Abstract
Takotsubo syndrome (TTS) is an acute and reversible form of heart failure characterized by transient left ventricular dysfunction, typically triggered by acute stress stimuli. TTS, also referred to as "stress cardiomyopathy", may paradoxically be triggered not only by negative stressors but also by intense positive emotional experiences. Interestingly, TTS was sharply incremented during and following the COVID-19 pandemic. Despite increased clinical recognition, reliable biomarkers for early diagnosis and prognosis remains limited. Oxidative stress is increasingly recognized as a key mechanism in TTS, acting downstream of sympathetic overactivation, thus contributing to myocardial stunning, endothelial dysfunction, and inflammation. In this context, extracellular vesicles (EVs) have emerged as key mediators of intercellular communication and as potential circulating biomarkers, as they reflect the molecular state of their cells of origin. In this review, we summarize the current diagnostic approaches for TTS, including the InterTAK Diagnostic Score, imaging gold standards, and emerging biomarkers such as circulating miRNAs and EV cargo associated with TTS. Furthermore, we critically examine the mechanistic interplay between oxidative stress and EVs in TTS, highlighting translational perspectives and future directions for integrating EV-based biomarkers into personalized clinical management.