Aims: Pre-procedural imaging can facilitate scar-related ventricular tachycardia (VT) ablation, although only limited data have been reported. This prospective registry aimed to analyse procedural data and outcomes in a multi-centre setting of a pre-defined VT ablation strategy facilitated by the integration of pre-procedural imaging into the navigation system. Methods and results: Consecutive patients referred for scar-related left-sided VT ablation were prospectively enrolled at five European tertiary hospitals. Pre-procedural cardiac magnetic resonance (CMR)–derived scar maps and/or multi-detector computed tomography (MDCT)–derived wall thinning maps of the left ventricle (LV) were obtained and integrated into the navigation system. An endocardial or endoepicardial approach was chosen based on the scar distribution at pre-procedural imaging. The decision of performing a detailed electro-anatomical map (EAM) of the LV (image-aided) or to using the pre-procedural imaging for guiding the ablation without obtaining an EAM (image-guided) was left to the physician’s discretion. One hundred and seventy-one patients (71% with ischaemic cardiomyopathy) were included. Cardiac magnetic resonance was integrated in 159 (93%), MDCT in 113 (66%), and both in 101 (59%) procedures. Procedure-related complications occurred in 9 (5%) patients. At a mean follow-up of 18 ± 19 months, the overall survival and VT recurrence-free survival were 91 and 74.4%, respectively. There were no significant differences in long-term ablation outcomes based on the type of cardiomyopathy (P = 0.88) or the pre-procedural imaging modality employed (P = 0.33). An image-guided approach appears feasible, safe, and faster, with reduced procedure, radiofrequency, and fluoroscopy times, without compromising efficacy. Conclusion: In a large multi-centre prospective cohort, VT ablation facilitated by pre-procedural imaging is associated with favourable long-term outcomes.

BACKGROUND: Desmosomal gene variants (DGVs) have been associated with a diverse spectrum of phenotypic manifestations within arrhythmogenic cardiomyopathy, but data on genotype-specific outcomes are lacking. We investigated genotype-specific arrhythmic and heart failure (HF) outcomes in DGV carriers. METHODS: This cohort study included consecutive patients referred for screening for desmosomal genes. Carriers of pathogenic and rare (allele frequency <10 ^{− 4} ) variants of uncertain significance were included. The arrhythmic end point was the occurrence of a life-threatening arrhythmic event, defined as sudden cardiac death, aborted cardiac arrest, or hemodynamically unstable ventricular tachycardia. The end-stage HF outcome was the composite of a fatal HF episode or cardiac transplantation. RESULTS: We included 533 DGV carriers (59% male; median [interquartile range] age, 39 [22–54] years) from 214 families: 503 of 533 had a single DGV (212 [40%] PKP2 , 160 [30%] DSP , 97 [18%] DSG2 , 34 [6%] DSC2 ) and 30 of 533 (6%) double DGVs. Overall, 83 of 533 (16%) experienced a life-threatening arrhythmic event (at age 40 [33–51] years), and 14 of 533 (3%) experienced end-stage HF (at age 57 [50–60] years). Multivariable analysis demonstrated that, compared with nonmissense PKP2 variants, nonmissense DSP variants (hazard ratio [HR], 2.3 [95% CI, 1.3–4.1]; P =0.008), missense variants in hotspot domains in DSP (HR, 2.7 [95% CI, 1.2–6.2]; P =0.010) and PKP2 (HR, 3.6 [95% CI, 2.0–6.5]; P <0.001), male sex (HR, 1.7 [95% CI, 1.1–2.8]; P =0.021), and double DGVs (HR, 3.4 [95% CI, 1.7–6.9]; P <0.001) were associated with a higher risk of a life-threatening arrhythmic event. Nonmissense DSP variants (HR, 5.0 [95% CI, 1.5–18.2]; P =0.009) and double DGVs (HR, 4.7 [95% CI, 1.0–19.3]; P =0.044) were also associated with increased risk of end-stage HF. CONCLUSIONS: Among carriers of DGVs, genotype was associated with arrhythmic and HF outcomes, with type and location of the variant further modulating the natural history.

Among cardiomyopathies, the hypertrophic phenotype is the most common, and hypertrophic cardiomyopathy (HCM) phenocopies represent a heterogeneous group of conditions. They are defined by a left ventricular wall thickness ≥15 mm in the absence of other causes such as loading conditions, ischemia, or valvular disease. Although they mimic similar clinical and morphological features, their etiologies are distinct and include genetic, metabolic, and infiltrative mechanisms. Therefore, accurate classification and differential diagnosis are crucial for effective management and treatment. Sarcomeric HCM is the most frequent form, accounting for up to 60% of cases. However, numerous non-sarcomeric phenocopies exist, including amyloidosis, Fabry disease, glycogen storage disorders, RASopathies, and mitochondrial diseases. Clinical and imaging findings are essential to distinguish these entities from sarcomeric HCM. Electrocardiography, echocardiography, advanced modalities such as cardiac magnetic resonance (CMR), and specific laboratory tests all play a central role in guiding diagnosis. Genetic testing provides key insights into mutations and inheritance patterns, further supporting definitive diagnosis. Correct identification of an HCM phenocopy carries important therapeutic implications, as disease-specific treatments can significantly improve prognosis. For example, targeted therapies exist for amyloidosis, Fabry disease, and certain metabolic or mitochondrial disorders, underlining the clinical relevance of an accurate diagnosis. This review aims to provide an overview of HCM phenocopies and assist clinicians in diagnostic reasoning. The first part addresses classification according to pathophysiological mechanisms, clinical features, and genetic background. The second part focuses on the stepwise approach to differential diagnosis, integrating clinical assessment, laboratory evaluation, ECG, echocardiography, and CMR findings.

Aims: A personalized pulmonary vein isolation (PVI) approach aimed at ablation index (AI) titration according to multidetector computed tomography-derived left atrial wall thickness (LAWT) maps reported high effectiveness and efficiency outcomes for persistent atrial fibrillation (PeAF) ablation. To date, no randomized trials have compared this approach with the standard CLOSE protocol. This non-inferiority randomized controlled trial sought to compare a LAWT-guided PVI with CLOSE protocol-based for PeAF (NCT05396534). Methods and results: Consecutive patients referred for first-time PeAF ablation were randomized on a 1:1 basis. In the by-LAWT arm, the AI was titrated according to local LAWT, and the ablation line was personalized to avoid the thickest regions at the pulmonary vein antrum. In the CLOSE arm, LAWT information was not available to the operator; the ablation was performed according to the CLOSE study settings: AI is ≥400 at the posterior wall and ≥550 at the anterior wall. Primary endpoint was freedom from atrial arrhythmias recurrence. Secondary endpoints were the major complication rate, procedure time, radiofrequency time, and first-pass PVI rate. One hundred fifty-six patients were included. At 12 month follow-up, no significant difference occurred in atrial arrhythmia-free survival between groups (P = 0.50). In the by-LAWT group, a significant reduction in procedure time (60.5 vs. 80.0 min; P < 0.01) and RF time (14.4 vs. 28.6 min; P < 0.01) was observed. No difference was observed regarding first-pass PVI (P = 0.72) and the major complication rate (P = 0.99). Conclusions: The PeAF-by-LAWT trial is the first prospective randomized study to demonstrate that a personalized LAWT-guided PVI for PeAF ablation is non-inferior to the standard CLOSE protocol in terms of arrhythmia-free survival while significantly improving procedural efficiency. The study was not powered to detect differences in safety outcomes.

Background: Low-voltage area (LVA) ablation, in addition to pulmonary vein isolation (PVI), has been proposed as a new strategy in patients with atrial fibrillation (AF), but clinical trials have shown conflicting results. We performed a systematic review and meta-analysis to assess the impact of LVA ablation in patient undergoing AF ablation (PROSPERO-registered CRD42024537696). Methods: Randomized clinical trials investigating the role of LVA ablation in addition to PVI in patients with AF were searched on PubMed, Embase, and the Cochrane Library from inception to 22 April 2024. Primary outcome was atrial arrhythmia recurrence after the first AF ablation procedure. Secondary endpoints included procedure time, fluoroscopy time, and procedure-related complication rate. Sensitivity analysis including only patients with LVA demonstration at mapping and multiple subgroups analyses were also performed. Results: 1547 patients from 7 studies were included. LVA ablation in addition to PVI reduced atrial arrhythmia recurrence (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52–0.81, p < 0.001) with a number needed to treat to prevent recurrence of 10. No difference in procedure time (mean difference [MD] −5.32 min, 95% CI −19.01–8.46 min, p = 0.45), fluoroscopy time (MD −1.10 min, 95% CI −2.48–0.28 min, p = 0.12) and complication rate (OR 0.81, 95% CI 0.40–1.61, p = 0.54) was observed. Consistent results were demonstrated when considering only patients with LVA during mapping and in prespecified subgroups for AF type (paroxysmal vs. persistent), multicentric vs. monocentric trial, and ablation strategy in control group. Conclusions: In patients with AF, ablation of LVAs in addition to PVI reduces atrial arrhythmia recurrence without a significant increase in procedure time, fluoroscopy time, or complication rate.