# Long-term prognosis in Takotsubo syndrome compared to heart failure: observations from a global federated research network

## TL;DR

This study compares long-term outcomes of Takotsubo syndrome and heart failure, finding lower risks of certain adverse events in Takotsubo syndrome patients.

## Contribution

A global federated research network was used to compare long-term risks between Takotsubo syndrome and heart failure patients.

## Key findings

- Takotsubo syndrome was associated with lower risks of acute heart failure and arrhythmic events compared to heart failure.
- No significant differences were found in all-cause mortality between the two groups.
- Differences were more pronounced when comparing Takotsubo syndrome with heart failure with reduced ejection fraction.

## Abstract

To compare long-term outcomes of patients with Takotsubo syndrome (TTS) and heart failure (HF).

This retrospective observational study used the TriNetX global federated research network. Adult patients (≥18 years) discharged with a diagnosis of TTS (ICD-10-CM I51.81) or HF (I50.x) between 2018 and 2022 were identified. Primary outcomes were 3-year risk of all-cause death, major adverse cardiovascular events (MACE; myocardial infarction or ischaemic stroke), and acute HF. Secondary outcomes included myocardial infarction, ischaemic stroke, ventricular arrhythmias (ventricular tachycardia), malignant arrhythmias (ventricular fibrillation or cardiac arrest), and new-onset atrial fibrillation (AF). Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) before and after 1:1 propensity score matching (PSM). Subgroup analyses were performed by HF phenotype, age (≥65 vs <65 years), and mental health status.

The study included 2240 patients with TTS (mean age 62.6 ± 17.3 years; 73.7% female) and 265 564 patients with HF (69.3 ± 14.7 years; 45.8% female). After PSM, TTS was associated with a lower risk of acute HF (HR 0.622, 95% CI 0.539–0.717), ventricular arrhythmias (HR 0.637, 95% CI 0.441–0.919), malignant arrhythmias (HR 0.656, 95% CI 0.571–0.754), new-onset AF (HR 0.672, 95% CI 0.517–0.875), and myocardial infarction (HR 0.818, 95% CI 0.687–0.974), with no significant differences in the remaining outcomes. Differences were greater when TTS was compared with heart failure with reduced ejection fraction.

TTS is associated with lower risk of adverse events than HF. Further research is needed on mental health in its pathogenesis and prognosis.

Graphical AbstractAdjusted hazard ratios for long-term clinical outcomes in 2,240 patients with takotsubo syndrome and 265,564 with heart failure from a global federated research network. TTS was associated with lower risks of acute heart failure and arrhythmic events, with no significant difference in all-cause mortality.For image description, please refer to the figure legend and surrounding text.

Adjusted hazard ratios for long-term clinical outcomes in 2,240 patients with takotsubo syndrome and 265,564 with heart failure from a global federated research network. TTS was associated with lower risks of acute heart failure and arrhythmic events, with no significant difference in all-cause mortality.