Aim: To evaluate the long-term outcome of patients with Takotsubo syndrome (TTS) and severely reduced left ventricular ejection fraction (LVEF ≤ 35%) at presentation. Methods and results: The study population included 326 patients (mean age 69.5 ± 10.7 years, 28 male) with TTS enrolled in the Takotsubo Italian Network, divided into two groups according to LVEF (≤ 35%, n = 131; > 35%, n = 195), as assessed by transthoracic echocardiography at hospital admission. In-hospital events were recorded in both groups. At long-term follow-up (median 26.5 months, interquartile range 18–33), composite major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, heart failure, and TTS recurrence) and rehospitalization were investigated. Compared to patients with LVEF > 35%, patients with LVEF ≤ 35% were older (71.2 ± 10.8 vs. 68.4 ± 10.6 years; P = 0.026) and experienced more frequently cardiogenic shock (16% vs. 4.6%; P < 0.001), acute heart failure (28.2% vs. 12.8%; P = 0.001), and intra-aortic balloon pump support (11.5% vs. 2.6%; P = 0.001) in the acute phase. At long-term follow-up, higher rates of composite MACE (25.2% vs. 10.8%; P = 0.001) and rehospitalization for cardiac causes (26% vs. 13.3%; P = 0.004) were observed in these patients. LVEF ≤ 35% at admission [hazard ratio (HR) 2.184, 95% confidence interval (CI) 1.231–3.872; P = 0.008] and age (HR 1.041, 95% CI 1.011–1.073; P = 0.006) were independent predictors of MACE. Patients with LVEF ≤ 35% also had a significant lower freedom from composite MACE during long-term follow-up (χ2 = 11.551, P = 0.001). Conclusion: Left ventricular ejection fraction ≤ 35% at presentation is a key parameter to identify TTS patients at higher risk not only in the acute phase but also at long-term follow-up.
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