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 In the present phase of the study, the 502 patients submitted to CSM in 2006 were divided into groups. The first group was formed by the 52 CICSHpatients and, for comparison purposes, a second group of 450 patients without CICSH was studied. Survival data was assessed through active follow-up and review of Rio de Janeiro deaths database and the Rio de Janeiromedical admissions database. In the latter, we have searched for all patients who had permanent a pacemaker paid by the state government of Rio de Janeiro. In all cases, we have considered the cause of death described in Rio de Janeiro deaths database. Cardiovascular deaths were those registered under chapter IX of the International Statistical Classification of Diseases and Related Health Problems 10 th Revision (ICD‑10); ischemic heart disease deaths were those registered under ICD-10 codes I20 – I25, and trauma related deaths were those registered under ICD codes S00 – T14, T66 – T98, V01 – V29, V80 – V94, V98 – W19, W65 – W74, Y85 – Y89. Ethical approval The protocol was approved by the local ethics committee (approval statement number 2.383.341) conforming to the standards of the Brazilian National Committee of Research Ethics (resolution 466/2012). Statistical analysis All data were analyzed using the R Core Team (2018) software. The Shapiro-Wilk test was used to verify the normality of the data. Normally distributed continuous data are shown as mean and standard deviation and the differences between the two groups are compared using unpaired Student's t-test. Categorical data are presented as absolute and relative frequencies and are compared using χ 2 or Fisher's exact tests as appropriate. The level of statistical significance was set at 0.05. Time to event was defined as the time between the date of CSM and death or end of the study; December 31, 2017. The time to event was analyzed using the Kaplan-Meier survival curves, which were compared using the log-rank test. Risk factors associated with mortality were analyzed using the Cox regression analysis. Two models were created, the first adjusted by sex, age and presence of atherosclerosis; the second model made additional adjustments for smoking history, history of hypertension, diabetes and dyslipidemia. Results Patients’ characteristics In the first phase of the study, 52 CICSH patients were identified among the 502 patients submitted to CSM. 8 Only 7 of the 52 CICSH patients had a history of syncope and 40 of them used negative chronotropic drugs. Those 52 patients were advised to avoid inadvertent stimulation of the carotid sinus and, in 12, the dosage of negative chronotropic drugs was reduced. At that time, none of the 52 patients has been submitted to permanent pacemaker implantation. The baseline characteristics of the patients with and without CICSH are presented in table 1. Patients with CICSH were more likely to be male and had higher prevalence of structural heart disease and atherosclerosis. Follow-up of the 52 CICSH patients Twenty-seven of the 52 CICSH patients were actively followed up. At the end of the study, none of them had been submitted to permanent pacemaker implantation, 19 were alive and 8 had died. Data about the remaining 25 patients were retrieved at Rio de Janeiro databases of death and medical admissions. Twenty-one of those were dead and 4 were alive. None of those patients had been submitted to permanent pacemaker implantation. Overall, 29 of the 52 patients (55.8%) identified with CICSH had died at the end of the study (maximum follow up time of 11,6 years). Figure 1 Furthermore, the mortality rate of the 7 CICSH patients with history of syncope was 57,1%. This mortality rate was similar to that found in the 45 CICSH patients that did not have this symptom (55,5%). Follow-up of patients without CICSH We could not find any information in 42 of the 450 patients without CICSH. One hundred and two patients were actively followed up. Data about the remaining 306 patients without CICSH were retrieved at Rio de Janeiro databases of death and medical admissions. Overall, 201 of the 408 patients without CICSH were dead (49.3%) at the end of follow‑up, none had been submitted to permanent pacemaker implantation. One of the 207 patients that was alive at the end of follow-up had been submitted to permanent pacemaker implantation due do complete AV block. Patients with and without CICSH — Endpoint comparisons Figure 1 outlines the study design and compares the death rate of patients with and without CICSH. Figure 2 shows the distribution of responses to right and left CSM in patients who died during follow-up and in patients who were alive at the end of the study. Median duration of RR intervals observed during CSM were similar in both groups of patients. Table 2 compares the total mortality, cardiovascular mortality, mortality due to ischemic heart disease and trauma‑related mortality of the 52 CICSH patients with the 408 patients without CICSH. Survival curves are presented in figure 3. The total mortality rate of the 52 CICSH patients was 21.1% at 5 years and 51.9% at 10 years, with median survival time of 10.0 years (95% CI: 7.4 – 12.6 years). The survival curves of patients with and without CICSH were similar without any significant statistical difference. Both Cox regression models failed to reveal any association between CICSH and mortality. In both models, age at the time of CSM, and presence of atherosclerosis were independently associated with mortality. (Table 3) 246