Diagnosis of syncope and review of link with vitamin deficiencies

Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often as a result of an abrupt drop of systemic blood pressure. Typically, the inadequate cerebral nutrient flow is of relatively brief duration (8-10 seconds) and in relation to syncope it is by
definition spontaneously self-limited. 

Tilt testing is recommended where a cardiac cause of syncope has been outruled. It helps to differentiate between both orthostatic hypotension (OH) and reflex syncope as well as syncope occurring with jerk-like limb movements and epilepsy. Reproduction of symptoms here is diagnostic.¹ Vitamin B12 is implicated in causing autonomic dysfunction and hence is an important cause to rule out when assessing a patient with orthostatic hypotension and syncopeal symptoms.^2,3,4,5,6 Vitamin D is also known for causing orthostatic hypotension according to recent studies and its deficiency is very common in the general population, making it an important reversible cause of syncope due to OH.^7,8

The syncope unit in Midland Regional Hospital, Tullamore accepts patients who have being referred by their GP or are admitted to hospital for investigation of unexplained falls and syncope. The tests performed can include a head up tilt (HUT) and/or active stand (AS), prolonged tilt (PT) and carotid sinus massage (CSM).

Objective and method

The purpose of this study was to review diagnostic outcomes in patients’ syncope or pre-syncope through the use of tilt table testing, and to find the co-relation of its association with vitamin D and vitamin B12 deficiency after ruling out other causes of the symptoms.

This is a retrospective analysis of haemodynamic changes in response to tilt table testing, which were recorded by a non-invasive volume clamp technique (finometer). The following diagnoses were made:

• Orthostatic hypotension (OH)
• Carotid sinus syndrome (CSS)
• Neurocardiogenic syncope (NCS) 
• Postural orthostatic tachycardia syndrome (POTS).
• Blood levels of vitamin D and vitamin B12 were then checked.

Results

A total of 181 patients underwent investigation during a one year period from October 1, 2015 to September 30, 2016. The mean age of patients was 72 years and the male to female ratio was 1:1.9. Out of 181 patients, 100 of them had positive tilt table test. Out of the 100 patients with positive tilt table test, 46% (n = 46) met the criteria of OH. The mean systolic drop in blood pressure was 40mmHg and the mean diastolic drop was 20mmHg. 

Out of these 40% (n = 40) were diagnosed with CSS on the basis of spine and erect CSM manoeuvre, with 27.57% (n = 31) of these being vasodepressor and 13.29%( n = 9) being cardio-inhibitory. A total of 13% (n = 13) were diagnosed with POTS, all of whom were females. One patient from the investigation was diagnosed with NCS. 

Out of these 100 patients, 71 had vitamin B12 or vitamin D deficiency. Hence, only 29 patients had normal vitamin levels (see Figure 2). A total of 23% (n = 23) patients with syncope were vitamin B12 deficient; out of these 12% (n = 12) were diagnosed as OH and 9% (n = 9) with CSS, while 2% (n = 2) were diagnosed with POTS.

On the other hand 56% (n = 56) of patients with syncope had vitamin D deficiency, 24% (n = 24) of patients with CSS were deficient in vitamin D, 22% (n = 22) had OH and 12% (n = 12) were given the diagnosis of POTS. Nine patients had a deficiency of both vitamin D and vitamin B12. A total of 34 (60%) of the 56 patients with vitamin D deficiency and 13 patients (58%) with vitamin B12 deficiency were female with syncope diagnosed by tilt table testing (see Figure 3).

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Conclusion

This study indicates that: 

• The tilt table test is a useful tool in the diagnosis of syncope 
• Vitamin D and vitamin B12 deficiencies have a significant association with syncope
• Vitamin B12 and vitamin D deficiencies can culminate in syncope and therefore should be ruled out in all patients with syncope as they can be a cause of it.

Discussion

Orthostatic hypotension, first described by Bradbury and Eggleston in 1925,⁹ is defined as a fall in systolic blood pressure of at least 20mmHg or diastolic pressure of at least 10mmHg during the first three minutes of standing. Approximately 0.4% of all hospitalisations in the US are related to OH. In 17% of these cases OH is the primary diagnosis.¹⁰ Its prevalence increases with age because aging is associated with a decrease in baroreceptor sensitivity and responsiveness, reduced cardiac compliance and attenuation of the vestibulosympathetic reflex.

Immediately after a person stands, 500-1,000mL of blood pools in the lower extremities and splanchnic circulation. Venous return to the heart is reduced, which lowers cardiac output and blood pressure. The baroreceptors in the carotid sinus and aortic arch sense these changes. As part of the compensatory reflex, sympathetic outflow is increased and vagal activity is reduced. These responses cause an increase in peripheral resistance, venous return to the heart and cardiac output, thus preventing the fall in blood pressure. If this reflex fails, OH occurs.

Head-up tilt table testing is indicated in the diagnosis of recurrent syncope where initial history, clinical examination and appropriate neurological and cardiovascular investigations have been non-diagnostic. Tilt table testing may also be appropriate in patients with single syncopal episodes who have sustained injuries during attacks or who have experienced syncope while driving. Tilt testing may also be useful in the assessment of older patients with unexplained falls. Relative contraindications include proximal coronary artery stenosis, critical mitral stenosis, clinically severe left ventricular outflow obstruction and known severe cerebrovascular stenosis.¹¹

Vitamin B12 deficiency is a commonly found in older outpatients,⁵ and OH associated with this deficiency has been reported since the early 1960s. In 1962, Kalbfleisch and Woods² reported a case of OH associated with pernicious anaemia; the patient completely recovered after 12 weeks of parenteral vitamin B12 therapy.

Many investigators, including Beitzke et al,⁶ have suggested that any patient with OH should be screened for vitamin B12 deficiency, even in the absence of clinical neurologic signs or typical haematologic manifestation.

Vitamin D is of interest in orthostatic hypotension because of its suggested role in the cardiovascular system. Vitamin D has been shown to help manage high blood pressure and reduce hardening of arteries. Because of this, vitamin D deficiency could be involved in a lack of blood pressure control and subsequent orthostatic hypotension. It was studied in as section in the EPIDOS cohort study.⁸

References

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