Carotid Sinus Hypersensitivity

Carotid sinus hypersensitivity (CSH) is an exaggerated response to carotid sinus baroreceptor stimulation. It results in dizziness or syncope from transient diminished cerebral perfusion.[1]

Although baroreceptor function usually diminishes with age, some people experience hypersensitive carotid baroreflexes. For these individuals, even mild stimulation to the neck results in marked bradycardia and a drop in blood pressure.

CSH predominantly affects older males. It is a potent contributory factor and a potentially treatable cause of unexplained falls and  syncopal episodes in elderly people.[2, 3, 4] Yet, CSH is often overlooked in the differential diagnosis of presyncope and syncope.[5]

CSH, orthostatic hypotension, and vasovagal syncope are common conditions that are likely to coexist in patients with syncope and falls.[6]

The carotid sinus reflex plays a central role in blood pressure homeostasis. Changes in stretch and transmural pressure are detected by baroreceptors in the heart, carotid sinus, aortic arch, and other large vessels. Afferent impulses are transmitted by the carotid sinus, glossopharyngeal, and vagus nerves to the nuclei tractus solitarius and the para median nucleus in the brain stem. Efferent limbs are carried through sympathetic and vagus nerves to the heart and blood vessels, controlling heart rate and vasomotor tone.

In CSH, mechanical deformation of the carotid sinus (located at the bifurcation of the common carotid artery) leads to an exaggerated response with bradycardia or vasodilatation, resulting in hypotension, presyncope, or syncope.

The hemodynamic changes following carotid sinus stimulation are independent of body position. These changes have a distinct temporal pattern, with an initial fall in the cardiac output driven by heart rate, followed by a later fall in total peripheral resistance.[7]

CSH may be a part of a generalized autonomic disorder associated with autonomic dysregulation.[8] Data have been reported on neuronal degeneration with accumulation of hyperphosphorylated tau or alpha-synuclein in neurones in medulla, leading to impairment of central regulation of baroreflex responses and predispose elderly patients to CSH.[9]

However, the exact mechanism and site of abnormal sensitivity is unknown. The exaggerated response may be due to changes in any part of the reflex arc or the target organs. A potential mechanism for the symptomatic presentation of CSH (eg, syncope, blood pressure/heart rate changes) may be impaired cerebral autoregulation.[10]

Clinically and historically, 3 types of CSH have been described, as follows:

• The cardioinhibitory type comprises 70-75% of cases. The predominant manifestation is a decreased heart rate, which results in sinus bradycardia, atrioventricular block, or asystole due to vagal action on sinus and atrioventricular nodes. This response can be abolished with atropine.[11]

• The vasodepressor type comprises 5-10% of cases. The predominant manifestation is a vasomotor tone decrease without a change in heart rate. The significant resulting drop in blood pressure is due to a change in the balance of parasympathetic and sympathetic effects on peripheral blood vessels. This response is not abolished with atropine.

• The mixed type comprises 20-25% of cases. A decrease in heart rate and vasomotor tone occurs.

A proposal by a group of international experts suggests that the classification of CSH into 3 types as above should be revised. It has been suggested that all patients with CSH should be classified as "mixed" between vasodepression and cardioinhibition. This is because isolated cardioinhibitory CSH (asystole without fall in arterial pressure) does not occur.[12]

The terms spontaneous carotid sinus syndrome and induced carotid sinus syndrome have also been introduced to categorize patients who are presumed to have CSH, as follows:

• The term spontaneous carotid sinus syndrome refers to a clinical situation in which the symptoms can be clearly attributed to a history of accidental mechanical manipulation of the carotid sinuses (eg, taking pulses in the neck, shaving) and CSH is reproduced by carotid sinus massage. Spontaneous carotid sinus syndrome is rare and accounts for about 1% of causes of syncope.

• The term induced carotid sinus syndrome refers to a clinical situation in which a patient has no clear history of accidental mechanical manipulation of the carotid sinuses and has a negative result from workup for syncope, except for a hypersensitive response to carotid sinus massage, which can be attributed to the patient's symptoms. Induced carotid sinus syndrome is more prevalent than spontaneous carotid sinus syndrome and accounts for the bulk of patients with an abnormal response to carotid sinus massage observed in the clinical setting.

United States data

CSH is found in 0.5-9.0% of patients with recurrent syncope.

International data

CSH is observed in up to 14% of elderly nursing home patients and 30% of elderly patients with unexplained syncope and drop attacks.

Sex- and age-related demographics

CSH is more common in males than in females.

CSH is predominantly a disease of elderly people; it is virtually unknown in people younger than 50 years.

The long-term mortality rate is similar to the general population and patients with unexplained syncope. Untreated symptomatic patients have a syncope recurrence rate as high as 62% within 4 years.

Patients treated with a pacemaker have fewer syncopal attacks but may experience a recurrence rate as high as 16% in 4 years.

Mortality/Morbidity

CSH is associated with an increased risk of falls, drop attacks, bodily injuries, and fractures in elderly patients.

In the general population, the rates of mortality, sudden death, myocardial infarction, or stroke are unaffected by the presence of CSH.

Educate patients on how to recognize premonitory symptoms and avoid triggering events. In addition, educate patients regarding therapeutic actions such as methods to increase central fluid volume in the body

For patient education resources, see Brain & Nervous System Center as well as Dizziness.

Many patients remain asymptomatic. Among those who are symptomatic, the following symptoms and signs could be observed in clinical settings:

• Recurrent dizziness, near-syncope

• Recurrent syncope[13]

• Nonaccidental, unexplained falls[2]

• Symptoms produced by head turning or wearing garments with tight-fitting collars.

• Neck tumors, extensive neck scarring secondary to radical dissection or radiation fibrosis or neck trauma

• Possible prodrome or retrograde amnesia for the syncopal event

• Symptoms and signs produced when taking carotid pulse or during head and neck surgery

Signs of CSH found upon examination include the following:

• Hypotension

• Bradycardia

• Asystole

• Auscultation for carotid artery bruit prior to consideration of carotid sinus massage

CSH is associated with the following[14] :

• Predisposition for male sex

• Advanced age

• Hypertension

• Coronary artery disease

• Orthostatic hypotension

• Vasovagal syncope

• Alzheimer disease, Parkinson disease, dementia with Lewy body[15, 16]

• Concurrent medication with digitalis, beta-blockers, and methyldopa

The initial diagnostic workup for carotid sinus hypersensitivity (CSH) should rule out the following:

• Vasovagal syncope

• Orthostatic hypotension

• Situational syncope

• Sick sinus syndrome

• Cardiogenic syncope

• Other causes of syncope (eg, neurogenic, metabolic, psychogenic)

Any patient with syncope should be evaluated with the following:

• A carefully elicited history

• A thorough physical examination

• An ECG

Carotid sinus massage is the diagnostic maneuver of choice, but the technique has not been standardized. There are no controlled studies on the subject.[17, 18]

A commonly accepted massage method includes the following steps:

• Place the patient in the supine position with the neck slightly extended. The patient should lie supine for a minimum of 5 minutes before carotid sinus massage is applied.

• Massage over the point of maximal carotid impulse, medial to the sternomastoid muscle at the upper border level of the thyroid cartilage.

• Massage for 5-10 seconds on each carotid sinus consecutively, with a 1-minute interval between massages.

• Carotid sinus massage is preferably applied to first the right carotid sinus, as CSH is more prevalent on the right than on the left side.

• Continuously monitor surface ECG and blood pressure. Phasic, noninvasive, beat-to-beat blood pressure monitoring is preferred over using a cuff measurement.

A massage is considered to have a positive result if any of the following 3 criteria are met:

• Asystole exceeding 3 seconds (indicates cardioinhibitory CSH)

• Reduction in systolic blood pressure exceeding 50 mm Hg independent of heart rate slowing (indicates vasodepressor CSH)

• Combination of the above (indicates mixed CSH)

A less frequently used method consists of carotid sinus massage performed for 5 seconds on each side in the supine and 60º positions using the head-up tilt table. Substantial evidence shows that sensitivity and diagnostic accuracy of carotid sinus massage can be enhanced by performing the test with the patient in an upright position. Furthermore, the endpoint of a 50 mm Hg reduction in systolic blood pressure may be achieved with tilt, but not when supine.

Do not perform a carotid sinus massage if the patient is known to have transient ischemic attack, stroke, or myocardial infarction in the preceding 3 months. History of ventricular tachycardia, ventricular fibrillation, or carotid bruit on auscultation are relative contraindications to carotid sinus massage.

Some authors describe the use of carotid Doppler ultrasonography to guide carotid sinus massage in patients who have a carotid bruit on auscultation. Carotid sinus massage is performed only in patients with a carotid bruit when there is less than 70% stenosis on Doppler examination.

Although carotid sinus massage is usually a benign bedside procedure, a few case reports describe rare neurological deficit symptoms following the massage. Currently, the estimated incidence of neurological complications is less than 0.2%.

A single case report describes the induction of coronary artery spasm by carotid sinus massage.

Rare case reports describe the induction of atrial or ventricular arrhythmias by carotid sinus massage.

Carotid massage has its greatest clinical utility in elderly patients aged 60-80 years.

The positive predictive value of carotid massage remains undefined. Therefore, a clinician who finds a sensitive carotid sinus should consider other prognostically important causes of syncope and the presence of comorbid conditions.

In recent years, the scientific basis of the current diagnostic criteria for carotid sinus hypersensitivity (ie, blood pressure drop of ≥50 mm Hg and/or asystole of ≥3 s with carotid sinus massage) are called into question. Because the existing criteria is too sensitive to detect carotid sinus hypersensitivity, authors propose a new set of criteria (ie, blood pressure drop of ≥60 mm Hg, lasting for >6 s and/or asystole of ≥6 s with carotid sinus massage). This new set of criteria has yet to be validated by prospective studies.[12, 19]

Carotid sinus hypersensitivity is an often undiagnosed cause of syncope in the elderly. The timely diagnosis and treatment of carotid sinus hypersensitivity can improve morbidity and prevent complications.[20]

Management of carotid sinus hypersensitivity (CSH) is based on the frequency, severity, and consequences of each patient's symptoms.

Most patients can be treated with education, lifestyle changes, expectancy, and routine follow-up.

A few individuals who have incapacitating and recurrent symptoms may need the following treatments:

Pharmacotherapy has been used to treat recurrent, symptomatic conditions. However, no single agent has been proven to provide long-term effectiveness in large-scale, randomized, controlled trials.

Permanent pacemaker implantation is generally considered an effective treatment for cardioinhibitory CSH and mixed forms of CSH.

Current American College of Cardiology/American Heart Association/Heart Rhythm Society clinical practice guidelines consider permanent pacing therapy to be a class I indication (ie, general agreement exists that the therapy is effective and useful) in patients with recurrent syncope caused by carotid sinus stimulation in the absence of any drug that depresses the sinus node or atrioventricular conduction. Permanent pacing is considered a class IIa indication in patients with recurrent syncope without clear, provocative events and with a hypersensitive cardioinhibitory response. Permanent pacing is discouraged in patients with a hypersensitive cardioinhibitory response to carotid sinus stimulation in the absence of symptoms.[21, 22, 23, 24]

The consensus is that dual chamber pacing (DDD, DVI, DDI) is optimal in the patients. However, VVI mode is also effective in preventing recurrent syncope in some patients. AAI and VDD modes are considered inappropriate.

Cardiac pacing has little or no effect on the vasodepressor type of CSH and may not reduce the frequency of falls in patients with CSH. Permanent pacing may diminish but not entirely eliminate the symptoms in CSH.

Volume maintenance can control the vasodepressor form of CSH, preventing syncopal episodes by maintaining adequate central volume. An individual without another cardiovascular disease should increase salt intake and drink more fluids containing electrolytes.

Surgical denervation and radiological denervation of the carotid sinus nerve were techniques used previously, but they have been largely abandoned because of high complication rates.

Surgery remains an option for a patient with a neck tumor that is compressing the carotid sinus.

Consult an electrophysiologist or cardiologist to rule out cardiac arrhythmia and evaluate the patient for pacemaker implantation.

Obtain a surgical consultation and evaluation if the patient has a neck tumor that is compressing the carotid sinus.

No general activity restrictions are necessary.

Patients should be aware of prodromal symptoms of presyncope or syncope. In such circumstances, immediately assuming supine posture is recommended to prevent syncope and/or falls.

Precipitating events, such as wearing tight neck collars or sudden rotating neck movements, should be avoided.

Follow-up for carotid sinus hypersensitivity (CSH) should be based on the severity of symptoms and the treatment modality. Patients on any form of treatment require regular follow-up to monitor the effects of treatment versus the adverse effects of intervention. Follow-up for patients who rarely have symptoms may be on an as-needed basis.

Although a variety of pharmacological agents has been used empirically to treat recurrent, symptomatic CSH, no single agent has been unequivocally proven to provide long-term effectiveness in large-scale, randomized controlled trials. Some observers have successfully used the serotonin reuptake inhibitors sertraline and fluoxetine in patients who were unresponsive to dual-chamber pacing.

A randomized, controlled pilot study showed that treatment with midodrine, an alpha-1 agonist, could significantly decrease the rate of symptoms and the degree of hypotension in the vasodepressor form of CSH. Treatment with midodrine was also associated with an elevation of a mean 24-hour ambulatory blood pressure level.[25] Midodrine induces arterial and venous capacitance constriction and has minimal cerebral and cardiac effects. It is indicated for the treatment of symptomatic orthostatic hypotension.

Fludrocortisone is another agent that can be used in this setting.

The US Food and Drug Administration has not yet approved these agents for the management of CSH.