Type 2 diabetes is independently associated with all-cause mortality secondary to ventricular tachyarrhythmias

Weidner, Kathrin; Behnes, Michael; Schupp, Tobias; Rusnak, Jonas; Reiser, Linda; Bollow, Armin; Taton, Gabriel; Reichelt, Thomas; Ellguth, Dominik; Engelke, Niko; Hoppner, Jorge; El‐Battrawy, Ibrahim; Mashayekhi, Kambis; Weiß, Christel; Borggrefe, Martin; Akın, İbrahim

doi:10.1186/s12933-018-0768-y

Cited by 30 publications

(19 citation statements)

References 51 publications

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“…without AMI is independently associated with an increase of all-cause mortality in patients presenting with ventricular tachyarrhythmias on admission [44]. In the EMBODY trial, glycemic control levels were even in the two groups.…”

Section: Discussionmentioning

confidence: 93%

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

Shimizu

Kubota

Hoshika

et al. 2020

Preprint

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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

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Section: Discussionmentioning

confidence: 93%

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

Shimizu

Kubota

Hoshika

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Glycemic variability is associated with cardiovascular autonomic neuropathy [41,42], and hyperglycemia results in ventricular tachycardia in patients hospitalized with AMI [43]. Moreover, the presence of T2DM without AMI is independently associated with an increase of all-cause mortality in patients presenting with ventricular tachyarrhythmias on admission [44]. In the EMBODY trial, glycemic control levels were even in the two groups.…”

Section: Discussionmentioning

confidence: 99%

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

Shimizu

Kubota

et al. 2020

Cardiovasc Diabetol

125

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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 ms 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.

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“…Patients presented with VT/VF who had diabetes portend worse long-term all-cause mortality at 2 years as compared to patients without diabetes [ 89 ]. Hyperglycemia was associated with prolonged QT interval, increased QT dispersion, and higher risk of developing VT in acute MI patients [ 90 , 91 ].…”

Section: Effects Of Metformin On Ventricular Arrhythmias: Evidence Frmentioning

confidence: 99%

Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient

Nantsupawat

Wongcharoen

Chattipakorn

2020

Cardiovasc Diabetol

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Metformin has been shown to have various cardiovascular benefits beyond its antihyperglycemic effects, including a reduction in stroke, heart failure, myocardial infarction, cardiovascular death, and all-cause mortality. However, the roles of metformin in cardiac arrhythmias are still unclear. It has been shown that metformin was associated with decreased incidence of atrial fibrillation in diabetic patients with and without myocardial infarction. This could be due to the effects of metformin on preventing the structural and electrical remodeling of left atrium via attenuating intracellular reactive oxygen species, activating 5′ adenosine monophosphate-activated protein kinase, improving calcium homeostasis, attenuating inflammation, increasing connexin-43 gap junction expression, and restoring small conductance calcium-activated potassium channels current. For ventricular arrhythmias, in vivo reports demonstrated that activation of 5′ adenosine monophosphate-activated protein kinase and phosphorylated connexin-43 by metformin played a key role in ischemic ventricular arrhythmias reduction. However, metformin failed to show anti-ventricular arrhythmia benefits in clinical trials. In this review, in vitro and in vivo reports regarding the effects of metformin on both atrial arrhythmias and ventricular arrhythmias are comprehensively summarized and presented. Consistent and controversial findings from clinical trials are also summarized and discussed. Due to limited numbers of reports, further studies are needed to elucidate the mechanisms and effects of metformin on cardiac arrhythmias. Furthermore, randomized controlled trials are needed to clarify effects of metformin on cardiac arrhythmias in human.

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Type 2 diabetes is independently associated with all-cause mortality secondary to ventricular tachyarrhythmias

Cited by 30 publications

References 51 publications

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient

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