Reverse Remodeling of LV in Patients with Diabetes/Prediabetes and Heart Failure with Reduced Ejection Fraction Treated with Empagliflozin
Authors of the British study SUGAR-DM-HF published in February 2021 examined whether empagliflozin reduces left ventricle (LV) volume in patients with type 2 diabetes mellitus (DM), prediabetes, and heart failure with reduced ejection fraction (EF). This favorable reverse remodeling of the LV could be a mechanism through which empagliflozin achieves reduced hospitalization rates for heart failure and overall mortality in these patients.
Methodology, Course, and Goals of the Study
The aim of the multicenter randomized double-blind placebo-controlled study SUGAR-DM-HF (Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure) was to evaluate the effects of empagliflozin on the hearts of patients with type 2 DM or prediabetes and NYHA class II-IV heart failure with a left ventricular ejection fraction ≤ 40%. Patients were randomized in a 1:1 ratio to receive the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin 10 mg once daily or placebo plus standard therapy.
The primary combined observed parameters were the change in LV volume at the end of systole relative to body surface area and global longitudinal strain over the time between the study entry and week 36 of treatment. Both parameters were measured using magnetic resonance imaging (MRI). Secondary observed parameters included LV volume at the end of diastole, LV ejection fraction, intensification of diuretic therapy, symptomatology according to the Kansas City Cardiomyopathy Questionnaire Total Symptom Score and the distance in the 6-minute walk test (6MWT), B-lines on lung ultrasound, and biomarkers such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP).
Observed Population
A total of 105 patients with an average age of 68.7 years were randomized, 73.3% of whom were men. Most (78.1%) had diagnosed diabetes, while the others were in a prediabetic state. The average value of the left ventricular ejection fraction was 32.5%, with 77.1% of the enrolled having NYHA class II heart failure and 22.9% class III. All patients were on standard heart failure treatment.
Results
Empagliflozin reduced the indexed LV volume at the end of systole significantly more than placebo: a difference of 6.0 ml/m2 (p = 0.015). However, no difference was observed in the change of global longitudinal LV strain between the groups.
Among secondary observed parameters, empagliflozin treatment, compared to placebo, showed a significantly greater reduction in LV volume at the end of diastole by 8.2 ml/m2 (p = 0.0042) and a 28% reduction in NT-proBNP levels (p = 0.038). Other observed parameters did not differ between the groups.
Conclusion
Treatment with the SGLT2 inhibitor empagliflozin leads to favorable LV remodeling in patients with type 2 diabetes or prediabetes and heart failure with reduced EF. This finding could at least partly explain the beneficial effect of SGLT2i on clinical outcomes in heart failure with reduced LV EF. The British study provided a more precise picture of the impact of SGLTi on heart structure compared to previous works that used ultrasound or radionuclide imaging methods.
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- Source: Lee M. M. Y., Brooksbank K. J. M., Wetherall K. et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation 2021 Feb 9; 143 (6): 516−525, doi: 10.1161/CIRCULATIONAHA.120.052186.
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