4. Discussion

The sudden death is the primary cause of death in patients suffering from Chagas disease, representing around 60% of the total cases [11], hence the importance of its study. Our study clearly evidenced that in Chagasic patients, the higher percentage of cases of sudden death occurred during the nighttime (Figures 1, 3, and 5). When we analyzed the non-sudden death results, no difference between the Chagasic and non-Chagasic arms was observed (Figures 2 and 4). Our results agree with those of Lopes et al. [8], who demonstrated a sudden death predominance in Chagasic patients during the nighttime. On the other hand, our study also agrees with previous studies in the non-Chagasic population in the United States, which were a predominance of sudden death cases occurred in the morning [7, 8]. The importance of our study lies in two milestones:

(1) This study represents the largest series reported to date comparing the sudden death circadian rhythm in Chagasic and non-Chagasic patients. (2) The fact that this study represents a series where all included patients belonged to the same center within a Latin American country, allowing a better group comparison.

The potential mechanisms for the sudden death circadian variation in the general population are not entirely clear, especially since due to the interaction among them, it is difficult to independently determine the importance of each factor. The proposed mechanisms include:

a. Autonomic nervous system alterations.

It is being proposed that both the sympathetic nervous system and the parasympathetic system may stimulate the circadian variation. Using the frequency domain, it has been demonstrated an unfavorable variability profile of the heart rate in the morning time. [14–17] This may be caused by both the sympathetic tone endogen variations and the increasing level of physical activity [15–17]. The use of beta-blockers reduces or removes the morning peak of ischemic and arrhythmic events [18–22], which supports the hypothesis of increasing adrenergic tone, since this same effect is not achieved via antiarrhythmic non-beta blockers medication [23]. Generally, the HRV indexes significantly decrease during the daytime and increase during the night [24–30].On the other hand, the variations of autonomic tone and parasympathetic-sympathetic balance have been proposed as the cause, which have been analyzed through heart rate variations (HRV) [31–35].

b. Morning variations of the electrophysical properties.

In both invasive electrophysiological studies [28] and non-invasive studies using permanent pacemaker telemetry [15, 31], circadian variation of the ventricular refractory has been demonstrated, being the last lower during the morning time and higher during sleep. 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 interval [33].

c. Circadian variation of ischemic episodes.

deaths in Chagasic patients vs. non-Chagasic patients, a significant difference in any of the

The sudden death is the primary cause of death in patients suffering from Chagas disease, representing around 60% of the total cases [11], hence the importance of its study. Our study clearly evidenced that in Chagasic patients, the higher percentage of cases of sudden death occurred during the nighttime (Figures 1, 3, and 5). When we analyzed the non-sudden death results, no difference between the Chagasic and non-Chagasic arms was observed (Figures 2 and 4). Our results agree with those of Lopes et al. [8], who demonstrated a sudden death predominance in Chagasic patients during the nighttime. On the other hand, our study also agrees with previous studies in the non-Chagasic population in the United States, which were a predominance of sudden death cases occurred in the morning [7, 8]. The importance of our

(1) This study represents the largest series reported to date comparing the sudden death circadian rhythm in Chagasic and non-Chagasic patients. (2) The fact that this study represents a series where all included patients belonged to the same center within a Latin American

The potential mechanisms for the sudden death circadian variation in the general population are not entirely clear, especially since due to the interaction among them, it is difficult to independently determine the importance of each factor. The proposed mechanisms include:

It is being proposed that both the sympathetic nervous system and the parasympathetic system may stimulate the circadian variation. Using the frequency domain, it has been demonstrated an unfavorable variability profile of the heart rate in the morning time. [14–17] This may be caused by both the sympathetic tone endogen variations and the increasing level of physical activity [15–17]. The use of beta-blockers reduces or removes the morning peak of ischemic and arrhythmic events [18–22], which supports the hypothesis of increasing adrenergic tone, since this same effect is not achieved via antiarrhythmic non-beta blockers medication [23]. Generally, the HRV indexes significantly decrease during the daytime and increase during the night [24–30].On the other hand, the variations of autonomic tone and parasympathetic-sympathetic balance have been proposed as

the cause, which have been analyzed through heart rate variations (HRV) [31–35].

In both invasive electrophysiological studies [28] and non-invasive studies using permanent pacemaker telemetry [15, 31], circadian variation of the ventricular refractory has been demonstrated, being the last lower during the morning time and higher during sleep.

analyzed ranges was not observed.

150 Circadian Rhythm - Cellular and Molecular Mechanisms

study lies in two milestones:

country, allowing a better group comparison.

a. Autonomic nervous system alterations.

b. Morning variations of the electrophysical properties.

4. Discussion

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


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 would be in line with our results.
