Takotsubo syndrome: pathophysiological insights and innovations in patient care

Takotsubo syndrome, also known as broken heart syndrome, was first described in Japan in the 1990s and presents as acute heart failure caused by transient contractile dysfunction that mimics acute coronary syndrome but is not caused by acute coronary obstruction. Takotsubo syndrome accounts for as much as 2-3% of suspected coronary syndromes and is considerably more common in women than in men. In this Review, we discuss the historical background and clinical features of Takotsubo syndrome and our evolving understanding of its pathophysiology. The hallmark feature of Takotsubo syndrome is transient left ventricular dysfunction linked to emotional or physical stressors. Despite advances in our understanding of the clinical presentation and possible pathophysiological mechanisms of Takotsubo syndrome, this condition continues to challenge our fundamental understanding of human anatomy and physiology, particularly regarding how acute emotional and physical stressors can trigger such profound cardiovascular dysfunction. Although the definitive mechanisms remain elusive, current hypotheses largely centre on catecholamine surges and sympathetic nervous system hyperactivation. Diagnostic criteria have been developed by the Mayo Clinic and European Society of Cardiology working groups but, in the absence of randomized controlled clinical trials, no specific treatments for Takotsubo syndrome are available. In this Review, we highlight the complex pathophysiology of Takotsubo syndrome, with an emphasis on the interplay between emotional stress and cardiac health, and call for the development of evidence-based management protocols.