Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

Abstract

Broken Heart Syndrome, also known as Takotsubo Syndrome (TS), is sudden and transient dysfunction of the left and/or right ventricle which often mimics Acute Coronary Syndrome (ACS). Japan was the first country to describe this syndrome in the 1990s, and since then it has received a lot of attention from researchers all around the world. Although TS was once thought to be a harmless condition, recent evidence suggests that it may be linked to serious complications and mortality on par with Acute Coronary Syndrome (ACS). The understanding of TS has evolved over the past few years. However, its exact etiology is still poorly understood. It can be classified into two main types: Primary and Secondary TS. Primary TS occurs when the symptoms of myocardial damage, which is typically preceded by emotional stress, are the reason for hospitalization. Secondary TS is seen in patients hospitalized for some other medical, surgical, obstetric, anesthetic, or psychiatric conditions, and the dysfunction develops as a secondary complication due to the activation of the sympathetic nervous system and the release of catecholamines. The etiopathogenesis is now proposed to include adrenergic hormones/stress, decreased estrogen levels, altered microcirculation, endothelial dysfunction, altered inflammatory response via cardiac macrophages, and disturbances in the brain-heart axis. The role of genetics in disease progression is becoming the focus of several upcoming studies. This review focuses on potential pathophysiological mechanisms for reversible myocardial dysfunction observed in TS, and comprehensively describes its epidemiology, clinical presentation, novel diagnostic biomarkers, and evolving principles of management. We advocate for more research into molecular mechanisms and promote the application of current evidence for precise individualized treatment.