Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome

BACKGROUND: Takotsubo syndrome is an acute cardiac emergency characterized by transient left ventricular systolic dysfunction typically following a stressful event. Despite its rapidly rising incidence, its pathophysiology remains poorly understood. Furthermore, it may pass unrecognized especially if timely diagnostic imaging is not performed. Defective myocardial calcium homeostasis is a central cause of contractile dysfunction and has not been explored in takotsubo syndrome. We aimed to investigate myocardial calcium handling using manganese-enhanced magnetic resonance imaging during the acute and recovery phases of takotsubo syndrome. METHODS: Twenty patients with takotsubo syndrome (63 ± 12 years, 90% female) and 20 age, sex and cardiovascular risk factor matched volunteers (59 ± 11 years, 70% female) were recruited from the Edinburgh Heart Centre between March 2020 and October 2021. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging during index hospitalization with repeat manganese-enhanced magnetic resonance imaging performed after at least 3 months. RESULTS: Compared to matched control volunteers, patients had a reduced left ventricular ejection fraction (51±11 versus 67±8 %, P<0.001), increased left ventricular mass (86±11 versus 57±14 g/m(2), P<0.001) and, in affected myocardial segments, elevated native T1 (1358±49 versus 1211±28 ms, P<0.001) and T2 (60±7 versus 38±3 ms, P<0.0001) values at their index presentation. During manganese-enhanced imaging, kinetic modelling demonstrated a substantial reduction in myocardial manganese uptake (5.1±0.5 versus 8.2±1.1 mL/100 g of tissue/min respectively, P<0.0001) consistent with markedly abnormal myocardial calcium handling. Following recovery, left ejection fraction, left ventricular mass and T2 values were comparable to matched control volunteers. Despite this, native and post-manganese T1 and myocardial manganese uptake remained abnormal compared to matched control volunteers (6.6±0.5 versus 8.2±1.1 mL/100 g of tissue/min, P<0.0001). CONCLUSIONS: In patients with takotsubo syndrome, there is a profound perturbation of myocardial manganese uptake which is most marked in the acute phase but persists for at least 3 months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial edema, suggesting abnormal myocardial calcium handling may be implicated in the pathophysiology of takotsubo syndrome. Manganese-enhanced magnetic resonance imaging has major potential to assist in the diagnosis, characterization, and risk stratification of patients with takotsubo syndrome.