Clinical characteristics and outcomes of primary vs. secondary takotsubo syndrome
M Kitagawa, K Kato, K Miyakoda, S Wakabayashi, Y Sakai, N Oka, S Okino, K Katano, J Harada, H Miyahara, T Ikoma, A Sakamoto, H Goto, H Kitahara, Y KobayashiAbstract
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.figure