Incremental “Therapeutic” Myocardial Exposure to Catecholamines: Incidence and Impact in Takotsubo Syndrome

Although Takotsubo syndrome (TS) was once considered to be rare and largely benign, it is now recognized to represent a major cause of cardiac morbidity and mortality, especially in ageing women. The biochemical precipitant of attacks of TS is an increase in catecholamine concentrations within the myocardium, engendering inflammatory activation via biased post-receptor signalling at myocardial β₂-adrenoceptor level. Cases of TS have been reported in patients treated with catecholamines, and with antidepressants which limit catecholamine re-uptake. In the current investigation, we sought to delineate the extent and potential impact of this “iatrogenic” form of TS.

Patients’ data from a regional registry of 301 consecutive cases of TS were evaluated after exclusion of patients (n = 20) in whom TS had occurred in association with life threatening extracardiac disease states. A total of 55 (18%) of patients were identified as having antecedent exposure to potentially “iatrogenic” agents (tricyclic antidepressants in 24 cases, β₂-adrenoceptor agonists in 15). Demographics, including proportion of male patients, did not differ significantly between patients with and without “iatrogenic” TS, but plasma concentrations of the catecholamine metabolite normetanephrine tended to be greater (median 1149 pmol/L vs 938 pmol/L; p = 0.03). Long-term survival (median follow-up 3 years) was marginally (p = 0.13) worse for patients with “iatrogenic” TS.

Potentially iatrogenic precipitation of TS attacks (via iatrogenic elevation of catecholamine levels and β₂-adrenoceptor stimulation) is common, associated with greater elevation of plasma normetanephrine concentrations, and also with a trend towards increased long-term mortality when compared to the remainder of TS patients.