Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes

Abstract

Sodium–glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization for heart failure in type 2 diabetes (T2D) patients. Utilising cardiovascular magnetic resonance imaging (CMR) and 31phosphorus magnetic resonance spectroscopy(<sup>31</sup>P-MRS) in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2i empagliflozin on myocardial energetics, cellular volume, function and perfusion. Eighteen T2D patients underwent CMR and <sup>31</sup>P-MRS scans before and after twelve-week empagliflozin treatment. Plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycaemic control underwent an identical scan protocol on a single visit.<i> </i>Empagliflozin treatment was associated with significant improvements in PCr/ATP ratio (1.52 to 1.76, p=0.009). This was accompanied by a 7% absolute increase in the mean LVEF (p=0.001), 3% absolute increase in the mean global longitudinal strain (p=0.01), 8 ml/m2 absolute reduction in the mean myocardial cell volume (p=0.04) and 61% relative reduction in the mean NT-proBNP (p=0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected.<b> </b>Empagliflozin thus ameliorates the ‘cardiac energy-deficient’ state, regresses adverse myocardial cellular remodelling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate heart failure in T2D.

Cardiovascular magnetic resonance imaging and spectroscopy in clinical long-COVID-19 syndrome: a prospective case–control study

“…Phosphorus-cardiovascular magnetic resonance spectroscopy ( 31 P-CMRS) 31 P-CMRS was performed to obtain the PCr/ATP from a voxel placed in the mid-ventricular septum, with subjects lying supine and a 31 P transmitter/receiver cardiac coil (Rapid Biomedical GmbH, Rimpar, Germany) placed over the heart, in the iso-center of the magnet on a 3T CMR system (Prisma, Siemens Healthineers, Erlangen, Germany) as previously described [9].…”

Cardiac mechanisms of the beneficial effects of SGLT2 inhibitors in heart failure: Evidence for potential off-target effects

“…The first study examining SGLT2i and cardiac PCr/ATP, demonstrated that acute treatment with empagliflozin, dapagliflozin or canagliflozin was without effect on PCr/ATP in healthy isolated mouse hearts [69]. In T2DM patients that were treated for 12 weeks with empagliflozin, myocardial PCr/ATP ratio increased significantly from 1.52 to 1.76, together with increases in cardiac function [169]. However, in another study no effect of a 12 weeks empagliflozin treatment on cardiac PCr/ ATP ratio was observed in overweight T2DM patients [170].…”

Coexistent Diabetes Is Associated With the Presence of Adverse Phenotypic Features in Patients With Hypertrophic Cardiomyopathy

“…The CMR protocol (Supplementary Material, scan protocol figure) consisted of cine imaging with a steady-state free precession sequence, native pre-and postcontrast T1 mapping, stress and rest perfusion, and LGE. diabetesjournals.org/care Native T1 maps were acquired in three short-axis slices, including segments with maximal wall thickness, with use of a breath-held modified look-locker inversion recovery acquisition as previously described (23). Postcontrast T1 mapping acquisition was performed 15 min after last contrast injection.…”

“…While the precontrast native T1 map measurements were comparable across the groups, median myocardial ECV measurements were significantly higher for the HCM groups (HV 25% [interquartile range 23-26], HCM 27% [22][23][24][25][26][27][28][29][30][31], HCM-DM 31% [27-43]; P = 0.006) (Supplementary Material).…”

“…P-MRS was performed to obtain the PCr/ATP from a voxel placed in the midventricular septum, with subjects lying supine and a 31 P transmitter/receiver cardiac coil (Rapid Biomedical GmbH, Rimpar, Germany) placed over the heart, in the iso-center of the magnet on a 3.0 Tesla magnetic resonance system (Prisma; Siemens Healthineers, Erlangen, Germany), as previously described (23).…”