Carotid sinus hypersensitivity and carotid sinus syndrome

INTRODUCTION — Carotid sinus hypersensitivity (CSH) manifests as a greater than normal fall in heart rate and/or blood pressure in response to stimulation of the carotid artery baroreceptors. Carotid sinus syndrome (CSS) is a type of reflex syncope or near-syncope in which symptoms (eg, syncope, lightheadedness) are caused by CSH manifesting during daily activities.

CSH and CSS will be reviewed here. Other types of reflex syncope, including vasovagal syncope, as well as the pathogenesis, etiology, and evaluation of syncope, are discussed separately. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation" and "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".)

DEFINITIONS

●Carotid sinus hypersensitivity – CSH is a clinical finding of a greater than normal fall in heart rate (HR) and/or systemic blood pressure (BP) in response to stimulation of the carotid baroreceptors, as tested by carotid sinus massage (CSM). Criteria for CSH vary and are discussed below. (See 'Test interpretation' below.)

CSH itself is not a clinical syndrome. It commonly occurs in individuals with no history of symptoms such as syncope (most often in older males). In individuals with a prior history of syncope or presyncope, identifying CSH by CSM is a key element in the diagnosis of CSS but CSH alone is not diagnostic of CSS.

●Carotid sinus syndrome – CSS is a type of reflex syncope or near-syncope with symptoms (eg, syncope, lightheadedness) caused by CSH manifesting during activities of daily life that put pressure on the carotid sinus (eg, turning the neck, looking upward). When CSS manifests as syncope it is called carotid sinus syncope. (See 'Clinical manifestations' below.)

PREVALENCE — CSH is a commonly observed physical finding, but CSS is an uncommon cause of symptoms, accounting for approximately 1 percent of syncope cases [1]. CSS is almost entirely restricted to older (>65 year old) male patients. Older individuals and males are more likely to have an abnormal CSH response even if they do not have CSS [2-5].

The prevalence of CSH depends upon the diagnostic criteria utilized. CSH, identified by commonly used sensitive but nonspecific criteria (eg, asystole of ≥3 s), is commonly observed in older adults (39 percent in an unselected sample of older adults [mean age 71 years]) in a community practice [2]. CSH is commonly observed in individuals with no prior presyncope or syncope (eg, 20 percent [6] and 35 percent [2]), in unselected syncope patients (eg, 14 percent), and in patients with syncope unexplained by initial screening (eg, 49 percent [7]) [6-9].

PATHOPHYSIOLOGY — The carotid baroreceptors, specialized tissues sensitive to mechanical pressure, are located bilaterally in the carotid sinuses at the base of the internal carotid arteries just above the bifurcation of the internal and external carotid arteries (figure 1). These baroreceptors are physiologically important for blood pressure (BP) control and, to a lesser extent, heart rate (HR) control, acting through a reflex arc.

The carotid sinus reflex arc is composed of:

●An afferent limb arising from mechanoreceptors in the internal carotid artery and terminating in the cardiovascular control centers in the vagal nucleus and the vasomotor center in the medulla.

and

●An efferent limb with two components:

•Innervation of the sinoatrial and atrioventricular (AV) nodes via the vagus nerve and the parasympathetic ganglia.

•Inhibition of sympathetic nervous tone to the heart and blood vessels.

The site of the abnormality that causes the hypersensitive response in patients with CSH has not been definitively established. Several possible causes have been postulated, and several factors may be operative in any patient, such as:

●Increased responsiveness of the peripheral receptors.

●Increased responsiveness of the baroreceptor region due to comorbidities such as atherosclerotic vascular disease, nearby neck surgery, or irradiation that alters the receptor milieu.

●Abnormal proprioception responses in nearby neck muscles that modify the manner in which central sites interpret baroreceptor afferent signals.

●Increased responsiveness of midbrain reflex sites.

CSS symptoms are deemed to result from CSH-induced excessive and inappropriate cardioinhibition (ie, slowing of HR) and/or vasodilation, yielding a drop in BP. Both cardioinhibition and vasodilation transiently diminish brain perfusion. (See 'Types of abnormal responses' below.)

CLINICAL MANIFESTATIONS — Patients with CSS may present with a variety of symptoms following carotid baroreceptor stimulation, but one or more of the following presentations are most common:

●Lightheadedness/presyncope

●Syncope

●Otherwise unexplained falls in older patients

A careful medical history is required to develop a clinical suspicion of CSS. Although a clear relationship between neck movements and symptom episodes is rarely established, a history of syncope following accidental manipulation of the carotid sinuses should be sought. The index of suspicion for CSH is increased by a history of syncope in the setting of activities associated with possible pressure on the carotid sinus (eg, neck movement, fitting a tie, or shaving) and by presence of any of the following risk factors: older age, male sex, atherosclerotic disease, abnormalities of the structure of the neck (eg, prior neck surgery and/or irradiation), or tumors in the region of the carotid sinuses.

DIAGNOSTIC EVALUATION

Approach to diagnosis — In a patient with possible or suspected CSS, the first step of the diagnostic evaluation is to perform an initial evaluation including a careful history to determine the circumstances (including any pressure on the neck) and characteristics associated with the presenting symptoms (eg, syncope, lightheadedness, or collapse). As CSS is one of many potential causes for syncope, near-syncope, or an unexplained fall, this initial evaluation enables exclusion of other possible causes of syncopal or nonsyncopal symptoms (algorithm 1). An overview of the diagnostic approach to lightheadedness, near-syncope, and syncope in general is provided separately. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".)

Along with careful exclusion of other possible causes of symptoms, the primary test for CSS is carotid sinus massage (CSM).

When to perform CSM — In patients over age 50 with syncope or presyncope of unknown etiology despite an initial evaluation (algorithm 1) (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation"), we recommend performing CSM to evaluate for possible CSS. This recommendation is similar to those in major society guidelines that recommend CSM in patients with syncope with uncertain cause after the initial evaluation [10,11].

Although history of pressure in the region of the carotid sinuses prior to syncope or risk factors for CSS raises the index of suspicion for CSS, absence of these features does not exclude CSS, so the indication for CSM to assess for CSS is broad.

CSS is diagnosed by the combination of reproducing appropriate spontaneous symptoms with documented CSH following CSM (best performed with the patient upright but protected from falling). When CSH is documented following CSM, concurrent symptoms provide the most convincing evidence for CSS. An asymptomatic "positive" response for CSH is less specific than CSH with reproduction of symptoms, particularly if a full evaluation for other causes of syncope has not yet been performed.

By history, spontaneous syncope symptoms can be reasonably attributed to mechanical manipulation of the carotid sinuses resulting in CSH. CSS is one of many potential causes for syncope, near-syncope, or unexplained fall symptoms. Careful history taking is crucial to establishing the diagnosis. The finding of CSH in older adult patients should not be construed as diagnostic for the presenting symptoms (ie, lightheadedness, syncope, falls) unless other causes of the symptoms have been eliminated or the history clearly relates symptoms to neck movement or mechanical distortion.

Contraindications to CSM — CSM should be avoided in patients at risk for stroke due to carotid artery disease, including those with one or more of the following clinical features, although data are lacking on the risk of stroke with CSM [10,11]:

●Prior transient ischemic attack (TIA) or stroke within the past three months.

●Clinically significant carotid stenosis (eg, ≥70 percent carotid artery stenosis).

●Prior complication (eg, TIA or stroke) from CSM.

●Carotid bruit (unless carotid Doppler ultrasound studies have excluded significant stenosis).

●Since a carotid bruit is not a sensitive indicator of carotid artery disease, some have suggested performing carotid Doppler ultrasound studies in patients with coronary artery disease or peripheral artery disease, since such patients are at high risk for stroke [12].

CSM procedure — CSM methodology varies among laboratories, but one recommended method for evaluation of CSH/CSS follows:

Monitoring — Beat-to-beat blood pressure (BP) monitoring (preferably not by sphygmomanometer) and continuous heart rate (HR) monitoring by electrocardiogram (ECG; single-lead telemetry is adequate) are performed throughout the CSM procedure. The recordings are best achieved with a beat-to-beat noninvasive HR/BP monitor system (eg, Finapres).

Patient position — The patient may be studied first while supine, but upright posture is usually needed to reproduce symptoms. Symptom reproduction is the best method to secure a diagnosis of CSS.

If supine study is done first, then the subject is initially placed in a horizontal supine position with the neck extended (ie, chin raised away from the chest) to maximize access to the carotid artery. However, symptoms associated with CSH are rarely induced unless CSM is carried out with the patient upright. The carotid sinus is usually located near the arterial impulse inferior to the angle of the mandible at the level of the thyroid cartilage (figure 1).

If the response in a horizontal supine position is nondiagnostic and symptoms are not reproduced, the procedure should be repeated with the patient seated upright or positioned head-up on a tilt table at 70 to 80 degrees (but gently secured to prevent a fall) [10,11]. The diagnostic yield is likely to increase by performing CSM during head-up tilt, as this is likely to induce a greater degree of hypotension and is thus more likely to reproduce symptoms [13,14]. In a report of 1149 patients over 55 years of age presenting with unexplained syncope, CSH provoked by CSM was observed in 223 patients (19 percent); in one-third of these patients, a response to CSM was elicited during upright tilt after a negative response to supine massage [14].

Technique — Firm, steady massage (with a vertical up and down movement) is applied at the region of the carotid baroreceptors (at the carotid artery just below the angle of the mandible and medial to the sternocleidomastoid muscle) (figure 1) [12]. Pressure is applied to only one carotid sinus at a time (generally, first on the right and then on the left with patient upright either seated or on a tilt table), usually for 10 to 12 s; the carotid artery should not be occluded. Up and down motion may be more effective, but some argue that steady pressure may be more reproducible [10,15]. For older patients, some clinicians start CSM with 3 s of gentle pressure and, if no response, then apply firmer pressure. Reproduction of syncope symptoms is the best endpoint [11].

If the initial response is nondiagnostic, the procedure should be repeated on the contralateral side (unless contraindicated) following a one- to two-minute delay.

In some patients, it may be useful to repeat the CSM after atropine administration in order to differentiate the hypotensive contributions of the cardioinhibitory and vasodepressor components of the reflex. However, in terms of assessing if a pacemaker may be useful in a given patient, the reproducibility of the atropine intervention is not fully established. Further, it is important to be aware that the reflex fatigues with multiple massage attempts over a short time, and, consequently, repetitive tests may inherently result in a diminished response. A rest period of approximately 15 to 20 min should be included between baseline tests and drug testing [16].

Test interpretation — Criteria for and types of abnormal responses are discussed below. (See 'Criteria for abnormal responses' below and 'Types of abnormal responses' below.)

Criteria for abnormal responses — Experts disagree on what constitutes a "positive" (ie, abnormal) response to CSM suggesting CSH (and CSS if the patient’s clinical symptoms are reproduced). The disagreement mainly focuses on the length of the HR pause that is considered abnormal.

●Stringent criteria – Reproduction of the patient’s symptoms (eg, syncope or presyncope) with an HR (ventricular) pause of ≥6 s or a fall in mean arterial BP to <60 mmHg lasting for ≥6 s is the most diagnostic finding for CSS [5]. If these HR and BP criteria are met without symptoms, the test may still be considered positive but is less specific. These criteria are based upon observational studies suggesting that at least 6 s of asystole may be required to cause syncope or presyncope [17,18].

●Less specific criteria – Less specific criteria (sensitive but nonspecific) are included in the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society syncope guideline (a HR [ventricular] pause >3 seconds and/or a fall in systolic BP ≥50 mmHg) [10] and in the 2018 European Society of Cardiology syncope guidelines (a ventricular pause >3 s and/or a drop in systolic BP >50 mmHg) [11].

Types of abnormal responses — Abnormal responses to CSM (as defined above) (see 'Criteria for abnormal responses' above) are classified as:

●Cardioinhibitory – There is an abnormal decline in HR without an abnormal decline in BP.

●Vasodepressor – There is an abnormal decline in BP without an abnormal decline in HR.

or

●Mixed – There are abnormal declines in HR and BP.

In most cases with an abnormal response (including responses associated with reproduction of clinical symptoms consistent with CSS), the response is "mixed," indicating that symptoms in patients with CSS are commonly a combination of HR slowing and vasodilation. A combination of HR and BP responses is a typical feature of all reflex faints, including vasovagal syncope. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies", section on 'Reflex syncope'.)

CSM may unmask CSH in older adult patients, but this should not be automatically deemed a diagnostic finding of CSS in patients with lightheadedness, syncope, or falls [3]. Thus, alternative causes should be explored before attributing syncope to CSH in older adult patients. Given the limited sensitivity and specificity of CSM for diagnosing CSS, some have advocated using stricter criteria for identification of CSH [5].

DIAGNOSIS — CSS is diagnosed when all three of following conditions are met:

●The patient has a clinical history of syncope (or presyncope).

●Causes of syncope/collapse (algorithm 1) other than CCS have been reasonably excluded by history and laboratory testing. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".)

●The patient’s response to carotid sinus massage (CSM) is abnormal (showing CSH) and reproduces the patients’ clinical symptoms. As noted above, stringent or less specific criteria may be used to identify an abnormal response. (See 'Criteria for abnormal responses' above.)

An abnormal response to CSM without reproducing the patient’s presenting symptoms is a less specific finding, particularly in older adults. Such as response suggests a diagnosis of CSS only if other causes of the symptoms have been excluded, particularly if the patient’s history clearly relates symptoms to pressure on or movement of the neck movement. A positive (abnormal) response to CSM suggests CSH, but itself does not establish CSH as a cause of syncope.

Thus, CSS is diagnosed when spontaneous syncope symptoms can be reasonably attributed to mechanical manipulation of the carotid sinuses. Unfortunately, obtaining a clear history of carotid sinus stimulation is challenging and uncommon.

DIFFERENTIAL DIAGNOSIS — As for other types of syncope (or presyncope), suspected CSS should be distinguished from other causes of syncope and/or collapse (algorithm 1).

From a pathophysiologic standpoint, carotid sinus syncope is similar to other forms of reflex syncope such as vasovagal syncope in involving cardioinhibitory and vasodilatory components. However, precipitating factors for these two types of reflex syncope differ. CSS is attributed to mechanical stress on hypersensitive carotid baroreceptors whereas vasovagal syncope is most often triggered by emotional events, painful stimuli, or prolonged upright posture. Other reflex faints (eg, defecation syncope, swallow syncope, trumpet blowers syncope) may also need to be considered depending on the specific circumstances of the patient presentation. (See 'Clinical manifestations' above and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".)

A full discussion of the differential diagnosis of syncope in adults is presented separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".)

MANAGEMENT

Approach to management — The management of patients with CSH depends upon whether symptoms are present or absent.

●Asymptomatic patients (isolated CSH) – Patients with isolated CSH who remain asymptomatic require no specific therapy other than counselling to avoid movements or positions that may accidentally stimulate the carotid baroreceptors.

●CSS (symptomatic CSH) – CSS is a multifaceted syndrome in terms of symptoms (type and frequency) as well as pathophysiology. Consequently, it is important to consider the risks associated with treating the patient every day for prevention of events which may be infrequent. Treatment of patients with CSS depends upon the type of abnormal response to carotid stimulation (cardioinhibitory and/or vasodilatory response), as described below. (See 'Permanent pacing' below and 'Pharmacologic therapy' below.)

General management

Education — General treatment measures for CSS include education regarding the nature, risks, and prognosis of the condition [10]. The patient should be advised to avoid accidental mechanical manipulation of the carotid sinuses such as might occur if they receive medical or chiropractic treatments to the neck area or wear tight collars.

Risks of CSS to the patient and bystanders should be discussed in detail. Lightheadedness and near-syncope may not cause frank loss of consciousness but can cause inattention and slow reaction times during operation of vehicles and machinery. The latter promotes the chances of accidents and falls with potential for major injury. Syncope may occur with a similar or greater potential for hazard to the patient and others if the patient loses control of a vehicle or other machine or simply falls in a crowded environment. (See 'Driving restrictions' below.)

Driving restrictions — Our approach to driving restriction recommendations for patients with CSS is generally consistent with the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society syncope guidelines (table 1) [10], though supporting evidence is limited. It is also important to consult relevant local laws and regulations.

●Patients with CSH alone but without symptoms – No restriction.

●Patients with untreated CSS (ie, known or suspected [by history] relation of symptoms to CSH in the absence of alternative cause) – Not fit to drive.

●Patients with CSS treated with a permanent pacemaker to overcome a predominant cardioinhibitory component – May drive after one week of observation to ensure stable pacing system is in place.

●Patients with CSS (known or suspected) in whom the vasodepressor component is dominant (a relatively rare condition) who are treated to diminish vasodilation – May drive after a reasonable observation period to demonstrate treatment effectiveness.

Recommendations for commercial drivers are linked to local and/or federal government department of transportation or comparable regulatory body regulations [19]. Generally, a symptom-free period of six months is required, but regulations differ among geographic regions. Practitioners must be aware of local laws and regulations in their region, which may differ from professional society guidelines. (See "Syncope in adults: Management and prognosis", section on 'Driving restrictions'.)

Pharmacologic therapy — Pharmacologic therapy is a component of therapy for patients with CCS with a predominantly vasodilatory response to carotid sinus massage (CSM), but relatively little is known of the optimal treatment of such patients, as these cases seem to be rare (or at least rarely recognized) and therefore difficult to study.

As an initial step, drugs such as vasodilators or diuretics that may exacerbate the condition should be reduced or discontinued, if feasible.

Although some therapies for vasovagal syncope (such as salt loading and vasoconstrictors) may be expected to be helpful, such treatments may cause supine hypertension and are usually undesirable in the older patient population with CSS [10]. Vasoconstrictive drugs such as midodrine or droxidopa may be used (as prescribed for orthostatic hypotension (see "Treatment of orthostatic and postprandial hypotension", section on 'Sympathomimetic agents')), but limited data are available to support their use for CSS [11,20]. Additionally, vasoconstrictive drugs must be used cautiously to minimize the risk of hypertension. In individuals with CSS and essential hypertension (a common combination), it is necessary to use vasoconstrictors during waking hours and short-acting antihypertensives at bedtime to diminish supine hypertension.

Permanent pacing

Indication — For patients with recurrent syncope diagnosed with CSS (see 'Diagnosis' above) (whether by stringent criteria or by less specific criteria (see 'Criteria for abnormal responses' above)) with either a cardioinhibitory or "mixed" response to CSM resulting in asystole for more than three to six seconds, we suggest referral for permanent cardiac pacemaker implantation. The certainty of a beneficial response is highest for patients meeting stringent criteria for CSS including reproduction of symptoms with CSM. (See 'Permanent pacing' above.)

This recommendation is in broad agreement with major society guidelines [10,11].

Most patients with CSS have a cardioinhibitory or mixed response and thus are candidates for pacemaker therapy, although residual vasodepressor response may diminish overall pacing effectiveness. Patients with CSS with a dominant vasodilatory response (drop in systolic blood pressure >50 mmHg) without associated cardioinhibition are unlikely to respond to pacemaker therapy [21]. Consequently, each patient must be carefully evaluated for cardioinhibitory versus vasodepressor contributions to hypotension before a pacemaker intervention is advised. If cardioinhibition predominates, then pacing may be helpful, as discussed below.

Permanent pacing is not indicated for a cardioinhibitory response to carotid sinus stimulation in patients with no history of symptoms (such as syncope or presyncope) or with only vague symptoms (ie, pacing is not indicated for CSH).

A positive cardioinhibitory response (asystole >3 to 6 s) during CSM is thought to be predictive of an asystolic mechanism of spontaneous syncope, but only limited evidence is available to support this approach [17,22]. As an example, in a study of 18 patients with recurrent syncope and cardioinhibitory response to CSM and 36 patients with recurrent syncope and negative response to CSM, insertable cardiac monitors (also sometimes referred to as implantable cardiac monitors or implantable loop recorders) identified the following [22]:

●Asystole with syncope in 16 of 18 (89 percent) patients with a positive cardioinhibitory response to CSM.

●Asystole with syncope in 18 of 36 (50 percent) patients with a negative cardioinhibitory response to CSM.

In CSS, most studies suggest a benefit from pacing despite the concern that both cardioinhibitory and vasodepressor mechanisms may be operating. This observation differs from observations of other reflex conditions such as the vasovagal faint in which a predominant vasodepressor component may undermine the value of pacing therapy. Why these two forms of reflex syncope respond differently to pacemaker therapy is unknown, but may be due to a higher frequency of cardioinhibitory response in patients with CSS than with other types of reflex syncope.

Two small randomized trials found that pacing reduced the rate of syncope recurrence in patients with CSS [23,24]. Dual-chamber pacing is beneficial in patients with CSS who have a cardioinhibitory response, but not in those with a pure vasodilatory response [21].

Pacing may prevent nonmechanical falls as well as syncope in some patients populations. This was suggested by the SAFE PACE trial, in which 175 patients seen in an emergency facility because of a nonmechanical fall without loss of consciousness were randomly assigned to a dual-chamber pacemaker or no therapy [25], but not confirmed in SAFE PACE 2 [26].

Choice of pacemaker — When a pacemaker is placed, dual-chamber pacing is generally favored [10,11]. Single-chamber AAI (atrial demand) pacing is not recommended for patients with CSS, as transient AV block may occur during an episode and eliminate any potential pacing benefit. This approach is in general agreement with published society guidelines [10]. (See "Permanent cardiac pacing: Overview of devices and indications" and "Modes of cardiac pacing: Nomenclature and selection".)

In a study of 21 patients with CSS and syncope or near-syncope, patients were randomized to VVI (ventricular demand), DDDR (dual-chamber with rate modulation), or DDDR pacing with sudden bradycardia response (SBR) in a double-blinded sequential crossover basis with six months in each mode [27]. There were 29 syncopal and 258 presyncopal events among 21 patients during the preceding six months. Following pacing, there were two syncopal events in two patients and 17 presyncopal events in 12 patients in six months, and these events were not related to the three pacing methods. While these data do not support one specific mode of pacing, some patients have a better hemodynamic response to AV sequential pacing, and, if this is known a priori, we suggest a dual-chamber pacemaker be implanted from the start. Failure of pacing most likely would be due to the patient having a prominent vasodepressor component of the CSS reflex, similar to what may happen in patients with vasovagal syncope.

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Vagal maneuvers (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definitions (See 'Definitions' above.)

•Carotid sinus hypersensitivity (CSH) – CSH is a clinical finding of greater than normal fall in heart rate (HR) and/or systemic blood pressure (BP) in response to carotid sinus massage (CSM). Criteria for an abnormal response to CSM vary (see 'Test interpretation' above). CSH itself is not a clinical syndrome. It occurs in individuals with and without a history of symptoms such as syncope.

•Carotid sinus syndrome (CSS) – CSS is a type of reflex syncope with symptoms (eg, syncope, lightheadedness) caused by CSH manifesting during activities of daily life that put pressure on the carotid sinus (eg, turning the neck, looking upward). When CSS manifests as syncope it is called carotid sinus syncope. (See 'Clinical manifestations' above.)

●Prevalence – CSH is a commonly observed physical finding but an uncommon cause of symptoms (as in CSS). CSS is a relative rare cause of syncope, accounting for approximately 1 percent of syncope cases. Older individuals and males are more likely to have an abnormal CSH response even if they do not have CSS.

●Clinical presentation – The most common presenting symptoms of CSS are lightheadedness/presyncope, syncope, and otherwise unexplained falls. Although a clear relationship between neck movements and symptom episodes is rarely established, a history of syncope following accidental manipulation of the carotid sinuses should be sought. (See 'Clinical manifestations' above.)

●When to perform CSM to diagnose CSS – In patients over age 50 with syncope or presyncope of unknown etiology despite an initial evaluation (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation"), we recommend performing CSM to evaluate for possible CSS. However, false positive results are common in older adults, so other potential causes of syncope or collapse should be excluded (algorithm 1). (See 'Diagnostic evaluation' above and 'When to perform CSM' above.)

Although a history of pressure in the region of the carotid sinuses prior to syncope or presence of a risk factor for CSS raises the index of suspicion, absence of these features does not exclude CSS, so the indication for CSM to assess for CSS is broad.

●Contraindications to CSM – CSM should be avoided in patients at risk for stroke due to carotid artery disease, including those with prior transient ischemic attack (TIA) or stroke within the past three months, clinically significant carotid stenosis, or carotid bruit. (See 'Contraindications to CSM' above.)

●Abnormal responses to CSM – Criteria for a positive (ie, abnormal) response to CSM are controversial, ranging from stringent criteria that are more specific to less specific criteria that are more sensitive. The test is most diagnostic for CSS when stringent criteria are met with reproduction of symptoms (see 'Criteria for abnormal responses' above):

•Stringent criteria – A HR pause of ≥6 s or a fall in systolic BP to <60 mmHg lasting for ≥6 s.

•Less specific criteria – a HR pause >3 s or a fall in systolic BP of ≥50 mmHg.

●Types of abnormal responses – An abnormal response to CSM may be cardioinhibitory (greater than normal decline in HR), vasodilatory (greater than normal fall in BP) or mixed (greater than normal fall in HR and BP). (See 'Types of abnormal responses' above.)

●General management (See 'Approach to management' above and 'General management' above.)

•For CSH – Patients with isolated CSH who remain asymptomatic require no specific therapy other than counselling to avoid movements or positions that may accidentally stimulate the carotid baroreceptors.

•For CSS – General measures include education regarding CSS risks, applicable driving restrictions, and treatment options. Pharmacologic therapy is an option for patients with a vasodilatory response to CSM. (See 'General management' above.)

●Permanent pacing – For patients with recurrent syncope diagnosed with CSS (by either stringent or less specific criteria) with a cardioinhibitory or "mixed" response to CSM resulting in asystole for more than three to six seconds, we suggest permanent cardiac pacemaker implantation (Grade 2C). The certainty of a beneficial response is highest for patients meeting stringent criteria for CSS, including reproduction of symptoms with CSM. (See 'Permanent pacing' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Brian Olshansky, MD, who contributed to earlier versions of this topic review.