medwireNews: Treatment with the sodium-glucose cotransporter (SGLT)2 inhibitor empagliflozin is associated with a reduction in myocardial extracellular volume (ECV) among individuals with type 2 diabetes and coronary artery disease, suggests an analysis of data from the EMPA-HEART CardioLink-6 trial.
This mechanism “may contribute to the cardiovascular benefits observed in patients with [type 2 diabetes] and coronary artery disease who are treated with SGLT2 inhibitors,” write Kim Connelly (St Michael’s Hospital, Toronto, Ontario, Canada) and colleagues in JACC: Cardiovascular Imaging.
The researchers analyzed data from 74 participants with an average diabetes duration of 11.4 years who were treated with empagliflozin 10 mg/day or placebo in addition to standard care.
They found that average left ventricular (LV) ECV, measured by cardiac magnetic resonance (CMR) imaging, decreased from 29.6% at baseline to 28.7% at the 6-month follow-up among the 39 individuals treated with empagliflozin, but increased from 30.6% to 31.1% among the 35 people given placebo, resulting in a significant adjusted difference of 1.40% between the groups. LV mass indexed to body surface area also decreased to a significantly greater degree in the empagliflozin group, with an adjusted between-group difference of 3.5 g/m2.
Moreover, Connelly and team say that there was a “concomitant and significant reduction” in the indexed extracellular compartment volume (adjusted difference=1.5 mL/m2), and a nonsignificant “trend toward decrease” in the indexed intracellular compartment volume with empagliflozin versus placebo treatment, suggesting “that reverse [extracellular matrix] remodeling occurred in parallel to the decline in LV mass.”
By contrast, empagliflozin was not associated with changes in circulating levels of the tissue remodeling biomarkers matrix metalloproteinase-2 (MMP-2) and soluble suppressor of tumorgenicity (sST2), but the researchers caution that larger studies evaluating a greater range of biomarkers are needed “before conclusions can [be] obtained regarding the role of sST2 and MMP2 in the LV mass and ECV regression observed in the current study.”
Writing in an editorial comment, Stephen Nicholls and Nitesh Nerlekar, both from Monash University in Melbourne, Victoria, Australia, say that the study results “contribute to the published data characterizing the impact of SGLT2 inhibitors on the heart,” but “the degree to which they provide a clear mechanism underscoring the beneficial effects of these agents on heart failure outcomes is uncertain.”
Nevertheless, “the findings do highlight the utility of serial CMR imaging to elucidate the potential direct cardiac effects of medical therapies,” they add.
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JACC Cardiovasc Imaging 2021; doi:10.1016/j.jcmg.2020.10.017
JACC Cardiovasc Imaging 2021; doi: 10.1016/j.jcmg.2020.11.003