Cardiac Autonomic Dysfunction in Diabetics Patients With Syncope
Condition: Syncope, Vasovagal
MeSH terms: Syncope; Syncope, Vasovagal
Study type: Observational

Summary: 
      Study hypothesis: cardiac autonomic dysfunction may affect vaso vagal syncope recurrences in
      type 2 patients with diabetes vs. patients without diabetes.

      Background: vaso vagal syncope and its recurrences may be due to alterations in autonomic
      system function, that may be more frequent in diabetics. Heart rate variability (HRV) is a
      valid test to study sympathetic and vaso vagal tone dysfunction. However, in this study
      authors investigated the correlation between HRV alterations and diabetes in a population of
      patients affected by syncope, and classified as vaso vagal syncope by Head Up Tilt Test (HUT)
      exam. Secondly, authors assessed these alterations as causes of vaso vagal syncope recurring
      at 12 months of follow up in type 2 patients with diabetes under sodium-glucose transporter 2
      inhibitors (SGLT2-inhibitors) vs. other hypoglycemic drugs .. Materials and Methods: In a
      multicenter study authors studied T2DM patients under SGLT2-I therapy (n 426) vs. those that
      did not receive the SGLT2-I therapy (n 2195), and affectede by vaso vagal syncope. All
      enrolled patients were in stable sinus rate before to perform ECG Holter, and the Head Up
      Tilt Test (HUT). However, before to perform the HUT all patients performed a 24 hours ECG
      Holter, to asses sinus rhythm , heart rate, and HRV. Then, these patients performed a
      123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy to assess cardiac autonomic
      dysfunction.

      Moreover, authors performed a propensity score matching (PSM) analysis to evaluate 160
      SGLT2-I users vs. 160 Non-SGLT2-I users' patients.
    

Detailed description: 
      Vaso vagal syncope recurrence is a relevant clinical problem (1). In fact, despite the vaso
      vagal syncope event is a transient loss of consciousness with rapid onset, short duration,
      and spontaneous complete recovery after the event, it may be complicated by physical injury
      (2). Conversely, the syncope recurrence rate is about 35%, and it causes a physical injury
      until the 29% (3). In addition, the vaso vagal syncope has a frequency between 15% and 39%,
      with annual number of episodes about 18.1-39.7 per 1000 patients, and an incidence of 6.2 per
      1000 person-years, that grows up after 70 years of age with rate annual 19.5 per thousand
      individuals after 80 years (3). The patients with type 2 diabetes mellitus (T2DM) represent a
      percentage about the 30% of all the subjects with syncope (4). About the pathophysiology of
      syncope a central role is played by autonomic nervous system (5). To date, the autonomic
      nervous system regulates the hemodynamic stability by maintaining a stable blood pressure and
      heart rate under normal and abnormal physiologic conditions (5). Consequently, the
      dysfunction of this complex regulatory system, and of its interaction with sensor systems as
      baroreceptors, mechanoreceptors, chemoreceptors, may alter the vascular reactivity, leading
      to the clinical event and to future recurrences (5). Multiple factors affecting the autonomic
      system balance may trigger and cause a syncope event, as the result of an inappropriate
      response of the autonomic nervous system, with excessive vagal tone, and sympathetic tone
      withdrawal (2). In this setting, authors may note the diabetes as a common cause of autonomic
      system dysfunction (6). Moreover, T2DM may cause a severe form of autonomic system
      dysfunction affecting the cardiac autonomic regulation, and named as cardiac autonomic
      neuropathy (CAN), (6). Intriguingly, patients with diabetes experience a parasympathetic
      denervation, with an early augmentation of sympathetic tone, then leading to impaired heart
      rate variability, resting tachycardia, exercise intolerance, abnormal blood pressure
      regulation, and orthostatic hypotension (7). In addition, in T2DM there is a compensatory
      increase in the cardiac sympathetic tone in response to subclinical peripheral denervation
      (7). However, the T2DM may be seen as a relevant risk factor and a trigger to alter the
      autonomic system balance, and to cause vaso vagal syncope. In this context, the SGLT2-I are
      hypoglycemic drugs that might modulate the systemic and cardiac sympathetic dysfunction. On
      the other hand, the effects of the SGLT2-I therapy on the diabetic autonomic dysfunction and
      the vaso vagal syncope recurrence at follow up is not well established. Moreover, the recent
      studies cannot come to definitive conclusion about the impact of SGLT2-I on the vaso vagal
      syncope events, and about its future recurrences in patients with type 2 diebetes mellitus
      (T2DM). Conversely, heart rate variability (HRV) is a simple, reproducible and
      well-recognized method for evaluating sympatho vagal activity (8, 9). In this setting, the
      123I-MIBG is an imaging exam to evaluate the cardiac autonomic dysfunction. Indeed, the 123I
      is an analogous of norepinephrine, and the entity of its myocardial captation is an index of
      cardiac innervation.

      However, in this study authors evaluated the autonomic dysfunction as alteration in HRV, and
      123I-MIBG, and its relevance to cause vaso vagal syncope, and the vaso vagal syncope
      recurrence in SGLT2-I users vs. Non-SGLT2-I users' patients with T2DM at 12 months of follow
      up.
    

Intervention name(s): ecg Holter,; cardiac scintigraphy
Intervention type(s): Other; Diagnostic Test
Intervention description(s): all patients before to perform an head up tilt test for syncope evaluation will be steadied by ecg Holter to assess heart rate, heart rate variability.; all patients before to perform an head up tilt test for syncope evaluation will receive a the 123I-MIBG, which is a norepinephrine analogous, to calculate the late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR). Thus, we evaluated the H/Mlate as the index of global neuronal function due to norepinephrine uptake and the WR as the index of sympathetic tone.
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Included patients with clinical history of vaso vagal syncope, as diagnosed by head up tilt
        test. These patients, aged between 18 and 75 years, received an ecg Holter before to
        perform head up tilt test evaluation. These patients presented with vaso vagal syncope in
        absence of neuropathy, arterial hypertension, heart failure and coronary heart disease or
        depression of left ventricle ejection fraction (LVEF < 55%).