SGLT2-inhibitors reduce the cardiac autonomic neuropathy dysfunction and vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus: the SCAN study.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) the vaso-vagal syncope (VVS) recurrence could be due to the alteration of autonomic system function, evaluated by heart rate variability (HRV), and by 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy indexes: Heart to Mediastinum ratio (H/Mlate), and Washout rate (WR). The SGLT2-I could modulate/reduce autonomic dysfunction in T2DM patients with VVS. This effect could reduce the VVS recurrence in T2DM patients. METHODS: In a prospective multicenter study, after propensity score matching, we studied a population of 324 T2DM patients with VVS, divided into 161 SGLT2-I-users vs. 163 Non-SGLT2-I users. In these patients as SGLT2-I-users vs. Non-SGLT2-I users, we investigated the HRV and 123I-MIBG modifications and VVS recurrence at 12 months of follow-up. RESULTS: At follow-up end, the SGLT2-I-users vs. Non-SGLT2-I users had best glucose homeostasis and lower values of inflammatory markers, and resting heart rate (p < 0.05). The SGLT2-I-users vs. Non-SGLT2-I users evidenced the lowest low frequency/high frequency ratio (LF/HFr), a significant difference for all the indexes of autonomic dysfunction via ECG Holter analysis, and higher values of H/Mlate (p < 0.05). Finally, comparing SGLT2-I-users vs. Non-SGLT2-I users, we found a higher rate of VVS recurrence events, specifically of the vasodepressor VVS recurrence at 1-year follow-up (p < 0.05). We did not find a significant difference of mixed and cardio-inhibitory VVS recurrence events at 1 year of follow-up in the study cohorts (p > 0.05). At the Cox regression analysis H/Mlate (0.710, [0.481-0.985]), and SGLT2-I therapy (0.550, [0.324-0.934]) predicted all causes of syncope recurrence at 1 year of follow-up. CONCLUSIONS: Non-SGLT2-I users vs. SGLT2-I-users had alterations of the autonomic nervous system, with a higher rate of VVS recurrence at 1 year of follow-up. The indexes of cardiac denervation predicted the VVS recurrence, while the SGLT2-I reduced the risk of VVS recurrence. CLINICAL TRIAL REGISTRATION NUMBER: NCT03717207.

Impact of Admission Hyperglycemia on Heart Failure Events and Mortality in Patients With Takotsubo Syndrome at Long-term Follow-up: Data From HIGH-GLUCOTAKO Investigators.

OBJECTIVE: To investigate admission hyperglycemia effects on the sympathetic system and long-term prognosis in Takotsubo syndrome (TTS). RESEARCH DESIGN AND METHODS: In patients with TTS and hyperglycemia (n = 28) versus normoglycemia (n = 48), serum norepinephrine and 123I-labeled metaiodobenzylguanidine (MIBG) cardiac scintigraphy were assessed. Heart failure (HF) occurrence and death events over 2 years were evaluated. RESULTS: At hospitalization, those with hyperglycemia versus normoglycemia had higher levels of inflammatory markers and B-type natriuretic peptide and lower left ventricular ejection fraction. Glucose values correlated with norepinephrine levels (R 2 = 0.39; P = 0.001). In 30 patients with TTS, 123I-MIBG cardiac scintigraphy showed lower late heart-to-mediastinum ratio values in the acute phase (P < 0.001) and at follow-up (P < 0.001) in those with hyperglycemia. Patients with hyperglycemia had higher rates of HF (P < 0.001) and death events (P < 0.05) after 24 months. In multivariate Cox regression analysis, hyperglycemia (P = 0.008), tumor necrosis factor-α (P = 0.001), and norepinephrine (P = 0.035) were independent predictors of HF events. CONCLUSIONS: Patients with TTS and hyperglycemia exhibit sympathetic overactivity with a hyperglycemia-mediated proinflammatory pathway, which could cause worse prognosis during follow-up.