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Background: The cardiovascular (CV) benefits of sodium-glucose transport protein 2 inhibitors have been attributed, in part, to cardiac reverse remodelling. The EMPA-HEART CardioLink-6 study reported that sodium-glucose cotransporter-2 inhibition for 6 months with empagliflozin was associated with a significant reduction in left ventricular mass indexed to body surface area (LVMi). In this sub-analysis, we evaluated whether baseline LVMi may influence how empagliflozin affects cardiac reverse remodelling. Methods: A total of 97 patients with type 2 diabetes and coronary artery disease were randomized to empagliflozin (10 mg/d) or matching placebo for 6 months. The study cohort was divided into those whose baseline LVMi was ≤ 60 g/m2 and those who had a baseline LVMi > 60 g/m2. Subgroup comparisons were conducted using a linear regression model adjusted for baseline values (ANCOVA) that included an interaction term between LVMi subgroup and treatment. Results: Baseline LVMi was 53.3 g/m2 (49.2–57.2) and 69.7 g/m2 (64.2–76.1) for those with baseline ≤ 60 g/m2 (n = 54) and LVMi > 60 g/m2 (n = 43) respectively. The adjusted difference of LVMi regression between those randomized to empagliflozin and placebo were − 0.46 g/m2 (95% CI: −3.44, 2.52, p = 0.76) in the baseline LVMi ≤ 60 g/m2 subgroup and − 7.26 g/m2 (95% CI: −11.40, −3.12, p = 0.0011) in the baseline LVMi > 60 g/m2 subgroup (p-for-interaction = 0.007). No significant associations were found between baseline LVMi and 6-month change in LV end systolic volume-indexed (p-for-interaction = 0.086), LV end diastolic volume-indexed (p-for-interaction = 0.34), or LV ejection fraction (p-for-interaction = 0.15). Conclusions: Patients with higher LVMi at baseline experienced greater LVM regression with empagliflozin. [ABSTRACT FROM AUTHOR]

Aims: The duration of type 2 diabetes mellitus (T2DM) is an important determinant of diabetes severity. The EMPA‐HEART CardioLink‐6 trial reported significant left ventricular (LV) mass indexed to body surface area (LVMi) regression in patients treated with the sodium‐glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin for 6 months. This exploratory sub‐analysis of the same trial investigated the association between T2DM duration and LVMi regression. Methods and results: A total of 97 individuals with T2DM and coronary artery disease (CAD) were randomly assigned to receive empagliflozin 10 mg daily or placebo. LVMi was measured at the baseline and 6 month visit using cardiac magnetic resonance imaging. The study population was divided into those with a baseline T2DM duration <10 years (n = 40) or ≥10 years (n = 57). A linear model adjusting for baseline values in each of the subgroups (ANCOVA) was used to assess the treatment effect of 6 month change in LVMi, LV end systolic volume indexed to body surface area, LV end diastolic volume indexed to body surface area and LV ejection fraction. Patients in the T2DM duration <10 years group (38 males [95.0%], median age 63 [IQR: 55 years to 70 years]) had a median T2DM duration of 4 years (IQR: 2.0 years to 7.0 years). Those in the T2DM duration ≥10 years group (52 males [91.2%], median age 65 [IQR: 57 years to 71 years]) had a median duration of 15 years (IQR: 12 years to 20 years). There was no significant difference in baseline LVMi according to T2DM duration (median 62 g/m2 [IQR: 53.1 g/m2 to 70.0 g/m2] for T2DM duration <10 years; median 57.5 g/m2 [IQR: 52.1 g/m2 to 66.2 g/m2] for T2DM duration ≥10 years; P = 0.11). Empagliflozin was associated with reductions in LVMi irrespective of duration of T2DM above and below 10 years (T2DM duration <10 years group, mean adjusted difference −2.90 g/m2 [95% CI: −6.64 g/m2 to 0.84 g/m2]; T2DM duration ≥10 years group, mean adjusted difference −3.69 g/m2 [95% CI: −0.14 g/m2 to −7.24 g/m2]; Pinteraction = 0.07). Conclusions: In the EMPA‐HEART CardioLink‐6 trial, empagliflozin treatment was associated with reductions in LVMi in people with T2DM and CAD irrespective of the duration of diabetes assessed categorically above and below 10 years. [ABSTRACT FROM AUTHOR]

Aims: The neutrophil‐to‐lymphocyte ratio (NLR) is a marker of systemic inflammation and plays a critical role in the assessment and prognosis in patients with heart failure. The EMPA‐HEART CardioLink‐6 trial demonstrated that patients with type 2 diabetes (T2D) and coronary artery disease (CAD) treated with a sodium–glucose transport protein 2 inhibitor for 6 months experienced regression in left ventricular mass. Given this, we evaluated the relationship of baseline NLR and cardiac reverse remodelling in the entire cohort of this trial. Methods and results: A total of 97 individuals were randomized to receive empagliflozin (10 mg/day) or placebo for 6 months. The primary outcome of the trial was change in left ventricular mass indexed to body surface area (LVMi) from baseline to 6 months as measured by cardiac magnetic resonance imaging. In our analysis, the cohort was stratified above and below an NLR level of 2. To assess the treatment effect on the 6 month change in NLR, we used a linear model adjusting for baseline differences in NLR [analysis of covariance (ANCOVA)] that included an interaction term between the baseline NLR and treatment. To assess the treatment effect on the 6 month change in LVMi in each of the subgroups divided by baseline NLR, we used an ANCOVA adjusting for baseline differences in LVMi that included an interaction term between the subgroups and treatment. The results of the regression models were summarized as adjusted differences with two‐sided 95% confidence intervals (CIs). Patients who exhibited an elevated baseline NLR demonstrated higher LVMi and left ventricular end‐diastolic volume indexed to body surface area than those with a lower NLR. In patients with an NLR < 2 and NLR ≥ 2, the adjusted difference in LVMi between the empagliflozin‐ and placebo‐treated patients was −2.98 g/m2 (95% CI: −6.18 to 0.22 g/m2) (P value = 0.067) and −4.43 g/m2 (95% CI: −8.50 to −1.11 g/m2), respectively (Pinteraction = 0.60). Conclusions: Empagliflozin treatment is associated with consistent reductions in LVMi in patients with T2D and CAD independent of baseline NLR. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated to promote reverse cardiac remodeling in people with diabetes or heart failure. While it has been theorized that SGLT2 inhibitors might afford similar benefits in people without diabetes or prevalent heart failure, this has not been evaluated. We sought to determine if SGLT2 inhibition with empagliflozin leads to a decrease in left ventricular (LV) mass in people without type 2 diabetes or significant heart failure. Methods: Between April 2021 and January 2022, 169 individuals, 40-80 years of age, without diabetes but with risk factors for adverse cardiac remodeling were randomized to empagliflozin (10 mg/day; n=85) or placebo (n=84) for 6 months. The primary outcome was the 6-month change in LV mass indexed (LVMi) to baseline body surface area (BSA) as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to baseline BSA and LV ejection fraction. Results: Among the 169 participants (141 men [83%], mean age 59.3 ± 10.5 years), baseline LVMi was 63.2 ± 17.9 g/m2 and 63.8 ± 14.0 g/m2 for the empagliflozin- and placebo-assigned groups, respectively. The difference (95% CI) in LVMi at 6 months in the empagliflozin group vs. placebo group adjusted for baseline LVMi was -0.30 g/m2 (-2.1,1.5 g/m2) (P=0.74). Median baseline (IQR) NT-proBNP was 51 pg/mL (20, 105 pg/mL) and 55 pg/mL (21, 132 pg/mL) for the empagliflozin- and placebo-assigned groups, respectively. The 6-month treatment effect of empagliflozin vs. placebo (95% CI) on blood pressure and NT-proBNP (adjusted for baseline values) were -1.3 mmHg (-5.2, 2.6 mmHg) (P=0.52), 0.69 mmHg (-1.9, 3.3 mmHg) (P=0.60) and -6.1 pg/mL (-37.0, 24.8 pg/mL) (P=0.70) for systolic blood pressure, diastolic blood pressure and NT-proBNP, respectively. No clinically meaningful between group differences in LV volumes (diastolic and systolic indexed to baseline BSA) or ejection fraction were observed. No difference in adverse events was noted between the groups. Conclusions: Among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, SGLT2 inhibition with empagliflozin did not result in a meaningful reduction in LVMi after 6 months. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04461041clinicaltrials.gov Identifier: NCT04461041. [ABSTRACT FROM AUTHOR]