Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome

Abstract

ObjectiveThe advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population.MethodsThis was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death.ResultsThe study population included 825 patients (median age: 72.0 (63.0–78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047).ConclusionsIn this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.

β-blockers and outcomes of Takotsubo syndrome: need more clinical data

“…As for outcomes, non-cardiac deaths accounted for 76% (60/79) of all deaths during the follow-up in the study by Silverio et al ,4 which is comparable to the RETAKO study (72%, 39/54) 9. This finding suggests that the majority of deaths in patients experiencing TTS are non-cardiac.…”

“…In the current issue of Heart , Silverio et al examined the association between BBs and long-term survival using 825 patients in the Takotsubo Italian Network registry 4. The authors demonstrated that BB prescription at discharge was significantly associated with lower all-cause mortality after TTS (6.8% vs 13.6%; adjusted hazard ratio (aHR)=0.563, 95% confidence interval (CI)=0.356 to 0.889, p=0.014) during a median follow-up of 24 months, particularly with lower non-cardiac mortality (4.9% vs 10.7%; aHR=0.525, 95% CI=0.309 to 0.893, p=0.018) rather than cardiac mortality (1.8% vs 3.0%; aHR=0.699, 95% CI=0.284 to 1.722, p=0.436).…”

“…The study design and main results of eight original studies (sample size >200) regarding BB use for TTS1 4 6–11 are summarised in table 1. All were non-randomised studies.…”

“…Among them, two studies focused on the in-hospital outcomes, both demonstrating no significant association between BB use and better outcomes 6 7. The remaining six studies examined the effectiveness of BB on longer follow-up outcomes, demonstrating inconsistent results 1 4 8–11. In addition to the observational design, several limitations and considerations need to be acknowledged in these studies (table 2): (1) the effect of BBs for TTS might be different between preadmission users (ie, patients who already took BBs before admission with TTS) and new users (ie, patients who start to take BBs after admission with TTS); (2) the effect of BBs may not be the ‘class effect’ but rather different across BB subclasses3; (3) medication continuation/discontinuation and adherence could modify the impact of BBs on prognosis; (4) given the high age of patients with TTS, the effectiveness of BBs needs to be weighed against their potential adverse effects (eg, bradycardia, hypotension, or those-related injuries or hospitalisations); (5) whether TTS is complicated by left ventricular outflow tract obstruction (prevalence 10%–25%2) or not could be a key factor, especially in assessing acute-phase outcomes because BBs appear effective in reducing the gradients in the outflow tract2 3; (6) last but not least, patients’ general conditions (eg, frailty5) could be confounders in outcome assessment in this elderly population and thus should be adjusted for a fair comparison between BB users and non-users unless it is a randomised comparison.…”

“…Thus, although TTS is considered an acute heart failure syndrome mimicking acute coronary syndrome, it may be worth exploring a therapeutic strategy to reduce the non-cardiac mortality among patients with TTS. If we investigate the effectiveness of cardiovascular drugs such as BBs, it may be reasonable to focus on patients who develop cardiogenic shock due to TTS (as suggested by Almendro-Delia et al 9 and Silverio et al 4) or those with residual cardiac dysfunction after TTS12 (ie, subpopulation at high risk of cardiac events), although it would often be difficult to enrol a sufficient number of such subgroup patients for analyses.…”