Current challenges in pharmacological treatment of Takotsubo syndrome: is there a long way to go?

Beta-blockers (BB) and angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) should be considered in the management of Takotsubo Syndrome (TTS) due to their potential to aid left ventricular (LV) recovery. However, therapeutic strategies in TTS rely on clinical experience and expert consensus, and the impact of BB and ACEi/ARB on outcomes remains uncertain.

To investigate whether BB and ACEi/ARB therapy after discharge in TTS patients are associated with long-term major cardiovascular events.

We retrospectively evaluated consecutive patients admitted to our center with TTS over the past 15 years. Patients were categorized based on BB and ACEi/ARB prescriptions at discharge and baseline characteristics, clinical management and outcomes were compared. Association between medical treatment and major adverse cardiovascular and cerebrovascular events (MACCE), including death, cerebrovascular events, myocardial infarction, heart failure and recurrency, was analyzed using multivariate Cox regression.

A total of 121 patients were included, with a mean age of 71±12 years, predominantly female (86%). Most presented with chest pain (82.6%) and 36.7% had ST-segment elevation. During hospitalization, 32.5% of patients developed heart failure, 12.6% required non-invasive ventilation and 4.2% progressed to cardiogenic shock. In-hospital mortality was 3.3%, with a median hospital stay of 5±4 days.

At discharge, 66.1% were on BB, 78.5% on ACEi, and 58% on both. When comparing patients on BB to those not on BB, no significant differences were found in age (70±12 vs. 72±12 years, p=0.353), comorbidities, pro-BNP levels (3103, IQR 909-6148 vs. 3400, IQR 1212-7703 mg/dl) or peak troponin (0.40, IQR 0.21-0.70 vs. 0.57, IQR 0.29-1.0 mg/dl), and left ventricular ejection fraction (LVEF) on admission (41.8±10.2% vs. 40.7±12.3%, p=0.508) and at discharge (51.0±10.2% vs. 53.3±13.2%, p=0.674). Men were less frequently prescribed BB than women (41.2% vs. 74.5%, p=0.006).

Patients with chronic renal disease received ACEi less frequently (54% vs. 86%, p=0.01). No significant differences were observed between the ACEi and non-ACEi group regarding other comorbidities, age, gender, lab tests or LVEF.

During a median follow-up of 32 months (IQR 11-55), 37.6% of patients experienced a MACCE event. Adjusted Cox regression analysis revealed that patients on BB therapy had a significantly lower risk of MACCE events (HR 0.452, 95% CI 0.228-0.896, p=0.021), while ACEi/ARB therapy did not show a comparable risk reduction (HR 0.669, 95% CI 0.256-1.747, p=0.433).

In our study, patients discharged on BB had a significant reduction in MACCE events, highlighting its potential as a beneficial therapy in TTS management. In contrast, ACEi/ARB therapy did not demonstrate similar risk reduction, underscoring the need for randomized prospective trials to establish evidence-based treatment strategies for TTS.

Cox regression analysis for BB