Compression Stockings to Combat Vasovagal Syncope: What Is the Rationale?

the Rationale?

M. M

, F. G

, A. R

Introduction

Syncope is defined as a sudden, transient loss of consciousness and postural tone due to cerebral hypoperfusion, followed by spontaneous recovery [1].

Syncope is a common symptom that affects up to 35–50% of the general pop- ulation: it is the reason for 1–3% of emergency room visits and 1–6% of hos- pital admissions [2]. Syncope may have different causes: cardiovascular, non- cardiovascular and unexplained. The most frequent type of syncope is the vasovagal syncope, who accounts at least 35% of loss of consciousness.

Physiopathology of Vasovagal Syncope

The vasovagal faint is a heterogeneous condition and may be triggered by central stimuli (pain, extreme emotions, psychic stress) and peripheral stim- uli (reduction in venous return to the heart, such as in prolonged standing, hot environments, hypovolaemia, or redistribution of blood volume). In daily life vasovagal syncope is common while the subject is standing [3]. On standing, the increased gravitational forces results in pooling of 500–800 ml of blood in the distensible veins below the level of the heart, i.e., the veins of the legs and the splanchnic veins, thus reducing venous return to the heart.

This leads to a decrease in arterial blood pressure and cardiac output. In normal subjects there is an autonomic compensatory reflex that keeps the arterial blood pressure and the cardiac output almost normal, through vaso- constriction and tachycardia, due to sympathetic activation and parasympa-

Division of Cardiology, Cardiovascular Department, Umberto I Hospital, Mestre-

Venice, Italy

thetic withdrawal, respectively. In patients who are prone to vasovagal syn- cope, this compensatory reflex is inadequate. Hargreaves and Muir [4]

demonstrated, during orthostatic challenge, a larger increase in calf volume in patients with recurrent vasovagal syncope and a trend to greater periph- eral blood pooling and reduced venous volume variability than in normal subjects. It has been postulated that, in patients with vasovagal syncope, the reduction of venous return activates an abnormal reflex, similar to the Bezold–Jarisch reflex, triggered by a vigorous contraction of an almost empty ventricular cavity. It activates intramyocardial mechanoreceptors inappropriately (the unmyelinated vagal C fibres), causing paradoxical sym- pathetic inhibition (peripheral vasodilation) and parasympathetic activation (bradycardia) with cerebral hypoperfusion and syncope [5]. However, the pathophysiology of vasovagal syncope is probably not so schematic, and other potential mechanisms may be responsible for this condition, such as afferent signals arising from atrial or pulmonary baroreceptors, or even from higher central nervous system centres.

Treatment of Vasovagal Syncope

In the majority of subjects vasovagal syncope is a benign condition that does not represent a threat to life and does not significantly impair quality of life.

Consequently, a specific treatment is usually not indicated, and recurrence may be easily prevented by reassurance and counselling of the patient. In a minority of subjects, however, the syncopal episodes are much more fre- quent and often occur in the absence of predictable circumstances or warn- ing symptoms. These episodes may be accompanied by physical injury and represent the so-called ‘malignant’ or ‘atypical’ vasovagal syncope. In these cases, as also in patients with a potential occupational hazard (pilots, truck drivers, commercial painters, roofers, and so on), a specific treatment is gen- erally recommended.

Many forms of treatment are promoted for vasovagal syncope: non-phar- macological/physical, pharmacological, and electrical. None of them has been demonstrated to be surely effective in preventing syncopal recurrences.

The substantial inefficacy of currently available therapeutic options for

patients with recurrent or malignant vasovagal syncope justifies the search

for alternative treatments.

Compression Elastic Stockings

One of the measures suggested in the past for the treatment of vasovagal syncope, but never tested with clinical studies, is the use of compression elastic stockings. The rationale for this therapy is the reduction in venous pooling and the increase in venous return that compression elastic stockings may induce.

Several studies have investigated the haemodynamic and clinical effects of this therapy in different clinical settings, but to the best of our knowledge no studies have been performed to evaluate the effects of compression elastic stockings in patients with vasovagal syncope. Buhs et al. [6] studied healthy subjects during daily activity that requires nearly continuous standing and walking: under those conditions, it has been shown that graduated elastic stockings had a direct anatomic effect which can be related to the transmural pressure in the veins that preserve dilation in the deep, superficial, and per- forating venous system of the lower leg.

In patients with chronic venous insufficiency, compression elastic stock- ings have been shown to reduce the residual volume fraction, which is an indicator of improving calf muscle pump function and reflux in vein seg- ments [7]. These favourable effects of compression elastic stockings in patients with chronic venous insufficiency seem to be a consequence of shifting blood from the superficial to the deep venous compartment of the legs [8]. This promotes venous return to the heart by means of blood milk- ing caused by muscle contraction [9–17].

In patients with orthostatic hypotension caused by adrenergic failure, compression elastic stockings reduce the decrease in standing blood pres- sure by increasing total peripheral resistance and reducing venous capability [18]. In daily life this leads to a reduction of hypotension-related symptoms, such as dizziness and increased heart rhythm, and an improvement in quali- ty of life [19].

Stic Stoc Trial

On the basis of these observations, we have planned a multi-centre, ran-

domised, placebo-controlled study, the ‘ElaSTIC STOCkings for the preven-

tion of recurrent vasovagal syncope TRIAL’ (Stic Stoc Trial).

Aim of the Study

The aim of the study is to ascertain whether, among patients suffering from recurrent vasovagal syncope, compression elastic stockings reduce the num- ber affected by syncope recurrences, prolong the time to the first recurrence, and improve quality of life.

Study Design

Enrolled patients will be randomised to active treatment (compression elas- tic stockings) or placebo (non-compression stockings). The compression elastic stockings exert a pressure of 20–30 mmHg around the calves, which corresponds to class II of the European CEN classification [17]. The inactive treatment, the placebo, looks like the elastic compression stockings, but does not exert haemodynamic effects. The clinicians, nurses, and enrolled patients will be blinded to the type of stockings being worn.

Inclusion and Exclusion Criteria

To be enrolled, patients will have to meet the following criteria: vasovagal syncope and positive head-up tilt testing; at least 6 syncopal events in the patient’s lifetime, the latest occurring no more than 6 months before enrol- ment. The following constitute exclusion criteria: non-vasovagal syncope;

chronic venous and arterial insufficiency ; recent (< 6 months) acute myocardial infarction; chronic severe non-cardiac diseases (terminal neopla- sia, neurological disease, etc.); pregnancy.

Other Therapies

During the study period, the use of pacemakers or drugs for the prevention of vasovagal syncope, such as β-blockers, α

-agonists, fludrocortisone, sero- tonin uptake inhibitors, theophylline, and scopolamine, will not be allowed.

Quality of Life

The patient’s quality of life will be evaluated through a questionnaire (SF-36) filled out before treatment and again after 6 and 12 months.

Follow-Up

During follow-up, with a mean duration of 12 months, each enrolled patient

will wear the stockings during the day time. Patients will be asked to keep a

clinical diary, specifying the number, severity, and time of syncopal and pre-

syncopal events, the circumstances in which they occur, and any associated

traumas. Patients also have to report the days in which they do not wear the

stockings, the reason why, and any adverse effects. Every 3 months, patients will be clinically assessed.

Primary Endpoint

The primary clinic endpoint will be syncope, since this can be easily assessed and has been successfully used in previous studies. Patients are examined within 7 days of a fainting episode. To verify the syncopal episode, patients and witnesses are asked to describe the event and the circumstances in which it occurs, stating in particular whether there was complete loss of con- sciousness. Patients are also examined to evaluate any severe trauma result- ing from the event. The number of patients who experience syncope during follow-up, the frequency of syncope (number of times per month), and the time to first recurrence are taken as the parameters to measure the primary clinical event.

Secondary Endpoints

The secondary endpoints will be the following: (1) the number of patients with pre-syncopal recurrences, the frequency of pre-syncopal events, and time to the first pre-syncopal recurrence; (2) quality of life.

References

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