Celestino Sardu1, M Massimo Massetti2, Pietro Rambaldi3, Gianluca Gatta4, Salvatore Cappabianca5, Ferdinando Carlo Sasso6, Matteo Santamaria7, Mario Volpicelli8, Valentino Ducceschi9, Giuseppe Signoriello10, Giuseppe Paolisso11, Raffaele Marfella12. 1. Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: drsarducele@gmail.com. 2. Cardiovascular and Arrhythmias Department "Gemelli Molise", Campobasso, Italy; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Rome, Italy. 3. Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: pietro.rambaldi@unicampania.it. 4. Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: gianluca.gatta@unicampania.it. 5. Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: salvatore.cappabinaca@unicampania.it. 6. Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: ferdinandocarlo.sasso@unicampania.it. 7. Cardiovascular and Arrhythmias Department "Gemelli Molise", Campobasso, Italy. Electronic address: matteo.santamaria@gemellimolise.it. 8. Cardiovascular Diseases and Electrophysiology Unit, "S. Maria della Pietà Hospital", Naples, Italy. 9. Cardiovascular Diseases and Electrophysiology Unit, "Vecchio Pellegrini Hospital", Naples, Italy. 10. Department of Mental Health, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: giuseppe.signoriello@unicampania.it. 11. Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; "Mediterranea Cardiocentro", Naples, Italy. Electronic address: giuseppe.paolisso@unicampania.it. 12. Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; "Mediterranea Cardiocentro", Naples, Italy. Electronic address: raffaele.marfella@unicampania.it.
Abstract
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.
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.