Takotsubo syndrome in the context of pre-existing non-ischemic cardiomyopathy: mechanistic and clinical implications

Takotsubo syndrome (TTS), a transient left ventricular (LV) dysfunction typically precipitated by acute emotional or physical stress, is classically observed in individuals with structurally normal hearts. However, its occurrence in patients with established non-ischemic cardiomyopathy (NICMP) represents a striking clinical paradox that challenges our current understanding of both disease entities. This comprehensive review examines the complex pathophysiological mechanisms underlying this phenomenon, with particular emphasis on supraphysiological catecholamine surge and biased β-adrenergic receptor signaling, inflammatory-mediated sensitization, intrinsic mitochondrial dysfunction and mechanically-induced cytokine amplification.