Distinct clinical phenotypes of takotsubo syndrome with cardiopulmonary arrest: impact on outcomes

Background Cardiopulmonary arrest (CPA) is a life-threatening complication of Takotsubo syndrome (TTS). Conversely, TTS may also develop secondary to the physiological stress of CPA or its resuscitation. Despite potentially distinct underlying mechanisms, these scenarios are often considered a single clinical entity. Whether TTS triggering CPA and TTS occurring after CPA represent distinct clinical phen9otypes with different prognostic implications remains unclear. Purpose To determine whether TTS-associated CPA comprises distinct clinical phenotypes and to evaluate differences in clinical characteristics, in-hospital events, and long-term mortality. Methods In this retrospective registry of 447 consecutive patients with TTS, we identified 38 patients who experienced CPA immediately prior to TTS diagnosis. CPA included ventricular tachycardia/fibrillation (VT/VF), pulseless electrical activity, or asystole. Patients were categorized into two groups: (1) TTS-induced CPA, defined as CPA without an alternative identifiable cause, suggesting TTS as the precipitating event (n=16); and (2) post-CPA TTS, defined as TTS occurring after CPA due to a separate identifiable condition (e.g., sepsis or subarachnoid hemorrhage) (n=22). Baseline characteristics and in-hospital cardiovascular events (including cardiogenic shock and recurrent VT/VF) were compared between groups. Long-term survival was assessed using Kaplan–Meier analysis and Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results There were no significant differences in age (65.8±9.2 vs. 60.0±18.0 years, p=0.81) or sex distribution (56.2% vs. 77.3% female, p=0.29) between the groups. In-hospital cardiogenic shock occurred with similar frequency (43.8% vs. 54.5%, p=0.74). However, all-cause in-hospital mortality was significantly higher in the TTS-induced CPA group (43.8% vs. 9.1%, p=0.02). Recurrent VT/VF after TTS diagnosis occurred in 100% of the TTS-induced CPA group compared with 13.6% in the post-CPA TTS group (p<0.01). During follow-up, the TTS-induced CPA phenotype was associated with significantly worse long-term survival (HR 0.30, 95% CI 0.31–0.90, p=0.022). Conclusions TTS-associated CPA comprises two clinically distinct phenotypes with markedly different arrhythmic burden and mortality risk. TTS-induced CPA is associated with substantially worse short- and long-term outcomes, underscoring the need for intensified monitoring and risk stratification in this high-risk subgroup.