The term idiopathic ventricular fibrillation (IVF) describes survivors of unexplained cardiac arrest (UCA) without a specific diagnosis after clinical and genetic testing. Previous reports have described a subset of IVF individuals with ventricular arrhythmia initiated by short-coupled trigger premature ventricular contractions (PVCs) for which the term short-coupled ventricular fibrillation (SCVF) has been proposed. The aim of this article is to establish the phenotype and frequency of SCVF in a large cohort of UCA survivors. We performed a multicentre study including consecutive UCA survivors from the CASPER registry. Short-coupled ventricular fibrillation was defined as otherwise unexplained ventricular fibrillation initiated by a trigger PVC with a coupling interval of <350 ms. Among 364 UCA survivors, 24/364 (6.6%) met diagnostic criteria for SCVF. The diagnosis of SCVF was obtained in 19/24 (79%) individuals by documented ventricular fibrillation during follow-up. Ventricular arrhythmia was initiated by a mean PVC coupling interval of 274 ± 32 ms. Electrical storm occurred in 21% of SCVF probands but not in any UCA proband (P < 0.001). The median time to recurrent ventricular arrhythmia in SCVF was 31 months. Recurrent ventricular fibrillation resulted in quinidine administration in 12/24 SCVF (50%) with excellent arrhythmia control. Short-coupled ventricular fibrillation is a distinct primary arrhythmia syndrome accounting for at least 6.6% of UCA. As documentation of ventricular fibrillation onset is necessary for the diagnosis, most cases are diagnosed at the time of recurrent arrhythmia, thus the true prevalence of SCVF remains still unknown. Quinidine is effective in SCVF and should be considered as first-line treatment for patients with recurrent episodes. Short-coupled ventricular fibrillation (SCVF) is a distinct primary electrical disorder accounting for at least 6.6% of otherwise idiopathic VF. Quinidine is highly effective for SCVF.

Aims: There is limited information on the role of screening with electrocardiography (ECG) for identifying cardiovascular diseases associated with sudden cardiac death (SCD) in a non-select group of adolescents and young adults in the general population. Methods and results: Between 2012 and 2014, 26 900 young individuals (aged 14–35 years) were prospectively evaluated with a health questionnaire and ECG. Individuals with abnormal results underwent secondary investigations, the costs of which were being based on the UK National Health Service tariffs. Six hundred and seventy-five (2.5%) individuals required further investigation for an abnormal health questionnaire, 2175 (8.1%) for an abnormal ECG, and 114 (0.5%) for both. Diseases associated with young SCD were identified in 88 (0.3%) individuals of which 15 (17%) were detected with the health questionnaire, 72 (81%) with ECG and 2 (2%) with both. Forty-nine (56%) of these individuals received medical intervention beyond lifestyle modification advice in the follow-up period of 24 months. The overall cost of the evaluation process was €97 per person screened, €17 834 per cardiovascular disease detected, and €29 588 per cardiovascular disease associated with SCD detected. Inclusion of ECG was associated with a 36% cost reduction per diagnosis of diseases associated with SCD compared with the health questionnaire alone. Conclusion: The inclusion of an ECG to a health questionnaire is associated with a five-fold increase in the ability to detect disease associated with SCD in young individuals and is more cost effective for detecting serious disease compared with screening with a health questionnaire alone.

Background: Familial cascade screening is well established in patients with heritable cardiac disease and in cases of sudden arrhythmic death syndrome. The clinical benefit of family screening in idiopathic ventricular fibrillation (IVF) is unknown. Methods: Patients with IVF were identified from national and institutional registries. All underwent systematic and comprehensive clinical evaluation to exclude identifiable causes of cardiac arrest with a minimum requirement of ECG, cardiac (echocardiogram or magnetic resonance imaging) and coronary imaging, exercise ECG, and sodium channel blocker provocation. Additional investigations including genetic testing were performed at the physician’s discretion. First-degree relatives who were assessed with at least a 12-lead ECG were included in the final cohort. Results of additional investigations, performed at the physician’s discretion, were also recorded. Results were coded as normal, abnormal, or minor findings. Results: We identified 201 first-degree relatives of 96 IVF patients. In addition to a 12-lead ECG, echocardiography was performed in 159 (79%) and ≥1 additional investigation in 162 (80%) relatives. An inherited arrhythmia syndrome was diagnosed in 5 (3%) individuals from 4 (4%) families. Two relatives hosted the DPP6 risk haplotype identified in a single proband, one of whom received a primary prevention implantable cardioverter defibrillator. In 3 separate families, an asymptomatic parent of the IVF proband developed a type 1 Brugada ECG pattern during sodium channel blocker provocation. All were managed with lifestyle measures only. The early repolarization (ER) ECG pattern was present in 16% probands and was more common in relatives in those families than those where the proband did not have early repolarization (25% versus 8%, P =0.04). Conclusions: The yield of family screening in relatives of IVF probands is low when the proband is comprehensively investigated. The significance of J wave syndromes in relatives and the role for systematic sodium channel blocker provocation are, however, uncertain and require further research.

Aims: Pathogenic gain-of-function variants in CACAN1C cause type-8 long QT syndrome (LQT8). We sought to describe the electrocardiographic features in LQT8 and utilize molecular modelling to gain mechanistic insights into its genetic culprits. Methods and results: Rare variants in CACNA1C were identified from genetic testing laboratories. Treating physicians provided clinical information. Variant pathogenicity was independently assessed according to recent guidelines. Pathogenic (P) and likely pathogenic (LP) variants were mapped onto a 3D modelled structure of the Cav1.2 protein. Nine P/LP variants, identified in 23 patients from 19 families with non-syndromic LQTS were identified. Six variants, found in 79% of families, clustered to a 4-residue section in the cytosolic II–III loop region which forms a region capable of binding STAC SH3 domains. Therefore, variants may affect binding of SH3-domain containing proteins. Arrhythmic events occurred in similar proportions of patients with II–III loop variants and with other P/LP variants (53% vs. 48%, P = 0.41) despite shorter QTc intervals (477 ± 31 ms vs. 515 ± 37 ms, P = 0.03). A history of sudden death was reported only in families with II–III loop variants (60% vs. 0%, P = 0.03). The predominant T-wave morphology was a late peaking T wave with a steep descending limb. Exercise testing demonstrated QTc prolongation on standing and at 4 min recovery after exercise. Conclusion: The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II–III loop. This represents a ‘mutation hotspot’ in LQT8. A late-peaking T wave with a steep descending limb and QT prolongation on exercise are commonly seen.

Aims Membrane-bound angiotensin-converting enzyme (ACE)2 is the main cellular access point for SARS-CoV-2, but its expression and the effect of ACE inhibition have not been assessed quantitatively in patients with heart failure. The aim of this study was to characterize membrane-bound ACE2 expression in the myocardium and myocardial vasculature in patients undergoing heart transplantation and to assess the effect of pharmacological ACE inhibition. Methods and results Left ventricular (LV) tissue was obtained from 36 explanted human hearts from patients undergoing heart transplantation. Immunohistochemical staining with antibodies directed against ACE2 co-registered with cardiac troponin T (cTnT) and α-smooth muscle cell actin (SMA) was performed across the entire cohort. ACE2 receptor expression was quantitatively assessed throughout the myocardium and vasculature. ACE2 was consistently expressed throughout the LV myocardium (28.3% ± 22.2% of cardiomyocytes). ACE2 expression was also detected in small calibre blood vessels (range, 2–9 μm), albeit at quantitatively much lower levels (5% ± 9% of blood vessels). There was no significant difference in ACE2 expression between patients receiving ACE inhibitors prior to transplantation and ACE inhibitor-negative controls (P > 0.05). ACE2 expression did not differ significantly between the different diagnostic groups as the underlying reason for heart transplantation (ANOVA > 0.05). N-terminal pro-brain natriuretic peptide (NT-proBNP) (R² = 0.37, P = 0.0006) and pulmonary capillary wedge pressure (PCWP) (R² = 0.13, P = 0.043) assessed by right heart catheterization were significantly correlated with greater ACE2 expression in cardiomyocytes. Conclusions These data provide a comprehensive characterization of membrane-bound cardiac ACE2 expression in patients with heart failure with no demonstrable effect exerted by ACE inhibitors.

Introduction: Pulsed-field ablation (PFA) is a novel modality for pulmonary vein isolation in patients with atrial fibrillation (AF). We describe the initial uptake and experience of PFA using a pentaspline catheter across selected National Health Service England (NHSE) centres. Methods: Data collected by NHSE Specialised Services Development Programme regarding AF ablation procedures using a single-shot, pentaspline, multielectrode PFA catheter (FARAWAVE, Boston Scientific) between June 2022 and August 2024 were aggregated and analysed to examine procedural metrics, acute efficacy and safety outcomes over 3-month follow-up. Results: 1034 procedures were submitted. The patients were 32.1% female, mean age 63.8±10.7 years, 53.1% paroxysmal AF and 89.7% first-time AF ablation. Procedures were performed by 48 consultant operators at nine NHSE centres, with a mean of 115 procedures per centre (range 25–264). 93.7% of procedures were performed under general anaesthesia. Median skin-to-skin procedure time was 74 min (IQR 55–96 min) and fluoroscopy time 20 min (IQR 15–27 min). Electroanatomical mapping was used in 15.3%. In first-time ablation cases, acute isolation of all pulmonary veins was achieved in 99.5% of patients. Left atrial (LA) posterior wall ablation using the PFA catheter was performed in 11.0% of cases; additional LA radiofrequency ablation was performed in 0.6%. The major and minor acute procedural complication rates were, respectively, 1.3% and 3.1%, with no reports of periprocedural death or atrio-oesophageal fistula. 63.8% of patients were discharged on the day of procedure. Follow-up data were available for 870 procedures (84.1%). In the 3 months following ablation, hospitalisation for arrhythmia occurred in 3.2%, with 0.9% rehospitalised for procedural-related complications. Conclusion: In this real-world, nationwide registry of a pentaspline PFA catheter, efficacy, safety and efficiency outcomes were comparable to those from previous PFA studies in patients with AF.