“From translation to integration: What is the next step in addressing the complexity of atrial fibrillation mechanisms?”
Hosted by the Cardiac Bioelectricity and Arrhythmia Center (CBAC)
Abstract: Over many years, basic, translational and clinical research has generated a wealth of insights into the basic pathomechanisms of AF. However, more recently, most of the significant progress was based on empirical clinical research and the current pipelines for new pharmacological compounds for AF are drying out. In addition, the progress in catheter ablation for AF was modest and largely driven by improvement of ablation technology rather than to advances in mechanistic understanding of AF.
A factor significantly contributing to the limited progress in therapeutic interventions for AF is the complexity and diversity of disease mechanisms leading to AF. Despite the fact that the need for better understanding of mechanistic AF subtypes has been recognized in consensus conferences years ago progress in defining a realistic and effective strategy in order to systematically investigate the mechanistic heterogeneity of AF has been limited so far. This is only partially due to the lack of tools to address the complexity of AF mechanisms but is primarily caused by the logistic challenge to bring these technologies together in an integrative research approach.
Traditional cellular and animal models of AF have provided very valuable insights into the general mechanisms of the arrhythmia but per design are limited in their ability to capture the population-wide heterogeneity of AF mechanisms. Mechanistic computer models are increasingly used to investigate the effect of assumed pathomechanisms of AF particularly on the organ level in proof-of-principle studies and have become important tools for translation and integration of AF research. In addition, atrial tissue samples provide an extremely important source of information on individual AF mechanisms and their molecular and structural alterations can be studied large-scale. When such studies are performed in clinically well-characterized patients, clinical features (serum biomarkers, ECG markers, imaging, age, sex, comorbidity profile) can be determined that identify the leading molecular mechanism in this patient. The ultimate goal of this approach is to develop a classification of AF, which is based on clinical signs and symptoms that inform on leading pathophysiological mechanism of AF in an individual patient enabling therapeutic approaches tailored to these mechanisms. Such an approach requires an integrated and continued research approach involving cardiologists, electrophysiologists, cardio-surgeons, epidemiologists, experts in biomedical engineering and data scientists. Given the increasing restrictions of health care budgets, addressing the diversity of AF mechanisms and the dynamics thereof is vital for the development of patient-tailored therapeutic approaches. The urgent need for an integrated research approach to AF cannot be overemphasized.
For inquiries contact Huyen Nguyen.