3. Results

estimated that approximately 300,000 individuals with T. cruzi infection live in the United States,

The sudden death circadian variation has been demonstrated in two large-scale studies, the Framingham Heart Study [7] and the Massachusetts Death Certificate Study [8]. Both studies show a peak of sudden deaths between 7 and 11 am with a lower incidence during sleep, which is similar to the rate of ischemic and arrhythmic events [9, 10]. The sudden death is the main cause of death in those patients with the Chagas disease, being responsible of the 55–65% of their deaths [11]. Lopes et al. [12] demonstrated that there is a sudden death circadian rhythm in Chagasic patients. In this study, 50 cases of Chagasic sudden death, along with 473 cases of nonsudden natural death, were compared in several centers. To the best of our knowledge, this is the first report that compares the rhythm of the sudden and nonsudden death of Chagasic patients vs. non-Chagasic patients with cases

A retrospective study of a consecutive series of sudden death cases, registered within our department between 1963 and 2011, including the ECG records, Holter records from sudden death victims, autopsies, and the Death report by the relatives. The Chagas disease diagnosis was performed through serological studies, or a necroscopic study was performed in the cases

The date and time of death were collected from necropsy protocols and/or emergency clinical

Sudden cardiac death (SCD) is generally defined as a sudden and unexpected pulseless event, but noncardiac conditions need to be excluded before the occurrence of a primary cardiac event can be confirmed [13]. A case of established SCD is an unexpected death without obvious extracardiac cause, occurring with a rapid witnessed collapse, or if unwitnessed, occurring within 1 h after the onset of symptoms [13]. A probable SCD is an unexpected death without obvious extracardiac cause that occurred within the previous 24 h [13]. In any situation, the death should not occur in the setting of a prior terminal condition, such as a malignancy that is not in remission or end-stage chronic obstructive lung disease [13]. In our study,

A total of 266 cases were analyzed; 56.7% of the subjects were male with an average age of 54.6 years, which were divided into four groups: Group A: Chagasic patients with sudden death, n = 38; Group B: non-Chagasic patients with sudden death, n = 58; Group C: Chagasic patients with non-sudden death, n = 89; and Group D: non-Chagasic patients with non-sudden

The results were assessed using exploratory data analysis (EDA) and comparison of ratio differential. As the statistic validation rule, a p-value <0.05 was considered as statistically

histories, as well as data obtained from relatives and witnesses.

we included both established and probable SCD.

with 30,000–45,000 cardiomyopathy cases and 63–315 congenital infections annually [6].

within a same center.

of autopsies.

death, n = 81.

significant.

2. Material and methods

146 Circadian Rhythm - Cellular and Molecular Mechanisms

A total number of cases per hour of sudden death in patients with and without Ch are shown in Figure 1. Figure 2 shows the number of cases per hour of nonsudden death in patients with and without Ch. After analyzing the data divided into 12-h periods (day and night), significant differences were observed. Figure 3 shows the percentages of cases from the SD groups occurring during night and day. Forty four point seven per cent (44.7%) (17/38) of the sudden deaths in Group A (Ch) occurred between 6 am and 5:59 pm, while for Group B (non-Ch), 70.7% (41/58) of the patients died within that time (p < 0.005). Between 6 pm and 5:59 am, 55.3% (21/38) of the deaths of Group A (Ch) occurred in that time compared to 29.3% (17/58) from Group B (p < 0.005). Figure 4 shows the data of nonsudden death cases. 49.4% (40/81) of Group C (Ch non-SD) died between 6 am and 5:59 pm compared to 59.6% (53/89) of Group D (non-Ch, non-SD), (p not significant), while between 6 pm and 5:59 am, 50.6% of Group C (Ch, non-SD) cases died compared to 40.4% (36/53) of Group D (non-Ch, non-SD) (p was not significant).

In order to perform a more detailed analysis, the percentages of cases were grouped within 3-h periods: (6–8, 9–11, 12–14, 15–17, 18–20, 21–23, 24–2, 3–5). Figure 5 shows the circadian rhythm of sudden death in Chagasic patients (Group A) compared to the non-Chagasic patients (Group B). Within these periods, a higher death percentage in the Chagasic group is observed within the 21–23 h interval (34 vs. 3%, p = 0.0001), while the non-Chagasic arm presented a higher percentage of cases within the 9–11 h range (43 vs. 3%, p < 0.0001), of 24 to 21 2 h (10 vs. 0% p < 0.005), and from 3 to 5 h (7 vs. 0%, p < 0.005). The difference of the other analyzed periods was not significant. When comparing the number of cases of non-sudden

Figure 1. Sudden death of circadian rhythm.

Figure 2. Circadian rhythm of nonsudden death.

Figure 4. Comparison of 12-h periods of nonsudden death in Chagasic vs. non-Chagasic patients.

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Figure 5. Sudden death circadian rhythm in Chagasic patients compared to non-Chagasic patients.

Figure 3. Comparison of 12-h periods of sudden death of Chagasic and non-Chagasic patients.

Figure 4. Comparison of 12-h periods of nonsudden death in Chagasic vs. non-Chagasic patients.

Figure 2. Circadian rhythm of nonsudden death.

148 Circadian Rhythm - Cellular and Molecular Mechanisms

Figure 3. Comparison of 12-h periods of sudden death of Chagasic and non-Chagasic patients.

Figure 5. Sudden death circadian rhythm in Chagasic patients compared to non-Chagasic patients.

deaths in Chagasic patients vs. non-Chagasic patients, a significant difference in any of the analyzed ranges was not observed.

This variation does not seem to be related to the potassium or circulating catecholamine levels [31]; on the other hand, it would be aligned with the variations of the maximum QT

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A peak in the morning and in the afternoon of ischemia-related conditions, such as the myocardial infraction [22, 34, 35], anginal crisis [36–38], and strokes, [39, 40] has been reported. These episodes have been related to morning variations of the endothelial function [41] and of thrombogenesis biochemical markers [42–46]. Durgan et al. [47] demonstrated that there is a relation between the date time and the tolerance to reperfusion-ischemia in cardiomyocytes of isolated mice, being the lowest tolerance during the morning time. The factors that may bias for the circadian rhythm to be different in patients with Chagas

1. The autonomic balance of Chagasic patients, which has been evidenced by several authors [48–50]. Cardiac autonomic dysfunction, characterized mainly by parasympathetic depression, is present in human and experimental Chagas disease, even in patients with

3. The presence of antibodies against the adrenergic receivers may reduce the morning

Abello et al. [54], when analyzing 22 Chagasic patients with third-generation implantable defibrillators, demonstrated a ventricular tachycardia circadian rhythm pattern, characterized by a frequency peak between noon and 18:00 h with a nadir between 24:00 and 6:00 h, which

The sudden death circadian rhythm in Chagasic patients significantly differs from that of the non-Chagasic patients, showing a greater prevalence during the nighttime. Further studies are

Regarding the certainty of the time of death, the study limitation is common to that of all sudden death studies, since the time of death, which is mostly reported by a witness, decreasing the accuracy of the data. In most of the times, we ignored the personal history of the patients (previous pathology, concomitant treatment, etc.) because the death occurred suddenly. Also,

needed in order to analyze both the prognostic implications and the therapeutic ones.

interval [33].

c. Circadian variation of ischemic episodes.

minor ECG alterations [51]. 2. The endothelial dysfunction [52].

would be in line with our results.

5. Conclusion

6. Limitations

disease are not clear; however, several hypotheses have been posed:

adrenergic activity, hence, suppressing the morning peak [53].
