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 (R2 = 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.

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<b>OBJECTIVES</b>: To investigate admission hyperglycemia effects on the sympathetic system and long-term prognosis in Takotsubo syndrome (TTS). <p><b>RESEARCH DESIGN AND METHODS: </b>in TTS hyperglycemics (n=28) vs normoglycemics (n=48) serum norepinephrine and 123I-MIBG cardiac scintigraphy (123I-MIBGcS) were assessed. Heart failure (HF) occurrence and deaths events over 2-years were evaluated.</p> <p><b>RESULTS: </b>At hospitalization, hyperglycemics vs normoglycemics had higher levels of inflammatory markers, BNP and lower left ventricle ejection fraction (LVEF). Glucose values correlated with norepinephrine levels (R²=0.39, p=0.001). In 30 TTS patients, 123I-MIBGcS showed lower H/M_late valuesin the acute phase (p<0.001) and at follow-up (p<0.001) in hyperglycemic patients. Hyperglycemics had a higher rate of HF events (p<0.001) and deaths (p<0.05) after 24-months. At multivariate Cox Regression analysis, hyperglycemia (p=0.008), TNF-α (p=0.001) and norepinephrine (p=0.035) were independent predictors of HF events.</p> <p><b>CONCLUSIONS: </b>TTS hyperglycemic patients exhibit a sympathetic overactivity with a hyperglycemia-mediated pro-inflammatory pathway which could cause a worse prognosis during follow-up.<b><br> </b></p>

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, we studied a population of 607 T2DM patients affected by VVS, as SGLT2-I-users (n 161) vs. Non-SGLT2-I users (n 446). Thus, in 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 baseline, and follow-up end Non-SGLT2-I users vs. SGLT2-I-users over-expressed the inflammatory markers and norepinephrine, with worse glucose homeostasis and significant difference of HRV parameters, H/Mlate, and the WR (p<0.05). Non-SGLT2-I users vs. SGLT2-I-users had higher recurrence of all causes VVS, and of vasodepressor, and mixed VVS (p<0.05). The Cox regression analysis showed that the H/Mlate (0.710, CI 95% [0.481-0.985]; p 0.024), and SGLT2-I (0.550, CI 95% [0.324-0.934]; p 0.027) predicted all VVS recurrence. 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.

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