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

Sardu, Celestino; Massetti, Massimo; Rambaldi, Pietro; Gatta, Gianluca; Cappabianca, Salvatore; Sasso, Ferdinando Carlo; Santamaria, Matteo; Volpicelli, Mario; Ducceschi, Valentino; Signoriello, Giuseppe; Paolisso, Giuseppe; Marfella, Raffaele

doi:10.1016/j.metabol.2022.155243

Cited by 31 publications

(21 citation statements)

References 36 publications

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“…In our cohort, the improved modulation of sympathetic tone could be reflected by a lower heart rate in patients treated with SGLT2-i. Indeed, previous reports have shown a more balanced autonomic system activity in patients treated with SGLT2-i when compared with non-SGLT2-i users, also in patients without structural heart disease (19). Another beneficial effect of SGLT2-i is protection against hyperglycemia-induced sympathetic overstimulation (45,46).…”

Section: Discussionmentioning

confidence: 97%

“…In T2DM patients, the SGLT2-i have been shown to improve cardiac function ( 17 ), reduce hospitalizations, and positively impact prognosis in patients with stable ischemic heart disease undergoing surgical revascularization ( 18 ). In addition, they have an ameliorative effect on sympathetic tone, potentially reducing arrhythmic burden ( 19 ). Patients with AMI, even those with T2DM, are prone to developing new-onset arrhythmias due to autonomic, electrical, and structural remodeling, and glycemic fluctuations ( 20 , 21 ).…”

Section: Introductionmentioning

confidence: 99%

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In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study

Cesaro

Gragnano²,

Paolisso³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundSodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients.ObjectivesTo investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users).MethodsPatients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non-SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization.ResultsThe study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-i users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs. 15.7%, p = 0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually (p = 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR = 0.35; 95%CI 0.14–0.86; p = 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-i therapy remained an independent predictor of VT/VF occurrence (OR = 0.20; 95%CI 0.04–0.97; p = 0.046) but not of AF occurrence.ConclusionsIn T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control.Trial registrationData are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov, identifier: NCT05261867.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study

Cesaro

Gragnano²,

Paolisso³

et al. 2022

Front. Cardiovasc. Med.

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“…The state of the autonomic nervous system is important for the vascular system to adequately respond to the gravity challenge. Disturbances in this system inevitably lead to clinical orthostatic disturbances and adequate correction reduces the risk of recurrent syncope [ 39 ]. Adaptive orthostatic processes also include the activation of the renin–angiotensin–aldosterone system [ 40 ] and the release of catecholamines and vasopressin [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Detection of Preclinical Orthostatic Disorders in Young African and European Adults Using the Head-Up Tilt Test with a Standardized Hydrostatic Column Height: A Pilot Study

et al. 2022

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Arterial hypertension (AH) remains the most common disease. One possible way to improve the effectiveness of the primary prevention of AH is to identify and control the preclinical orthostatic disturbances that precede the development of AH. The aim of the study was to determine the feasibility of a new protocol for the head-up tilt test (HUTT) with a standardized hydrostatic column height for the detection of asymptomatic orthostatic circulatory disorders and their racial differences in young African and European adults. Methods. In total, 80 young healthy adults (40 African and 40 European) aged 20–23 years performed the HUTT with a standardized hydrostatic column height of 133 cm. The hemodynamic parameters were recorded using a Task Force Monitor (3040i). The cardio-ankle vascular index (CAVI) was measured using a VaSera VS-2000 volumetric sphygmograph. Results. The baseline and orthostatic hemodynamic changes in both racial groups were within normal limits. Orthostatic circulatory disturbances were not detected in 70% of the European participants and 65% of the African participants; however, preclinical orthostatic hypertension, which precedes AH, was detected using the new HUTT protocol in 32.5% of the African participants and 20% of the European participants. The baseline CAVI was higher in the European group compared to the African group. Conclusion. The results of this study showed the feasibility of the detection of preclinical orthostatic disturbances in young adults and the detection of their racial differences using the HUTT protocol, providing the use of a standard gravity load. Further study on the evolution of preclinical orthostatic disturbances and their relation to increased vascular stiffness is necessary among large samples.

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“…However, this was not confirmed in a recent experiment [ 139 ]. Moving on to the effects of SGLT2i on CAN, in a study of patients with type 2 DM and vasovagal syncope recurrence, SLGT2i use was associated with a significantly lower low frequency/high frequency ratio and norepinephrine serum levels and a higher Heart to Mediastinum ratio in 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy at the conclusion of the study [ 140 ]. These SGLT2i-mediated effects might indicate more balanced autonomic system activity and an induced improvement in CAN.…”

Section: A Novel Era In Heart Failure Pharmacotherapy: Sglt2 Inhibitorsmentioning

confidence: 99%

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

Theofilis

Oikonomou

Tsioufis

et al. 2023

Life

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Diabetes mellitus (DM) and heart failure (HF) are frequently encountered afflictions that are linked by a common pathophysiologic background. According to landmark studies, those conditions frequently coexist, and this interaction represents a poor prognostic indicator. Based on mechanistic studies, HF can be propagated by multiple pathophysiologic pathways, such as inflammation, oxidative stress, endothelial dysfunction, fibrosis, cardiac autonomic neuropathy, and alterations in substrate utilization. In this regard, DM may augment myocardial inflammation, fibrosis, autonomic dysfunction, and lipotoxicity. As the interaction between DM and HF appears critical, the new cornerstone in DM and HF treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i), may be able to revert the pathophysiology of those conditions and lead to beneficial HF outcomes. In this review, we aim to highlight the deleterious pathophysiologic interaction between DM and HF, as well as demonstrate the beneficial role of SGLT2i in this field.

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

Cited by 31 publications

References 36 publications

In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study

In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study

Detection of Preclinical Orthostatic Disorders in Young African and European Adults Using the Head-Up Tilt Test with a Standardized Hydrostatic Column Height: A Pilot Study

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

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