis was present in 72/78 (92%) versus 68/77 (88%) PVs in the 90- and 50-W energy setting groups, respectively; effect size: 72/78-68/77=0.040, lower 95% CI=-0.051 (noninferiority limit=-0.1, ie, noninferiority is met). No complications occurred. There was no difference in 12-month atrial fibrillation-free survival between the 90- and 50-W groups (P =0.2). CONCLUSIONS: Similarly high rates of durable PVI and arrhythmia-free survival were achieved with 90 and 50 W. Procedure, left atrial dwell, and radiofrequency times were shorter with 90 W compared with 50 W. The sample size is too small to conclude the safety and long-term efficacy of the high and very high-power short-duration PVI; further studies are needed to address this topic. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05459831.

Machine-Learning-Based Prediction of 1-Year Arrhythmia Recurrence after Ventricular Tachycardia Ablation in Patients with Structural Heart Disease.

BACKGROUND: Ventricular tachycardia (VT) recurrence after catheter ablation remains a concern, emphasizing the need for precise risk assessment. We aimed to use machine learning (ML) to predict 1-month and 1-year VT recurrence following VT ablation. METHODS: For 337 patients undergoing VT ablation, we collected 31 parameters including medical history, echocardiography, and procedural data. 17 relevant features were included in the ML-based feature selection, which yielded six and five optimal features for 1-month and 1-year recurrence, respectively. We trained several supervised machine learning models using 10-fold cross-validation for each endpoint. RESULTS: We observed 1-month VT recurrence was observed in 60 (18%) cases and accurately predicted using our model with an area under the receiver operating curve (AUC) of 0.73. Input features used were hemodynamic instability, incessant VT, ICD shock, left ventricular ejection fraction, TAPSE, and non-inducibility of the clinical VT at the end of the procedure. A separate model was trained for 1-year VT recurrence (observed in 117 (35%) cases) with a mean AUC of 0.71. Selected features were hemodynamic instability, the number of inducible VT morphologies, left ventricular systolic diameter, mitral regurgitation, and ICD shock. For both endpoints, a random forest model displayed the highest performance. CONCLUSIONS: Our ML models effectively predict VT recurrence post-ablation, aiding in identifying high-risk patients and tailoring follow-up strategies.

Sex differences in one-year recurrence and all-cause mortality following catheter ablation of ventricular tachycardia in structural heart disease.

Aims: We aimed to establish sex-specific predictors for 1-year VT recurrence and 1-year all-cause mortality in patients with structural heart disease undergoing catheter ablation. Methods: We analyzed data of 299 patients recorded in our structured registry. These included medical history, echocardiography parameters, laboratory results, VT properties, procedural data. Results: Out of the 299 patients, 34 (11%) were female. No significant difference was found between women and men in terms of VT recurrence (p = 0.74) or mortality (p = 0.07). In females, severe mitral regurgitation (MR), tricuspid regurgitation (TR), presentation with incessant VT, and preprocedural electrical storm (ES) were associated with increased risk of VT recurrence. Diabetes, implanted CRT, VT with hemodynamic instability, ES and advanced MR were the risk factors of mortality in women. ACEi/ARB use predicted a favorable outcome in both endpoints among females. In men, independent predictors of VT recurrence were the composite parameter of ES and multiple ICD therapies, presentation with incessant VT, severe MR, while independent predictors of mortality were age, LVEF, creatinine and previously implanted CRT. Conclusion: According to our investigation, there are pronounced sex differences in predictors of recurrence and mortality following VT ablation.

Activity and Coupling to Hippocampal Oscillations of Median Raphe GABAergic Cells in Awake Mice.

Ascending serotonergic/glutamatergic projection from the median raphe region (MRR) to the hippocampal formation regulates both encoding and consolidation of memory and the oscillations associated with them. The firing of various types of MRR neurons exhibits rhythmic modulation coupled to hippocampal oscillatory activity. A possible intermediary between rhythm-generating forebrain regions and entrained ascending modulation may be the GABAergic circuit in the MRR, known to be targeted by a diverse array of top-down inputs. However, the activity of inhibitory MRR neurons in an awake animal is still largely unexplored. In this study, we utilized whole cell patch-clamp, single cell, and multichannel extracellular recordings of GABAergic and non-GABAergic MRR neurons in awake, head-fixed mice. First, we have demonstrated that glutamatergic and serotonergic neurons receive both transient, phasic, and sustained tonic inhibition. Then, we observed substantial heterogeneity of GABAergic firing patterns but a marked modulation of activity by brain states and fine timescale coupling of spiking to theta and ripple oscillations. We also uncovered a correlation between the preferred theta phase and the direction of activity change during ripples, suggesting the segregation of inhibitory neurons into functional groups. Finally, we could detect complementary alteration of non-GABAergic neurons' ripple-coupled activity. Our findings support the assumption that the local inhibitory circuit in the MRR may synchronize ascending serotonergic/glutamatergic modulation with hippocampal activity on a subsecond timescale.