Myocardial vulnerability to catecholaminergic stress in takotsubo cardiomyopathy: pathophysiological mechanisms of transient ventricular dysfunction – a narrative review

Abstract

Takotsubo cardiomyopathy constitutes a syndrome of acute heart failure whose pathophysiology remains incompletely elucidated, despite recent advances in translational and clinical research. This study analyzes the mechanisms underlying myocardial vulnerability to catecholaminergic stress, with emphasis on the conversion of adrenergic insult into transient ventricular dysfunction. This is a narrative literature review of an analytical and integrative nature, conducted using the PubMed database, with the selection of studies published between 2021 and 2025, available in full-text format, and directly related to the central pathophysiological axes of the syndrome. Observational, translational, and experimental original studies were included, addressing neuroautonomic predisposition to stress, coronary microvascular dysfunction, endothelial instability, myocardial edema, disturbances in intracellular calcium handling, metabolic reprogramming, sterile inflammation, and the persistence of functional alterations after the acute phase. The literature demonstrates that the syndrome cannot be reduced to a nonspecific functional response to stress, but rather results from the convergence of central stress hyperreactivity, catecholamine overload, microvascular hypoperfusion, disruption of excitation–contraction coupling, and metabolic-inflammatory impairment. The findings also indicate that recovery of ejection fraction does not necessarily imply full biological restitution of the myocardium. It is concluded that Takotsubo cardiomyopathy should be understood as a complex syndrome of myocardial vulnerability, whose apparent functional transience does not encompass the full pathophysiological depth of the injury.