Abstract Body (Do not enter title and authors here):
Background:
We previously demonstrated a significantly increased inpatient mortality of COVID-19 infection-induced male Takotsubo (TTS) patients during the early pandemic period. Since then, our management of COVID-19 prevention and treatment have evolved significantly, reducing both hospitalization and mortality rates. With these advancements, we have analyzed the clinical characteristics and outcomes of reported COVD-19-associated TTS patients since the initial pandemic.

Research Question: What are the clinical characteristics and mortality outcomes of COVID-19-associated TTS patients especially in the context of improved prevention and treatment?

Aims: To identify clinical characteristics and outcome correlates in patients with COVID-19-associated TTS.

Methods:
We completed a systematic review of 191 patients with TTS from 95 published case reports, 13 case series, and 4 observational cross-sectional/cohort studies published from April 1, 2020 to May 1, 2024 (PubMed). We performed clustering analysis using the clinical, imaging, and inpatient mortality data of 78 patients, which categorized groups of patients based on how closely associated or similar they are relative to other groups. Following this, we applied feature analysis to identify which features contributed the most to the clustering results.

Results:
Of all TTS cases, the mean age was 64.2±16.1 with 32.9% males. A total of 122 (63.9%) had COVID-19 infection, 21 (11.0%) had COVID-19 vaccination, and 50 (26.2%) patients had other triggers (2 patients had both COVID-19 infection and a non-infectious trigger). In-hospital mortality was 28.6% (16 of 56) for males and 13.2% (15 of 114) for females (p-value = 0.01). There was no association between COVID-19 vaccine administration and in-hospital mortality (0%, 0 of 21). There were notable differences in the clinical and demographic characteristics of TTS patients before and after September 2021 based on clustering analysis. Feature analysis indicated that COVID-19-induced TTS strongly correlated with in-hospital mortality and long-term adverse outcome in male patients.

Conclusion:
More male TTS patients were found during the pandemic than is expected of the traditional TTS archetype. A triad of “male, COVID-19 infection and TTS” appears to predict higher inpatient mortality. Compared to our prior study, inpatient mortality rates for TTS COVID patients have declined for all groups. Vaccine-induced TTS is associated with a benign clinical phenotype.