Biomedical subjects

Jacob Tfelt-Hansen

Publications and source records attributed to Jacob Tfelt-Hansen.

3 recordsLinked to original sources

PubMed2026

Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification.

BACKGROUND AND AIMS: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with β-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on β-blocker monotherapy. METHODS: The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter-defibrillator shock, sudden cardiac arrest (SCA), and sudden cardiac death. Near-fatal or fatal AEs (nf/fAEs) included all AEs except for arrhythmic syncope. Prediction models using Cox regression were developed and internally and externally validated. RESULTS: A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced ≥1 AE over a median follow-up of 5.1 [interquartile range (IQR), 7.7] and 2.4 (IQR, 4.4) years, respectively. Predictors of AE were arrhythmic syncope or SCA prior to diagnosis and age at β-blocker initiation. In the derivation and validation cohorts, the optimism-corrected C-indices of the models for AE were 0.67 [95% confidence interval (CI) 0.62-0.72] and 0.59 (95% CI 0.48-0.71), respectively. For nf/fAEs, ventricular arrhythmia severity before β-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68-0.80) and 0.60 (95% CI 0.47-0.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59-1.41) for AE and 1.00 (95% CI 0.69-1.32) for nf/fAE. CONCLUSIONS: These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on β-blocker monotherapy at low and high risk for future AEs while treated with β-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.

Humans↗

PubMed2026

Diagnosis and management of very rare primary arrhythmia syndromes in children and adults: a Clinical Consensus Statement of the European Heart Rhythm Association of the ESC and the Association of Cardiovascular Nursing & Allied Professions of the ESC, endorsed by the Association for European Paediatric and Congenital Cardiology.

Very rare and ultra-rare primary inherited arrhythmia syndromes (IAS) represent a heterogeneous group of disorders associated with a significant risk of sudden cardiac death, often manifesting from foetal life to early adulthood. Current guidelines primarily address more common IAS and provide limited, non-specific recommendations for these rare entities, particularly in paediatric populations. This European Heart Rhythm Association Clinical Consensus Statement, developed in collaboration with the Association of Cardiovascular Nursing and Allied Professions and endorsed by the Association for European Paediatric and Congenital Cardiology, integrates available evidence with expert opinion. Recommendations were formulated through structured discussion and voting, following ESC consensus methodology, with a focus on clinically actionable gene-disease associations. The document provides a comprehensive framework for the diagnosis and management of very rare IAS, including calmodulinopathies, Andersen-Tawil syndrome, Timothy syndrome, TRDN-related disease, calcium release deficiency syndrome, and other atypical channelopathies. It highlights age-specific clinical presentations, the importance of genetic testing, and tailored therapeutic strategies, including pharmacological treatments, left cardiac sympathetic denervation, and selective use of implantable cardioverter-defibrillators. Special attention is given to paediatric considerations, foetal diagnosis, and the role of multidisciplinary care. The document also addresses arrhythmic risk in metabolic and cardiomyopathic conditions, as well as the importance of molecular autopsy and family screening in sudden unexplained death. This consensus document fills a critical gap by providing expert-driven, pragmatic guidance for the management of very rare IAS across the lifespan. It underscores the need for specialized care, international collaboration, and prospective registries to improve evidence generation, risk stratification, and patient outcomes in this vulnerable population.

Humans↗

PubMed2026

Clinical Profile and Mode of Initiation of Spontaneous Ventricular Tachyarrhythmias in Patients With Brugada Syndrome (START-BrS).

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.

Adult↗