ABC | Volume 111, Nº3, September 2018

Original Article Medeiros et al Obstructive sleep apnea in chagas disease Arq Bras Cardiol. 2018; 111(3):364-372 to severe OSA was independently associated with cardiac remodeling parameters, including larger left atrium dimension and a higher prevalence of ventricular dysfunction, especially in the subgroup of patients with Chagas cardiomyopathy. Taken together, our study emphasizes the concept that OSA may contribute to a poor prognosis in patients with CD. OSA is a prevalent condition in patients with cardiovascular disease, 20 and our study confirms its high frequency in patients with CD. Particular characteristics of studied OSA patients deserves some comments: First, the presence of higher BMI and neck circumference in patients with moderate to severe OSA as compared to patients with mild or no OSA denotes a typical phenotype of the disease (Table1). However, the lack of excessive daytime sleepiness, a characteristic of OSA patients from the overall population referred to sleep laboratories may explain the low awareness of OSA in patients with cardiovascular disease. 21 This finding is in line with other populations with cardiovascular diseases, including heart failure 22 and hypertrophic cardiomyopathy. 23 The low prevalence of central sleep apnea in our sample is in contrast with a previous study that evaluated sleep disorders in patients with heart failure (LVEF < 45%), including CD. Silva et al. 24 included 24 patients with CD, of which only 12% had OSA, but 44% of whom had Cheyne-Stokes respiration. The median LVEF of our sample was within the normal range (60%) and the majority of our sample did not have heart failure. Moreover, we excluded patients with decompensated heart failure from our study, which may explain the different frequencies. OSA is recognized as being a cause of hypertension. 25 In our sample, hypertension was more frequent in the group with moderate to severe OSA and this group used more antihypertensive drugs. However, only systolic BP during sleep was higher in patients with moderate-to-severe OSA. This finding may be related to the fact that the study took place in a reference center for cardiology, where most patients are being properly treated for hypertension. The relatively low frequency of atrial and ventricular arrhythmias in our study may be also explained by the exclusion of more severe cases of CD cardiomyopathy. Our study demonstrated that in patients with CD, OSA is independently associated with left atrial enlargement. This finding is consistent with other OSA populations 7,23,26 Rossi et al. 27 conducted a meta-analysis of 1,157 patients who took part in 18 heart failure studies, and concluded that left atrial enlargement was associated with a worse prognosis, regardless of age, functional class, ejection fraction or diastolic function pattern, 28 reinforcing the importance of our findings. In our study, moderate to severe OSA was also associated with a lower left ventricular longitudinal strain and a four-fold higher proportion of ventricular dysfunction than patients with no OSA. This finding is consonant with an earlier study that evaluated patients referred to a sleep laboratory and may impact negatively on mortality. 6,29 There are several mechanisms that can contribute to cardiac remodeling in OSA patients 30 One possible explanation for the heart remodeling in our study may be partially explained by the increased frequency of hypertension and higher nocturnal systolic blood pressure, as well as increased frequency of abnormal blood pressure dip in the moderate to severe OSA group. Taken together, the increased hypertension burden may increase arterial stiffness and left ventricular afterload, contributing to these abnormalities. 7 Moreover, inspiratory efforts during the apneas generate negative intrathoracic pressure, which leads to an increase in the left ventricular afterload and a decrease in the left ventricular preload, which in turn cause a reduction in the ejection volume and may induce left atrial enlargement, as demonstrated in our study. Intermittent hypoxia may also influence cardiac contractility, directly or indirectly, thereby reducing cardiac output. 22 OSA induces hypoxia, hypercapnia and sleep arousals, thus promoting an increase in sympathetic activity and hence, in blood pressure. 31 Long-term exposure to high sympathetic nerve activity can induce hypertrophy and apoptosis of the cardiac myocytes 32 and thereby cause left ventricular dysfunction. These adverse hemodynamic effects may be more pronounced in individuals with heart failure, 33 as shown in our subgroup with Chagas cardiomyopathy compared with patients with the indeterminate form. The major strength of the present study is that it is the largest and one of the only cohorts evaluating the association between sleep apnea in patients with CD. The recruitment of consecutive patients with well-characterized CD not referred to a sleep laboratory may generalizes the findings of our study, as does the use of gold-standard techniques to assess blood pressure (ABPM) and respiratory effort (inductance plethysmography belts). 11 The study has some potential limitations. A portable sleep monitor that does not measure sleep duration was used. Thus, measurements of the AHI were taken based on the total recording time and not on the total length of sleep, although this device has already been validated against full polysomnography. 34 Furthermore, our findings are derived from a cross-sectional study and we cannot infer causality, but only an independent association between OSA and heart remodeling. The fact that we could not demonstrate the same atrial and ventricular remodeling findings in the subgroup of patients with the indeterminate form of CD could be due to the small number of patients in this category. Moreover, the absence of increased incidence of arrhythmias in OSA patients in this study should be analyzed with caution, as 24 h Holter monitoring could not detect intermittent arrhythmias. New studies with technologies that analyze long periods of time are warranted. Conclusion OSA is common and independently associated with atrial and ventricular remodeling in patients with CD. The improvement in OSA recognition and treatment may contribute to reducing the morbidity attributed to CD. Author contributions Conception and design of the research: Medeiros CA, Oliveira Júnior W, Pedrosa RP; Acquisition of data: Medeiros CA, Secundo IV, Martins SM, Pedrosa RP; Analysis and interpretation of the data: Medeiros CA, Secundo IV, Silveira CAM, del Castilho JM, Albuquerque ALT, Martins SM, Pedrosa RP; Statistical analysis: Pedrosa RP; Writing of the manuscript: Medeiros CA, Martins SM, Lorenzi-Filho G, Pedrosa RP; Critical revision of the manuscript for intellectual content: Oliveira Júnior W. 370