Carotid sinus syndrome

 Carotid sinus syndrome

It has long been observed that pressure at the site where the common carotid artery bifurcates produces a reflex that leads to slowing in heart rate and fall in blood pressure. In some individuals an abnormal response to carotid massage (CSM) is observed. A ventricular pause lasting more than 3 seconds and/or a fall in systolic blood pressure of more than 50 mm/Hg defines carotid sinus hypersensitivity.  When associated with spontaneous syncope, an abnormal response to carotid massage CSM defines the carotid sinus syndrome (CSS).

Precise methodology and results of CSM are reported in the guidelines on syncope (1). It should be emphasised that reproduction of symptoms during CSM is a strong argument for the diagnosis of carotid sinus syndrome (CSS) and not only carotid hypersensitivity. Increasing importance has been handed to the execution of the massage also in the upright position, usually using a tilt table (2). Other than a higher positivity rate compared with supine massage only, the importance of performing upright massage is due to the better possibility of evaluating the magnitude of the vasodepressor component and of reproducing symptoms.

How frequent is CSS

 In the evaluation of the patient with syncope, the strategy for assessment for CSS varies widely among physicians and among hospitals and clinics. For example, in the EGSYS study (3), the execution of CSM among patients referred urgently for syncope to 28 general hospitals ranged from 0% in some hospitals to 58% in another (median 12.5%) (Fig 1). As a consequence, the reported incidence of CSS also varies widely in literature from 1% to 60% (3 ).   

Figure 1. Incidence of execution of carotid sinus massage
(expressed as percentage of total patients admitted) among 28 hospitals participating to the EGSYS study (3). Each bar represents one hospital. The vertical dotted lines are those corresponding to the 25th, 50th and 75th percentiles of distribution.

Even when strict adherence to the criteria of appropriateness of the guidelines are used, the incidence of CSS varies widely upon the clinical settings (general versus selected populations, age and gender, etc).  The following data could be taken as reference:

• CSM should be appropriately performed in 14% of adult patients referred for syncope in the emergency departments and CSS found in 4% (one out of four test performed) (4)
• CSM should be appropriately performed in 56% of adult patients referred in a specialised syncope unit for evaluation of unexplained syncope and CSS found in 14% (one out of four test performed) (5)
• CSS was found in 26% of 1719 consecutive patients performing appropriately CSM for syncope of uncertain origin (one out of four test performed) (2). This percentage rises up to 60% in patients with syncope and sick sinus syndrome (6)
• The rate of positive responses to CSM increases with age, ranging from 4% in patients <40 yrs to 41% in pts >80 yrs (2).

Among patients with CSS, two thirds are males, 45% have a dominant cardioinhibitory form, 40% a mixed form and 15% a dominant vasodepressor form; in the cardioinhibitory and mixed forms the mean ventricular pause is >6 s duration (2). Major trauma (defined as bone segments fracture, intracranial haemorrhage, internal organ lesions requiring urgent, specific treatment; retrograde amnesia or focal neurologic defect) are more frequent in CCS that to the other patients with syncope afferring to the emergency department (24% versus 4.8% ) (7)

Is a positive CSM diagnostic the cause of syncope?

Since a positive response to CSM can be frequently found even in many patients without syncope, its diagnostic value is questionned because of low specificity.  It is well known that abnormal responses are frequently observed in subjects without syncope, for example, in 17–20% of asymptomatic patients affected by various types of cardiovascular diseases (8) and in 38% of asymptomatic patients with severe narrowing of the carotid arteries (9).

The relationship between CSS and spontaneous, otherwise unexplained syncope had been supposed in an older study (10) using a pacemaker designed to detect asystolic episodes. Long pauses (6 sec) were detected in 53% of the patients with CSS during 2 years of follow-up, suggesting that a positive response to carotid massage predicts the occurrence of spontaneous asystolic episodes. This correlation was recently confirmed by means of documentation of spontaneous episodes by an Implantable Loop Recorder (ILR) in 18 patients affected by cardioinhibitory CSS detected by CSM (maximum pause of 5.5-1.6 s [range 3.6 to 8.5 s]) (11). Asystole >3 s (average longest pause of 9 [8-18] s) was observed at the time of the spontaneous syncope in 16 (89%) of CSH patients.  Sinus arrest was the most frequent finding and was observed in 72% of these.  

Therefore, how to interpret these apparently discordant findings?

Carotid sinus susceptibility is present in many subjects who have not yet manifested its clinical syndrome, i.e., syncope. In other words, the potential number of patients who might suffer from  CSS is higher than those who have actually manifested it. 

Nevertheless, from a practical point of view, a positive response to CSM should be considered diagnostic of the cause of syncope only in patients with a high likelihood of being affected by neurally-mediated syncope identified by relatively straightforward initial evaluation and clinical features, in accordance with the recommendations of current guidelines (high pre-test probability) (1). Indeed, when competitive diagnosis of syncope are still present, the finding of a positive CSM might be unrelated to the cause of syncope. In these cases, the predictive value of CSM is lower and other tests are needed to confirm the mechanism of syncope.

Is cardiac pacing effective?

Pacing has been considered as a therapeutic option for CSS in the early 70’s when some case-reports demonstrated that recurrences of syncope were abolished after implantation of a pacemaker (12). Series then confirmed that pacing in patients with CSS could significantly reduce the number of syncope (13). Non randomised comparative studies were in accordance with these preliminary results and in the mid 80’s pacing became a recognised treatment of CSS (14). The first randomised trial which compared pacing in 60 patients and no pacemaker was reported in 1992 (15). After a mean follow up of 36 10 months, syncope recurred respectively in 9% and 57 % of the patients in pacing and control group (p<0.0002).

A recent randomised trial (16) confirmed the results of the previous one. Sixty patients with CSS were randomised to receive a permanent pacemaker (n=30) or no pacing (n=30).  At 12 months, the rate of syncope was 40% in non-treated patients compared with 10% in the paced patients (p= 0.008).

Finally, in the already mentionned ILR study (11), after ILR documentation, 14 patients with asystole received dual-chamber pacemaker implantation; during 35-22 months of follow-up, 2 syncopal episodes recurred in 2 patients (14%) and presyncope occurred in another 2 patients (14%). Syncope burden decreased from 1.68 (95% confidence interval 1.66-1.70) episodes per patient per year before to 0.04 (0.038-0.042) after pacemaker implant (98% relative risk reduction).

When the pre-test likelihood of being affected by neurally-mediated syncope was less certain, as was the case for example of the patients with accidental fall of uncertain origin (17), cardiac pacing was still effective compared to no pacing group, but syncope recurrence burden (0.32 episodes per year) remained 8 times higher than that observed in the above mentionned ILR study.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

Conclusion:

The main conclusions are:

The systematic execution of CSM performed according to the method of symptoms reveals that CSS is a frequent cause of syncope in the elderly; its rate is probably underestimated because the massage is not systematically performed in clinical practice

• CSM response predicts the mechanism of spontaneous syncope
• Cardiac pacing is effective to prevent and to reduce the burden of recurrences in patients with cardioinhibitory and mixed forms of CSS and a high likelihood of being affected by neurally-mediated syncope identified by relatively straightforward initial evaluation and clinical features