Atrial cardiomyopathy: from knowledge gaps to clinical impact
Abstract
Abstract Background Atrial cardiomyopathy (AtCM) is increasingly recognised as an underlying atrial substrate contributing to atrial fibrillation (AF), heart failure (HF), and cardio-embolic stroke. However, diagnostic criteria, disease thresholds, and targeted treatment strategies remain poorly defined. Objective To describe the rationale, structure, and translational strategy of the EmbRACE (Electro-Molecular Basis and the theRapeutic management of Atrial Cardiomyopathy, fibrillation and associated outcomEs) network, a national consortium established to address key knowledge gaps in AtCM. Methods EmbRACE integrates mechanistic research, computational modelling, clinical trials, and implementation science within seven interconnected work packages. Human atrial tissue biobanking and deep phenotyping (WP1) enable molecular profiling of candidate pathways (WP2), which are validated in experimental models (WP3). Computational modelling and artificial intelligence (WP4) integrate multimodal clinical and biological data to derive composite AtCM phenotypes and severity frameworks. Substrate-targeting clinical trials evaluate AF ablation (RACE X; WP5), weight reduction using GLP‑1 agonists (DUTCH-WAIST; WP6), and optimised rate control using calcium channel antagonists (SMART-VERAPAF; WP6). Implementation science (WP7) focuses on guideline integration, decision-support tools, and governance of AI-based risk models. EmbRACE establishes a translational pipeline from mechanistic discovery to clinical application. By integrating tissue-level insights with multimodal risk modelling and interventional trials, the consortium aims to define clinically meaningful AtCM thresholds, to validate indirect markers, and to determine whether targeted treatment modifies disease progression and clinical outcomes. Conclusion EmbRACE provides a multidisciplinary framework to transform AtCM from a theoretical construct into a clinically actionable entity, enabling earlier detection, improved risk stratification, and AtCM-directed therapy in cardiovascular prevention.
