BackgroundLeft atrial (LA) fibrosis contributes to atrial fibrillation (AF) recurrence beyond pulmonary vein triggers, yet its non-invasive identification pre-ablation remains challenging. While invasive voltage mapping may identify low-voltage areas (LVAs) as a surrogate of atrial substrate abnormality, it is impractical for systematic screening.ObjectiveThis single-center retrospective pilot study evaluated the diagnostic performance of predefined ECG morphological criteria for detecting LVAs.MethodsLVAs were used as a surrogate marker for atrial fibrosis and defined as bipolar voltage of <0.50 mV on invasive mapping in sinus rhythm or CS pacing. Four ECG criteria were evaluated: (1) history of atypical atrial flutter, (2) negative atrial vector attenuation in V1, (3) presence of typical or atypical advanced interatrial block (types I–IV), and (4) poor terminal P-wave progression in V4–V6. The presence of at least one of these criteria was considered indicative of LVAs. Diagnostic performance of the ECG criteria was assessed against invasive voltage mapping as the reference standard. Five electrophysiologists independently analyzed 12-lead ECGs (100 mm/s, 40 mm/mV) from 78 patients undergoing first-time AF ablation.ResultsLVAs were present in 35 patients. The predefined ECG-based criteria demonstrated sensitivity 85.7% (95% CI: 70.6–93.7), specificity 95.4% (95% CI: 84.5–98.7), positive predictive value 93.8% (95% CI: 79.9–98.3), and negative predictive value 89.1% (95% CI: 77.0–95.3), with an overall diagnostic accuracy of 91.0% (95% CI: 82.6–95.6) and an AUC of 0.905 (95% CI: 0.838–0.972). Interatrial block and poor terminal P-wave progression were the most frequent predictors.ConclusionsThis proof-of-concept study demonstrated promising diagnostic performance for morphological ECG-criteria in detecting left-atrial LVAs. The proposed four-criteria model correlated strongly with invasive voltage mapping and may represent a promising candidate for further validation as a non-invasive tool for pre-procedural identification of atrial substrate.

Highly trained endurance athletes can develop complex ventricular arrhythmias despite normal structural cardiac imaging, creating major diagnostic challenges. This case series describes 3 young cyclists presenting with symptomatic ventricular arrhythmias from the right ventricle (RV), in whom conventional investigations, including transthoracic echocardiography and cardiac magnetic resonance, revealed no structural abnormalities. Prolonged rhythm monitoring prompted electroanatomical mapping, which revealed discrete to diffuse low-voltage areas across the RV outflow tract, RV inferior wall, and apex; findings compatible with an arrhythmogenic substrate and raising the possibility of early or concealed arrhythmogenic cardiomyopathy. All 3 athletes had long-standing exposure to high-intensity endurance training, which may be relevant in susceptible individuals, although no causal relationship can be inferred from these cases. These observations highlight the limitations of relying solely on conventional imaging in athletes with persistent symptomatic arrhythmias and suggest that, in carefully selected cases, prolonged rhythm monitoring and electroanatomical mapping may offer complementary diagnostic insights when concealed arrhythmogenic cardiomyopathy is suspected.

BACKGROUND:Most pulsed field ablation (PFA) technologies for atrial fibrillation use microsecond-scale pulses. Nanosecond pulses, by virtue of their short duration, enable larger pulse amplitudes to project lesion depth, without near-field thermal effects. OBJECTIVES:The goal of this study was to determine the outcomes of treating paroxysmal atrial fibrillation using a novel circular nanosecond PFA (nsPFA) catheter. METHODS:In a first-in-human study of patients with symptomatic paroxysmal atrial fibrillation, the nsPFA catheter was used to deliver 2.5-second or 5-second applications. Invasive remapping assessed lesion durability at 2 to 3 months, with additional nsPFA for incomplete lesions. Follow-up included transtelephonic monitoring and Holter monitoring at 6 and 12 months. RESULTS:At 3 centers, 177 patients (mean age 61 ± 10 years; 36% female; left atrial diameter 41 ± 5 mm) underwent pulmonary vein isolation (PVI) using 2.5-second (n = 36 patients) or 5-second (n = 141) applications. Additional ablation was at the posterior wall (n = 87), cavotricuspid isthmus (n = 11), or mitral isthmus (n = 29). All (100%) lesions were acutely successful, with transpired PVI time of 12 ± 5 minutes, and total left atrial dwell time for the nsPFA catheter of 19 ± 13 minutes. Total procedure and fluoroscopy times were 61 ± 27 minutes and 9 ± 6 minutes, respectively. Three (of 177 [1.7%]) primary serious adverse events occurred: inflammatory pericardial effusion, hemolysis with acute kidney injury, and stroke. Post procedure brain magnetic resonance imaging (35 patients) revealed 11.4% silent cerebral events (DWI+ / ADC-reduced) and 11.4% silent cerebral lesions (SCE plus FLAIR+). PVI durability with the 5-second applications was 91%. The 1-year estimate for freedom from atrial arrhythmia was 89.7% (95% CI: 80.5%-94.6%). CONCLUSIONS:nsPFA demonstrated reasonable safety, good lesion durability, and favorable 1-year clinical effectiveness. (Evaluation of the CellFX® Nano-Pulsed Field Ablation [PFA] 360 Catheter Endocardial Ablation System for the Treatment of Atrial Fibrillation. NCT06696170).

BACKGROUND:Pulsed field ablation (PFA) is a promising treatment for atrial fibrillation. We report 1-year freedom from atrial arrhythmia outcomes using monopolar PFA delivered through 3 commercial, contact force-sensing focal catheters. METHODS:ECLIPSE AF (Safety & Clinical Performance Study of Catheter Ablation With the Centauri System for Patients With Atrial Fibrillation; NCT04523545) was a prospective, single-arm, multicenter study evaluating acute and chronic safety and performance using the CENTAURI system to deliver focal PFA with TactiCath SE, StablePoint, and ThermoCool ST. Patients with paroxysmal or persistent atrial fibrillation underwent pulmonary vein (PV) isolation under deep sedation or general anesthesia and returned for remapping at 90 days to evaluate chronic durability. Freedom from atrial arrhythmia was evaluated continuously through 12 months using standard rhythm monitoring for symptomatic episodes and 24-hour Holter at 6 and 12 months. RESULTS:Eighty-two patients (74% male, 51.2% paroxysmal, and 58.5% deep sedation) were treated. PV isolation was achieved in 100% of targeted veins (322/322) with first-pass isolation in 92.2% (297/322). There were 4 primary safety events in 4 patients (4.9%, 4/82); 1 nonembolic stroke due to exacerbated cardiac tamponade secondary to catheter perforation and 3 hemorrhagic vascular access complications. There were no incidences of adverse event fistula, diaphragmatic paralysis, myocardial infarction, pericarditis, thromboembolism, PV stenosis, transient ischemic attack, or death. Eighty patients (98%) underwent remapping. Optimized PFA cohorts 3, 4, and 5 showed per-patient isolation rates of 60%, 73%, and 81% and per-PV isolation rates of 84%, 90%, and 92%, respectively. One-year freedom from atrial arrhythmia was 80.2% (95% CI, 69.7%-87.4%) for the entire patient sample, including 41 patients who underwent repeat focal PFA with the CENTAURI system at remapping. CONCLUSIONS:This study demonstrated that optimization of focal PFA with 3 contact force-sensing, solid-tip ablation catheters resulted in the progressive improvement of PV isolation durability at 3-month remapping and high freedom from atrial arrhythmia survival rates, providing a promising focal PFA treatment option integrated with current ablation workflows.

Background The impact of pulmonary vein isolation (PVI) using pulsed field ablation (PFA) on left atrial (LA) function remains incompletely understood. Objective To compare the effects of PVI performed with PFA vs radiofrequency ablation (RFA) on LA mechanical function in patients with paroxysmal atrial fibrillation (PAF), using serial echocardiographic strain analysis. Methods In this prospective, single-center study, patients undergoing a first-time PVI for PAF with either RFA or PFA were included. All participants underwent transthoracic echocardiography with 2-dimensional speckle tracking analysis at 3 time points: at baseline (immediately before ablation), in the acute phase (immediately after ablation), and in the chronic phase (3 months post-ablation). LA reservoir strain (LASr) and LA contraction strain (LASct) were assessed as primary parameters of LA mechanical function. Results A total of 59 patients were analyzed (RFA: 28; PFA: 31). In the PFA group, LASr and LASct decreased significantly in the acute phase (LASr: 26.5 ± 5.8% to 22.9 ± 6.6%, P = .010; LASct: 12.2 ± 3.6% to 8.6 ± 3.1%, P < .001). At 3-month follow-up, LASr had recovered to baseline levels (25.8 ± 7.9%, P = .531), while LASct remained significantly reduced (10.9 ± 4.3%, P = .031). In contrast, no significant changes in LASr or LASct were observed in the RFA group at any time point. Conclusion PVI using PFA is associated with acute LA stunning, with persistent impairment in contractile function at 3 months despite recovery of reservoir function. These findings suggest subtle, lasting alterations in atrial mechanics not observed with RFA.

AIMS:Initial clinical studies of pulsed field ablation (PFA) to treat atrial fibrillation (AF) indicated a >90% durability rate of pulmonary vein isolation (PVI). However, these studies were largely conducted in single centres and involved a limited number of operators. We aimed to describe the electrophysiological findings and outcomes in patients undergoing repeat ablation after an initial PF ablation for AF. METHODS AND RESULTS:In the MANIFEST-REDO study, we investigated patients who underwent repeat ablation due to clinical recurrence-AF or atrial tachycardia (AT)-following first-ever PVI with a pentaspline PFA catheter (Farawave, Boston Scientific Inc.). At 22 centres, 427 patients (age 64 ± 11 years; 37% female) were included. Of note, the recurrent arrhythmia leading to the repeat ablation was paroxysmal AF (51%), persistent AF (30%), or AT (19%). At the repeat procedure, the PV reconnection rates were 30% (left superior pulmonary vein), 28% (left inferior pulmonary vein), 33% (right superior pulmonary vein), and 32% (right inferior pulmonary vein). In 45% of patients, all PVs were durably isolated at the beginning of the repeat procedure, with the previous use of any imaging or mapping modality being univariately associated with durable PVI. After a post-redo follow-up period of 284 (90-366) days, the primary effectiveness endpoint (freedom from documented AF/AT lasting ≥30 s after 3-month blanking without class I/III antiarrhythmic drugs or symptoms) was achieved in 65% of patients, with significant differences between groups (PAF 65% vs. PersAF 56% vs. AT 76%; P = 0.04). Persistent AF as recurrent arrhythmia after the initial PFA ablation predicted AT/AF recurrence after repeat ablation [hazard ratio 1.241 (95% confidence interval 1.534-1.005); P = 0.045]. The procedural complication rate was 2.8%. CONCLUSION:In repeat procedures for AF/AT performed after an index procedure with PFA for AF, PV reconnections are not uncommon. Repeat procedures can be performed safely and with an acceptable subsequent success rate.

Background:Arrhythmogenic cardiomyopathy (ACM) is characterized by fibrofatty replacement of myocardium, predisposing to ventricular arrhythmias and sudden cardiac death. Arrhythmogenic cardiomyopathy is often linked to desmosomal gene mutations, particularly PKP2, which encodes plakophilin-2, a key structural protein in cardiac intercalated discs. In individuals with PKP2 mutations, exercise has been shown to accelerate disease progression. Case summary:A 22-year-old male semi-professional rower presented with palpitations, pre-syncope, and a history of presumed myocarditis with subepicardial fibrosis on cardiac magnetic resonance (CMR). Workup revealed anterior T-wave inversions on resting ECG and sustained monomorphic right ventricular (RV) outflow tract tachycardia, induced during exercise testing. Repeat CMR showed RV dysfunction and non-ischaemic RV and LV fibrosis with fibrofatty replacement. The patient met diagnostic criteria for biventricular ACM and underwent catheter ablation targeting the arrhythmic substrate. A multidisciplinary team carefully considered ICD therapy. However, due to the limited extent of the arrhythmic substrate, the exercise-induced nature of the ventricular tachycardia, and the successful ablation, ICD implantation was deferred at this stage. An ILR was implanted for continuous rhythm monitoring, with a low threshold for future ICD placement. High-intensity sports restriction, pharmacological therapy, and genetic counselling were initiated. Genetic testing identified a pathogenic PKP2 mutation. Discussion:This case highlights the complex interplay of genetic predisposition, myocardial inflammation, and exercise in ACM expression. The presumed myocarditis likely represented a 'hot phase' of ACM, accelerating structural cardiac changes. High-intensity exercise then acted as a 'second hit,' triggering phenotypic expression. Multidisciplinary evaluation combining rhythm monitoring, imaging, and genetic testing was key to diagnosis and management.

BACKGROUND:Whether successful catheter ablation for atrial fibrillation eliminates the need for long-term oral anticoagulant therapy is unknown. METHODS:We conducted an international, open-label, randomized, blinded-outcome-assessment trial involving 1284 patients who had undergone successful catheter ablation for atrial fibrillation at least 1 year earlier and had a CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a higher risk of stroke) of 1 or more (or ≥2 for women or for patients in whom vascular disease was a risk factor). Patients were randomly assigned to receive either aspirin (at a dose of 70 to 120 mg daily, depending on availability in the local jurisdiction) or rivaroxaban (at a dose of 15 mg) and followed for 3 years. Magnetic resonance imaging (MRI) of the head was performed after enrollment and at 3 years. The primary outcome was a composite of stroke, systemic embolism, or new covert embolic stroke (defined by ≥1 new infarct measuring ≥15 mm on MRI) at 3 years. RESULTS:A total of 641 patients were assigned to the rivaroxaban group and 643 to the aspirin group. A primary-outcome event occurred in 5 patients (0.31 events per 100 patient-years) in the rivaroxaban group and in 9 patients (0.66 events per 100 patient-years) in the aspirin group (relative risk, 0.56; 95% confidence interval [CI], 0.19 to 1.65; absolute risk difference at 3 years, -0.6 percentage points; 95% CI, -1.8 to 0.5; P = 0.28). New cerebral infarcts measuring less than 15 mm occurred in 22 of 568 patients (3.9%) in the rivaroxaban group and in 26 of 590 patients (4.4%) in the aspirin group (relative risk, 0.89; 95% CI, 0.51 to 1.55). Fatal or major bleeding (the composite primary safety outcome) had occurred in 10 patients (1.6%) with rivaroxaban and in 4 patients (0.6%) with aspirin (hazard ratio, 2.51; 95% CI, 0.79 to 7.95) at 3 years. CONCLUSIONS:Among patients who had had successful catheter ablation for atrial fibrillation at least 1 year earlier and had risk factors for stroke, treatment with rivaroxaban did not result in a significantly lower incidence of a composite of stroke, systemic embolism, or new covert embolic stroke than treatment with aspirin. (Funded by Bayer and others; OCEAN ClinicalTrials.gov number, NCT02168829.).

Pulmonary vein isolation (PVI) is one of the corner stones of therapy for atrial fibrillation. New ablation technologies using pulsed field (PFA) energy are emerging as a promising alternative to conventional radiofrequency (RFA) energy. The effect on left atrial (LA) function of this energy form however has not been well described. The aim of this study is to examine the effect of PVI with RFA or PFA on LA remodeling and mechanical function in patients with paroxysmal atrial fibrillation (PAF). This is a single center prospective study that included patients who were scheduled for a first ablation in the form of PVI because of PAF. The choice between PFA or RFA was made on a random basis. In the PFA group, PVI was performed using a multi-electrode pentaspline PFA catheter. In the RFA group, a conventional focal, solid tip, contact force sensing irrigated ablation catheter with radiofrequency energy was used. Included patients underwent serial dedicated echocardiograms with a focus on LA function using strain analyses: one baseline echo just before the procedure, one in the acute phase just after the procedure and one in the chronic phase at three months follow-up. Image quality had to be sufficient to allow for appropriate strain analyses. We included 28 patients in the RFA and 31 in the PFA group. Baseline characteristics in both groups were comparable, as can be seen in the table provided. Follow-up strain data were available in the acute phase for 22 patients in the RFA group and 27 in the PFA group. In the chronic phase, these were available in 26 and 29 patients respectively. In the RFA group, LA reservoir strain (LASr) as well as contraction strain (LASct) values did not differ significantly between the baseline and acute phase (23,7 ±7,5% vs 23,0 ±7,7%, p=0,571 and 11,1 ±4,7% vs 9,6 ±4,1%, p=0,085, respectively), and they remained unchanged in the chronic phase as compared to baseline (25,4 ±7,3% vs 25,4 ±7,5%, p=0,567 and 11,4 ±4,7% vs 12,0 ±4,7%, p=0,364, respectively). In the PFA group however, LASr as well as LASct were reduced significantly in the acute phase (26,5 ±5,8% vs 22,9 ±6,6%, p=0,010 and 12,2 ±3,6% vs 8,6 ±3,1%, p<0,001, respectively). In the chronic phase, LASr recovered to the baseline value (26,5 ±5,7% vs 25,8 ±7,9%, p=0,213), LASct remained significantly reduced (12,4 ±3,6% vs 10,9 ±4,3%, p=0,031). In the acute phase after PVI by PFA, there is an effect of LA stunning as is evidenced by a reduction in both LASr as well as in LASct, which is not seen after PVI in the RFA group. In the chronic phase after PFA, global LA function seems to recover as is evidenced by normalization of LASr, the atrial contraction however is still reduced which is not the case in the RFA group. This might indicate that PVI with PFA causes some degree of atrial dysfunction which is not seen after RFA.Baseline characteristics Results

Aim: Pulmonary vein isolation (PVI) is a widely accepted and effective treatment for atrial fibrillation (AF). Even though success rates have been climbing, some patients experience AF recurrence after ablation. This study aimed to identify predictors of AF recurrence, with a focus on the potential role of premature atrial contractions (PAC). Methods: A retrospective single-center analysis was conducted on 185 patients with AF who underwent primo PVI at a single center between 07/2014 and 01/2017. Patients underwent AF ablation using radiofrequency ablation (n = 61), by the CARTO (n = 50) and EnSite (n = 11) mapping systems, and the endoscopic laser balloon (n = 124). Exclusion criteria were combined procedures or the absence of a 24-hour Holter recording three months post-ablation. The primary endpoint was freedom from atrial arrhythmia 12 months after ablation with an application of a 90-day blanking period. Results: Survival analysis revealed a significant difference in AF recurrence rates between low and high PAC burden groups (log-rank test, p = 0.004). ROC-analysis identified an optimal PAC burden cut-off of 57 PAC’s over 24 hours (AUC 0.69). This association remained significant in multivariable Cox proportional hazards analysis, with a hazard ratio of 3.38 (p = 0.021). Conclusions: PAC burden measured on 24-hour Holter monitoring at three months proved to be an independent predictor of AF recurrence following PVI. Multivariable analysis confirmed a significant hazard ratio of 3.38 for AF recurrence within one year. An optimal predictive threshold of 57 PAC demonstrated high negative predictive value for AF recurrence.

BackgroundPulmonary vein isolation (PVI) alone is insufficient to treat many patients with persistent atrial fibrillation (PersAF). Adjunctive left atrial posterior wall (LAPW) ablation with thermal technologies has revealed lack of efficacy, perhaps limited by the difficulty in achieving lesion durability amid concerns of esophageal injury.ObjectivesThis study aims to compare the safety and effectiveness of PVI + LAPW ablation vs PVI in patients with PersAF using pulsed-field ablation (PFA).MethodsIn a retrospective analysis of the MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-approval Clinical Use of Pulsed Field Ablation) registry, we studied consecutive PersAF patients undergoing post-approval treatment with a pentaspline PFA catheter. The primary effectiveness outcome was freedom from any atrial arrhythmia of ≥30 seconds. Safety outcomes included the composite of acute and chronic major adverse events.ResultsOf the 547 patients with PersAF who underwent PFA, 131 (24%) received adjunctive LAPW ablation. Compared to PVI-alone, patients receiving adjunctive LAPW ablation were younger (65 vs 67 years of age, P = 0.08), had a lower CHA2DS2-VASc score (2.3 ± 1.6 vs 2.6 ± 1.6, P = 0.08), and were more likely to receive electroanatomical mapping (48.1% vs 39.0%, P = 0.07) and intracardiac echocardiography imaging (46.1% vs 17.1%, P < 0.001). The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmias was not statistically different between groups in the full (PVI + LAPW: 66.4%; 95% CI: 57.6%-74.4% vs PVI: 73.1%; 95% CI: 68.5%-77.2%; P = 0.68) and propensity-matched cohorts (PVI + LAPW: 71.7% vs PVI: 68.5%; P = 0.34). There was also no significant difference in major adverse events between the groups (2.2% vs 1.4%, respectively, P = 0.51).ConclusionsIn patients with PersAF undergoing PFA, as compared to PVI-alone, adjunctive LAPW ablation did not improve freedom from atrial arrhythmia at 12 months.

Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5’ untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for similar to 1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.