Key result
Secondary takotsubo syndrome linked to ~2.8-fold higher odds of cardiogenic shock vs primary TTS.
Why the study?
Takotsubo syndrome can be classified into primary and secondary forms based on triggering factors, but differences in clinical characteristics and short-term outcomes between these two entities remain incompletely understood.
Does secondary takotsubo syndrome increase the risk of in-hospital adverse events (ventricular arrhythmias, cardiogenic shock, and in-hospital death) compared to primary takotsubo syndrome in patients enrolled in the JapanTAK registry?
Cohort (n=447)
Does secondary takotsubo syndrome increase the risk of in-hospital adverse events (ventricular arrhythmias, cardiogenic shock, and in-hospital death) compared to primary takotsubo syndrome in patients enrolled in the JapanTAK registry?
Secondary takotsubo syndrome is an independent risk factor for cardiogenic shock and is associated with significantly higher rates of cardiogenic shock and in-hospital mortality compared to primary takotsubo syndrome, highlighting the importance of trigger-based classification for early risk stratification.
Secondary TTS may inform in-hospital risk stratification; extends registry observations but leaves causal mechanisms and interventions open for trials.
Background Takotsubo syndrome (TTS) exhibits heterogeneous clinical presentations and outcomes. Based on triggering factors, TTS can be classified into primary and secondary forms; however, differences in clinical characteristics and short-term outcomes between these two entities remain incompletely understood. Purpose To compare clinical characteristics and in-hospital outcomes between patients with primary and secondary TTS. Methods Patients with TTS enrolled in the JapanTAK registry between 2010 and 2021 were retrospectively analyzed. TTS was classified as primary when triggered by emotional stress, physical activities, or no obvious stress, and as secondary when triggered by medical illness, trauma, or injuries. Clinical characteristics and in-hospital events (ventricular arrhythmias, cardiogenic shock, and in-hospital death) were compared between groups. Multivariable logistic regression analysis was performed to identify factors associated with cardiogenic shock. Results A total of 447 patients were included, of whom 238 (53.2%) were classified as secondary TTS. Acute neurological disease and acute infectious disease were the most common triggers of secondary TTS (Figure). Compared with primary TTS, patients with secondary TTS were younger (73.5 ± 11.4 vs. 70.9 ± 13.3 years, p=0.026), less frequently female (88.0% vs. 76.1%, p=0.001), and less likely to present with chest pain (60.8% vs. 12.2%, p<0.001). Primary TTS patients had higher prevalence of hypertension (57.9% vs. 47.5%, p=0.029), dyslipidemia (41.6% vs. 24.4%, p<0.001), and cardiovascular disease (21.5% vs. 14.3%, p=0.048). Secondary TTS patients more frequently had pulmonary disease (11.0% vs. 18.1%, p=0.045), cerebrovascular disease (13.9% vs. 22.7%, p=0.020), and cancer (18.2% vs. 26.5%, p=0.041). Secondary TTS was associated with lower LVEF at diagnosis (45.0 [39.4–55.9] vs. 40.0 [35.0–50.0] %, p<0.001), higher BNP levels (228.5 [65.4–504.0] vs. 378.4 [130.4–973.2] pg/mL, p<0.001), higher CRP levels (0.11 [0.05–0.43] vs. 1.66 [0.32–6.00] mg/dL, p<0.001), and higher white blood cell counts (7,800 [6,400–10,180] vs. 11,250 [7,575–14,800] /μL, p<0.001). There was no significant difference in ventricular arrhythmias (2.4% vs. 6.3%, p=0.065); however, cardiogenic shock (5.3% vs. 18.5%, p<0.001) and in-hospital death (2.4% vs. 11.8%, p<0.001) occurred more frequently in secondary TTS. On multivariable analysis, secondary TTS (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.3–6.0, p=0.0084) and lower LVEF (OR 0.97 per 1% increase, 95% CI 0.95–0.99, p=0.012) were independently associated with cardiogenic shock. Conclusions Secondary TTS is associated with significantly worse short-term outcomes, including cardiogenic shock and in-hospital mortality, and represents an independent risk factor for cardiogenic shock. Distinguishing between primary and secondary TTS may be clinically important for early risk stratification and management.
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Kitagawa et al. (2026) conducted a cohort in Takotsubo syndrome (n=447). Secondary takotsubo syndrome vs. Primary takotsubo syndrome was evaluated on Cardiogenic shock (OR 2.8, 95% CI 1.3-6.0, p=0.0084). Secondary takotsubo syndrome had higher rates of cardiogenic shock (18.5% vs 5.3%; OR 2.8, 95% CI 1.3-6.0) and in-hospital death (11.8% vs 2.4%, p<0.001) than primary TTS.
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