Impaired Myocardial Calcium Uptake in Patients With Diabetes Mellitus: A Manganese-Enhanced Cardiac Magnetic Resonance Study

The pathophysiology of diabetic cardiomyopathy is complex and may involve dysregulated myocardial calcium uptake, which has been demonstrated in animal models.1 Manganese is a paramagnetic calcium analog for voltage-gated L-type calcium channels on cardiac myocytes, and manganese-enhanced cardiac magnetic resonance (CMR) provides a novel method of assessing myocardial calcium uptake in vivo.2 We aimed to determine whether myocardial calcium uptake is altered in people with type 1 or type 2 diabetes without cardiac disease.

This was a prospective, 2-center, case-control study. We enrolled subjects with type 1 or type 2 diabetes, 18 to 75 years of age, with no prior history or symptoms of cardiac disease. Age-matched control volunteers without diabetes or known cardiac disease were recruited for comparison. Ethical approval was granted by the United Kingdom National Research Ethics Service (17/WM/0192, 20/NS/0037 and 20/WM/0304). Where applicable, subjects taking calcium-channel blockers withheld these medications 48 hours prior to study entry. All participants underwent manganese-enhanced CMR, performed using standardized imaging protocols on 3.0-T scanners. Initial imaging assessment of cardiac structure and function was performed with cine imaging. T1 mapping was then performed precontrast in a mid–short-axis slice position using a modified Look-Locker inversion recovery sequence (Siemens MyoMaps). An intravenous infusion of manganese dipyridoxyl diphosphate (5 μmol/kg [0.1 mL/kg] at 1 mL/min; Exova SL Pharma) was commenced and repeated T1 maps at the same location were performed every 2.5 minutes for 30 minutes.

Image analysis was performed at a core laboratory blinded to all participant details. Cardiac chamber volumes, mass, and function were assessed using cvi42 software (v5.13.5; Circle CVI) as described previously.3 Participants with regional wall motion abnormalities or reduced left ventricular ejection fraction were excluded. For analysis of manganese uptake, regions of interest were drawn in the midventricular inferoseptal segment and the myocardial blood pool for all T1 maps from 0 to 30 minutes (Figure 1A).