Can currently available data on takotsubo syndrome therapies guide us to manage future cases?

To the Editor

Santoro et al.¹ reported on 2,453 patients with a focus on the effects of long-term drug therapy with renin angiotensin system inhibitors (RASi), following their discharge after suffering takotsubo syndrome (TTS), with a median follow-up of 31 months, employing data from the international multicenter German/Italian/Spanish Takotsubo (GEIST) registry. Analyses pertained to the subgroups of 63% of patients who received and of 37% of patients who did not receive RASi upon their discharge, further amplified by a 1:1 propensity score analysis, with 583 patients per group, matching for important variables. The authors found that RASi was independently associated with lower mortality in the overall cohort, while the patients who received RASi were also older, had a higher prevalence of hypertension and diabetes, higher admission left ventricular ejection fraction (LVEF), and lower rates of in-hospital complications; however, a mortality benefit was not found in patients treated with RASi in the propensity score matched patients overall, while such benefit was found in the patients with an admission LVEF ≤40%, and diabetes.

I have some comments and inquiries for the authors’ kind consideration: (1) Since the management realities internationally include prescribing RASi and/or β-blockers (BB) upon discharge of patients who have suffered TTS, it is important to evaluate the long-term response of patients to RASi, BB, and RASi/BB; the authors,² and others,^3,4 have previously dealt with this issue, and although the present article,¹ provides information on the rates of BB prescriptions for the patients who were or were not prescribed RASi (ie 80.6% vs 55.7%, P < 0.01), it would be of value to provide an insight about the response of patients to the 3 different therapies (ie RASi, BBB, and RASi/BB) based on the authors’ 2,453 patient cohort. (2) If the numbers of patients are not adequate based on the cohort of the GEIST takotsubo registry, perhaps combining the data of GEIST, the Spanish National Takotsubo (RETAKO) Registry database, and the International Takotsubo (InterTAK) Registry, for such undertaking may be worth attempting. (3) This study¹ provided information corresponding to a median of 31 months of follow-up; also considering the other problems mentioned by the authors in their article's “limitations”, the registries should be upgraded to provide information on longer follow-ups, and the details about continuation/interruption of the administered drug therapies, based on the enrolled patients’ true clinical trajectories. (4) Recent studies reveal that a protracted ventricular dysfunction, as assessed by speckle-tracking strain echocardiography analysis may be related to persistent microscopic fibrosis, involving both the previously poorly contracting as well as normal and hyperkinetic myocardial territories (ie, “global fibrosis”), detected acutely;⁵ accordingly, 1 wonders whether antifibrotic agents (eg, spironolactone, pirfenidone, sacubitril/valsartan, tranilast, and relaxin) have any role in the hospital and postdischarge phase of TTS. Thus, it appears that we still do not have enough documented therapeutic insights from the existing literature for the long-term management of patients with TTS and prevention of its recurrence.

Funding

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Declaration of competing interest

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