{"id":10798,"date":"2021-08-02T13:19:50","date_gmt":"2021-08-02T12:19:50","guid":{"rendered":"https:\/\/touchcardio.com\/?p=10798"},"modified":"2021-08-12T19:10:01","modified_gmt":"2021-08-12T18:10:01","slug":"vasovagal-syncope-a-review-of-current-and-future-strategies","status":"publish","type":"post","link":"https:\/\/touchcardio.com\/syncope\/journal-articles\/vasovagal-syncope-a-review-of-current-and-future-strategies\/","title":{"rendered":"Vasovagal Syncope: A Review of Current and Future Strategies"},"content":{"rendered":"
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Vasovagal syncope is common, and while it is usually associated with a benign prognosis, it results in significant physical and psychological morbidity for affected individuals. Despite comprehensive understanding of the underlying pathophysiology, there have been few definitive therapeutic advances until recent randomized, controlled trials in pharmacotherapy, pacing and cardioneuroablation. In this review, we highlight the increasing recognition that the condition is multifactorial, and emphasize and discuss multifaceted management approaches, including education, psychological wellbeing, dietary and fluid intake, pharmacotherapy and cardiac intervention.<\/p>\n<\/div>\n

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Syncope \u2013 a rapid onset, transient loss of consciousness with spontaneous complete recovery, and resulting from cerebral hypoperfusion \u2013 is common.1<\/span> With a cumulative lifetime incidence of 35\u201350%, syncope accounts for 1\u20133% of emergency department visits.2\u20134<\/span> Vasovagal syncope (VVS) is the most common cause of syncope.4<\/span>\u00a0While VVS is usually associated with a benign prognosis, it is linked with notable morbidity and psychological distress, particularly if there is a delay in diagnosis.5<\/span>\u00a0Also, its prognosis may not be as benign as has been assumed, as it appears to carry an increased likelihood of cardiovascular disease in later life.6<\/span>\u00a0Recurrent VVS is associated with impaired quality of life, and functional impairment similar to other chronic diseases such as back pain and rheumatoid arthritis.7,8<\/span>\u00a0Psychosocial impairment, somatisation, anxiety and depression are common.8<\/span><\/p>\n

Despite advances in the understanding of the pathophysiology of VVS, significant uncertainty remains. Individuals with VVS represent a heterogenous patient population, and different mechanisms are likely to contribute. These mechanisms are still not fully understood. Therefore, determining dominant mechanisms and modifying therapies accordingly is not always possible. In this review, we first describe the pathophysiology of the condition and discuss an approach for evaluating patients with VVS, emphasising holistic, multifaceted care. We also discuss current and emerging therapies. While some practical, conservative measures remain effective and are recommended, newer interventions, such as pacing and ganglionic plexus ablation, may bring relief for some patients.<\/p>\n

Pathophysiology of vasovagal syncope<\/span><\/p>\n

When a healthy person stands up, gravitational forces cause 500\u20131000 mL of blood to pool in the pelvic, abdominal and leg vessels, resulting in reduced venous return to the heart. Baroreceptor firing in the carotid sinus increases dynamically in response to reduced stretch of the vessel wall caused by a fall in arterial pressure. This results in increased sympathetic tone and withdrawal of parasympathetic (vagal) tone, which is mediated by the nucleus solitarius in the brainstem. As a result, the heart rate increases, and peripheral vasoconstriction occurs. Blood pressure (BP) recovers, or is maintained, allowing the individual to continue standing.9<\/span>\u2013<\/span>13<\/span><\/p>\n

VVS is a neural reflex involving the autonomic nervous system. This is manifested by the vagally mediated Bezold\u2013Jarisch reflex. In response to reduced filling of the left ventricle or the right atrium by reduced venous return (due to venous pooling in the splanchnic bed), parasympathetic activity is increased and sympathetic activation is decreased. A triad of bradycardia, hypotension and altered respiratory pattern ensues.12<\/span>\u00a0Four stages have been described below and are illustrated in\u00a0Figure 1<\/span><\/em>.10<\/span><\/p>\n

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1. An early stabilization phase after standing, when lower body venous pooling occurs, resulting in decreased ventricular filling followed by compensatory vasoconstriction to increase systemic vascular resistance. Cardiac output is maintained or slightly falls.<\/p>\n

2. Circulatory instability occurs when cardiac output falls slightly but compensatory systemic vascular resistance rises; in this period there may be oscillation of BP, suggesting a failing or stressed servo-mechanism. This period is dominated by falling BP known as vasodepression.<\/p>\n

3. Terminal hypotension and syncope, which is marked by a sudden fall in BP due to the onset of cardioinhibition and usually preceded by sympathetic withdrawal, possibly related to the well-recognized epinephrine peak beginning to fall. With cardioinhibition (vagal influence), the heart rate falls steeply even to asystole. The duration of vasodepression is approximately 9 minutes before onset of cardioinhibition.14<\/span>\u00a0During this phase, autonomic symptoms such as flushing and nausea may be expected. Pancreatic polypeptide levels rise in the terminal phase, probably as a marker of vagal activity and relates to nausea or vomiting. This change may continue into recovery.15<\/span> The point at which syncope occurs depends on the speed and extent of hypotension and cerebral autoregulation. It is known that cerebral oxygenation begins to fall early in stage 2 and is <60% at syncope when the BP is usually <60 mmHg.16<\/span><\/p>\n

4. The final stage is recovery; when the individual is supine after losing consciousness, venous return increases by the gravitational change draining the splanchnic pooling into the right heart, rapidly improving preload, stroke volume and cardiac output to provide resumption of cerebral perfusion (Figure 1<\/span><\/em>).10\u201312<\/span><\/p>\n

The different heart rate and BP behaviours during orthostasis can be classified into collapse patterns, which are described and later modified by the Vasovagal Syncope International Study (VASIS).17 <\/span>The intention was to be able to correctly target any therapy. Unfortunately, this has proved less reliable than hoped. Nevertheless, the VASIS classification remains widely used in practice. The most common form (type 1) is a mixed pattern of vasodepression and cardioinhibition. Type 2 describes patterns dominated by cardioinhibition. Type 2A is less severe than 2B, which includes asystole. Type 3 is a pattern in which vasodepression dominates and heart rate fall is present but minimal.<\/p>\n

Neuroendocrine activity plays a part in the reflex probably as a protective mechanism and begins with vasopressin release, followed by epinephrine. High epinephrine levels have a vasodilatory effect on skeletal muscle, favouring some fall in BP.10,12<\/span>\u00a0Other neurotransmitters that can modulate neuroendocrine status include serotonin, adenosine and opioids.12<\/span><\/p>\n

Evaluation<\/p>\n

When assessing an individual with suspected VVS, a comprehensive history and witness account are crucial for making a diagnosis. A detailed description of the circumstances around the event should be elicited, including the ambient environment, temperature, provoking factors, posture at the time of syncope (and the duration of that posture) and the individual\u2019s general health and hydration status at the time. Autonomic symptoms prior to syncope, such as sensations of warmth, nausea, light-headedness, visual dimming and auditory dimming, are very common. Previous episodes, along with medical history and medication history should be recorded. Care should be taken to consider a differential diagnosis, asking specifically about lateral tongue bite, prolonged loss of consciousness and prolonged confusion after the episode, which suggest a seizure. Full details are reported together with the potential for a definite diagnosis by this approach in >90% of those presenting.3,18<\/span>\u00a0Absent or very brief prodrome, or injury suggesting lack of warning, should prompt exclusion of arrhythmia or structural heart disease. However, brief or absent prodromes occur in older subjects with VVS mostly due to retrograde amnesia.19<\/span>\u00a0Detailed physical examination and electrocardiogram should be performed to exclude \u2013 as far as possible \u2013 structural heart disease, although echocardiography may be needed in some.<\/p>\n

Tilt table tests are valuable for confirming the diagnosis.1<\/span>\u00a0In common with most medical tests, sensitivity and specificity are not perfect, so a negative tilt table test does not exclude VVS.20,21<\/span> However, a recent meta-analysis showed a discriminatory ability to detect VVS, with an odds ratio of 12.5 compared with asymptomatic individuals.22<\/span>\u00a0Recent European Society of Cardiology (ESC) guidelines recommend the use of tilt table testing in VVS (Class 2A) for:<\/p>\n