Structural analysis of the TPI-Manchester, a thermolabile variant of human triosephosphate isomerase.

Human triosephosphate isomerase G122R, also known as TPI-Manchester, is a thermolabile variant detected in a screening of more than 3400 individuals from a population in Ann Arbor, Michigan. Here, the crystallographic structure of G122R was solved to determine the molecular basis of its thermal stability. Structural analysis revealed an increase in the flexibility of residues at the dimer interface, even though R122 is about 20 Å away, suggesting that long-range electrostatic interactions may play a key role in the mutation effect.

Mitochondrial Variation in Anopheles gambiae and Anopheles coluzzii: Phylogeographic Legacy and Mitonuclear Associations With Metabolic Resistance to Pathogens and Insecticides.

Mitochondrial DNA has been a popular marker in phylogeography, phylogeny, and molecular ecology, but its complex evolution is increasingly recognized. Here, we investigated mitochondrial DNA variation in Anopheles gambiae and Anopheles coluzzii, in relation to other species in the Anopheles gambiae complex, by assembling the mitogenomes of 1,219 mosquitoes across Africa. The mitochondrial DNA phylogeny of the Anopheles gambiae complex was consistent with previously reported highly reticulated evolutionary history, revealing important discordances with the species tree. The three most widespread species (An. gambiae, An. coluzzii, and Anopheles arabiensis), known for extensive historical introgression, could not be discriminated based on mitogenomes. Furthermore, a monophyletic clustering of the three saltwater-tolerant species (Anopheles merus, Anopheles melas, and Anopheles bwambae) in the Anopheles gambiae complex also suggested that introgression and possibly selection shaped mitochondrial DNA evolution. Mitochondrial DNA variation in An. gambiae and An. coluzzii across Africa revealed significant partitioning among populations and species. A peculiar mitochondrial DNA lineage found predominantly in An. coluzzii and in the hybrid taxon of the African "far-west" exhibited divergence comparable to the interspecies divergence in the Anopheles gambiae complex, with a geographic distribution matching closely An. coluzzii's geographic range. This phylogeographic relict of the An. coluzzii and An. gambiae split was associated with population and species structure, but not with the rare Wolbachia occurrence. The lineage was significantly associated with single nucleotide polymorphisms in the nuclear genome, particularly in genes associated with pathogen and insecticide resistance. These findings underline potential mitonuclear coevolution history and the role played by mitochondria in shaping metabolic responses to pathogens and insecticides in Anopheles.

Evaluation of pulsed field ablation lesion characteristics using an in vitro vegetable model.

BACKGROUND: In vitro models to evaluate cardiac pulsed field ablation (PFA) have not been well established. We sought to create a standardized vegetable model and staining protocol for assessing unipolar PFA using a surface electrode. METHODS: We exposed potato slabs to unipolar PFA in a saline bath using a 3.5 mm electrode catheter and grounding pad connected to a custom-built high-voltage generator. Lesions were clearly visualized after staining with 2,3,5-triphenyltetrazolium chloride (TTC) using a timed protocol to reveal a necrotic center and a periphery of electroporated cells with intact mitochondria. RESULTS: Lesion volume increased linearly with increasing voltage and logarithmically with repetitive PFA applications. CONCLUSION: The findings observed in this vegetable model using a TTC staining protocol are consistent with findings observed with cardiomyocytes.

Lesion characteristics using high-frequency low-tidal volume ventilation versus standard ventilation during ablation of paroxysmal atrial fibrillation.

INTRODUCTION: High-frequency low-tidal-volume (HFLTV) ventilation during radiofrequency catheter ablation (RFCA) for paroxysmal atrial fibrillation (PAF) has been shown to be superior to standard ventilation (SV) in terms of procedural efficiency, acute and long-term clinical outcomes. Our study aimed to compare ablation lesions characteristics utilizing HFLTV ventilation versus SV during RFCA of PAF. METHODS: A retrospective analysis was conducted on patients who underwent pulmonary vein isolation (PVI) for PAF between August 2022 and March 2023, using high-power short-duration ablation. Thirty-five patients underwent RFCA with HFLTV ventilation and were matched with another cohort of 35 patients who underwent RFCA with SV. Parameters including ablation duration, contact force (CF), impedance drop, and ablation index were extracted from the CARTONET database for each ablation lesion. RESULTS: A total of 70 patients were included (HFLTV = 35/2484 lesions, SV = 35/2830 lesions) in the analysis. There were no differences in baseline characteristics between the groups. While targeting the same ablation index, the HFLTV ventilation group demonstrated shorter average ablation duration per lesion (12.3 ± 5.0 vs. 15.4 ± 8.4 s, p < .001), higher average CF (17.0 ± 8.5 vs. 10.5 ± 4.6 g, p < .001), and greater impedance reduction (9.5 ± 4.6 vs. 7.7 ± 4.1 ohms, p < .001). HFLTV ventilation group also demonstrated shorter total procedural time (61.3 ± 25.5 vs. 90.8 ± 22.8 min, p < .001), ablation time (40.5 ± 18.6 vs. 65.8 ± 22.5 min, p < .001), and RF time (15.3 ± 4.8 vs. 22.9 ± 9.7 min, p < .001). CONCLUSION: HFLTV ventilation during PVI for PAF was associated with improved ablation lesion parameters and procedural efficiency compared to SV.

High-frequency low-tidal volume ventilation improves procedural and long-term clinical outcomes in persistent atrial fibrillation ablation: Prospective multicenter registry.

BACKGROUND: High-frequency, low-tidal volume (HFLTV) ventilation increases the efficacy and efficiency of radiofrequency catheter ablation (RFCA) of paroxysmal atrial fibrillation. Whether those benefits can be extrapolated to RFCA of persistent atrial fibrillation (PeAF) is undetermined. OBJECTIVE: The purpose of this study was to evaluate whether using HFLTV ventilation during RFCA in patients with PeAF is associated with improved procedural and long-term clinical outcomes compared to standard ventilation (SV). METHODS: In this prospective multicenter registry (REAL-AF), patients who had undergone pulmonary vein isolation (PVI) + posterior wall isolation (PWI) for PeAF using either HFLTV ventilation or SV were included. The primary efficacy outcome was freedom from all-atrial arrhythmias at 12 months. Secondary outcomes included procedural and long-term clinical outcomes and complications. RESULTS: A total of 210 patients were included (HFLTV=95 vs. SV=115) in the analysis. There were no differences in baseline characteristics between the groups. Procedural time (80 [66-103.5] minutes vs 110 [85-141] minutes; P <.001), total radiofrequency (RF) time (18.73 [13.93-26.53] minutes vs 26.15 [20.30-35.25] minutes; P <.001), and pulmonary vein RF time (11.35 [8.78-16.69] minutes vs 18 [13.74-24.14] minutes; P <.001) were significantly shorter using HFLTV ventilation compared with SV. Freedom from all-atrial arrhythmias was significantly higher with HFLTV ventilation compared with SV (82.1% vs 68.7%; hazard ratio 0.41; 95% confidence interval [0.21-0.82]; P = .012), indicating a 43% relative risk reduction and a 13.4% absolute risk reduction in all-atrial arrhythmia recurrence. There was no difference in long-term procedure-related complications between the groups (HFLTV 1.1% vs SV 0%, P = .270). CONCLUSION: In patients undergoing RFCA with PVI + PWI for PeAF, the use of HFLTV ventilation was associated with higher freedom from all-atrial arrhythmias at 12-month follow-up, with significantly shorter procedural and RF times compared to SV, while reporting a similar safety profile.

Kinetic Study and Reaction Mechanism of the Gas-Phase Thermolysis Reaction of Methyl Derivatives of 1,2,4,5-Tetroxane.

Tetroxane derivatives are interesting drugs for antileishmaniasis and antimalaric treatments. The gas-phase thermal decomposition of 3,6,-dimethyl-1,2,4,5-tetroxane (DMT) and 3,3,6,6,-tetramethyl-1,2,4,5-tetroxane (acetone diperoxide (ACDP)) was studied at 493-543 K by direct gas chromatography by means of a flow reactor. The reaction is produced in the injector chamber at different temperatures. The resulting kinetics Arrhenius equations were calculated for both tetroxanes. Including the parent compound of the series 1,2,4,5-tetroxane (formaldehyde diperoxide (FDP)), the activation energy and frequency factors decrease linearly with the number of methyl groups. The reaction mechanisms of ACDP and 3,6,6-trimethyl-1,2,4,5-tetroxane (TMT) decomposition have been studied by means of the DFT method with the BHANDHLYP functional. Our calculations confirm that the concerted mechanism should be discarded and that only the stepwise mechanism occurs. The critical points of the singlet and triplet state potential energy surfaces (S- and T-PES) of the thermolysis reaction of both compounds have been determined. The calculated activation energies of the different steps vary linearly with the number of methyl groups of the methyl-tetroxanes series. The mechanism for the S-PES leads to a diradical O···O open structure, which leads to a C···O dissociation in the second step and the production of the first acetaldehyde/acetone molecule. This last one yields a second C···O dissociation, producing O2 and another acetone/acetaldehyde molecule. The O2 molecule is in the singlet state. A quasi-parallel mechanism for the T-PES from the open diradical to products is also found. Most of the critical points of both PES are linear with the number of methyl groups. Reaction in the triplet state is much more exothermic than the singlet state mechanism. Transitions from the singlet ground state, S0 and low-lying singlet states S1-3, to the low-lying triplet excited states, T1-4, (chemical excitation) in the family of methyl tetroxanes are also studied at the CASSCF/CASPT2 level. Two possible mechanisms are possible here: (i) from S0 to T3 by strong spin orbit coupling (SOC) and subsequent fast internal conversion to the excited T1 state and (ii) from S0 to S2 from internal conversion and subsequent S2 to T1 by SOC. From these experimental and theoretical results, the additivity effect of the methyl groups in the thermolysis reaction of the methyl tetroxane derivatives is clearly highlighted. This information will have a great impact for controlling these processes in the laboratory and chemical industries.

A Patch Wearable Cardioverter-Defibrillator for Patients at Risk of Sudden Cardiac Arrest.

BACKGROUND: For many patients, sudden cardiac arrest (SCA) risk is elevated temporarily. Wearable cardioverter-defibrillators (WCDs) can monitor and treat SCA during these temporary periods. Traditional WCDs can be uncomfortable, require frequent maintenance, and cannot be used when showering, resulting in poor compliance and avoidable SCA deaths. The Jewel is a novel, water-resistant patch-wearable cardioverter-defibrillator (P-WCD) with a machine learning detection algorithm designed to improve compliance and protection against SCA. OBJECTIVES: This study aims to demonstrate the safety and clinical effectiveness of a novel P-WCD. METHODS: The Jewel IDE Study, a prospective, single-arm study conducted at 30 U.S. sites, enrolled patients at SCA risk due to ventricular tachycardia/ventricular fibrillation who were not candidates for or refused an implantable defibrillator. The primary safety endpoint was <15% patients with clinically significant cutaneous adverse device effects and the primary effectiveness endpoint was <2 inappropriate shocks/100 patient-months. Secondary endpoints were ≥1 successful ventricular tachycardia/ventricular fibrillation conversion and wear time compliance of >14.1 h/d. RESULTS: A total of 305 patients (mean age: 57.9 years; 30.2% female, 27.9% non-White) were enrolled, of which 290 had available device data. The clinically significant cutaneous adverse device effect rate was 2.30% (upper 1-sided 98% CI: 4.80); none were severe. No device-related deaths or serious adverse events were reported. The inappropriate shock rate was 0.36/100 patient-months (upper 1-sided 98% CI: 1.53). Of 11 shocks in 9 patients, 9 shocks were adjudicated to be appropriate. Eight of 9 shocks were successful with a single shock. Median wear time compliance was 23.5 (20.7-23.9) h/d. CONCLUSIONS: The novel P-WCD is a safe and effective WCD with high patient compliance. There were no deaths due to noncompliance and a high number of successful conversions (Jewel IDE study [A Clinical Evaluation of the Jewel P-WCD in Subjects at High Risk for Sudden Cardiac Arrest]; NCT05201495).

Understanding Lesion Creation Biophysics and Improved Lesion Assessment during Radiofrequency Catheter Ablation. The Perfect Combination to Achieve Durable Lesions in Atrial Fibrillation Ablation.

Atrial fibrillation (AF) is a prevalent arrhythmia, while pulmonary vein isolation (PVI) has become a cornerstone in its treatment. The creation of durable lesions is crucial for successful and long-lasting PVI, as inconsistent lesions lead to reconnections and recurrence after ablation. Various approaches have been developed to assess lesion quality and transmurality in vivo, acting as surrogates for improved lesion creation and long-term outcomes utilizing radiofrequency (RF) energy. This review manuscript examines the biophysics of lesion creation and different lesion assessment techniques that can be used daily in the electrophysiology laboratory when utilizing RF energy. These methods provide valuable insights into lesion effectiveness, facilitating optimized ablation procedures and reducing atrial arrhythmia recurrences. However, each approach has its limitations, and a combination of techniques is recommended for comprehensive lesion assessment during AF catheter ablation. Future advancements in imaging techniques, such as magnetic Resonance Imaging (MRI), optical coherence tomography, and photoacoustic imaging, hold promise in further enhancing lesion evaluation and guiding treatment strategies.

Measures to Prevent Infection in Cardiac Implantable Electronic Device Replacements or Upgrades.

Cardiac implantable electronic device (CIED) infections represent one of the most threatening complications associated with device implantation, due to an increase in morbidity and mortality rates, as well as healthcare costs. Besides, it is important to highlight that when compared to the initial implantation of a device, the risks associated with procedures like generator changes, lead and pocket revisions, or device upgrades double. Consequently, to address this issue, various scoring systems, like the PADIT (Prior Procedures, Age, Depressed Renal Function, Immunocompromised Status, Type of Procedure), the RI-AIAC (Ricerca Sulle Infezioni Associate a ImpiAnto o Sostituzione di CIED), and the Shariff score, along with predictive models, have been developed to identify patients at a greater risk of infection. Moreover, several interventions have been assessed to evaluate their role in infection prevention ranging from improving skin preparation and surgical techniques to considering alternative strategies such as the subcutaneous Implantable Cardioverter-Defibrillator (ICD). Methods like antimicrobial prophylaxis, pocket irrigation, chlorhexidine gluconate pocket lavage, capsulectomy, and the use of antibacterial envelopes have been also explored as preventive measures. In this review, we provide a comprehensive assessment of CIED infections in patients undergoing repeat procedures and the strategies designed to reduce the risk of these infections.

Recurrent monomorphic ventricular tachycardia in a patient with myocarditis-Importance of understanding and targeting midmyocardial anatomic substrate.

INTRODUCTION: Patients with viral myocarditis can present with challenging life-threatening arrhythmias. Catheter ablation can be a life-saving procedure in some patients with recurrent drug-refractory ventricular arrhythmias. METHODS AND RESULTS: A patient with three prior ablations targeting two different monomorphic ventricular tachycardias (MMVTs) presented with recurrent ventricular tachycardia (VT). Consequently, he underwent epicardial mapping with adjuvant AI-enabled CT images with the creation of a three-dimensional model, which demonstrated a midmyocardial scar. Fractionated potentials were noted during mapping in this region, and entrainment suggested an inner loop. Interestingly, pacing showed two different QRS morphologies identical to his previously ablated VTs with a long stim-QRS at this region. Epicardial ablation carried on during the VT successfully terminated it, but the VT remained inducible and required endocardial ablation to make it noninducible. CONCLUSION: This case emphasizes the importance of recognizing possible three-dimensional VT circuits in some patients and the need to understand and target mid-myocardial substrate from both the endocardium and epicardium to achieve the elimination of the VT circuits.

Sex Differences in Left Bundle Branch Area Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy.

BACKGROUND: Women respond more favorably to biventricular pacing (BIVP) than men. Sex differences in atrioventricular and interventricular conduction have been described in BIVP studies. Left bundle branch area pacing (LBBAP) offers advantages due to direct capture of the conduction system. We hypothesized that men could respond better to LBBAP than BIVP. OBJECTIVES: This study aims to describe the sex differences in response to LBBAP vs BIVP as the initial cardiac resynchronization therapy (CRT). METHODS: In this multicenter prospective registry, we included patients with left ventricular ejection fraction ≤35% and left bundle branch block or a left ventricular ejection fraction ≤40% with an expected right ventricular pacing exceeding 40% undergoing initial CRT with LBBAP or BIVP. The composite primary outcome was heart failure-related hospitalization and all-cause mortality. The primary safety outcome included all procedure-related complications. RESULTS: There was no significant difference in the primary outcome when comparing men and women receiving LBBAP (P = 0.46), whereas the primary outcome was less frequent in women in the BIVP group than men treated with BIVP (P = 0.03). The primary outcome occurred less frequently in men undergoing LBBAP (29.9%) compared to those treated with BIVP (46.5%) (P = 0.004). In women, the incidence of the primary endpoint was 24.14% in the LBBAP group and 36.2% in the BIVP group; however, this difference was not statistically significant (P = 0.23). Complication rates remained consistent across all groups. CONCLUSIONS: Men and women undergoing LBBAP for CRT had similar clinical outcomes. Men undergoing LBBAP showed a lower risk of heart failure-related hospitalizations and all-cause mortality compared to men undergoing BIVP, whereas there was no difference between LBBAP and BIVP in women.

Feasibility, Efficacy, and Safety of Fluoroless Ablation of VT in Patients With Structural Heart Disease.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) typically requires radiation exposure with its potential adverse health effects. A completely fluoroless ablation approach is achievable using a combination of electroanatomical mapping and intracardiac echocardiography. Nonetheless, data in patients undergoing VT ablation are limited. OBJECTIVES: This study aimed to determine the feasibility, efficacy, and safety of VT ablation in patients with structural heart disease using a zero-fluoroscopy approach. METHODS: This multicenter study included consecutive patients with ischemic and nonischemic cardiomyopathy undergoing fluoroless VT ablation. Patients requiring epicardial access or coronary angiography were excluded. RESULTS: Between 2017 and 2023 a total of 198 patients (aged 66.4 ± 13.4 years, 76% male, 48% ischemic) were included. Most patients (95.4%) underwent left ventricular (LV) mapping and/or ablation, which was conducted via transseptal route in 54.5% (n = 103), via retrograde aortic route in 43.4% (n = 82), and using a combined approach in 2.1% (n = 4). Two-thirds of patients had a cardiac device, including a biventricular device in 15%; 2 patients had a LV assist device, and 1 patient had a mechanical aortic valve prosthesis. The mean total procedural time was 211 ± 70 minutes, and the total radiofrequency time was 30 ± 22 minutes. During a follow-up period of 22 ± 18 months, the freedom from VT recurrence was 80%, and 7.6% of patients underwent a repeated ablation. Procedural-related complications occurred in 6 patients (3.0%). CONCLUSIONS: Fluoroless ablation of VT in structural heart disease is feasible, effective, and safe when epicardial mapping/ablation is not required.

Surrogate indices of insulin resistance using the Matsuda index as reference in adult men-a computational approach.

Background: Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men. Methods: A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust. Results: The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01). Conclusions: The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

Multimorbidity patterns and trajectories in young and middle-aged adults: a large-scale population-based cohort study.

Introduction: The presence of multiple chronic conditions, also referred to as multimorbidity, is a common finding in adults. Epidemiologic research can help identify groups of individuals with similar clinical profiles who could benefit from similar interventions. Many cross-sectional studies have revealed the existence of different multimorbidity patterns. Most of these studies were focused on the older population. However, multimorbidity patterns begin to form at a young age and can evolve over time following distinct multimorbidity trajectories with different impact on health. In this study, we aimed to identify multimorbidity patterns and trajectories in adults 18-65 years old. Methods: We conducted a retrospective longitudinal epidemiologic study in the EpiChron Cohort, which includes all inhabitants of Aragón (Spain) registered as users of the Spanish National Health System, linking, at the patient level, information from electronic health records from both primary and specialised care. We included all 293,923 patients 18-65 years old with multimorbidity in 2011. We used cluster analysis at baseline (2011) and in 2015 and 2019 to identify multimorbidity patterns at four and eight years of follow-up, and we then created alluvial plots to visualise multimorbidity trajectories. We performed age- and sex-adjusted logistic regression analysis to study the association of each pattern with four- and eight-year mortality. Results: We identified three multimorbidity patterns at baseline, named dyslipidaemia & endocrine-metabolic, hypertension & obesity, and unspecific. The hypertension & obesity pattern, found in one out of every four patients was associated with a higher likelihood of four- and eight-year mortality (age- and sex-adjusted odds ratio 1.11 and 1.16, respectively) compared to the unspecific pattern. Baseline patterns evolved into different patterns during the follow-up. Discussion: Well-known preventable cardiovascular risk factors were key elements in most patterns, highlighting the role of hypertension and obesity as risk factors for higher mortality. Two out of every three patients had a cardiovascular profile with chronic conditions like diabetes and obesity that are linked to low-grade systemic chronic inflammation. More studies are encouraged to better characterise the relatively large portion of the population with an unspecific disease pattern and to help design and implement effective and comprehensive strategies towards healthier ageing.

Left atrial appendage closure for patients with atrial fibrillation at high intracranial haemorrhagic risk.

BACKGROUND AND OBJECTIVES: Although left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH), outcome data are scarce. We assessed the detailed neurological indications for LAAC and outcomes after LAAC in high ICH risk patients. METHODS: Study population included consecutive patients with NVAF who underwent LAAC in a single hospital network between January 2015 and October 2021 because of prior ICH or the presence of high ICH risk imaging markers on brain MRI (cerebral microbleeds (CMBs)). Primary safety and efficacy outcome measures were the occurrence of ICH and thromboembolic events, respectively, after LAAC. RESULTS: Among 146 patients with NVAF who underwent LAAC for high ICH risk, 122 had a history of ICH, while 24 presented with high ICH risk imaging markers only. Mean age was 75.7±7.61, 42 (28.8%) were women. Mean CHA2DS2-VASc score was 5.23±1.52. Of 122 patients with ICH history, 58 (47.5%) had intraparenchymal haemorrhage (IPH), 40 (32.8%) had traumatic ICH (T-ICH) and 18 (14.7%) had non-traumatic subdural haemorrhage. Of 85 patients with brain MRIs including necessary sequences, 43 (50.6%) were related to cerebral amyloid angiopathy and 37 (43.5%) to hypertensive microangiopathy. While 70% of patients were discharged on oral anticoagulants (OAC), 92% were not taking OAC at 1 year. Over 2.12 years mean follow-up, one patient had recurrent non-traumatic IPH (incidence rate (IR) 0.32 per 100 patient-years), five had T-ICH (IR 1.61 per 100 patient-years) and six had an ischaemic stroke (IR 1.94 per 100 patient-years). CONCLUSIONS: Among patients with NVAF at high ICH risk, LAAC demonstrated a low risk of recurrent ICH or ischaemic stroke compared with previously published data. LAAC in high ICH risk populations should be considered in clinical practice per FDA approval and recent guidelines.

Real-world data of radiofrequency catheter ablation in paroxysmal atrial fibrillation: Short- and long-term clinical outcomes from the prospective multicenter REAL-AF Registry.

BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: The purpose of this study was to assess the contemporary real-world practice approach and short and long-term outcomes of RF CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClincalTrials.gov Identifier: NCT04088071) Registry, patients undergoing RF CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2470 patients undergoing CA from January 2018 to December 2022 were included. Mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedural and total RF times of 95.4 ± 41.7 minutes and 22.1±11.8 minutes, respectively. At 1-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing pulmonary vein isolation vs pulmonary vein isolation plus ablation approaches. The complication rate was 1.9%. CONCLUSION: Refinement of RF CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows resulted in excellent short- and long-term clinical outcomes.