SGLT2 inhibitor therapy in patients with acute Takotsubo syndrome

Background takotsubo syndrome (TTS) is an acute heart failure (HF) condition characterized by transient systolic dysfunction, myocardial edema and absent myocardial scarring. Despite recovery of left ventricular ejection fraction (LVEF), short- and long-term prognosis is similar to that of patients with acute myocardial infarction and specific treatments are currently lacking. The SGLT2 inhibitors Dapagliflozin and Empagliflozin are drugs with a recent guideline indication in acute and chronic HF, however, data specifically on TTS patients are not available. The aim of the present study was to investigate the effects of SGLT2 inhibitors in the treatment of patients hospitalized for acute TTS. Methods consecutive TTS patients who initiated an SGLT2 inhibitor at hospital admission were propensity-score matched (PSM) in a 1:2 ratio with untreated TTS from our historical cohort. All patients underwent a timely CMR imaging with T2 mapping assessment within 1 week of hospitalization (median 5 days, interquartile range 3, 6 days). PSM was performed including variables known to be associated with time to recovery of systolic function and edema extent. Results the final analysis included n=22 TTS patients treated with an SGLT2 inhibitor (age 75±8 years; 91% female – n=13 treated with Dapagliflozin and n=9 with Empagliflozin) and n=44 untreated matched TTS. Standardized mean difference for all PSM matching variables (age, sex, presence of coronary artery disease, malignancy, neurological conditions, admission LVEF and time from hospital admission to CMR examination) was <0.100 between groups. The in-hospital treatment was well-tolerated without relevant side-effects or drug discontinuation. LVEF in treated TTS patients was similar vs untreated on admission (39±9% vs 39±10%, p=0.971), but higher at CMR examination performed with similar delay (55±9% vs 50±9%, p=0.048). CMR tissue characterization showed lower septal and global T2 mapping values in the SGLT2 treated group (56±5 msec vs 59±7 msec, p=0.034; 55±4 msec vs 57±7 msec, p=0.049 respectively). After discharge, the treatment with an SGLT2 inhibitor was prescribed for at least 6 months in all patients, a single discontinuation was observed at follow-up (4.5 %). At a median follow-up of 197 days (interquartile range 86, 564), a trend towards lower all-cause mortality in SGLT2 inhibitors treated patients was found (log-rank p=0.076). Conclusions SGLT2 inhibitors were well tolerated in the acute phase of TTS and associated with favorable short-term effects, including quicker recovery of systolic function and lower myocardial edema burden. Exploratory analysis of mid-term follow-up indicates potential prognostic relevance of this pharmacological treatment.