The natural history of carotid sinus syncope and the effect of cardiac pacing
Open accessAbstract
This editorial refers to ‘The role of pacemaker in hypersensitive carotid sinus syndrome’ by R. Lopes et al., on page 572. Despite the fact that permanent cardiac pacing for patients affected by cardioinhibitory carotid sinus syncope (CSS) is ranked as a class I or class IIa indication by the most recent European and American guidelines,1–3 the evidence supporting these recommendations is weak (level of evidence B or C), due to the lack of large randomized trials. The reason is that pacemaker implantation for CSS is a common clinical practice accepted by most cardiologists since the pioneering phase of cardiac pacing in the early 1970s4,5 when the methodology of evidence-based medicine was not as rigorous as today. Many studies were observational without a control group and only two small trials were randomized with no treatment control arm.6,7 On the other hand, the natural history of patients with recurrent severe symptoms is not well known because these patients are usually treated, thus lacking an estimation of the expected benefit of pacing therapy. Finally, recent reports8,9 raise some concerns regarding the specificity of the current criteria for carotid sinus hypersensitivity (defined as ≥3 s asystole and/or fall in systolic blood pressure of ≥50 mmHg) as they are arbitrary and frequently observed in the general older population. A recent randomized trial failed to show any benefit of cardiac pacing in patients with carotid sinus hypersensitivity and unexplained recurrent falls.10 Therefore, a question arises as to what the real usefulness of pacing therapy is and which patients need this therapy. Lopes et al.11 performed a retrospective analysis of 138 patients who were followed-up for ∼5 years, thus adding an important contribution to the effect of cardiac pacing in CSS patients. Taking into account this study, in this article we tried to summarize the current knowledge about pacing therapy of this old syndrome. We performed a MedLine search among peer-review journals in the English language for articles dealing with the natural and unnatural history of CSS; we excluded case reports. We found 12 studies6,7,11–20 which reported sufficient follow-up data for analysis. In total, we were able to analyse the natural history of 305 patients and the effect of cardiac pacing in another 601 patients affected by severe recurrent syncope. The results are shown in Figure 1. The studies were largely heterogeneous in regard to the selection of patients, duration, and position (supine or standing) of the carotid sinus massage, criteria for identification of mixed forms, and different mode of pacing (single- vs. dual-chamber). Despite these limitations, the figure suggests that syncopal recurrence rates during follow-up with pacing ranged between 0 and 20%, whereas the recurrence of syncope was always higher in untreated patients, with the rates between 20 and 60%. Syncope recurrence rate reported in 12 studies of untreated and treated CSS patients plotted against the duration of the follow-up. In total, the studies accounted for 305 untreated and 601 treated patients. The specificity of carotid sinus massage increases if reproduction of spontaneous syncope during carotid massage is a requisite for positivity of the test. The so-called ‘Method of Symptoms' requires a longer duration of the massage, in general for 10 s. The recent ESC guidelines on syncope2 recommend that CSS be diagnosed if spontaneous symptoms are reproduced together with the documentation of an abnormal reflex. Figure 2 shows the results of metanalysis of three controlled studies6,7,15 in which carotid sinus massage was performed according to the ‘Method of Symptoms'. The studies were sufficiently homogeneous (Mantel–Haenszel heterogeneity test: P = 0.39). The mean length of the pause induced by the carotid sinus massage ranged from 5.2 to 7.3 s. During a mean observation period of up to 3.3 years, syncope recurred in 9% of patients treated with a pacemaker and in 38% of control untreated patients. The cumulative odds ratio was 0.15 (95% CI 0.06–0.36). Finally, in a registry of 169 consecutive patients treated with permanent pacemaker in our departments from 1988 to 1994,19 the actuarial estimate of syncopal recurrence was 7% at 1 year, 16% at 3 years, and 20% at 5 years. Relative risk reduction of syncope recurrence after pacemaker therapy in three controlled studies in which CCS was diagnosed by means of the ‘Method of Symptoms'. PM, pacemaker; n/N, patients with syncope recurrence/total patients. Cardiac pacing seems less effective in preventing pre-syncope than syncope. Indeed, pre-syncope and minor symptoms have been reported in 25,6 27,7 and 43%20 patients after pacemaker implant. Moreover, two randomized trials6,7 failed to show the superiority of cardiac pacing compared with no pacing in reducing the rate of pre-syncope. It seems that pacing transforms syncope to pre-syncope probably because it is effective in counteracting the asystoli
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Patients with positive tilt tests have a three-fold greater probability of syncope recurrence after dual-chamber pacing than those with negative tilt tests.
“Patients who have positive tilt tests have a three-fold greater probability of syncope recurrence after dual chamber pacing than those with negative tilt tests 293,295 ; thus, when tilt testing is positive, caution must be recommended over pacemaker implantation.”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [293]
The main text (page not available) reports a 2.7-fold higher risk of syncope recurrence in tilt-positive than tilt-negative patients with carotid sinus syndrome and pacemakers, which reasonably supports the approximate three-fold figure. It does not establish that this comparison was specifically after dual-chamber pacing, and it notes that Lopes et al. did not confirm the result. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn a meta-analysis of three studies with a control group of untreated patients, syncope recurred in 9% of 85 paced patients and 38% of 91 controls (relative risk 0.24, 95% CI 0.12-0.48).
“In a metaanalysis of the three studies 293 with a control group of untreated patients, syncope recurred in 9% of 85 paced patients and in 38% of 91 controls (relative risk 0.24, 95% CI 0.12-0.48).”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [293]
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- Authors
- Brignole, M., & Menozzi, C.
- Affiliations
- Presidio Ospedaliero (IT)
- Santa Maria Nuova Hospital (IT)
- Corresponding author
- Brignole, M.
- ORCID
- Brignole, M.
- Venue
- Europace
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-29
- Volume
- 13
- Issue
- 4
- Pages
- 462-464
- ISSN
- 1099-5129 (ISSN-L)
- 1532-2092
- OpenAlex
- W2115763436
- Cited by
- 49
- References
- 28
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 3 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 10 · 2012: 1
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EP Europace (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- carotid sinus syncope, carotid sinus hypersensitivity, cardiac pacing, pacemaker therapy, natural history (disease), recurrent syncope, carotid sinus massage, asystole, blood pressure drop, evidence-based medicine, older adults, follow-up outcomes
- MeSH terms
- Cardiac Pacing, Artificial, Humans, Pacemaker, Artificial, Recurrence, Syncope, Treatment Outcome
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