INTRODUCTION:Atrial fibrosis is an adverse factor for arrhythmia recurrences and thromboembolic events in atrial fibrillation (AF). Cardiac magnetic resonance imaging (CMRi) has emerged as a noninvasive tool for its assessment, though evidence remains conflicting. METHODS AND RESULTS:Sixty ablation-naïve patients with AF scheduled for first-time catheter ablation were enrolled (78% men, 67% paroxysmal AF, 73% heart failure reduced ejection fraction [HFrEF]). Prior to the procedure, CMRi was performed in sinus rhythm (SR) on a 1.5T system using a high-resolution (1.3 mm isotropic) free-breathing 3D LGE sequence with echo-navigator end-expiratory gating and whole-heart coverage. Left atrium (LA) fibrosis was quantified using the commercially available ADAS 3D software, with fibrosis defined at four image intensity ratios (IIR) thresholds (0.97, 1.2, 1.32, and 1.61 times mean blood-pool signal intensity). High-density electroanatomical mapping (EAM) was performed in SR, and low-voltage substrates (LVS) were quantified at three bipolar voltage thresholds (0.5, 0.25, and 0.1 mV). LVS-EAM were identified in 97%, 88%, and 45% of patients at 0.5, 0.25, and 0.1 mV, respectively. LGE-CMRi was detected in 100%, 97%, 63%, and 17% of patients at IIR thresholds of 0.97, 1.2, 1.32, and 1.61, respectively. Quantitative correlation between CMR- and EAM-derived fibrosis was negligible to weak across all threshold combinations. When fibrosis was analyzed dichotomously, agreement was highest between EAM 0.5 mV and CMR IIR 0.97 (0.97, 95% CI [0.92, 1.00]; p < 0.001) and IIR 1.2 (1, 95% CI [1.00, 1.00]; p < 0.001), and between EAM 0.25 mV and CMR IIR 0.97 (0.87 95% CI [0.76, 0.97]; p < 0.001) and IIR 1.2 (0.9, 95% CI [0.81, 0.99]; p < 0.001). CONCLUSIONS:In an ablation-naïve AF population with a predominance of HFrEF patients, CMR- and EAM-derived measures of atrial fibrosis showed poor quantitative correlation across multiple threshold combinations. Although agreement improved when fibrosis was analyzed dichotomously (presence vs. absence of fibrosis), the highest agreement was observed at the most sensitive threshold combinations. The findings of our study highlight the need for standardized, validated, and reproducible CMR protocols for native atrial fibrosis assessment in order to provide a noninvasive alternative to EAM.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia treated increasingly with catheter ablation, yet recurrence rates remain high. Genetic factors contribute to both AF susceptibility and response to therapy. This review summarises evidence on how common AF-associated variants, polygenic risk scores and rare monogenic variants influence ablation outcomes. Common single-nucleotide polymorphisms at loci such as 4q25 near PITX2 and 16q22 within ZFHX3 predispose to AF, but their individual effects on ablation success are modest. Polygenic risk scores aggregate small effects across many variants and have been linked to atrial conduction abnormalities and higher post-ablation recurrence, although they are not yet used routinely in clinical practice. In early-onset or familial AF, pathogenic variants in cardiomyopathy genes (e.g., TTN) may create an atrial cardiomyopathy yet do not necessarily preclude successful ablation, whereas LMNA mutations are associated with extensive fibrosis and poor outcomes. Genetic variation affects atrial electrical and structural remodeling, ectopic trigger distribution, fibrosis and autonomic tone, all of which influence ablation efficacy. Current guidelines do not recommend routine genetic testing for most patients; however, genotyping may inform risk stratification and follow-up in selected populations. Future work should integrate polygenic scores with clinical risk factors and explore genotype-guided procedural strategies and adjunctive therapies. We additionally address the relationship between genetic susceptibility and thromboembolic risk, the interplay between obesity, its genetic determinants, and AF perpetuation, and how ablation modality (radiofrequency, cryoballoon, and pulsed-field ablation) may interact with genetically determined substrate. A proposed clinical algorithm integrates genetic evaluation into the ablation pathway.

Abstract Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, typically driven by age, obesity, and other conventional cardiovascular risk factors. However, a subset of patients develop early-onset AF—often before 65 years of age in the absence of structural heart disease—suggesting alternative mechanisms beyond acquired risk. Emerging evidence implicates pathogenic variants in cardiomyopathy-associated genes as key drivers in this population. This review synthesizes contemporary evidence linking cardiomyopathy gene variants, particularly in TTN, LMNA, MYH7, and PKP2, to early-onset AF. Across multiple sequencing cohorts, pathogenic or likely pathogenic variants are identified in 5–20% of young AF patients, with prevalence rising sharply at younger ages. TTN truncating variants confer up to a two-fold increased risk of AF and a 10-fold higher risk of subsequent dilated cardiomyopathy, whereas LMNA mutations are associated with aggressive atrial fibrosis, conduction disease, and early recurrence after catheter ablation. Longitudinal studies demonstrate that genotype-positive AF patients face higher risks of heart failure, sudden cardiac death, and progression to overt cardiomyopathy. These findings redefine early-onset AF as a potential sentinel manifestation of inherited myocardial disease rather than an isolated electrical disorder. Genetic testing—especially in individuals with AF onset ≤45 years or a family history of cardiomyopathy—enables early detection, cascade screening, and personalized surveillance. Integrating genomics, advanced imaging, and electrophysiological management supports a precision medicine framework that may improve outcomes by identifying and intervening before structural disease develops.

Background/Objectives: About one-third of patients who receive cardiac resynchronization therapy (CRT) do not show meaningful clinical improvement. One possible reason is that current criteria for diagnosing left bundle branch block (LBBB) do not clearly separate true conduction block from other conditions that can produce a similar QRS pattern, since they rely mainly on surface ECG features. The Strauss criteria have been proposed as a stricter alternative. They include sex-specific QRS duration thresholds and require a mid-QRS notch or slur, with the goal of better identifying patients whose conduction abnormality may be correctable. Selecting candidates on this basis reflects a personalized-medicine approach that matches resynchronization to the individual conduction substrate rather than applying a single wide-QRS threshold to all patients. In this review, we assess whether LBBB defined by the Strauss criteria is linked to better CRT outcomes, and we examine how these criteria have been used in the design of randomized clinical trials investigating conduction system pacing (CSP). Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted (last updated April 2026) in accordance with PRISMA 2020 guidelines. Evidence was drawn from two groups of studies: (1) observational studies comparing CRT outcomes in Strauss-positive versus Strauss-negative patients, and (2) randomized CSP trials conducted in populations enriched using either Strauss-type or typical LBBB morphology. Results: A total of 17 comparative studies (n ≈ 4200) were included in Part 1; most (14 of 17) reported outcomes favouring Strauss-defined LBBB, with the greatest signal in non-ischemic cardiomyopathy, although these were mostly small retrospective studies with heterogeneous outcome definitions. However, two large registry analyses found no incremental benefit of strict over conventional criteria. In Part 2, six randomized controlled trials were analyzed. The HeartSync-LBBP trial (n = 200, 36-month follow-up) demonstrated significantly lower rates of mortality or heart failure hospitalization with LBBP compared to BiVP (8% vs. 28%; HR 0.26; 95% CI 0.12-0.57), with 98% technical success for LBBP. In contrast, the PhysioSync-HF trial (n = 173) showed superiority of BiVP, with CSP success of only 69% and 42.8% of procedures performed by less experienced operators. Similarly, the LEFT-BUNDLE-CRT trial (n = 176) found that LBBAP did not meet non-inferiority criteria compared to BiVP (RR 0.95; 95% CI 0.88-1.02). Conclusions: Strauss-defined LBBB is associated with improved CRT outcomes in observational studies, particularly in non-ischemic cardiomyopathy; this reflects an association rather than established superiority or causal benefit, and no randomized trial has yet compared Strauss-guided against guideline-based patient selection. In randomized CSP trials, both operator experience and patient selection appear to be critical determinants of success. BiVP remains effective even in patients meeting strict Strauss criteria. Further research is needed to determine whether the application of Strauss criteria improves outcomes beyond current guideline-based patient selection.

BACKGROUND:Sudden cardiac death (SCD) remains a leading cause of mortality in patients with hypertrophic cardiomyopathy (HCM). Accurate identification of individuals at high risk is essential for guiding implantable cardioverter-defibrillator (ICD) therapy. Global longitudinal strain (GLS), an echocardiographic parameter derived from speckle-tracking imaging, reflects subclinical left ventricular systolic dysfunction and may serve as an adjunctive risk marker for fatal ventricular arrhythmias (VAs). METHODS:A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed and the Cochrane Library were searched from inception to April 2025 for studies assessing the association between GLS and SCD and/or fatal VAs in HCM. RESULTS:Out of 1050 identified records, seven studies comprising 2167 patients (mean age 54.7 years) met inclusion criteria. All included studies were of moderate-to-high quality (Newcastle-Ottawa Scale ≥6). In the pooled quantitative synthesis of three studies, patients with reduced GLS (<15%) had a significantly higher risk of fatal VAs [hazard ratio/odds ratio (HR/OR): 1.10, 95% (confidence interval) CI 1.04-1.17]. On the other hand, 1% worsening of GLS was not associated with SCD and/or fatal VAs (HR/OR: 1.09, 95% CI 0.89-1.33). A combined meta-analysis using data from seven studies showed a significant association between GLS and SCD and/or fatal VAs in patients with HCM (HR/OR: 1.10, 95% CI 1.03-1.18). CONCLUSIONS:GLS is associated with risk of fatal arrhythmic events in HCM and may help identify higher-risk patients, but evidence from observational studies does not prove causality and may be confounded. GLS could aid shared decision-making about ICDs in borderline cases when combined with established risk factors, but should not be used alone. Prospective multicenter studies with standardized imaging are needed to validate thresholds, confirm added prognostic value, and show impact on outcomes.

Introduction: The presence of a chronic total occlusion (CTO) has been associated with increased risk of sudden cardiac death (SCD) and/or ventricular arrhythmias (VAs). This study aimed to evaluate the impact of CTO revascularization on SCD and/or VAs. Methods: A systematic review of the literature was performed to identify studies evaluating the association between CTO revascularization and risk of SCD and/or VAs. Results: Six studies were included in the final meta-analysis. The total sample size included 2,017 participants for the assessment of the primary outcome of interest and 868 participants for the assessment of the secondary outcome of interest. In 5 studies examining the association between CTO revascularization and risk of SCD and/or VAs, CTO revascularization was not associated with a statistically significant reduction in the risk of SCD and/or VAs (HR: 0.78; 95% CI: 0.38 to 1.60; p = 0.50, I2 = 87%). Conversely, in 2 studies examining the association between IRA-CTO revascularization and risk of SCD and/or VAs, IRA-CTO revascularization was associated with 79% lower risk of SCD and/or VAs (HR: 0.21; 95% CI: 0.10 to 0.43; p < 0.0001, I2 = 0%). Discussion: CTO revascularization overall was not associated with a lower risk of SCD and/or VAs. In contrast, IRA-CTO revascularization was associated with a lower risk of SCD and/or VAs. However, the study has several limitations, primarily due to the observational nature of the included studies. Conclusion: Successful revascularization of an IRA-CTO should be attempted to reduce the burden of VAs and reduce the risk of SCD.

Background Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (ACM) may overlap clinically, but shared mechanisms remain unclear. RYR1 mutations have not been previously linked to these arrhythmia syndromes. Case Summary A 32-year-old man with a family history of BrS presented with palpitations and positional ventricular tachycardia. Ajmaline testing unmasked a diagnostic type 1 BrS electrocardiographic pattern. Cardiac magnetic resonance showed subtle right ventricular dyskinesia and focal left ventricular fibrosis, meeting borderline ACM criteria. Electrophysiological study showed noninducible ventricular arrhythmias, but premature ventricular contractions were reproducibly provoked in the left-lateral position. After shared decision-making, an implantable cardioverter-defibrillator was implanted for primary prevention. Genetic testing revealed a pathogenic truncating RYR1 variant (p.Arg2920∗). Discussion This case illustrates a novel association of RYR1 mutation with overlapping BrS-ACM features. Shared connexome and calcium-handling abnormalities may underlie this phenotype. Take-Home Messages RYR1 mutations may contribute to overlapping BrS-ACM phenotypes. Careful imaging, provocative testing, and genetic assessment can guide management.

Background Data on the spontaneous onset of ventricular tachyarrhythmias (VTAs) in Brugada syndrome (BrS), including polymorphic ventricular tachycardia (PVT) and monomorphic ventricular tachycardia (MVT), remain limited. Objectives The goal of this study was to compare the clinical profile and mode of initiation of PVT and MVT in BrS. Methods This retrospective multicenter registry included 154 patients with BrS from 29 centers with documented VTA initiation captured by implantable cardioverter-defibrillator (94.9%) or electrocardiogram (5.1%). A total of 234 VTAs were analyzed, and initiation patterns were classified by using predefined electrocardiographic criteria. Results PVT was observed in 80.5% of patients, MVT in 16.9%, and both in 2.6%. Patients with MVT tended to be older, exhibit drug-induced Brugada electrocardiogram, and were more frequently White. Pause-dependent initiation occurred in approximately 25% of PVT and approximately 33% of MVT episodes. Coupling intervals initiating PVT were nonsignificantly shorter than for MVT (median 368 milliseconds vs 395 milliseconds), with a significantly lower prematurity index and faster early arrhythmia cycle length. Antecedent premature ventricular complexes were present in approximately 43% of both VTA types, commonly sharing morphology with the initiating premature ventricular complex. The prevalence of pathogenic/likely pathogenic SCN5A mutation did not differ between groups. Conclusions In this largest analysis to date of spontaneous VTA onset in BrS, MVT occurred in a substantial minority and was associated with older age, White ethnicity, drug-induced electrocardiogram pattern, and a preceding tachycardia. Initiation patterns were broadly similar across arrhythmia types, although PVT exhibited a significantly lower prematurity index and faster early cycle length despite only nonsignificant shorter coupling intervals. These findings refine the clinical and electrophysiological characterization of BrS-related arrhythmias and delineate distinct features of PVT and MVT initiation.

Background:We conducted a multicenter study to compare procedural and 1-year outcomes of pulmonary vein isolation (PVI) using lattice-tip (LT) vs pentaspline (PS) pulsed field ablation catheters in patients with paroxysmal atrial fibrillation. Objective:This study aimed to compare procedural metrics and arrhythmia-free survival during the 1-year follow-up. Methods:Procedures were performed between August 2023 and December 2024. A propensity score matching technique was adopted (LT-to-PS ratio 1:2). Results:Among 447 patients with paroxysmal atrial fibrillation undergoing first-time PVI with either an LT (n = 74) or a PS catheter (n = 391), propensity score matching yielded 50 (LT group) and 100 patients (PS group), respectively. No differences were reported for first-pass isolation per patient (96% [LT group] vs 97% [PS group]; P = .75) and per pulmonary vein (98.9% [LT group] vs 99.2% [PS group]; P = .75). The LT group showed longer procedural (56 vs 50; P < .0001) and dwelling times (40 vs 30; P < .0001) but reduced fluoroscopy times (5 vs 10; P < .0001). No differences were reported for overall (2% vs 2%; P = 1.0) and major complications (0% vs 0%; P = 1.0). At 1-year follow-up, similar freedom from atrial tachyarrhythmia (86.2% [LT group] vs 83% [PS group]; P = .59) and atrial fibrillation (90.7% [LT group] vs 85.8% [PS group]; P = .41) was observed. Conclusion:First-time PVI using an LT or a PS pulsed field ablation catheter showed high efficacy and 1-year freedom from atrial tachyarrhythmias, without differences between groups. The LT catheter yielded longer procedural and dwelling times, but a significant reduction in fluoroscopy time.

OBJECTIVE:Fluoroscopy-guided transseptal puncture (TSP) remains essential for left atrial access; however, it carries rare but serious risks, including cardiac tamponade. We report outcomes from one of the largest single-center registries assessing a modified needle-free technique for TSP. METHODS:A total of 4100 procedures requiring TSP were analyzed. RESULTS:Subjects with patent foramen ovale (PFO) (n = 322, 7.8%) were excluded from the analysis. The modified needle-free rotational probing of the fossa ovalis with the assembly technique was applied in 1335 patients under fluoroscopic guidance. Successful left atrial catheterization was achieved in 960 patients (72%), while conventional needle puncture was required in the remaining 375 (28%) patients. There were no major complications, including pericardial effusion, related to the non-puncture technique. The traditional needle approach was attempted in total in 2818 patients. Successful left atrial catheterization was achieved in 2813 patients (99.8%). Pericardial effusion without cardiac tamponade developed in four out of 2818 patients (0.14%) who underwent the traditional approach. In 12 out of 4100 patients (0.29%), a false impression of PFO led to interatrial septum dissection. No pericardial effusion was noted in these cases. Transient ST-segment elevation during TSP was observed in four cases (0.1%). CONCLUSION:This large-scale registry derived from a high-volume center suggests that the modified needle-free technique may represent a safe alternative to conventional TSP and could serve as a useful adjunct or an intermediate step in the TSP learning curve.

The widespread performance of catheter ablation for atrial fibrillation (AF) has significantly increased the incidence of complex atrial tachycardias (ATs) originating from a diseased or previously ablated myocardial substrate. Under these circumstances, extensive areas of fibrosis or lines of block may complicate the interpretation of activation maps and subsequently the successful diagnosis of the underlying mechanism of the AT. A novel ablation catheter, combining high density mapping and dual ablation properties has been recently released for the treatment of AF. The system has been proven highly effective for both the establishment of the diagnosis and the ablation of a variety of ATs in one of our previous studies. In the current study we aimed to assess the performance of the novel system in the establishment of the diagnosis and the ablation efficacy in a challenging cohort of patients presented with complex ATs and history of previous catheter ablation. Patients with documented ATs and history of previous catheter ablation or surgery were included in the study. Cases of cavotricuspid isthmus dependent atrial flutters were excluded. Activation mapping was used for the establishment of AT mechanism. Confirmation with entrainment was performed, whenever appropriate. Accuracy of the activation mapping in diagnosis, acute ablation efficacy (termination of AT during ablation followed by non-inducibility) and procedural characteristics were the study endpoints. Bidirectional block of linear lesions was validated with pacing maneuvers and activation remap. 11 patients were included (6 mitral flutters, 2 roof flutters, 2 focal/microreentry ATs and one macroreentrant AT involving the anterior wall of the left atrium). Proper diagnosis of the tachycardia mechanism was established by the activation map in all cases. In two cases with extensive atrial fibrosis, activation mapping revealed the area of a critical isthmus that led to immediate termination of the AT with one single lesion. Mean mapping time was 8.5±3.1 minutes with acquisition of 380.1±129 mean mapping points/minute. Mean ablation time was 40.2±22.7 seconds. Conversion to sinus rhythm during ablation was achieved in all cases with the exception of a mitral flutter that converted to cavotricuspid isthmus dependent atrial flutter. No major or minor complications occurred. In a cohort of patients with complex ATs and history of previous catheter ablation, the novel lattice tip catheter that combines high density mapping and dual ablation properties successfully suggested the underlying mechanism of the tachycardia by the pattern of activation in activation maps in all cases. The delivered lesions were highly effective with acute termination of ATs and achievement of bidirectional block in linear lesions.

The development of advanced atrioventricular block (AVB) in patients on bradycardic and/or antiarrhythmic therapy (drug-related AVB) represents a clinical challenge, raising the question of whether the AVB is directly caused by these agents (drug-induced AVB) or if the offending drugs exacerbate an underlying conduction system disease. Traditionally, β-blockers, non-dihydropyridine calcium channel blockers, class Ic/III antiarrhythmics, and digoxin have been considered reversible causes of advanced AVB. However, recent evidence shows a weak cause-and-effect relationship between these drugs and AVB in the elderly, along with high recurrence rates of AVB despite initial resolution after drug discontinuation. This may also apply to patients on high doses of these medications, drug combinations, or with additional reversible factors such as hyperkalemia. Despite these considerations, the European Guidelines do not suggest permanent pacing for AVB due to transient causes that are correctable, including bradycardic/antiarrhythmic drug therapy. On the other hand, the American Guidelines recommend permanent pacing for selected patients with symptomatic second- or third-degree AVB who are on stable, necessary antiarrhythmic or β-blocker treatment, without waiting for drug washout or reversibility. Notably, an accumulating body of evidence indicates that true drug-induced AVB is rare, while recurrence rates are high. Therefore, early permanent pacing should be recommended, especially for frail elderly patients. Moreover, in patients with drug-related AVB and atrial tachyarrhythmias, adopting an early permanent pacing approach seems prudent when bradycardic and/or antiarrhythmic treatment is necessary. Finally, delays in permanent pacing are not justified when temporary pacing is needed, given the increased associated risks in such cases.

The detection of frequent premature ventricular contractions (PVCs) in an athlete represents one of the most important red flags during pre-participation screening. We report the case of a 6-year-old asymptomatic male athlete practicing basketball and sailing, who was examined for pre-participation screening. His resting electrocardiogram showed very frequent, isolated, monomorphic PVCs. The PVCs exhibited a left bundle branch block morphology with an inferior axis and R/S wave precordial transition in lead V3. The most likely origin of PVCs was considered the left ventricular outflow tract. Resting transthoracic echocardiography revealed reduced left ventricular systolic function, with an ejection fraction of 43%, indicating the possible existence of PVC-induced cardiomyopathy. We detected 43,149 isolated monomorphic PVCs (PVC burden: 40%) on 24-h ambulatory electrocardiographic monitoring. Initiation of treatment with atenolol 12.5 mg twice a day led to inadequate reduction of PVCs, with 29,452 isolated monomorphic PVCs (PVC burden: 29%) still observed on 24-h ambulatory electrocardiographic monitoring. After adding flecainide 25 mg twice daily to atenolol treatment, 24-h ambulatory electrocardiographic monitoring revealed complete resolution of ventricular arrhythmias, with no PVCs detected. Left ventricular systolic function recovered to normal. At 12 years of age, the athlete remained on combination therapy with atenolol and flecainide, continued participating in sports, and remained completely asymptomatic with normal cardiac examinations. The optimization of drug treatment was favored over catheter ablation since the athlete was a child and the probable origin of PVCs was the left ventricular outflow tract. This case report highlights that flecainide at a relatively low dose as an add-on therapy to a beta-blocker was highly effective and safe for treating high-burden PVCs originating from the ventricular outflow tract in a juvenile athlete.

Brugada phenocopy (BrP) is the electrocardiographic appearance of a Brugada pattern due to various reversible causes that is completely resolved after the correction of the underlying abnormalities. In this short communication, we describe a 56-year-old man who had a transient BrP induced by hyponatremia due to thiazide diuretic therapy. A detailed review of the literature revealed that hyponatremia represents an uncommon cause of BrP while, in many of the published cases, concomitant electrolyte disturbances such as hyperkalemia were present. However, even isolated hyponatremia may provoke a BrP. Clinicians should be aware of this rare cause of BrP, which is reversible and has a favorable outcome.