ABC | Volume 114, Nº2, February 2020

Original Article Lacerda et al. Mortality in cardioinhibitory carotid sinus hypersensitivity Arq Bras Cardiol. 2020; 114(2):245-253 Table 3 – Cox regression results and relation between CICSH and all-cause mortality Odds Ratio 95% Confidence Interval p value Cox model 1 CICSH present 0.921 0.618 – 1.372 0.686 Age 1.037 1.022 – 1.051 < 0.001 Male sex 1.144 0.874 – 1.498 0.328 Atherosclerosis 1.733 1.321 – 2.276 < 0.001 Cox model 2 CICSH present 0.946 0.633 – 1.412 0.785 Age 1.043 1.028 – 1.058 < 0.001 Male sex 1.078 0.820 – 1.418 0.588 Hypertension 1.032 0.745 – 1.431 0.847 Dyslipidemia 0.645 0.486 – 0.855 0.002 Diabetes 1.529 1.135 – 2.062 0.005 Smoking 1.617 1.090 – 2.400 0.0170 Atherosclerosis 1.884 1.408 – 2.522 < 0.001 CICSH: cardioinhibitory carotid sinus hypersensitivity. resulting from ischemic stroke, and two from ischemic heart disease. 17 The fourth patient died after colectomy done after mesenteric infarction. 18 The second clinical, 18 trial recruited 141 elderly patients with a history of syncope or unexplained fall attributed do the presence of CICSH.Patients were randomized to dual-chamber pacing or received an implantable loop recorder. After 2 years of follow-up, fall and syncope recurrence were similar in both groups. This trial has been criticized because the larger RR interval triggered by CSM was 3.1 seconds. Hence, the magnitude of cardioinhibitory response was considered to be small. According to pathophysiological studies, cerebral ischemic anoxia reserve time is around 7 seconds in healthy military personnel, 19 and a ventricular pause of 3 seconds is not likely to lead to loss of consciousness. 20 So, a ventricular pause of 3 seconds is not likely to produce syncope. Based on this reasoning and based on an epidemiologic study that showed that the 95 th percentile for CSM response was 7.3 seconds, Krediet et al. 20 have proposed 6 seconds as a new cut off for the diagnosis of CICSH. 20 In the present study, the largest RR interval triggered by CSM was 10.3 seconds, and the 95 th percentile for CSM response was 4.5 seconds. Thirteen of the 502 patients submitted to CSM had an asystole episode ≥6 seconds. (Figure 4) At the end of follow-up, the mortality rate of this small group of patients was 53.8%, which is similar to the percentage found in the 447 patients followed up without a pause ≥6 seconds (53.8% vs. 49.9%; p value: 0.77). Study limitations Besides reducing the heart rate and prolonging or blocking atrioventricular conduction, CSM may trigger a fall in blood pressure. 1,2 The blood pressure fall observed after CSM is a rapid and transient phenomenon. To be properly observed, this phenomenon must be documented on a beat-by-beat basis using invasive methods or digital pletismography. 1 Furthermore, this blood pressure fall is more commonly observed with the patient in the upright position on a tilt table. 1,6 In 2006, in the first phase of the present study, devices used to evaluate blood pressure non-invasively on a beat‑by‑beat basis and tilt tables were not available in Rio de Janeiro public hospitals, so we have evaluated blood pressure response manually with a sphygmomanometer in the supine position. This method lacks sensitivity 1,6 and, for this reason, we have decided to present only the heart rate response to CSM. Only 7 of the 52 CICSH patients had a history of unexplained syncope, and none of them had recurrent syncope. This population had CSH, and was not affected by real CSS. It is difficult to conduct a study on the natural history of cardioinhibitory carotid sinus syncope because cardiac pacing is indicated to reduce symptoms in these patients. 1 According to many authors, this treatment could also modify the natural history of CICSH, reducing the mortality of patients with CSS. 5,7 As we have seen, pacing is also justified by the concern that a prolonged asystole episode could lead to serious trauma, brain injury, pause-dependent ventricular arrhythmias and death. 5,7 Our results suggest that this concern is excessive. However, we have to emphasize that in their most recent guidelines, the Brazilian Society of Cardiology and the European Society of Cardiology continue to recommend pacing for patients with CICSH and recurrent syncope. 1,2 It must be stressed that it is very important to document the association between symptoms and bradycardia because pauses and bradycardias without clinical significance can be easily induced by CSM in elderly individuals, especially when these patients are on negative chronotropic drugs. 1,2 250