Pathophysiology of Reflex Syncope: A Review

Wayne O. Adkisson MD; David G. Benditt MD


J Cardiovasc Electrophysiol. 2017;28(9):1088-1097. 

In This Article

Specific Reflex Faints

Vasovagal Syncope

VVS is the most common form of syncope and far away the most common cause of reflex syncope in all age groups; although in older patient groups other forms of syncope become increasingly prevalent, VVS still accounts for approximately 50% of faints.[16,17] For example, Del Rosso and colleagues reported that even in patients 65 years of age or older, VVS ("neurally mediated" in the publication) was the cause of syncope in 54% of the patients studied.[16] Parry and Tan have provided a similar estimate[17] (Figure 3).

Figure 3.

Reflex syncope is the most common cause of syncope. Reflex syncope remains the most common cause of syncope in older populations. However, in older populations syncope due to orthostatic hypotension, cardiac disease and arrhythmia are seen more frequently than in younger syncope patients. (chart A). (Figure constructed from data provided in Ref. [17]) [Color figure can be viewed at]

As noted in the earlier discussion of nomenclature, VVS is a specific diagnostic term reserved for reflex syncope resulting from emotional triggers or in the absence of an obvious trigger, other than upright posture.

In 1951, Greenfield reported an early effort to understand the pathophysiology of the emotional faint. He made use of the fact that a student had fainted while watching venipuncture being performed on another person. The student volunteered to be monitored while venipuncture was again performed. It was noted that the second time the student observed venipuncture being performed was "less effective." Given that "…the subject did not faint, a needle was inserted in his arm, but no blood was withdrawn." Alas, this too failed to result in a faint: "It was therefore decided to increase the stimulus by asking him to drink the few ml of blood he had seen withdrawn from the other person's arm. This was immediately effective and a negligible amount of blood was swallowed."[18] The pain of needle insertion was felt to be "little" and therefore the faint was attributed to the emotional stimuli. In the end, it was concluded that the circulatory changes seen in an emotional faint were "similar to those in post-haemorrhagic fainting." At the time, the bradycardia often seen during anesthesia in trauma victims was felt to be triggered by vigorous contractions of the relatively "empty" ventricles. This concept of under-filled ventricles leading to overactivation of cardiac mechanoreceptors as the initiating factor in VVS remains to this day. Likewise, this concept remains controversial to this day.

The association of upright posture with VVS also contributed to the idea of "central hypovolemia" being an important initiating trigger. Upon assuming an upright posture, 500–1,000 mL of blood is displaced from the upper to lower parts of the body.[6] The classic teaching is that displacement of this volume of blood results in a decline in venous return to the heart and a fall in SV via the Frank Starling mechanism. The latter in turn leads to a fall in CO and a decline in the stretch of the arterial baroreceptors (Figure 1) that, in health, is usually effectively compensated for by an increase in contractility via sympathetic activation. However, in susceptible patients, and especially after prolonged upright posture and/or diminished central volume (e.g., dehydration), the resulting increase in contractility in the face of under-filled ventricles is thought to excessively activate mechanoreceptors in the inferoposterior wall of left ventricle (which transmit signals centrally via vagal afferent C fibers). This sequence of event then leads to the abrupt withdrawal of peripheral sympathetic activation, with a concomitant increase in parasympathetic activation–the net outcome is various degrees of vasodepression and/or cardioinhibition.[19] If sufficiently severe, symptomatic hypotension may occur.

The VVS pathophysiology summarized here may seem to provide a plausible and highly satisfactory explanation for the faint. Or it does so until one recalls that patients have been described with apparent VVS after heart transplantation. It is difficult to invoke ventricular mechanoreceptor participation in the afferent limb of VVS in patients with de-enervated hearts. On the other hand, heart transplantation may not isolate certain atrial low pressure receptors, aortic arch receptors, or receptors in the pulmonary arteries. Further, reinnervation may occur over time and provide a possible explanation. In any case, observations such as these underscore the fact that we simply do not completely understand the complex mechanisms at play in VVS.

Carotid Sinus Syndrome

CSS refers to a form of reflex syncope that is thought to be triggered primarily by mechanical manipulation of the carotid sinus region. However, a brief note clarifying the nomenclature is needed before we proceed. Specifically:

Carotid sinus syndrome refers to the syndrome of syncope related to manipulation of the region of the carotid artery sinus.

Carotid sinus hypersensitivity (CSH) was principally defined in 1933 by Weiss and Baker[20] and their definitions, with some modification, remain in use today. CSH in an individual refers to an abnormal finding during carotid sinus massage (CSM) but may not be indicative of CSS unless a clinical correlation is able to be established. Currently, three categories of CSH in response to CSM for 5–10 seconds are recognized: (1) cardioinhibitory if CSM resulted in asystole for >3 seconds in the absence of a fall in BP, (2) vasodepressor if CSM results in a drop in BP of at least 50 mmHg without asystole, or (3) mixed if both asystole and fall in BP occurred.

CSS, as defined above, is a rare cause of syncope. CSH, on the other hand, is more common, especially in the elderly (and particularly in elderly males); CSH has been demonstrated in 39% of a random sample of patients over the age of 65.[21] Patients with unexplained syncope in whom syncope during diagnostic testing results from CSH during CSM are referred to as having "induced carotid sinus syncope" in distinction from the rare patients with spontaneous CSS. Maintaining this distinction is rapidly becoming futile, and the vast majority of patients labeled as having "carotid sinus syndrome" in contemporary evaluations will almost certainly have induced carotid sinus syncope. In this discussion, CSS includes both spontaneous and induced syncope related to carotid sinus manipulation. Recommendations regarding the performance of CSM can be found in the 2009 European Society of Cardiology guidelines.[2]

The afferent pathways, central processing, and efferent pathways involved in CSS are relatively well defined. The afferent limb involves neural pathways, predominantly traveling in the carotid sinus, glossopharyngeal, and vagus nerves. What is less clear is the mechanisms that cause the baroreceptor reflex to malfunction and cause syncope. A variety of conditions may contribute: atherosclerotic disease in the carotid sinus bulb, degenerative changes in either the afferent limb or central processing centers, and unilateral loss of function both in the carotid sinus, as well as proprioception in the sternocleidomastoid muscle (such as may occur after head and neck surgery or radiation) have all been proposed as possible mediators of CSS.[22] In an individual patient, CSS susceptibility is, most likely, multifactorial.

Situational Syncope

The situational syncope syndromes are often grouped into categories (Table 1). It should be noted at the outset that it is not clear that the situational syncopes in a particular category share a common pathophysiology. Even less is known about the afferent reflex limbs of these syndromes than in VVS or CSS. For the most part, each of the various situational faints is rare making investigations into mechanisms extremely difficult. Cough syncope is perhaps the most common of the situational faints and as such has been the most amenable to study.

The 2009 European Society guidelines on syncope list several examples of situational syncope but do not elaborate on the pathophysiology distinct to each.[2] Nonetheless, there are observations and hypotheses worth our consideration.

Situational syncope related to respiratory tract. This category includes "cough syncope," "wind instrument player syncope," "sneeze syncope," "laugh syncope," and "weight lifter syncope." Classically, respiratory situation syncope, with exceptions, has been thought to be triggered by a Valsalva-like maneuver, which, by raising intrathoracic pressure, results in a decrease in venous return and central hypovolemia that leads to syncope through reflex mechanisms analogous to VVS.

It is thought that laugh (gelastic)[23] and sneeze syncope may involve triggers other than Valsalva, in that they result in a series of rapid changes in intrathoracic pressure, as opposed to the sustained increase in intrathoracic pressure seen in the other entities. We have observed transient AV block and less severe transient bradycardia in patients being evaluated for presumed spontaneous laugh syncope (unpublished data).

In the authors' experience, cough syncope is the most common respiratory situational syncope encountered. Early theories suggested that cough syncope resulted from the Valsalva-like effect of cough, leading to a fall in venous return. More recently, we demonstrated that, compared to controls, the degree of hypotension induced by volitional cough was greater, the chronotropic response to hypotension was reduced, and the duration of postcough hypotension was longer in cough syncope patients. Our findings tend to implicate a reflex mechanism for both intermittent brief coughs and repetitive prolonged coughing.[24]

Situational syncope related to the gastrointestinal tract.Swallow or deglutition syncope is syncope associated with the act of swallowing. This condition is often associated with esophageal pathology such as strictures and neoplasia.[25] Electrocardiographic monitoring often shows marked bradycardia, including asystole. This condition may overlap with CSS. Permanent pacing has been reported to be effective, but the data consist of case reports.[26]

Glossopharyngeal neuralgia which causes sudden and often very severe pain in the parts of the face/neck subtended by the glossopharyngeal nerve has also been associated with the syncope related to marked bradycardia. In some, the pain is triggered by swallowing. This condition is distinguished from deglutition and CSS by virtue of the syncope occurring in association with severe pain. Whether it differs from pain-triggered VVS is unclear. Successful therapy with carbamazepine and carbamazepine with permanent pacing has been reported.[27] Additionally, surgical intervention has recently been shown to be beneficial.[28]

Syncope during or shortly after defection is referred to as defecation syncope. Kapoor and colleagues described findings in 20 patients with this disorder.[29] In a later series, Bae et al. noted that defecation syncope was more commonly seen in women.[30] Valsalva during defecation has been postulated as a trigger, but the condition is not always associated with straining. Again, monitoring has demonstrated marked bradycardia and reports of permanent pacing relieving the symptoms can be found.[31] Finally, visceral pain and cramping have been associated with syncope, presumably by triggering VVS.

Situational syncope related to the genitourinary tract. Syncope during or shortly after micturition is, not surprisingly, referred to as micturition syncope.[32,33] The basis for these faints is not known with certainty but one pathophysiology explanation is that a full bladder may induce a hypertensive response that the baroreceptor system tries to modify. However, when the bladder is rapidly emptied, the hypotensive reflex is delayed in being turned off and the victim develops transient hypotension.[34]

Syncope may rarely be associated with coitus. From a physiologic standpoint, coitus is quite complicated, including both dynamic and isometric components, as well as periods of breath holding. As with any patient with syncope related to exertion, syncope during coitus should trigger an evaluation for underlying structural heart disease or arrhythmia as the etiology.