Evolution in electrophysiology 100 years after Einthoven: translational and computational innovations in rhythm control of atrial fibrillation

In 1924, the Dutch physiologist Willem Einthoven received the Nobel Prize in Physiology or Medicine for his discovery of the mechanism of the electrocardiogram (ECG). Anno 2024, the ECG is commonly used as a diagnostic tool in cardiology. In the paper 'Le Télécardiogramme', Einthoven described the first recording of the now most common cardiac arrhythmia: atrial fibrillation (AF). The treatment of AF includes rhythm control, aiming to alleviate symptoms and improve quality of life. Recent studies found that early rhythm control might additionally improve clinical outcomes. However, current therapeutic options have suboptimal efficacy and safety, highlighting a need for better rhythm-control strategies. In this review, we address the challenges related to antiarrhythmic drugs (AADs) and catheter ablation for rhythm control of AF, including significant recurrence rates and adverse side effects such as pro-arrhythmia. Furthermore, we discuss potential solutions to these challenges including novel tools, such as atrial-specific AADs and digital-twin-guided AF ablation. In particular, digital twins are a promising method to integrate a wide range of clinical data to address the heterogeneity in AF mechanisms. This may enable a more mechanism-based tailored approach that may overcome the limitations of previous precision medicine approaches based on individual biomarkers. However, several translational challenges need to be addressed before digital twins can be routinely applied in clinical practice, which we discuss at the end of this narrative review. Ultimately, the significant advances in the detection, understanding, and treatment of AF since its first ECG documentation are expected to help reduce the burden of this troublesome condition.