1. CAROTID SINUS SYNDROME Evidence review

2. Introduction The hypersensitive carotid sinus syndrome (CSS) is defined as syncope or presyncope resulting from an extreme reflex response to the carotid sinus stimulation. It affects 35–40 patients/million persons/year and is responsible for 1–20% of PP implantations and for 20–45% of unexplained falls or syncope in older patients. The CSS is more common in males (4:1) and in patients with diabetes and atherosclerosis Eltrafi A, King D et al; Postgrad Med J 2000 Davies AJ, Steen N et al; Age Ageing 2001

3. Questions to be answered…. How to identify a person with CSS? Role, reproducibility of CSM? Do we have to pace them? Pace mode selection? Recurrence of symptoms after pacing?

4. Age distribution CSH is an age-related phenomenon – Rarely diagnosed in patients with syncope < 50 years – Prevalence increases with advancing age Unexplained syncope—is screening for carotid sinus hypersensitivity indicated in all patients aged > 40 years? J Neurol Neurosurg Psychiatry 2006;77:1267–1270

6. Carotid sinus massage A ventricular pause lasting >3 s and/or a fall in systolic BP of >50 mmHg defines carotid sinus hypersensitivity (CSH). When associated with spontaneous syncope, CSH defines CSS.

7. Europace 2002 64 subjects with CICSH and unexplained or recurrent falls.(61% female, mean age 71·8 years, median 2 falls in the previous year) completed 1 yr F/U and had CSM performed on 4 occasions (twice before randomization, at 6 months and 1 yr). Results CICSH was demonstrated on 82% of occasions, 75% on right CSM and 77% whilst the subject was supine. Before randomization, and at 6 months and 1 year, 91%, 67%, and 70% of subjects had reproducible CICSH respectively. Half had CICSH on all 4 occasions. Only 17% had a consistent response on the same side in the same position

9. 272 participants(>65 yrs) underwent supine and upright carotid sinus massage with continuous heart rate and blood pressure monitoring. RESULTS: CSH was present in 107 individuals (39%); 24% had asystole of ≥3 seconds during CSM; and 16% had symptoms (including syncope) with CSM. Age (OR, 1.05; 95% CI, 1.00-1.09) and male sex (OR, 1.71; 95% CI, 1.04-2.82) were the only predictors of carotid sinus hypersensitivity. In 80 previously asymptomatic individuals, CSH was present in 28 (35%) and accompanied by symptoms in 10. CONCLUSION: CSH is common in older persons, even those with no history of syncope, dizziness, or falls. The finding of a hypersensitive response should not necessarily preclude further investigation for other causes of syncope.

10. Cardioinhibitory carotid sinus hypersensitivity predicts an asystolic mechanism of spontaneous neurally mediated syncope. Europace 2007, Maggi, Menozzi etal Correlated CSH with that observed during a spontaneous syncopal relapse by means of ILR. 18 CSM+ vs. 36 CSM- pts, suspected recurrent neurally mediated recurrent syncope. Asystole >3 s was observed at the time of the spontaneous syncope in 16 (89%) of CSH patients and in 18 (50%) of the control group (P = 0.007). Sinus arrest- 72 vs. 28%, P = 0.003 14 CSH patients with asystole received DDI. Syncope burden decreased from 1.68 to 0.04 episodes per yr per person. (98% relative risk reduction).

11. BENEFIT OF PACING

12. A randomized treatment/nontreatment prospective study. 60 pts affected by carotid sinus syndrome. They were randomly assigned to 2 groups: 28 patients to nonpacing group and 32 to VVI (n = 18) or DDD (n = 14) pacing group. Syncope recurred in 16 pts (57%) of the nonpacing group (mean follow-up 36 +/- 10 months) and in only 3 (9%) of the pacing group (mean follow-up 34 +/- 10 months) (p = 0.0002). 19 (68%) in the nonpacing group needed a secondary pacemaker implant because of the severity of symptoms. Reproducibility of carotid sinus reflex was tested after 15 +/- 8 months in 54 patients; an abnormal response to carotid sinus massage persisted in all 54.

13. Europace 2011 To assess the outcome of patients with CSS treated with pacemaker and to determine predictors of symptom recurrence. A retrospective analysis of 138 patients in whom pacemaker was implanted for CSS. Mean age was 69±10.7 yrs an 75.4% were men. Mean follow-up period was 4.9±4.4 yrs. 21 (15.2%) pts presented mixed CSS and 117 (84.8%) CICSS. After PPI, 115 (83.3%) pts had no further symptoms, 8 (5.8%) presented minor symptoms and in 15 (10.9%) the symptoms remained unchanged. Among pts with symptoms recurrence, 8 (38.1%) had mixed CSS and 15 (12.8%) cardioinhibitory CSS. Mixed CSS was the only independent predictor of symptoms recurrence in total population {hazard ratio (HR) 2.84 [95% CI 1.20–6.71]; P= 0.017.

14. JACC 2001 The aim of the study was to determine whether cardiac pacing reduces falls in older adults with CICSH.

15. RESULTS The primary outcome was the number of falls during one year of follow-up. Falls (without LOC) were reduced by two-thirds: controls reported 669 falls (mean 9.3; range 0 to 89) and paced patients 216 falls (mean 4.1; range 0 to 29). Odds ratio 0.42; 95% CI: 0.23- 0.75. Syncopes were also reduced but there were much fewer syncopal events than falls—28 episodes in paced patients and 47 in controls. Injurious events were reduced by 70% (202 vs 61).

16. Heart 2010 To assess the efficacy of dual-chamber pacing in older patients with CICSH and unexplained falls. A multicentre, double blind, randomised controlled trial. Patients aged >50 years, with two unexplained falls and/or one syncopal event in the previous 12 months for which no other cause is evident apart from CICSH. 141 pts -randomized to rate responsive pacemaker or implantable loop recorder. The primary outcome- the number falls after implantation.

17. Results 141 patients were recruited from 22 centres. Mean age was 78 years and mean follow-up 24 months. The overall relative risk of falling after device implantation compared with before was 0.23 (0.15 to 0.32). No significant reduction in falls was seen between paced and loop recorder groups (RR=0.79; 95% CI 0.41 to 1.50).

18. These results question the use of pacing in CICSH. The study was underpowered Patient characteristics differed from those in Safepace-1 (participants were physically and cognitively frailer)

19.  Patients: Consecutive subjects aged over 55 years with CSH with ≥ 3 unexplained falls in the 6 months preceding enrollment.  Intervention: Dual-chamber permanent pacing with rate drop response programming. The pacemaker was switched on (DDD/RDR) or off (ODO (placebo)) for 6 months, then crossed over to the alternate mode for a further 6 months.  The primary outcome: number of falls in paced and non-paced modes.  Results: 25 of 34 subjects (mean- 76.8 years (SD 9.0), 27 (79%) female) recruited completed the study. Pacing intervention had no effect on number of falls (4.04 (9.54) in DDD/RDR mode, 3.48 (7.22) in ODO; relative risk of falling in ODO mode 0.82, 95% CI 0.62 to 1.10).  Conclusion: Permanent pacing intervention had no effect on fall rates in older patients with CSH.

20. Role of pacing in CSS The role of pacemaker in hypersensitive carotid sinus syndrome Europace (2011) 13, 572–575 Permanent pacemaker is an effective treatment

24. MODE OF PACING

25. Is DDD Superior to VVI Pacing in Mixed Carotid Sinus Syndrome? An Acute and Medium-Term Study Pacing and Clinical Electrophysiology 1988;brignole et al 23 pts affected by symptomatic mixed carotid sinus syndrome- received a DDD pacemaker and entered a 2 month two period single-blind, randomized, cross- over study on DVI/DDD versus VVI mode. During the DVI/DDD period, no syncope occurred in any pts, minor symptoms persisted in 11 (48%) of them. During VVI period syncopes recurred in 3 pts, symptoms requiring the withdrawal of VVI pacing and premature DVI/DDD reprogramming in 8 pts, minor symptoms in 17 (74%). A comparison between 14 pts who preferred DVI/DDD period (Group A), and the remaining 9 who noted no preference between DVI/DDD and VVI period (Group B). Group A patients had a greater pacemaker effect (-34 ± 16 mmHg vs -16 ± 14 mmHg) and a higher prevalence of symptomatic pacemaker effect (50% vs 0%)of ventriculo-atrial conduction (78% vs 44%) and of orthostatic hypotension (50% vs 11%) DVI/DDD pacing is more effective than VVI in 61% of patients.

26. A study comparing VVI and DDI pacing in elderly patients with carotid sinus syndrome Shona J McIntosh et al; Heart 1997 Prospective double blind randomised cross over study. 30 consecutive pts >60 years with CSS referred for cardiac pacing. Patients underwent dual chamber PPI and randomised to 2 three month periods of VVI and DDI pacing. Main outcome measures-Responses to cardiovascular tests (vasodepression during CSM, pacemaker effect, postural BP measurements and response to head up tilt) and symptoms.

27. Results 11 pts were unable to tolerate VVI pacing and had to be withdrawn early from this limb of the study (group A). 14 pts had no preference (group B). No patient preferred VVI. Elderly patients with carotid sinus syndrome are likely to develop symptomatic hypotension following single chamber ventricular pacing.

29. RECURRENCE OF SYMPTOMS AFTER PACING?

31. All subjects who had had pacemaker implantation for cardio-inhibitory CSH were followed up. 2 groups: Pts- >1 episode of syncope and controls- without syncope or 1 syncope only. They were clinically evaluated and a new CSM done to record the response. Each subject had 2 CSMs, the first at enrolment and pacemaker implantation and the last at reevaluation. The mean followup period 72 months.

33. Syncope recurrence was seen in 35% of subject 28% had a vasodepressive effective SCM and 10% had symptoms during the maneuver. The pts selected and treated for cardio-inhibition changed their patterns at CSM (a new vasodepressive response) and by the appearance of OH, leaded to symptom recurrence. Dysautonomia may occur in these pts (association between CSH & OH). Indicates that CSH is a generalized autonomic disorder.