Current Landscape and Latest Advances of Stress Cardiomyopathy

Cardiovascular diseases (CVDs) are the leading cause of death globally. An estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths.[1] The Global Burden of Diseases, Injuries, and Risk Factors Study indicated that ischemic heart disease, ischemic stroke, and other cardiomyopathy ranked in the top 10 in the global ranking of cardiovascular deaths by cause between 1990 and 2021.[2] The pathogenesis of CVD is complex and diverse. As its research increasingly evolves, a special type of cardiomyopathy – stress cardiomyopathy – has gradually become a research hotspot. Stress cardiomyopathy, also known as Takotsubo syndrome (TTS), mimics the clinical presentation of acute coronary syndrome (ACS), yet typically shows no obstructive lesions in coronary angiography.[3] Its pathogenesis closely correlates with sympathetic nerve activation, microvascular dysfunction, and changes in hormone levels. Since the initial discovery in Japan in 1990,[4] TTS has been increasingly gaining worldwide awareness. In general, TTS is estimated to represent approximately 1%–3% of all cases and 5%–6% of female patients presenting with suspected ST-segment elevation myocardial infarction.[3] In the International Takotsubo (interTAK) registry, which was established at University Hospital Zurich in collaboration with 25 cardiovascular centers across 9 countries, female patients with TTS account for 89.8%, an average age of 66.8, and 90% postmenopausal [Figure 1].[3,5] Its incidence has increased, especially during the COVID-19 pandemic [Figure 1]. A large cohort study from Cleveland Clinic in 2020 showed that the proportion of TTS among patients with ACS increased from 1.8% before the pandemic to 7.8% during the pandemic.[6] Thus, it is essential to highlight that TTS has increasingly become one of the significant CVDs affecting human health.Figure 1: Common symptoms, triggers, trends, and characteristics of Takotsubo syndrome. TTS = Takotsubo syndromeThe most common symptoms of TTS are acute chest pain, dyspnea, or syncope and thus indistinguishable from acute myocardial infarction at the first glance [Figure 1].[3,5] On admission, clinical presentation strongly simulates ACSs and/or acute heart failure usually in the absence of obstructive coronary anatomy on invasive coronary angiogram.[3,7-10] As a unique subtype of CVDs, TTS research has evolved from the “broken heart syndrome” concept to exploring neural, endocrine, microcirculatory, and molecular metabolic mechanisms. With advanced diagnostic techniques and diverse treatment targets, TTS clinical management is becoming more individualized and precise, pioneering a new path for improving patient outcomes. Regardless of the substantial evidence on TTS, clinicians still face practical challenges in the diagnosis and management of TTS, potentially resulting in the underdiagnosis and mismanagement.[10,11] In this issue, authors from various institutions across the globe contributed their valuable work for publication. On behalf of the editorial team, I would like to express my sincere thanks to all authors. An article entitled “Novel Acquisitions and Supporting Evidence in Pathophysiology of Stress-Induced Cardiomyopathy: A Narrative Review” was contributed by Andrea Matteucci et al. It explored that stress cardiomyopathy affects the cardiovascular, neuroendocrine, and psychological systems. Its mechanisms include elevated catecholamine levels, microcirculatory dysfunction, molecular signaling changes, and inflammation, while circulating microRNAs may also play a role in the pathophysiology. In addition, genetic predisposition and physical and psychological factors may influence susceptibility. The review advocates for an integrated, multidisciplinary approach to deepen understanding of this complex condition. Francesco Maria Lisci et al. contributed their work titled “Takotsubo Syndrome: The Enigma of Women’s Depressed Heart – A State-of-the-Art Review.” They discussed the role of mindfulness-based interventions (MBIs) in treating and preventing TTS. TTS links to emotional and physical stress, and the brain–heart axis drives stress-induced cardiac dysfunction. MBIs improve stress management, emotional regulation, and cardiovascular health, complementing traditional treatments of TTS. The authors recommended integrating psychological interventions like MBIs into TTS management. Fulvio Cacciapuoti et al.’s study was titled “Beyond the Broken Heart: Unusual Triggers of Stress Cardiomyopathy – A Narrative Review.” They discussed the pathophysiology, uncommon triggers, and the role of advanced imaging techniques in stress cardiomyopathy. Stress cardiomyopathy is a dynamic and multifaceted condition that extends beyond its traditional association with acute stressors. It can be triggered by uncommon factors, including medical and surgical interventions, neurological incidents, prolonged stress, and infections such as COVID-19 [Figure 1]. Advanced imaging – echocardiography, cardiac magnetic resonance imaging, and computed tomography – enhances stress cardiomyopathy diagnosis, ensuring precise cardiac assessment and personalized treatment strategies. Strouthos et al. presented their work on “Heart Rate Variability Modulates the Relationship between Anxiety Symptoms and Emotional Responses to Anxiety-Provoking Imagery: A Cross-Sectional Study.” This study examined if heart rate variability (HRV) indices of parasympathetic control of the heart are related to the emotional responses of anxious individuals to anxiety imagery scenes in a community sample. Findings are consistent with prior literature and suggest that, even in community samples with high anxiety, high HRV is related to better emotion regulation and helps normalize anxious responses to threatening situations. Huang et al. commented on the InterTAK Registry from multidimensional perspectives including epidemiology and clinical heterogeneity, diagnostic refinement, prognostic stratification, pathophysiological insights, clinical management, academic legacy, and global impact as well as limitations and future directions. They highlighted that as the registry evolves, its legacy lies not only in advancing TTS science but also in modeling global collaboration to tackle CVDs. Future research is needed to translate these insights into targeted therapies, ultimately improving outcomes for this enigmatic condition. In summary, TTS research has made significant progress but still has unresolved issues such as its exact pathogenesis, early diagnostic markers, and proper management. As research deepens and technology innovates, our understanding will improve and advance further, providing better health care for patients. Contributors from various institutions across the globe are greatly appreciated for their efforts and support.