Non-ACS Presentation in Takotsubo Syndrome: A High-Risk Phenotype with Distinct Treatment Patterns and Worse Outcomes

Takotsubo syndrome (TTS) is frequently misdiagnosed as acute coronary syndrome (ACS), yet a substantial proportion of patients present without typical ACS features-often leading to delayed recognition and suboptimal management. The prognostic implications of the non-ACS phenotype remain poorly characterized, particularly in Asian populations.

This study aimed to investigate the treatment patterns and outcomes of non-ACS TTS.

Using data from the multicenter TAKOC (Takotsubo syndrome of Chinese patients) Registry (18 tertiary hospitals in China), we compared 421 TTS patients stratified by initial presentation: ACS-like (typical chest pain, ischemic electrocardiogram changes, and peak troponin >10-fold the upper limit of normal) versus non-ACS. Inverse probability of treatment weighting was applied to account for baseline imbalances.

Non-ACS TTS (n = 257, 61.0%) was associated with male sex, physical triggers, dyspnea as primary symptom, lower left ventricular ejection fraction, and higher incidence of cardiogenic shock. Paradoxically, despite significantly lower troponin levels, these patients experienced markedly higher 30-day all-cause mortality (adjusted HR: 2.28; 95% CI: 1.18-4.41; P = 0.017) and long-term mortality (adjusted HR: 2.44; 95% CI: 1.32-4.51; P = 0.043). Patients in the non-ACS group required more intensive in-hospital support-including diuretics, vasoactive drugs, and mechanical circulatory support; however, they received fewer cardiovascular medications (antiplatelets, beta-blockers, and renin-angiotensin-aldosterone system inhibitors) that were independently associated with lower 30-day mortality.

Non-ACS presentation defines a high-risk TTS subtype characterized by atypical symptoms and disproportionately poor outcomes-despite less pronounced biomarker elevation. These findings underscore the critical need for heightened clinical suspicion and exploring effective treatment strategies for patients with TTS. (Registration number: ChiCTR2300075095).