Background: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium–glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity.Methods: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency–to–high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT.Results: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were +11.6 and +9.1 msec in the empagliflozin (P=0.02) and placebo groups (P=0.06), respectively. Change in LF/HF ratio was –0.57 and –0.17 in the empagliflozin (P=0.01) and placebo groups (P=0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P=0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed.Conclusions: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events. Trial Registration: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442

Background: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium–glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity.Methods: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and T2DM in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency–to–high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT.Results: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were +11.6 and +9.1 msec in the empagliflozin (P=0.02) and placebo groups (P=0.06), respectively. Change in LF/HF ratio was –0.57 and –0.17 in the empagliflozin (P=0.01) and placebo groups (P=0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P=0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed.Conclusions: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2D and AMI. Early SGLT2 inhibitor administration in AMI patients with diabetes mellitus might be effective in improving cardiac nerve activity without any adverse events.Trial Registration: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442

This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Cardiology Journal" are listed in PubMed.

Background: Various optimal medical therapies have been established to treat heart failure (HF) with reduced ejection fraction (HFrEF). Both HFrEF and HF with preserved ejection fraction (HFpEF) are associated with poor outcomes. We investigated the effect of topiroxostat, an oral xanthine oxidoreductase inhibitor, for HFpEF patients with hyperuricemia or gout. Methods:In this nonrandomized, open-label, single-arm trial, we administered topiroxostat 40-160 mg/ day to HFpEF patients with hyperuricemia or gout to achieve a target uric acid level of 6.0 mg/dL. The primary outcome was rate of change in log-transformed brain natriuretic peptide (BNP) level from baseline to 24 weeks after topiroxostat treatment. The secondary outcomes included amount of change in BNP level, uric acid evaluation values, and oxidative stress marker levels after 24 weeks of topiroxostat treatment. Thirty-six patients were enrolled; three were excluded before study initiation.Results: Change in log-transformed BNP level was −3.4 ± 8.9% (p = 0.043) after 24 weeks of topiroxostat treatment. The rate of change for the decrease in BNP level was −18.0 (−57.7, 4.0 pg/mL; p = 0.041). Levels of uric acid and 8-hydroxy-2'-deoxyguanosine/creatinine, an oxidative stress marker, also significantly decreased (−2.8 ± 1.6 mg/dL, p < 0.001, and −2.3 ± 3.7 ng/mgCr, p = 0.009, respectively).Conclusions: BNP level was significantly lower in HFpEF patients with hyperuricemia or gout after topiroxostat administration; however, the rate of decrease was low. Further trials are needed to confirm our findings.