Patient-specific quantification of cardiorespiratory motion for cardiac stereotactic radioablation treatment planning.

Background: Cardiac radioablation is a new treatment for patients with refractory ventricular tachycardia (VT). The target for cardiac radioablation is subject to cardiorespiratory motion (CRM), the heart's movement with breathing and cardiac contraction. Data regarding the magnitude of target CRM are limited but are highly important for treatment planning. Objectives: The study sought to assess CRM amplitude by using ablation catheter geometrical data. Methods: Electroanatomic mapping data of patients undergoing catheter ablation for VT at 3 academic centers were exported. The spatial position of the ablation catheter as a function of time while in contact with endocardium was analyzed and used to quantify CRM. Results: Forty-four patients with ischemic and nonischemic cardiomyopathy and VT contributed 1364 ablation lesions to the analysis. Average cardiac and respiratory excursion were 1.62 ± 1.21 mm and 12.12 ± 4.10 mm, respectively. The average ratio of respiratory to cardiac motion was approximately 11:1. CRM was greatest along the craniocaudal axis (9.66 ± 4.00 mm). Regional variations with respect to respiratory and cardiac motion were observed: basal segments had smaller displacements vs midventricular and apical segments. Patient characteristics (previous cardiac surgery, height, weight, body mass index, and left ventricular ejection fraction) had a statistically significant, albeit clinically moderate, impact on CRM. Conclusion: CRM is primarily determined by respiratory displacement and is modulated by the location of the target and the patient's biometric characteristics. The patient-specific quantification of CRM may allow to decrease treatment volume and reduce radiation exposure of surrounding organs at risk while delivering the therapeutic dose to the target.

Pulmonary Vein Isolation for Atrial Fibrillation: Comparison of a Very High-Power Very Short-Duration (vHPvSD) Ablation Protocol versus a Hybrid Ablation Approach-Procedural and Mid-Term Outcome Data.

Background: Pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is a standard-of-care treatment in the rhythm control strategy of symptomatic atrial fibrillation (AF). Ablation protocols, varying in the power and duration of energy delivery, have changed rapidly in recent years. Very high-power very short-duration ablation (vHPvSD) is expected to shorten procedural times compared to conventional ablation approaches. However, the existing data suggest that this might come at the cost of lower first-pass isolation rates, a predictor of poor ablation long-term outcomes. This study aims to compare a vHPvSD protocol to a hybrid strategy, in which the power and duration of the energy transfer are adapted depending on the anatomical location. Methods: We retrospectively analyzed procedural and outcome data from 93 patients (55 vHPvSD vs. 38 hybrid) scheduled for de novo pulmonary vein isolation. A vHPvSD ablation protocol (90 Watt (W), 4 s) was compared to a hybrid protocol using vHPvSD on the posterior wall and 50 W HPSD (high-power short-duration) ablation guided by the Ablation Index along the remaining spots. Results: Ablation times were significantly shorter in the vHPvSD cohort (5.4 min. vs. 14.2 min, p < 0.001), thus resulting in a significant reduction in the overall procedural duration (91 min vs. 106 min, p = 0.003). The non-significant slightly higher first-pass isolation rates in the vHPvSD cohort (85% vs. 76%, p = 0.262) did not affect freedom from AF 6 months after the procedure (83% vs. 87%, p = 0.622). Conclusions: vHPvSD helps in shortening the PVI procedural duration, thus neither affecting first-pass isolation rates nor freedom from atrial tachyarrhythmia recurrence at 6 months after the index procedure.

Sex differences among subcutaneous implantable cardioverter-defibrillator recipients: a propensity-matched, multicentre, international analysis from the i-SUSI project.

AIMS: Women have been historically underrepresented in implantable cardioverter-defibrillator (ICD) trials. No data on sex differences regarding subcutaneous ICDs (S-ICD) carriers have been described. Aim of our study was to investigate sex-related differences among unselected S-ICD recipients. METHODS AND RESULTS: Consecutive patients enrolled in the multicentre, international i-SUSI registry were analysed. Comparisons between sexes were performed using a 1:1 propensity matching adjusted analysis for age, body mass index (BMI), left ventricular function, and substrate. The primary outcome was the rate of appropriate shocks during follow-up. Inappropriate shocks and other device-related complications were deemed secondary outcomes. A total of 1698 patients were extracted from the i-SUSI registry; 399 (23.5%) were females. After propensity matching, two cohorts of 374 patients presenting similar baseline characteristics were analysed. Despite similar periprocedural characteristics and a matched BMI, women resulted at lower risk of conversion failure as per PRAETORIAN score (73.4% vs. 81.3%, P = 0.049). Over a median follow-up time of 26.5 [12.7-42.5] months, appropriate shocks were more common in the male cohort (rate/year 3.4% vs. 1.7%; log-rank P = 0.049), while no significant differences in device-related complications (rate/year: 6.3% vs. 5.8%; log-rank P = 0.595) and inappropriate shocks (rate/year: 4.3% vs. 3.1%; log-rank P = 0.375) were observed. After controlling for confounders, sex remained significantly associated with the primary outcome (aHR 1.648; CI 0.999-2.655, P = 0.048), while not resulting predictor of inappropriate shocks and device-related complications. CONCLUSION: In a propensity-matched cohort of S-ICD recipients, women are less likely to experience appropriate ICD therapy, while not showing higher risk of device-related complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0473876.

Impact of ventricular tachycardia ablation in subcutaneous implantable cardioverter defibrillator carriers: a multicentre, international analysis from the iSUSI project.

AIMS: Catheter ablation (CA) of ventricular tachycardia (VT) has become an important tool to improve clinical outcomes in patients with appropriate transvenous implantable cardioverter defibrillator (ICD) shocks. The aim of our analysis was to test whether VT ablation (VTA) impacts long-term clinical outcomes even in subcutaneous ICD (S-ICD) carriers. METHODS AND RESULTS: International Subcutaneous Implantable Cardioverter Defibrillator (iSUSI) registry patients who experienced either an ICD shock or a hospitalization for monomorphic VT were included in this analysis. Based on an eventual VTA after the index event, patients were divided into VTA+ vs. VTA- cohorts. Primary outcome of the study was the occurrence of a combination of device-related appropriate shocks, monomorphic VTs, and cardiovascular mortality. Secondary outcomes were addressed individually. Among n = 1661 iSUSI patients, n = 211 were included: n = 177 experiencing ICD shocks and n = 34 hospitalized for VT. No significant differences in baseline characteristics were observed. Both the crude and the yearly event rate of the primary outcome (5/59 and 3.8% yearly event rate VTA+ vs. 41/152 and 16.4% yearly event rate in the VTA-; log-rank: P value = 0.0013) and the cardiovascular mortality (1/59 and 0.7% yearly event rate VTA+ vs. 13/152 and 4.7% yearly event rate VTA-; log-rank P = 0.043) were significantly lower in the VTA + cohort. At multivariate analysis, VTA was the only variable remaining associated with a lower incidence of the primary outcome [adjusted hazard ratio 0.262 (0.100-0.681), P = 0.006]. CONCLUSION: In a real-world registry of S-ICD carriers, the combined study endpoint of arrhythmic events and cardiovascular mortality was lower in the patient cohort undergoing VTA at long-term follow-up. CLINICALTRIALS.GOV IDENTIFIER: NCT0473876.

Effect of SGLT-2 inhibitors on arrhythmia events: insight from an updated secondary analysis of > 80,000 patients (the SGLT2i-Arrhythmias and Sudden Cardiac Death).

OBJECTIVE: We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs). BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk. METHODS: We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated. RESULTS: 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78-1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77-0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found. CONCLUSIONS: SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients.

Differences in underlying cardiac substrate among S-ICD recipients and its impact on long-term device-related outcomes: Real-world insights from the iSUSI registry.

BACKGROUND: Outcome comparisons among subcutaneous implantable cardioverter-defibrillator (S-ICD) recipients with nonischemic cardiomyopathies are scarce. OBJECTIVE: The aim of this study was to evaluate differences in device-related outcomes among S-ICD recipients with different structural substrates. METHODS: Patients enrolled in the i-SUSI (International SUbcutaneouS Implantable cardioverter defibrillator registry) project were grouped according to the underlying substrate (ischemic vs nonischemic) and subgrouped into dilated cardiomyopathy, hypertrophic cardiomyopathy, Brugada syndrome (BrS), arrhythmogenic right ventricular cardiomyopathy (ARVC). The main outcome of our study was to compare the rates of appropriate and inappropriate shocks and device-related complications. RESULTS: Among 1698 patients, the most common underlying substrate was ischemic (31.7%), followed by dilated cardiomyopathy (20.5%), BrS (10.8%), hypertrophic cardiomyopathy (8.5%), and ARVC (4.4%). S-ICD for primary prevention was more common in the nonischemic cohort (70.9% vs 65.4%; P = .037). Over a median (interquartile range) follow-up of 26.5 (12.6-42.8) months, no differences were observed in appropriate shocks between ischemic and nonischemic patients (4.8%/y vs 3.9%/y; log-rank, P = .282). ARVC (9.0%/y; hazard ratio [HR] 2.492; P = .001) and BrS (1.8%/y; HR 0.396; P = .008) constituted the groups with the highest and lowest rates of appropriate shocks, respectively. Device-related complications did not differ between groups (ischemic: 6.4%/y vs nonischemic: 6.1%/y; log-rank, P = .666), nor among underlying substrates (log-rank, P = .089). Nonischemic patients experienced higher rates of inappropriate shocks than did ischemic S-ICD recipients (4.4%/y vs 3.0%/y; log-rank, P = .043), with patients with ARVC (9.9%/y; P = .001) having the highest risk, even after controlling for confounders (adjusted HR 2.243; confidence interval 1.338-4.267; P = .002). CONCLUSION: Most S-ICD recipients were primary prevention nonischemic cardiomyopathy patients. Among those, patients with ARVC tend to receive the most frequent appropriate and inappropriate shocks and patients with BrS the least frequent appropriate shocks.

Intravenous Treprostinil in Severe Inoperable Chronic Thromboembolic Pulmonary Hypertension Using Implantable Pumps-Single-Center Experience over More Than a Decade.

The management of chronic thromboembolic pulmonary hypertension has significantly changed over the last decade with the availability of both specific therapies and interventional treatments. In parallel, implantable pumps for intravenous administration of treprostinil have broadened the spectrum of continuous prostanoid infusion. We evaluated the course of 17 consecutive patients with inoperable chronic thromboembolic pulmonary hypertension treated with treprostinil by means of an implantable infusion pump between 2011 and 2023 at our center. Complications associated with the infusion system were rare, leading to 0.4 unplanned surgical interventions during 17,160 patient days. No additional safety signals were detected, and clinical benefits achieved with subcutaneous treprostinil before pump implantation could be maintained in all patients. No catheter-related infections or thromboembolic events were observed. Implantable infusion pumps offer an attractive alternative to subcutaneous treprostinil for patients intolerant to the subcutaneous route, including those with chronic thromboembolic pulmonary hypertension.

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study.

AIMS: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION: Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high.

Impact of cryoballoon application abortion due to phrenic nerve injury on reconnection rates: a YETI subgroup analysis.

AIMS: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). The most frequent complication during CB-based PVI is right-sided phrenic nerve injury (PNI) which is leading to premature abortion of the freeze cycle. Here, we analysed reconnection rates after CB-based PVI and PNI in a large-scale population during repeat procedures. METHODS AND RESULTS: In the YETI registry, a total of 17 356 patients underwent CB-based PVI in 33 centres, and 731 (4.2%) patients experienced PNI. A total of 111/731 (15.2%) patients received a repeat procedure for treatment of recurrent AF. In 94/111 (84.7%) patients data on repeat procedures were available. A total of 89/94 (94.7%) index pulmonary veins (PVs) have been isolated during the initial PVI. During repeat procedures, 22 (24.7%) of initially isolated index PVs showed reconnection. The use of a double stop technique did non influence the PV reconnection rate (P = 0.464). The time to PNI was 140.5 ± 45.1 s in patients with persistent PVI and 133.5 ± 53.8 s in patients with reconnection (P = 0.559). No differences were noted between the two populations in terms of CB temperature at the time of PNI (P = 0.362). The only parameter associated with isolation durability was CB temperature after 30 s of freezing. The PV reconnection did not influence the time to AF recurrence. CONCLUSION: In patients with cryoballon application abortion due to PNI, a high rate of persistent PVI rate was found at repeat procedures. Our data may help to identify the optimal dosing protocol in CB-based PVI procedures. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03645577?term=YETI&cntry=DE&draw=2&rank=1 ClinicalTrials.gov Identifier: NCT03645577.

Safety and effectiveness of the first contact force ablation catheter with a flexible tip.

Background: Catheter ablation is an established therapy for paroxysmal atrial fibrillation (PAF). The TactiFlex Ablation Catheter, Sensor Enabled (TactiFlex SE) is a next-generation radiofrequency ablation catheter incorporating fiber optics-based contact force-sensing technology with a flexible, laser-cut tip. Objective: The study sought to evaluate the safety and effectiveness of the TactiFlex SE ablation catheter for treatment of drug-refractory PAF. Methods: The TactiFlex AF investigational device exemption was a prospective, nonrandomized, multicenter clinical study. Enrollment began on June 26, 2020 and completed June 18, 2021. Subjects with PAF underwent de novo pulmonary vein isolation and, if indicated, ablation for typical atrial flutter. Subjects were followed for 12 months. Results: Of the 355 subjects enrolled at 37 sites worldwide, 334 underwent ablation with the TactiFlex SE catheter. The Kaplan-Meier estimate of 12-month freedom from AF/atrial flutter (AFL)/atrial tachycardia recurrence was 72.9% (95% confidence interval [CI] 95% CI 67.2%-77.8%) and clinical success was 83.6% (95% CI 95% CI 78.1%-87.2%). As-treated analyses compared subjects treated at high power (left atrium time-averaged power setting 40-50 W; n = 222) vs low power (<40 W; n = 97). The Kaplan-Meier estimate of 12-month freedom from AF/AFL/atrial tachycardia recurrence was 76.4% (95% CI 69.3%-82.0%) and clinical success was 83.9% (95% CI 77.5%-88.6%) in the high-power group compared with 66.8% (95% CI 56.1%-75.5%) and 80.7% (95% CI 70.8%- 87.5%), respectively, in the low-power group. The primary safety event rate in all treated subjects was 4.3%; 4.1% in the HP group and 5.2% in the LP group (P = .7671). Conclusion: TactiFlex SE is safe and effective for treatment of drug-refractory PAF and concomitant AFL and enables more efficient procedures than previous generation catheters.

Healthcare Utilization and Outcomes in Atrial Fibrillation Patients Treated by Drug Therapy versus a Catheter Ablation Strategy-A Middle European Propensity Score Matched Cohort Study.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most prevalent arrhythmia, associated with increased mortality and morbidity and causing relevant costs. Treatment options consist of catheter ablation (PVI) and rate or rhythm control drugs (non-PVI). METHODS: We analyze inpatient and outpatient data from the Upper Austrian Health Insurance Fund. Data of patients with a first hospitalization for AF in the years 2005 to 2018 were examined, using propensity score matching (PSM) including all CHA2DS2-VASc variables and working "collar". RESULTS: Out of 21,791 AF patients, PSM identified 1013 well-matching pairs (PVI and non-PVI). Over a ten-year period, the PVI treatment strategy group reveals significantly higher inpatient and outpatient expenditures (€2200/year). Positive economic effects can be demonstrated by a 5.1 percentage points (pp) higher employment rate and fewer retirements (7.6pp). Of utmost important is the 5.8pp all-cause mortality reduction over 10 years in the PVI treatment strategy. CONCLUSIONS: A PVI based treatment strategy results in higher healthcare expenditures vs. drug therapy alone. Most of these higher costs were caused by the PVI procedures during this period. Thus, more effective and efficient methods are needed to further reduce costs for the intervention and prevent repeat procedures. The benefit of a PVI treatment strategy is seen in higher employment rates, which are crucial from a societal perspective and should be a strong argument for caregivers. We show a significant reduction in all-cause mortality, which we partly attribute to the PVI procedure itself, to a stricter risk factor assessment and treatment, and a tighter medical adherence.

Evolving Role of Catheter Ablation for Atrial Fibrillation: Early and Effective Rhythm Control.

Catheter Ablation (CA) is an effective therapeutic option in treating atrial fibrillation (AF). Importantly, recent data show that CA as a rhythm control strategy not only significantly reduces AF burden, but also substantially improves clinical hard endpoints. Since AF is a progressive disease, the time of Diagnosis-to-Intervention appears crucial. Recent evidence shows that earlier rhythm control is associated with a lower risk of adverse cardiovascular outcomes in patients with early AF. Particularly, CA as an initial first line rhythm control strategy is associated with significant reduction of arrhythmia recurrence and rehospitalization in patients with paroxysmal AF. CA is shown to significantly lower the risk of progression from paroxysmal AF to persistent AF. When treating persistent AF, the overall clinical success after ablation remains unsatisfactory, however the ablation outcome in patients with "early" persistent AF appears better than those with "late" persistent AF. "Adjunctive" ablation on top of pulmonary vein isolation (PVI), e.g., ablation of atrial low voltage area, left atrial posterior wall, vein of Marshall, left atrial appendage, etc., may further reduce arrhythmia recurrence in selected patient group. New ablation concepts or new ablation technologies have been developing to optimize therapeutic effects or safety profile and may ultimately improve the clinical outcome.

Not to Rush-Laboratory Parameters and Procedural Complications in Patients Undergoing Left Atrial Appendage Closure.

Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage. Logistic regression was performed and included age and left-ventricular function. Furthermore, the association between acute complications and long-term outcomes was evaluated. Results: A total of 405 consecutive patients with a median age of 75 years (37% female) were included. 47% had a history of stroke. Median CHA2DS2-VASc score was 4 (interquartile range, 3−5) and the median HAS-BLED score was 3 (2−4). Major procedural complications occurred in 7% of cases. Low haemoglobin (OR 0.8, 95% CI 0.65−0.99 per g/dL, p = 0.040) and end-stage kidney disease (OR 13.0, CI 2.5−68.5, p = 0.002) remained significant in multivariate analysis. Anaemia (haemoglobin < 12 and < 13 g/dL in female and male patients) increased the risk of complications 2.2-fold. Conclusions: The major complication rate was low in this high-risk patient population undergoing LAAC. End-stage kidney disease and low baseline haemoglobin were independently associated with a higher major complication rate.

Very High-Power Short-Duration (HPSD) Ablation for Pulmonary Vein Isolation: Short and Long-Term Outcome Data.

BACKGROUND: Circumferential pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is a standard of care intervention for patients with symptomatic atrial fibrillation (AF). During follow-up, a substantial number of patients need a redo procedure due to reconnections on the basis of insufficient non-transmural ablation lesions. High-power short-duration ablation (HPSD) is expected to create efficient lesions while causing fewer complications than in conventional RFA settings. The aim of this study was to compare one-year outcome data of very HPSD (90 Watt, 4 s) to a strategy using 50 Watt HPSD ablation guided by the CLOSE protocol using the Ablation Index (AI), an arbitrary unit composed of power, contact force and ablation time. METHODS: We retrospectively analyzed short and long-term (median follow-up 23.2 ± 9.9 months) outcome data from 52 patients that were scheduled for first-do-symptomatic PVI. A very HPSD ablation protocol with 90 Watt and a 4 s duration cut-off was compared to an HPSD CLOSE approach (50 Watts; AI 550 at the anterior LA wall; AI 400 at the posterior LA wall, the roof and the floor) in terms of freedom from AF recurrence in a long-term electrocardiogram (ECG) over a five days surveillance period. To gain an impression of the subjective sense of wellbeing, the Atrial Fibrillation Effects on QualiTy-of-Life (AFEQT) score was recorded. RESULTS: Overall freedom from AF was found in 81% (90 W 4 s) vs. 87.5% (50 W), (p = 0.52). There were 3 AF recurrences during the blanking period (90 W 4 s) vs. 1 (50 W). Within each population, one patient was scheduled for a redo-PVI-procedure. The AFEQT score was in favor of the 90 Watt 4 s approach (86.1 vs. 77.5; p = 0.37). CONCLUSION: Within our relatively small studied population, we found hints that in addition to shortening ablation times and radiation exposure without significantly increasing the rate of relevant intraprocedural complications, very high power short-duration ablation (90 W 4 s) provides comparable efficacy rates after one year.

Adjunctive Left Atrial Posterior Wall Isolation in Treating Atrial Fibrillation: Insight From a Large Secondary Analysis.

OBJECTIVES: This study evaluated the role of adjunctive left atrium posterior wall isolation (PWI) in preventing atrial fibrillation (AF) recurrence. BACKGROUND: The left atrium posterior wall is an arrhythmogenic substrate that contributes to the development of AF. METHODS: This was an updated pooled analysis that included clinical data regarding PWI plus pulmonary vein isolation (PVI) in treating AF. The primary outcome was recurrence of atrial tachyarrhythmias. RESULTS: A total of 26 studies with 3,287 patients with AF (age 61.7 ± 10.8 years) were included. Mean follow-up was 15.2 ± 8.4 months. Procedural success to achieve PWI was 92.8%. In paroxysmal AF, adjunctive PWI did not reduce the recurrence of all atrial arrhythmias (P = 0.21) or AF (P = 0.37); however, in persistent AF, adjunctive PWI was associated with substantially lower recurrence of all atrial arrhythmias (risk ratio: 0.74; P < 0.001) and AF (risk ratio: 0.67; P = 0.01), particularly when randomized data were included. Subgroup analyses based on meta-regression demonstrated that patients with older age, a larger left atrial diameter, and persistent AF benefited more significantly from the adjunctive PWI. Adjunctive PWI using either radiofrequency or a cryoballoon reduced AF recurrence, whereas using radiofrequency seemed to be associated with higher recurrence rate of atrial tachycardias and/or atrial flutter. Non-BOX adjunctive PWI rather than BOX PWI was associated with significantly lower recurrence of AF. The incidence of procedural adverse events between the PVI+PWI (3.2%) and PVI (2.8%) groups was low and similar. PVI+PWI needed longer ablation and/or procedural time but had similar fluoroscopy time. CONCLUSIONS: Adjunctive PWI can be achieved in most patients without compromising safety. Patients with persistent AF appear to benefit from this approach. The ablation technology and/or approach may affect the clinical outcome of PWI.

Ertugliflozin to reduce arrhythmic burden in ICD/CRT patients (ERASe-trial) - A phase III study.

Sodium glucose cotransporter 2 (SGLT2) have proven profound positive effects in heart failure with reduced ejection fraction (HFrEF). These effects are independent from the presence of diabetes. Metabolic effects, antiinflammatory, and antifibrotic properties are discussed as underlying mechanisms. Despite a strong correlation of ventricular arrhythmias with HFrEF, the impact of ertugliflozin on the ventricular arrhythmic burden has not been investigated, yet. Therefore, the Ertugliflozin to Reduce Arrhythmic burden in ICD ± CRT patientS (ERASe) trial was designed to investigate the efficacy and safety of ertugliflozin in patients with reduced and midrange ejection fraction (EF) with or without diabetes. METHODS: Within a multicentre, national, randomized, double-blind, placebo-controlled, phase 3b trial we aim to enrol a total of 402 patients across Austria. Patients with reduced or midrange EF and ICD ± CRT therapy >3 months and previous ventricular tachycardia (at least 10 documented VT episodes within the last 12 months) are randomized in a 1:1 ratio to ertugliflozin (5 mg once daily orally administered) or matching placebo. The primary endpoint of the ERASe trial is to investigate the impact of ertugliflozin on total burden of ventricular arrhythmias. Further objectives will include number of therapeutic interventions of implanted devices, atrial fibrillation and heart failure biomarkers. CONCLUSION: The ERASe trial will be the first trial to test ertugliflozin in heart failure patients with nonpreserved ejection fraction and ongoing ICD ± CRT therapy regardless of their diabetic status. The ERASe trial may therefore extend the concept of SGLT2 inhibition to improve cardiac remodelling, including reduced arrhythmic burden. Trial registration Identifier EudraCT Nr. 2020-002581-14 / ClinicalTrials.gov Identifier: NCT04600921.

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

BACKGROUND: Cryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce. METHODS: The YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible. RESULTS: A total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months. CONCLUSIONS: The incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article.

Anticoagulation in atrial fibrillation and liver disease: a pooled-analysis of >20 000 patients.

AIMS: Anticoagulation for atrial fibrillation patients with liver disease represents a clinical dilemma. We sought to evaluate the efficacy/safety of different anticoagulation, i.e. vitamin K antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in such patient group. METHODS AND RESULTS: This was a pooled-analysis enrolling up-to-date clinical data. Two subsets: subset A (VKA vs. Non-Anticoagulation) and subset B (NOACs vs. VKA) were pre-specified. The study outcomes were ischaemic stroke (IS)/thromboembolism (TE), major bleeding (MB), intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and all-cause mortality. A total of 20 042 patients' data were analysed (subset A: N = 10 275, subset B: N = 9767). Overall mean age: 71 ± 11 years, mean CHA2DS2-VASc score: 4.0 ± 1.8, mean HAS-BLED score: 3.6 ± 1.2. The majority of the patients had Child-Pugh category (A-B). As compared with Non-Anticoagulation, VKA seemed to reduce the risk of IS/TE [odds ratio (OR): 0.60, P = 0.05], but heighten the risk of all-bleeding events including MB (OR: 2.81, P = 0.01), ICB (OR: 1.60, P = 0.01), and GIB (OR: 3.32, P = 0.01). When compared with VKA, NOACs had similar efficacy in reducing the risk of IS/TE (OR: 0.82, P = 0.64), significantly lower risk of MB (OR: 0.54, P = 0.0003) and ICB (OR: 0.35, P < 0.0001), and trend towards reduced risk of GIB (OR: 0.72, P = 0.12) and all-cause mortality (OR: 0.79, P = 0.35). The favourable effects were maintained in subgroups of individual NOAC. CONCLUSIONS: VKA appears to reduce the risk of IS/TE but increase all-bleeding events. NOACs have similar effect in reducing the risk of IS/TE and have significantly lower risk of MB and ICB as compared with VKA. NOACs seem to be associated with better clinical outcome than VKA in patients with mild-moderate liver disease.

Low-Voltage Myocardium-Guided Ablation Trial of Persistent Atrial Fibrillation.

BACKGROUND: Clinically effective ablation approaches for patients with persistent atrial fibrillation (AF) are still being debated. So far, ablation targets and strategies beyond pulmonary vein isolation (PVI) have failed to show systematic outcome improvement in randomized controlled clinical trials. METHODS: We conducted a multicenter, randomized trial to determine whether PVI plus individualized substrate ablation of atrial low-voltage myocardium improves outcome in patients with persistent AF. We randomly assigned 324 patients in a 1:1 ratio to receive PVI alone (163 patients; PVI only) or PVI plus substrate modification (161 patients; PVI+SM). The primary study end point was the first recurrence of an atrial arrhythmia longer than 30 seconds after single ablation, with 3 months blanking, using serial 7-day electrocardiogram recordings over 12 months of observation. Patients were also encouraged to receive implantable cardiac monitors. RESULTS: The primary study end point occurred in 75 PVI-only patients (50%) and in 54 PVI+SM patients (35%) (Kaplan­Meier event rate estimates: hazard ratio=0.62, 95% confidence interval [CI]=0.43 to 0.88, log rank P=0.006). Adverse events occurred in three PVI-only patients (1.8%) and in six PVI+SM patients (3.7%) (difference: −1.9 percentage points, 95% CI=−5.5 to 1.7 percentage points). Implant monitoring was used in 242 patients. Among them, 65 PVI-only patients (55%) versus 47 PVI+SM patients (39%) experienced recurrences (difference: 15 percentage points, 95% CI=3 to 28 percentage points). CONCLUSIONS: In this randomized trial, PVI plus individualized ablation of atrial low-voltage myocardium significantly improved outcomes in patients with persistent AF. (ClinicalTrials.gov number, NCT02732626.)

Catheter ablation vs. antiarrhythmic drugs as 'first-line' initial therapy for atrial fibrillation: a pooled analysis of randomized data.

AIMS: Catheter ablation (CA) is recommended for patients with atrial fibrillation (AF) after failure of antiarrhythmic drugs (AADs). The role of CA as 'initial therapy' for AF is to be determined. METHODS AND RESULTS: Following PRISMA guideline an up-to-date pooled analysis of randomized data comparing ablation vs. AADs as first-line therapy for symptomatic AF was performed. The primary outcome was recurrence of atrial tachyarrhythmia. The secondary outcomes were improvement in quality-of-life (QoL) and major adverse events. A total of 997 patients from five randomized trials were enrolled (mean age 57.4 years, 68.6% male patients, 98% paroxysmal AF, mean follow-up 1.4 years). The baseline characteristics were similar between the ablation and AADs group. Overall pooled analysis showed that, as compared with AADs, CA as first-line therapy was associated with significantly higher freedom from arrhythmia recurrence (69% vs. 48%, odds ratio: 0.36, 95% confidence interval: 0.27-0.48, P < 0.001). This significance was maintained in subgroup analyses of 1- and 2-year follow-up (P < 0.001). Catheter ablation was associated with significantly greater improvement in QoL regarding AFEQT score and 36-Item Short-Form Health Survey score. The incidence of serious adverse events between ablation and AADs group (5.6% vs. 4.9%, P = 0.62) was similar. CONCLUSIONS: Catheter ablation as 'initial therapy' was superior to AADs in maintenance of sinus rhythm and improving QoL for patients with symptomatic paroxysmal AF, without increasing risk of serious adverse events.