Atrial cardiomyopathy (ACM) represents a constantly evolving concept, with increasing importance in contemporary research and clinical practice. A better understanding of the mechanisms involved in atrial remodeling and its clinical correlations especially with atrial fibrillation (AF) and other cardiometabolic comorbidities may induce a significant impact on the diagnosis, prognosis, and therapeutic approach of ACM-related comorbidities. Although initially described several decades ago, investigators have only recently highlighted that several renal, metabolic, and cardiovascular diseases are determining factors for atrial remodeling and subsequent ACM. Based on data from multiple recent studies, our research emphasizes the correlations between ACM and other coexisting pathologies including cardiovascular, respiratory, or metabolic diseases, with fibrosis being the most incriminated pathophysiological mechanism. In addition to the usual tests, the paraclinical assessment of ACM is increasingly based on the use of various cardiac biomarkers, while the cardiac magnetic resonance (CMR) has become an increasingly tempting diagnostic too for describing morphofunctional aspects of the heart chambers, with the gadolinium contrast enhanced CMR (LGE-CMR) emerging as a commonly used technique aiming to identify and quantify the precise extent of atrial fibrosis. Further research should be conducted in order to clarify our knowledge regarding atrial remodeling and, therefore, to develop new and improved therapeutic approaches in these patients.

Ischemia with nonobstructive coronary artery disease (INOCA) is increasingly recognized as a significant cause of angina, myocardial remodeling, and eventually heart failure (HF). Coronary microvascular dysfunction (CMD) is a major endotype of INOCA, and it is caused by structural and functional alterations of the coronary microcirculation. At the same time, atrial cardiomyopathy (ACM) defined by structural, functional, and electrical atrial remodeling has a major clinical impact due to its manifestations: atrial fibrillation (AF), atrial thrombosis, stroke, and HF symptoms. Both these pathologies share similar risk factors and have a high comorbidity burden. CMD causing INOCA and ACM frequently coexist. Thus, questions arise whether there is a potential link between these pathologies. Does CMD promote AF or the reverse? Which are the mechanisms that ultimately lead to CMD and ACM? Are both part of a systemic disease characterized by endothelial dysfunction? Lastly, which are the therapeutic strategies that can target endothelial dysfunction and improve the prognosis of patients with CMD and ACM? This review aims to address these questions by analyzing the existing body of evidence, offering further insight into the mechanisms of CMD and ACM, and discussing potential therapeutic strategies.