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.

Feasibility and image quality of bright-blood and black-blood phase-sensitive inversion recovery (BOOST) sequence in clinical practice using for left atrial visualization in patients with atrial fibrillation.

OBJECTIVES: Visualizing left atrial anatomy including the pulmonary veins (PVs) is important for planning the procedure of pulmonary vein isolation with ablation in patients with atrial fibrillation (AF). The aims of our study are to investigate the feasibility of the 3D whole-heart bright-blood and black-blood phase-sensitive (BOOST) inversion recovery sequence in patients with AF scheduled for ablation or electro-cardioversion, and to analyze the correlation between image quality and heart rate and rhythm of patients. METHODS: BOOST was performed for assessing PVs both with T2 preparation pre-pulse (T2prep) and magnetization transfer preparation (MTC) in 45 patients with paroxysmal or permanent AF scheduled for ablation or electro-cardioversion. Image quality analyses were performed by two independent observers. Qualitative assessment was made using the Likert scale; for quantitative analysis, signal to noise ratios (SNR) and contrast to noise ratios (CNR) were calculated for each PV. Heart rate and rhythm were analyzed based on standard 12-lead ECGs. RESULTS: All MTC-BOOST acquisitions achieved diagnostic quality in the PVs, while a significant proportion of T2prep-BOOST images were not suitable for assessing PVs. SNR and CNR values of the MTC-BOOST bright-blood images were higher if patients had sinus rhythm. We found a significant or nearly significant negative correlation between heart rate and the SNR and CNR values of MTC-BOOST bright-blood images. CONCLUSION: 3D whole-heart MTC-BOOST bright-blood imaging is suitable for visualizing the PVs in patients with AF, producing diagnostic image quality in 100% of cases. However, image quality was influenced by heart rate and rhythm. CLINICAL RELEVANCE STATEMENT: The novel 3D whole-heart BOOST CMR sequence needs no contrast administration and is performed during free-breathing; therefore, it is easy to use for a wide range of patients and is suitable for visualizing the PVs in patients with AF. KEY POINTS: • The applicability of the novel 3D whole-heart bright-blood and black-blood phase-sensitive sequence to pulmonary vein imaging in clinical practice is unknown. • Magnetization transfer-bright-blood and black-blood phase-sensitive imaging is suitable for visualizing the pulmonary veins in patients with atrial fibrillation with excellent or good image quality. • Bright-blood and black-blood phase-sensitive cardiac magnetic resonance sequence is easy to use for a wide range of patients as it needs no contrast administration and is performed during free-breathing.

Incidence and predictors of stroke and silent cerebral embolism following very high-power short-duration atrial fibrillation ablation.

AIMS: Cerebral thrombo-embolism is a dreaded complication of pulmonary vein isolation (PVI) for atrial fibrillation; its surrogate, silent cerebral embolism (SCE) can be detected by diffusion-weighted brain magnetic resonance imaging (bMRI). Initial investigations have raised a concern that very high-power, short-duration (vHPSD; 90 W/4 s) temperature-controlled PVI with the QDOT Micro catheter may be associated with a higher incidence of SCE compared with low-power long-duration ablation. We aimed to assess the incidence of procedural complications of vHPSD PVI with an emphasis on cerebral safety. METHODS AND RESULTS: We enrolled 328 consecutive patients undergoing their PVI procedure using vHPSD. A subgroup of 61 consecutive patients underwent diffusion-weighted bMRI within 24 h of the procedure, and incidence and predictors of SCE were studied. The mean procedure time and left atrial dwell time for the overall cohort were 69.6 ± 24.1 and 46.5 ± 21.5 min, respectively. First-pass isolation was achieved in 82%. No stroke or transient ischaemic attack occurred. Silent cerebral embolism was identified in 5 of 61 patients (8.2%). Silent cerebral embolism following procedures was significantly associated with lower baseline generator impedance (105.8 vs. 112.6 Ω, P < 0.0001) and with intermittent loss of catheter-tissue contact during ablation (14.1% vs. 6.1%, P < 0.0001). CONCLUSION: Very high-power, short-duration PVI is a safe technique with an excellent acute success rate. Silent cerebral embolism incidence in our cohort was below the previously reported range, with no clinically overt cerebral complications. Lower baseline generator impedance and loss of contact during ablation may contribute to a higher risk of SCEs.

Use of a new non-contrast-enhanced BOOST cardiac MR sequence before electrical cardioversion or ablation of atrial fibrillation-a pilot study.

Introduction: Left atrial appendage (LAA) thrombus is the most common source of embolization in atrial fibrillation (AF). Transesophageal echocardiography (TEE) is the gold standard method for LAA thrombus exclusion. Our pilot study aimed to compare the efficacy of a new non-contrast-enhanced cardiac magnetic resonance (CMR) sequence (BOOST) with TEE for the detection of LAA thrombus and to evaluate the usefulness of BOOST images for planning radiofrequency catheter ablation (RFCA) compared with left atrial (LA) contrast-enhanced computed tomography (CT). We also attempted to assess the patients' subjective experiences with TEE and CMR. Methods: Patients with AF undergoing either electrical cardioversion or RFCA were enrolled. Participants underwent pre-procedural TEE and CMR scans to evaluate LAA thrombus status and pulmonary vein anatomy. Patient experiences with TEE and CMR were assessed using a questionnaire developed by our team. Some patients scheduled for RFCA also had pre-procedural LA contrast-enhanced CT. In such cases, the operating physician was asked to subjectively define the quality of the CT and CMR scan on a scale of 1-10 (1 = worst, 10 = best) and comment on CMR's usefulness in RFCA planning. Results: Seventy-one patients were enrolled. In 94.4%, both TEE and CMR excluded, and in 1 patient, both modalities reported the presence of LAA thrombus. In 1 patient, TEE was inconclusive, but CMR excluded LAA thrombus. In 2 patients, CMR could not exclude the presence of thrombus, but in 1 of those cases, TEE was also indecisive. During TEE, 67%, during CMR, only 1.9% of patients reported pain (p < 0.0001), and 89% would prefer CMR in case of a repeat examination. The quality of the left atrial contrast-enhanced CT scans was better compared with the image quality of the CMR BOOST sequence [8 (7-9) vs. 6 (5-7), p < 0.0001]. Still, the CMR images were useful for procedural planning in 91% of cases. Conclusion: The new CMR BOOST sequence provides appropriate image quality for ablation planning. The sequence might be useful for excluding larger LAA thrombi; however, its accuracy in detecting smaller thrombi is limited. Most patients preferred CMR over TEE in this indication.

Remote Management of Patients with Cardiac Implantable Electronic Devices during the COVID-19 Pandemic.

Remote monitoring (RM) is the newest function of cardiac implantable electronic devices (CIEDs). In our observational retrospective analysis, we aimed to assess whether telecardiology could be a safe alternative to routine outpatient examinations during the COVID-19 pandemic. The in- and outpatient visits, the number of acute cardiac decompensation episodes, the RM data from CIEDs, and general condition were examined via questionnaires (KCCQ, EQ-5D-5L). Regarding the enrolled 85 patients, the number of personal patient appearances was significantly lower in the year following the pandemic outbreak compared to the previous year (1.4 ± 1.4 and 1.9 ± 1.2, p = 0.0077). The number of acute decompensation events was five before and seven during lockdown (p = 0.6). Based on the RM data, there was no significant difference in heart failure (HF) markers (all related p > 0.05); only patient activity increased after restrictions were lifted compared to that before the lockdown (p = 0.03). During restrictions, patients reported increased anxiety and depression compared to their previous state (p < 0.001). There was no subjective change in the perception of HF symptoms (p = 0.7). Based on the subjective perception and CIED data, the quality of life of patients with CIED did not deteriorate during the pandemic, but their anxiety and depression intensified. Telecardiology may be a safe alternative to routine inpatient examination.

Characteristics of Very High-Power, Short-Duration Radiofrequency Applications.

Introduction: Pulmonary vein isolation is the cornerstone of rhythm-control therapy for atrial fibrillation (AF). The very high-power, short-duration (vHPSD) radiofrequency (RF) ablation is a novel technology that favors resistive heating while decreasing the role of conductive heating. Our study aimed to evaluate the correlations between contact force (CF), power, impedance drop (ID), and temperature; and to assess their role in lesion formation with the vHPSD technique. Methods: Consecutive patients who underwent initial point-by-point RF catheter ablation for AF were enrolled in the study. The vHPSD ablation was performed applying 90 W for 4 s with an 8 ml/min irrigation rate. Results: Data from 85 patients [median age 65 (59-71) years, 34% female] were collected. The median procedure time, left atrial dwelling time, and fluoroscopy time were 70 (60-90) min, 49 (42-58) min, and 7 (5-11) min, respectively. The median RF time was 312 (237-365) sec. No steam pop nor major complications occurred. A total of 6,551 vHPSD RF points were analyzed. The median of CF, maximum temperature, and ID were 14 (10-21) g, 47.6 (45.1-50.4) °C, and 8 (6-10) Ohms, respectively. CF correlated significantly with the maximum temperature (p < 0.0001). A CF of 5 g and above was associated with a significantly higher temperature compared to those lesions with a CF below 5 grams (p < 0.0001). Bilateral first-pass isolation rate was 84%. The 6-month AF-recurrence rate was 7%. Conclusion: The maximum temperature and CF significantly correlate with each other during vHPSD applications. A CF ≥ 5 g leads to better tissue heating and thus might be more likely to result in good lesion formation, although this clinical study was unable to assess actual lesion sizes.

Impact of High-Power and Very High-Power Short-Duration Radiofrequency Ablation on Procedure Characteristics and First-Pass Isolation During Pulmonary Vein Isolation.

Introduction: High-power short-duration (HPSD) radiofrequency ablation has been proposed to produce rapid and effective lesions for pulmonary vein isolation (PVI). We aimed to evaluate the procedural characteristics and the first-pass isolation (FPI) rate of HPSD and very high-power short-duration (vHPSD) ablation compared to the low-power long-duration (LPLD) ablation technique. Methods: One hundred fifty-six patients with atrial fibrillation (AF) were enrolled and assigned to LPLD, HPSD, or vHPSD PVI. The energy setting was 30, 50, and 90 W in the LPLD, HPSD, and vHPSD groups, respectively. In the vHPSD group, 90 W/4 s energy delivery was used in the QMODE+ setting. In the other groups, ablation index-guided applications were delivered with 30 W (LPLD) or 50 W (HPSD). Results: Bilateral PVI was achieved in all cases. Compared to the LPLD group, the HPSD and vHPSD groups had shorter procedure time [85 (75-101) min, 79 (65-91) min, and 70 (53-83) min], left atrial dwelling time [61 (55-70) min, 53 (41-56) min, and 45 (34-52) min], total RF time [1,567 (1,366-1,761) s, 1,398 (1,021-1,711) s, and 336 (247-386) s], but higher bilateral FPI rate (57, 78, and 80%) (all p-values < 0.01). The use of HPSD (OR = 2.72, 95% CI 1.15-6.44, p = 0.023) and vHPSD (OR = 2.90, 95% CI 1.24-6.44, p = 0.014) ablation techniques were associated with a higher probability of bilateral FPI. The 9-month AF-recurrence rate was lower in case of HPSD and vHPSD compared to LPLD ablation (10, 8, and 36%, p = 0.0001). Moreover, the presence of FPI was associated with a lower AF-recurrence rate at 9-month (OR = 0.09, 95% CI 0.04-0.24, p = 0.0001). Conclusion: Our prospective, observational cohort study showed that both HPSD and vHPSD RF ablation shortens procedure and RF time and results in a higher rate of FPI compared to LPLD ablation. Moreover, the use of HPSD and vHPSD ablation increased the acute and mid-term success rate. No safety concerns were raised for HPSD or vHPSD ablation in our study.

Abutting Left Atrial Appendage and Left Superior Pulmonary Vein Predicts Recurrence of Atrial Fibrillation After Point-by-Point Pulmonary Vein Isolation.

INTRODUCTION: The role of the spatial relationship between the left superior pulmonary vein (LSPV) and left atrial appendage (LAA) is unknown. We sought to evaluate whether an abutting LAA and LSPV play a role in AF recurrence after catheter ablation for paroxysmal AF. METHODS: Consecutive patients, who underwent initial point-by-point radiofrequency catheter ablation for paroxysmal AF at the Heart and Vascular Center of Semmelweis University, Budapest, Hungary, between January of 2014 and December of 2017, were enrolled in the study. All patients underwent pre-procedural cardiac CT to assess left atrial (LA) and pulmonary vein (PV) anatomy. Abutting LAA-LSPV was defined as cases when the minimum distance between the LSPV and LAA was less than 2 mm. RESULTS: We included 428 patients (60.7 ± 10.8 years, 35.5% female) in the analysis. AF recurrence rate was 33.4%, with a median recurrence-free time of 21.2 (8.8-43.0) months. In the univariable analysis, female sex (HR = 1.45; 95%CI = 1.04-2.01; p = 0.028), LAA flow velocity (HR = 1.01; 95%CI = 1.00-1.02; p = 0.022), LAA orifice area (HR = 1.00; 95%CI = 1.00-1.00; p = 0.028) and abutting LAA-LSPV (HR = 1.53; 95%CI = 1.09-2.14; p = 0.013) were associated with AF recurrence. In the multivariable analysis, abutting LAA-LSPV (adjusted HR = 1.55; 95%CI = 1.04-2.31; p = 0.030) was the only independent predictor of AF recurrence. CONCLUSION: Abutting LAA-LSPV predisposes patients to have a higher chance for arrhythmia recurrence after catheter ablation for paroxysmal AF.

The effect of left atrial wall thickness and pulmonary vein sizes on the acute procedural success of atrial fibrillation ablation.

Nowadays, a novel contact-force guided ablation technique is used for enclosing pulmonary veins in patients with atrial fibrillation (AF). We sought to determine whether left atrial (LA) wall thickness (LAWT) and pulmonary vein (PV) dimensions, as assessed by cardiac CT, could influence the success rate of first-pass pulmonary vein isolation (PVI). In a single-center, prospective study, we enrolled consecutive patients with symptomatic, drug-refractory AF who underwent initial radiofrequency catheter ablation using a modified CLOSE protocol. Pre-procedural CT was performed in all cases. Additionally, the diameter and area of the PV orifices were obtained. A total of 1034 LAWT measurements and 376 PV area measurements were performed in 94 patients (mean CHA2DS2-VASc score 2.1 ± 1.5, mean age 62.4 ± 12.6 years, 39.5% female, 38.3% persistent AF). Mean procedure time was 81.2 ± 19.3 min. Complete isolation of all PVs was achieved in 100% of patients. First-pass isolation rate was 76% and 71% for the right-sided PVs and the left-sided PVs, respectively. No difference was found regarding comorbidities and imaging parameters between those with and without first-pass isolation. LAWT (mean of 11 regions or separately) had no effect on the acute procedural outcome on logistic regression analysis (all p ≥ 0.05). Out of all assessed parameters, only RSPV diameter was associated with a higher rate of successful right-sided first pass isolation (OR 1.01, p = 0.04). Left atrial wall thickness does not have an influence on the acute procedural success of PVI using ablation index and a standardized ablation protocol. RSPV diameter could influence the probability of right sided first-pass isolation.

The neural tissue around SU-8 implants: A quantitative in vivo biocompatibility study.

The use of SU-8 material in the production of neural sensors has grown recently. Despite its widespread application, a detailed systematic quantitative analysis concerning its biocompatibility in the central nervous system is lacking. In this immunohistochemical study, we quantified the neuronal preservation and the severity of astrogliosis around SU-8 devices implanted in the neocortex of rats, after a 2 months survival. We found that the density of neurons significantly decreased up to a distance of 20 µm from the implant, with an averaged density decrease to 24 ±â€¯28% of the control. At 20 to 40 µm distance from the implant, the majority of the neurons was preserved (74 ±â€¯39% of the control) and starting from 40 µm distance from the implant, the neuron density was control-like. The density of synaptic contacts - examined at the electron microscopic level - decreased in the close vicinity of the implant, but it recovered to the control level as close as 24 µm from the implant track. The intensity of the astroglial staining significantly increased compared to the control region, up to 560 µm and 480 µm distance from the track in the superficial and deep layers of the neocortex, respectively. Electron microscopic examination revealed that the thickness of the glial scar was around 5-10 µm thin, and the ratio of glial processes in the neuropil was not more than 16% up to a distance of 12 µm from the implant. Our data suggest that neuronal survival is affected only in a very small area around the implant. The glial scar surrounding the implant is thin, and the presence of glial elements is low in the neuropil, although the signs of astrogliosis could be observed up to about 500 µm from the track. Subsequently, the biocompatibility of the SU-8 material is high. Due to its low cost fabrication and more flexible nature, SU-8 based devices may offer a promising approach to experimental and clinical applications in the future.

Correction: Method for spike detection from microelectrode array recordings contaminated by artifacts of simultaneous two-photon imaging.

[This corrects the article DOI: 10.1371/journal.pone.0221510.].

Method for spike detection from microelectrode array recordings contaminated by artifacts of simultaneous two-photon imaging.

The simultaneous utilization of electrophysiological recordings and two-photon imaging allows the observation of neural activity in a high temporal and spatial resolution at the same time. The three dimensional monitoring of morphological features near the microelectrode array makes the observation more precise and complex. In vitro experiments were performed on mice neocortical slices expressing the GCaMP6 genetically encoded calcium indicator for monitoring the neural activity with two-photon microscopy around the implanted microelectrodes. A special filtering algorithm was used for data analysis to eliminate the artefacts caused by the imaging laser. Utilization of a special filtering algorithm allowed us to detect and sort single unit activities from simultaneous two-photon imaging and electrophysiological measurement.

A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology.

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks.