Abstract
Background
Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.
Objective
To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.
Methods
10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.
Results
Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’ wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.
Conclusion
An impairment of LA functions in Chagas cardiomyopathy was observed.
Keywords: Chagas Disease, Chagas Cardiomyopathy, Ventricular Dysfunction, Atrial Function/physiopathology, Echocardiography, Doppler/methods
Introduction
Chagas disease, an infectious illness caused by the protozoan Trypanosoma cruzi, was described by Carlos Chagas in 1909, but its pathogenesis has yet to be completely elucidated1.
Doppler echocardiography is the ideal method for cardiovascular research, especially anatomical and functional assessment, in patients with Chagas disease.
Tissue Doppler provides important additional information on cardiac function. The s’ wave is related to longitudinal left ventricular (LV) systolic function, while the e’ wave is related to LV diastolic function. One of the advantages of using the e' wave to assess LV diastolic function is less dependence on hemodynamic loading conditions, contrary to what occurs with the E wave of the mitral flow2-8.
The left atrial (LA) function is divided as follows:
Reservoir function: the left atrium stores pulmonary venous return during LV contraction and isovolumetric relaxation, getting 42% of the LV filling volume stored during these phases of the cardiac cycle9. Among the factors that influence it, the following must be highlighted: a) atrial contraction and relaxation, relaxation depending on contraction; b) LV contraction, which displaces the mitral annulus caudally; c) atrial stiffness and compliance; and d) right ventricular systole, which influences the flow in pulmonary veins.
Conduit function: the left atrium passively transfers blood to the left ventricle. It depends fundamentally on LV diastolic properties.
Pump function: the left atrium contracts actively during the final phase of ventricular diastole and contributes to 15%-30% of the LV end-diastolic volume. It depends on multiple factors, such as atrial contraction time, vagal stimulation, magnitude of the venous return (preload) and LV end-diastolic pressure (afterload).
When LV relaxation is abnormal, the reservoir and propulsion pump functions occupy a high percentage of the cardiac cycle, while the conduit function decreases. However, with the progressive increase in LV filling pressure and worsening of diastolic dysfunction, the left atrium acts predominantly as a conduit10-14.
The importance of assessing LA function has been highlighted in several clinical conditions, not only as part of pathophysiological mechanisms, but also as a prognostic factor15-24.
This study aimed at finding elements for the better and earlier recognition of the following:
changes in LA and LV functions in patients with Chagas disease;
differences in LA function parameters;
possible correlation between LA function data and Doppler echocardiographic parameters of LV systolic and diastolic function.
Methods
This study included patients selected consecutively at the Cardiomyopathy-Aortic Disease outpatient clinic of the Instituto do Coração, of the University of São Paulo Medical School, of both sexes, aged 18 to 55 years, who underwent clinical examination, electrocardiography, echocardiography, and laboratory tests (ELISA and immunofluorescence tests for Chagas disease, blood glucose and serum creatinine). Healthy age-matched volunteers were examined as a control group (CG).
The usual medications were maintained during the tests (angiotensin-converting-enzyme inhibitors, beta-blockers, diuretics in patients with LV systolic dysfunction).
The following exclusion criteria were considered: associated systemic diseases; ventricular arrhythmia or ventricular premature beats (≥ 10/hour on previous Holter, or frequent on physical examination); atrial fibrillation; moderate or severe mitral regurgitation; and implanted electronic cardiac devices.
Patients with Chagas disease were divided into three groups as follows:
Group I (GI): with the indeterminate form (asymptomatic with normal findings on electrocardiography, chest radiography and esophageal and colonic contrast studies);
Group II (GII): with electrocardiographic abnormalities and LV ejection fraction ≥ 0.55;
Group III (GIII): with electrocardiographic abnormalities and LV ejection fraction < 0.55.
Ethics Statement
This study was registered with the approval of CAPPesq (Ethics Committee for Analysis of Research Projects of the Hospital das Clínicas of the São Paulo University - No. 0713/08). All subjects included in this study provided written informed consent in accordance with ethical regulations.
Echocardiographic study
All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and Tissue Doppler Imaging studies using a commercially available ultrasound system (Sequoia, Acuson-Siemens, Mountain View, California, USA).
The quantitative measurements included LA e LV diameters on M-mode echocardiography, maximum, pre p-wave and minimum LA volumes (LAVmax, LAVpre and LAVmin, respectively) using the modified Simpson's method on two-dimensional echocardiography with 4-chamber view, in accordance with the American Society of Echocardiography (ASE) recommendations.
The LV ejection fraction was calculated using the Teichholz method for uniformization25-27.
Transmitral velocities were also obtained in accordance with the ASE. Measurements included E wave and A wave velocities, E/A ratio, and E wave deceleration time.
Tissue Doppler imaging was performed with apical 4-chamber view. Measurements included systolic (s’), early diastolic (e’) and late diastolic (a’) waves, which were obtained from the lateral and septal margins of the mitral annulus, and the mean between the two sites (e’average) was used to calculate the E/e’ ratio, which was also estimated from the LV filling pressure.
All examinations and measurements were made by one observer, and the mean of three to five consecutive cardiac cycles was used in this study.
Patients were positioned lying down on their left side, with 20° to 30° trunk inclination, and electrodes placed to obtain the electrocardiographic tracings.
All echocardiographic measurements were performed in accordance with the ASE recommendations26-28.
On two-dimensional echocardiography, the following parameters were calculated using the modified Simpson's method:
LAVmax (in mL), measured at end-systole, just before the mitral valve opening;
LAVmin (in mL), measured at end-diastole, just before the mitral valve closing and after the P wave;
LAVpre (in mL), measured immediately before the P wave (before atrial contraction).
The volumes and LV diastolic diameter were corrected for body surface area (BSA), which was calculated by using the Dubois’ method.
Assessment of LA function
The LA reservoir function was analyzed by use of total emptying fraction (TEF), calculated according to the following formula: TEF = (LAVmax - LAVmin) / LAVmax.
The LA conduit function was examined by use of passive emptying fraction (PEF), calculated according to the following formula: PEF = (LAVmax – LAVpre) / LAVmax.
The LA pump function was analyzed by use of active emptying fraction (AEF), calculated according to the following formula: AEF = (LAVpre - LAVmin) / LAVpre.
Statistical Analysis
The quantitative measures were described as means, medians, standard deviations and percentiles. Nonparametric Kruskal-Wallis test was applied to compare those measures among the four groups. When there were significant differences, the Bonferroni correction was used for multiple comparisons among the groups.
The relation between measures was assessed by Spearman correlation coefficient. When it was significant, a positive correlation coefficient (r) indicated that higher values of the variable x correspond to higher values of the variable y. If r was negative, the relation was reverse and higher values of the variable x correspond to smaller values of the variable y. According to the absolute r values, the correlations between variables were as follows: r < 0.3, weak correlation; r ≥ 0.3 and < 0.7, moderate correlation; and r ≥ 0.7, strong correlation.
The significance level adopted was "p" value < 5%. The Statistical Package for the Social Sciences (SPSS) software, version 19, was applied29,30.
Results
This study included 85 individuals as follows: CG, 10 individuals; GI, 26; GII, 30; and GIII, 19. The groups did not differ regarding the following parameters: mean age (p = 0.107); weight (p = 0.815); height (p = 0.880); BSA (p = 0.791); heart rate (p = 0.164); and sex (p = 0.492) (Table 1).
Table 1.
Variables | CG (n = 10) | GI (n = 26) | GII (n = 30) | GIII (n = 19) | p |
---|---|---|---|---|---|
mean ± SD | mean ± SD | mean ± SD | mean ± SD | ||
Age (years) | 40 ± 6 | 46 ± 6 | 43 ± 8 | 43 ± 7 | 0.11 |
Weight (kg) | 68 ± 13 | 68 ± 12 | 68 ± 11 | 71 ± 13 | 0.82 |
Height (cm) | 162 ± 8 | 163 ± 7 | 162 ± 9 | 164 ± 10 | 0.88 |
BSA (m2) | 1.70 ± 0.2 | 1.72 ± 0.2 | 1.70 ± 0.2 | 1.80 ± 0.2 | 0.79 |
SBP (mm Hg) | 109 ± 9 | 114 ± 10 | 118 ± 12 | 109 ± 10 | 0.05 |
DBP (mm Hg) | 70 ± 9 | 73 ± 8 | 72 ± 8 | 67 ± 8 | 0.14 |
HR (bpm) | 68 ± 10 | 70 ± 9 | 67 ± 9 | 64 ± 10 | 0.16 |
CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction ≥0.55; GIII: electrocardiographic abnormalities and LV ejection fraction < 0.55; SD: standard deviation; BSA: body surface area; SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate.
The baseline LA and LV echocardiographic parameters were as follows:
• Left atrium
There was a significant difference between groups in relation to LAVmax (p <0.0001). The mean value was higher in GIII as compared to CG (p = 0.001), GI (p = 0.0001) and GII (p = 0.012). Similarly, the mean values in GIII were higher when compared to GII and CG (p = 0.03). There was no significant difference between CG and GI.
There was a significant difference between groups in relation to LAVpre (p < 0.0001). The mean value was higher in GIII as compared to CG (p = 0.0004), GI (p = 0.0003) and GII (p = 0.012). Similarly, the mean values were higher when compared to GII and CG (p = 0.012). There was no significant difference between CG and GI.
There was a significant difference between groups in relation to LAVmin (p < 0.0001). The mean value was higher in GIII as compared to CG (p = 0.0003), GI (p < 0.0001) and GII (p = 0.0007). There was no significant difference in GI and GII as compared to CG, and between GI and GII (Table 2).
Table 2.
Variables | CG (n = 10) | GI (n = 26) | GII (n = 30) | GIII (n = 19) | p |
---|---|---|---|---|---|
mean ± SD | mean ± SD | mean ± SD | mean ± SD | ||
LVDD (mm/m2) | 25 ± 2.1 | 25.9 ± 2.3 | 28.4 ± 3.3# | 37.1 ± 5.0* | < 0.0001 |
LAVmax(ml/m2) | 23 ± 4.5 | 27 ± 6.4 | 31 ± 8.7# | 42 ± 12.1* | < 0.0001 |
LAVpre P(ml/m2) | 14 ± 3 | 17 ± 4.21 | 21 ± 6.5# | 32 ± 12* | < 0.0001 |
LAVmín(ml/m2) | 8.5 ± 2 | 9.8 ± 2.9 | 12.3 ± 5.9 | 24 ± 10.9* | < 0.0001 |
GIII values significantly different from those of other groups
GII values significantly different from CG values
CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction ≥ 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction < 0.55; LVDD: left ventricular diastolic diameter; LAVmax: maximum left atrial volume; LAVpre P: pre-P-wave left atrial volume; LAVmin: minimum left atrial volume.
• Left ventricle
There was a significant difference between groups regarding LV diastolic diameter (p <0.0001). The mean value was higher in GIII as compared to CG (p = 0.001), GI (p < 0.0001) and GII (p < 0.0001), and in GII as compared to CG (p = 0.05). There was no significant difference between CG and GI (Table 2).
Parameter of LV systolic function
• Ejection fraction
There was a significant difference between groups regarding LV ejection fraction (p < 0.0001). The mean value was lower in GIII as compared to CG (p = 0.001), GI (p < 0.0001) and GII (p < 0.0001). There was no significant difference between CG, GI and GII when compared to each other (Table 3).
Table 3.
Variables | CG (n = 10) | GI (n = 26) | GII (n = 30) | GIII (n = 19) | p |
---|---|---|---|---|---|
mean ± SD | mean ± SD | mean ± SD | mean ± SD | ||
E wave (cm/s) | 74.2 ± 12.7 | 71.9 ± 14.4 | 71.2 ± 17.4 | 68 ± 19.4 | 0.7635 |
A wave (cm/s) | 54.1 ± 4.9 | 62.5 ± 7.9 | 59.7 ± 12.0 | 58.9 ± 16.9 | 0.0949 |
E/A | 1.4 ±0.2 | 1.2 ± 0.3 | 1.2 ± 0.4 | 1.3 ± 0.6 | 0.2279 |
DTE (ms) | 174.4 ± 18.1 | 198.8 ± 30.7 | 198.9 ± 33.1 | 210 ± 64.6 | 0.1836 |
LVEF | 0.67 ± 0.05 | 0.66 ± 0.04 | 0.67 ± 0.06 | 0.41 ± 0.07* | < 0.0001 |
GIII values significantly different from those of other groups
CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction ≥ 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction < 0.55; E wave: E wave in mitral flow; A wave: A wave in mitral flow; E/A: E wave/A wave ratio; DTE: E wave deceleration time; LVEF: left ventricular ejection fraction.
Parameters of LV diastolic function:
• Mitral flow
There was no statistically significant difference between groups regarding E wave (p = 0.76), A wave (p = 0.09), E/A ratio (p = 0.22) and E wave deceleration time (p = 0.18) (Table 3).
• Tissue Doppler
There was a significant difference between groups (p = 0.0004) regarding e'lat evaluation on tissue Doppler. The mean value was lower in GIII as compared to CG (p = 0.0076), GI (p = 0.001) and GII (p = 0.036). There was no significant difference of mean values between CG, GI and GII.
There was a significant difference between groups (p <0.001) regarding e'sep evaluation on tissue Doppler. The mean value was lower in GIII as compared to CG (p = 0.0004), GI (p < 0.001) and GII (p = 0.0001). There was no significant difference of mean values when comparing CG, GI and GII.
A significant difference between groups was found (p < 0.001) regarding e'average evaluation on tissue Doppler. The mean value was lower in GIII as compared to CG (p < 0.001), GI (p < 0.001) and GII (p < 0.001). There was no significant difference of mean values between CG, GI and GII.
Regarding E/e'average, there was a significant difference between groups (p < 0.001). The mean value was significantly higher in GIII as compared to CG (p = 0.009), GI (p = 0.0001) and GII (p = 0.007). There was no significant difference of mean values between CG, GI and GII (Table 4).
Table 4.
Variables | CG (n = 10) | GI (n = 26) | GII (n = 30) | GIII (n = 19) | p |
---|---|---|---|---|---|
mean ± SD | mean ± SD | mean ± SD | mean ± SD | ||
S'lat | 11.4 ± 2.2 | 13.2 ± 2.0 | 13.5 ± 2.7 | 8.0 ± 1.9* | < 0.0001 |
e'lat | 15 ± 2.3 | 15.1 ± 3.2 | 13.3 ± 3.1 | 9.8 ± 3.7* | 0.0004 |
s'sep | 9.2 ± 2.8 | 10.6 ± 1.5 | 10.5 ± 2.0 | 7.3 ± 1.8* | < 0.0001 |
e'sep | 11.0 ± 2.1 | 10.5 ± 2.3 | 9.7 ± 1.8 | 7 ± 1.5* | < 0.0001 |
e'average | 13 ± 1.6 | 12.8 ± 2.5 | 11.3 ± 2.5 | 8.1 ± 2.6* | < 0.0001 |
E/e'average | 5.8 ± 1.5 | 5.7 ± 0.8 | 6.6 ± 2.3 | 9.6 ± 3.4* | < 0.0001 |
GIII values significantly different from those of other groups
CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction ≥ 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction < 0.55; s’lat: s wave in lateral wall (Tissue Doppler); e’lat: e wave in lateral wall (Tissue Doppler); s’sep: s wave in septal wall (Tissue Doppler); e’sep: e wave in septal wall (Tissue Doppler); e’average: the mean between e’latand e’sep; E/e’average: E wave/e’averageratio
Parameters of LA function
• Reservoir function
The TEF significantly differed between groups (p < 0.0001). The mean values were significantly lower in GIII as compared to CG (p = 0.003), GI (p < 0.001) and GII (p <0.001). The mean values did not significantly differ between CG, GI and GII (Table 5).
Table 5.
Variables | CG (n = 10) | GI (n = 26) | GII (n = 30) | GIII (n = 19) | P |
---|---|---|---|---|---|
mean ± SD | mean ± SD | mean ± SD | mean ± SD | ||
AEF (mL) | 0.38 ± 0.05 | 0.44 ± 0.08 | 0.42 ± 0.11 | 0.27 ± 0.11* | 0.0001 |
TEF (mL) | 0.63 ± 0.09 | 0.63 ± 0.08 | 0.62 ± 0.10 | 0.44 ± 0.13* | < 0.0001 |
PEF (mL) | 0.39 ± 0.12 | 0.35 ± 0.10 | 0.35 ± 0.10 | 0.23 ± 0.12 | 0.004 |
GIII values significantly different from those of other groups
CG: control group; GI: indeterminate form; GII: electrocardiographic abnormalities and LV ejection fraction > 0.55; GIII: electrocardiographic abnormalities and LV ejection fraction < 0.55; AEF: active emptying fraction; TEF: total emptying fraction; PEF: passive emptying fraction.
• Conduit function
The PEF significantly differed between groups (p = 0.004). The mean value was lower in GIII, but with no statistical significance, when comparing GIII and CG (p = 0.06), GI and GII (p = 0.06), and GII and GIII (p = 0.07) (Table 5).
• Pump function
The AEF significantly differed between groups (p = 0.0001). The mean value was lower in GIII when compared to CG (p = 0.05), GI (p < 0.0001) and GII (p = 0.002) (Table 5).
Analysis of the correlations
There was a negative correlation of E/e'average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e'average with s' (both septal and lateral walls) and the reservoir, conduit and pump functions. Table 6 describes the correlations among variables.
Table 6.
E/e'average | e'average | LVEF | s'sep | s'lat | |
---|---|---|---|---|---|
TEF | r = -0.26 | r = 0.53 | r = 0.35 | r = 0.33 | r= 0.28 |
p = 0.02 | p < 0.001 | p = 0.003 | p = 0.003 | p = 0.003 | |
PEF | r = -0.09 | r = 0.49 | r = 0.42 | r = 0.197 | r = 0.118 |
p = 0.44 | p < 0.001 | p < 0.001 | p = 0.135 | p = 0.378 | |
AEF | r = -0.36 | r = 0.39 | r = 0.35 | r = 0.37 | r= 0.34 |
p = 0.002 | p = 0.001 | p = 0.003 | p = 0.004 | p = 0.01 |
AEF: active emptying fraction; TEF: total emptying fraction; PEF: passive emptying fraction; s’lat: s wave in lateral wall (Tissue Doppler); s’sep: s wave in septal wall (Tissue Doppler); e’average: the mean between e’lat and e’sep; E/e’average: E wave/e’averageratio; LVEF: left ventricular ejection fraction.
Discussion
This study reveals important features and details of the relationship and interdependency of the systolic and diastolic functions of the left ventricle and left atrium.
The LA function has been extensively studied in recent decades, with great interest in the pathophysiological and prognostic implications and interrelation with LV systolic and diastolic functions. It has been investigated in several clinical situations and diseases. A hemodynamic study with simultaneous recording of pressure and volume curves is ideal to allow the assessment of LA relaxation and compliance, which directly influence LA filling. However, it is an invasive and costly exam, being reserved almost exclusively to experimental studies.
Echocardiography is a good alternative, being currently the method of choice for non-invasive LA analysis. Alterations in diastolic function properties or in any of LA functions (reservoir, conduit or pump) may interfere in LV filling. In addition to some cardiovascular diseases, the aging process modifies the LA size and some functions, especially the passive and active emptying.31
It is intuitive that all mechanisms involved in the process of LV filling and LA emptying are interdependent; therefore, the interpretation and importance of each of the influencing factors must be carefully analyzed.
For these reasons, in this study, patients with moderate or severe mitral dysfunction were excluded, as were those older than 55 years, although this criterion finds no support in the literature.32,33
Regarding Chagas cardiomyopathy, most published studies involve patients with LV systolic dysfunction, and use LA size as a prognostic marker, showing that individuals with higher volumes had more cardiovascular events. The LV diastolic dysfunction degree is also related to the LA volume, and most significant changes in this parameter occur when there is greater LV diastolic and systolic dysfunction.
Some studies of patients with Chagas cardiomyopathy and preserved LV systolic function have suggested that there is a higher risk of atrial fibrillation when the atrial diameter is high. Other authors, studying various degrees of systolic impairment, including a group of patients with Chagas disease’s indeterminate form and others without Chagas disease, have analyzed LA size and volume, and reported no significant differences between those groups regarding diastolic function. However, atrial functional parameters have not been considered.
In Brazil, Nunes et al.33 have highlighted the importance of assessing LA function, relating it to LV systolic and diastolic functions. More recently, Mancuso et al.34 have studied LA function, assessed by using LA total and active emptying fractions, and concluded that both decreased more in patients with Chagas cardiomyopathy than in those with idiopathic dilated cardiomyopathy34,35.
The indeterminate form of Chagas disease has usually no symptoms, or only electrocardiographic alterations. The same occurs when there is a mild systolic dysfunction. Clinical manifestations could vary and depend on the degree and type of the predominant involvement.
Functional capacity depends on cardiac output. Stroke volume results from the difference between LV systolic and end-diastolic volume. The LV end-diastolic volume depends on diastolic function and blood supply, being directly related to LA anatomical and functional properties36,37.
According to the disease classification criteria, GIII patients had significantly lower LV ejection fraction values as compared to the other groups. The mean value of this parameter in GIII (0.41) suggests moderate systolic function impairment.
Significantly lower values of the s wave in this group strengthen the evidence of myocardial damage, because this variable is related to longitudinal LV systolic function38.
The positive correlations of those two variables with TEF and AEF shown in this study corroborate the decrease in the reservoir function in chagasic patients with LV systolic dysfunction probably by reducing the caudal displacement of the mitral annulus during ventricular systole and the effect of succion at the beginning of diastole. Moreover, the decrease in the propulsion pump function may be related to impaired myocardial function.
The mitral flow variables, usually used to assess LV diastolic function, showed no significant difference between groups. However, when analyzed on tissue Doppler, some considerations should be highlighted.
Patients with normal LV ejection fraction (CG, GI and GII) had normal values of e'sep, e'lat, e'average and E/e'average < 8, indicating normal LV filling pressure. In contrast, GIII patients showed signs of LV diastolic dysfunction, when analyzed regarding the same variables, with values of e'sep and e'lat lower than normal for age range according to the ASE criteria.
The values of E/e'average were significantly higher in GIII (mean = 9.6). However, this result should be analyzed carefully. Values greater than 15 are indicative of increased LV filling pressure, while those lower than 8 are considered normal. When there are intermediary values, such as in GIII, the conclusion requires association with other data. In addition, E/e’ is not adequate to assess LV filling pressure in individuals without significant heart disease.
The LA volume, although significantly higher in GIII, can be interpreted in this study as a diastolic dysfunction parameter and there is chronic elevation of LV filling pressure39.
The absence of other variables that point to significant diastolic dysfunction, such as mitral flow behavior, indicates that patients in GIII have mild diastolic dysfunction, with probably normal LA filling pressure, consistent with clinical features (all in NYHA functional class II when evaluated). Drug action should also be considered in these results, because all patients in this group were on optimized medical treatment.
Reservoir, conduit and pump functions can be evaluated more consistently by analyzing the LA volume variation: the reservoir function, by using TEF; the conduit function, by using PEF; and the pump function, by using AEF.
The results of this study demonstrate that patients with LV dysfunction (GIII) had decreased LA reservoir and pump functions, which does not occur in patients with the indeterminate form and those with electrocardiographic alterations only.
The decrease in LA pump function is probably related to the LA involvement in chagasic myopathy, with consequent contractile injury and lower ejection during atrial systole, therefore, with larger atrial volume at the end of this phase of the cardiac cycle.
According to the definition of the two functions and the way they are calculated, in this study, the reservoir function deterioration might be related only to the LA and LV contractile function impairment. Other factors analyzed in this study that significantly contribute to the reservoir function (relaxation, stiffness and compliance) showed no significant differences.
Some facts regarding LA reservoir and pump functions should be considered. The negative correlations of E/e'average and these two parameters of atrial function demonstrate the influence of LV filling pressure (LA pressure or LV diastolic pressure) on LA filling and emptying.
Another highlight is the positive correlation of these two roles (reservoir and pump) with LV diastolic function, specifically with myocardial relaxation evaluated by using e’ wave.
The parameter used to assess conduit function (PEF) was lower in GIII, with statistical significance. The positive correlation of the e’ wave with the conduit function highlights the importance of diastolic dysfunction in LA passive emptying.
Usually, the clinical and pathophysiological mechanisms involved in heart failure have their focus on higher LV systolic and diastolic dysfunction. The present study demonstrates that LA can play a critical role in this process. Determining the functional boundary of each structure in this context is still a big challenge.
Conclusion
In patients with Chagas cardiomyopathy and LV systolic dysfunction, there was an impairment in LA reservoir, conduit and pump functions. Those with normal systolic function showed no alterations in these parameters. There was a correlation between LA function and LV systolic and diastolic functions assessed on tissue Doppler imaging.
Footnotes
Author contributions
Conception and design of the research:Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Salemi VMC, Mady C, Ianni BM. Acquisition of data:Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Mady C, Ianni BM. Analysis and interpretation of the data: Fragata CS, Matsumoto AY, Ramires FJA, Fernandes F, Buck PC, Nastari L, Mady C, Ianni BM. Statistical analysis: Fragata CS, Mady C, Ianni BM. Obtaining financing: Fragata CS. Writing of the manuscript:Fragata CS, Matsumoto AY, Buck PC, Salemi VMC, Nastari L, Mady C, Ianni BM. Critical revision of the manuscript for intellectual content: Fragata CS, Matsumoto AY, Fernandes F, Buck PC, Salemi VMC, Nastari L, Mady C, Ianni BM.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Sources of Funding
This study was funded by FAPESP.
Study Association
This article is part of the thesis of Doctoral submitted by Claudia da Silva Fragata, from Faculdade de Medicina da Universidade de São Paulo.
References
- 1.Chagas C. Nova tripanosomíase humana. Estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., sp., agente etiolójico de nova entidade mórbida do homem. Mem Inst Oswaldo Cruz. 1909;1:159–218. [Google Scholar]
- 2.Combellas I, Puigbo JJ, Acquatella H, Tortoledo F, Gomez JR. Echocardiographic features of impaired left ventricular diastolic function in Chagas's heart disease. Br Heart J. 1985;53(3):298–309. doi: 10.1136/hrt.53.3.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Garcia-Alvarez A, Sitges M, Pinazo MJ, Regueiro-Cueva A, Posada E, Poyatos S, et al. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage. PLoS Negl Trop Dis. 2010;4(9): doi: 10.1371/journal.pntd.0000826. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22(2):107–133. doi: 10.1016/j.echo.2008.11.023. [DOI] [PubMed] [Google Scholar]
- 5.Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997;30(2):474–480. doi: 10.1016/s0735-1097(97)88335-0. [DOI] [PubMed] [Google Scholar]
- 6.Ho CY, Solomon SD. A clinician's guide to tissue Doppler imaging. Circulation. 2006;113(10):e396–e398. doi: 10.1161/CIRCULATIONAHA.105.579268. [DOI] [PubMed] [Google Scholar]
- 7.Quiñones MA. Assessment of diastolic function. Prog Cardiovasc Dis. 2005;47(5):340–355. doi: 10.1016/j.pcad.2005.02.009. [DOI] [PubMed] [Google Scholar]
- 8.Mady C, Ianni BM, Arteaga E, Salemi VM, Silva PR, Cardoso RH, Ballas D. Maximal functional capacity and diastolic function in patients with cardiomyopathy due to Chagas' disease without congestive heart failure. Arq Bras Cardiol. 1997;69(4):237–241. doi: 10.1590/s0066-782x1997001000003. [DOI] [PubMed] [Google Scholar]
- 9.Grant C, Bunnel IL, Greene DG. The reservoir function of the left atrium during ventricular systole: an angiocardiographic study of atrial stroke volume and work. Am J Med. 1964;37:36–43. doi: 10.1016/0002-9343(64)90210-4. [DOI] [PubMed] [Google Scholar]
- 10.Castello R, Pearson AC, Lenzen P, Labovitz AJ. Evaluation of pulmonary venous flow by transesophageal echocardiography in subjects with a normal heart: comparison with transthoracic echocardiography. J Am Coll Cardiol. 1991;18(1):65–71. doi: 10.1016/s0735-1097(10)80219-0. [DOI] [PubMed] [Google Scholar]
- 11.Toma Y, Matsuda Y, Moritani K, Ogawa H, Matsuzaki M, Kusukawa R. Left atrial filling in normal human subjects: relation between left atrial contraction and left atrial early filling. Cardiovasc Res. 1987;21(4):255–259. doi: 10.1093/cvr/21.4.255. [DOI] [PubMed] [Google Scholar]
- 12.Fujii K, Ozaki M, Yamagishi T, Ishine K, Furutani Y, Nagano H, et al. Effect of left ventricular contractile performance on passive left atrial filling - clinical study using radionuclide angiography. Clin Cardiol. 1994;17(5):258–262. doi: 10.1002/clc.4960170508. [DOI] [PubMed] [Google Scholar]
- 13.Hoit BD, Walsh RA. Regional atrial distensibility. Pt 2Am J Physiol. 1992;262(5):H1356–H1360. doi: 10.1152/ajpheart.1992.262.5.H1356. [DOI] [PubMed] [Google Scholar]
- 14.Barbier P, Solomon SB, Schiller NB, Glantz SA. Left atrial relaxation and left ventricular systolic function determine left atrial reservoir function. Circulation. 1999;100(4):427–436. doi: 10.1161/01.cir.100.4.427. [DOI] [PubMed] [Google Scholar]
- 15.Rossi A, Zardini P, Marino P. Modulation of left atrial function by ventricular filling impairment. Heart Fail Rev. 2000;5(4):325–331. doi: 10.1023/a:1026507128973. [DOI] [PubMed] [Google Scholar]
- 16.Pagel PS, Kehl F, Gare M, Hettirick DA, Kersten JR, Wartier DC. Mechanical function of the left atrium: new insights based on analysis of pressure-volume relations and Doppler echocardiography. Anesthesiology. 2003;98(4):975–994. doi: 10.1097/00000542-200304000-00027. [DOI] [PubMed] [Google Scholar]
- 17.Hoit BD, Shao Y, Gabel M, Walsh RA. Influence of pericardium on left atrial compliance and pulmonary venous flow. Pt 2Am J Physiol. 1993;264(6):H1781–H1787. doi: 10.1152/ajpheart.1993.264.6.H1781. [DOI] [PubMed] [Google Scholar]
- 18.Prioli A, Marino P, Lanzoni L, Zardini P. Increasing degrees of left ventricular filling impairment modulate left atrial function in humans. Am J Cardiol. 1998;82(6):756–761. doi: 10.1016/s0002-9149(98)00452-4. [DOI] [PubMed] [Google Scholar]
- 19.Matsuda Y, Toma Y, Moritani K, Ogawa H, Kohno M, Miura T, et al. Assessment of left atrial function in patients with hypertensive heart disease. Hypertension. 1986;8(9):779–785. doi: 10.1161/01.hyp.8.9.779. [DOI] [PubMed] [Google Scholar]
- 20.Nagano R, Masuyama T, Naka M, Hori M, Kamada T. Contribution of atrial reservoir function to ventricular filling in hypertensive patients: effects of nifedipine administration. Hypertension. 1995;26(5):815–819. doi: 10.1161/01.hyp.26.5.815. [DOI] [PubMed] [Google Scholar]
- 21.Matsuda Y, Toma Y, Ogawa H, Matsuzaki M, Katayama K, Fujii T, et al. Importance of left atrial function in patients with myocardial infarction. Circulation. 1983;67(3):566–571. doi: 10.1161/01.cir.67.3.566. [DOI] [PubMed] [Google Scholar]
- 22.Dardas PS, Filippatos GS, Tsikaderis DD, Michalis LK, Goudevenos IA, Sideris DA, et al. Noninvasive indexes of left atrial diastolic function in hypertrophic cardiomyopathy. J Am Soc Echocardiogr. 2000;13(9):809–817. doi: 10.1067/mje.2000.105579. [DOI] [PubMed] [Google Scholar]
- 23.Kurt M, Wang J, Torre-Amione G, Nagueh SF. Left atrial function in diastolic heart failure. Circ Cardiovasc Imaging. 2009;2(1):10–15. doi: 10.1161/CIRCIMAGING.108.813071. [DOI] [PubMed] [Google Scholar]
- 24.Abhayaratna WP, Fatema K, Barnes ME, Seward JB, Gersh BJ, Bailey KR, et al. Left atrial reservoir function as a potent marker for first atrial fibrillation or flutter in persons > or = 65 years of age. Am J Cardiol. 2008;101(11):1626–1629. doi: 10.1016/j.amjcard.2008.01.051. [DOI] [PubMed] [Google Scholar]
- 25.Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recomendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978;58(6):1072–1083. doi: 10.1161/01.cir.58.6.1072. [DOI] [PubMed] [Google Scholar]
- 26.Schiller N, Shah P, Crawford M, De Maria A, Devereux RB, Feigenbaum H, et al. Recommendations for quantification of the left ventricle by two dimensional echocardiography. American Society of Echocardioghraphy Committee Standards Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2(5):358–367. doi: 10.1016/s0894-7317(89)80014-8. [DOI] [PubMed] [Google Scholar]
- 27.Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence or absence of asynergy. Am J Cardiol. 1976;37(1):7–11. doi: 10.1016/0002-9149(76)90491-4. [DOI] [PubMed] [Google Scholar]
- 28.Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Chamber Quantification Writing Group. American Society of Echocardiography's Guidelines and Standards Committee. European Association of Echocardiography Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440–1463. doi: 10.1016/j.echo.2005.10.005. [DOI] [PubMed] [Google Scholar]
- 29.Pereira JCR. Bioestatística em outras palavras. São Paulo: EDUSP-SP; 2010. [Google Scholar]
- 30.Siegel S, Castellan NJ., Jr . Nonparametric statistics for the behavioral science. 2ª ed. New York: McGraw-Hill; 1988. [Google Scholar]
- 31.Rosca M, Lancellotti P, Popescu BA, Piérard LA. Left atrial function: pathophysiology, echocardiographic assessment, and clinical applications. Heart. 2011;97(23):1982–1989. doi: 10.1136/heartjnl-2011-300069. [DOI] [PubMed] [Google Scholar]
- 32.Triposkiadis F, Tentolouris K, Androulakis A, Trikas A, Toutouzas K, Kyriadis M, et al. Left atrial mechanical function in the healthy elderly: new insights from a combined assessment of changes in atrial volume and transmitral flow velocity. J Am Soc Echocardiogr. 1995;8(6):801–809. doi: 10.1016/s0894-7317(05)80004-5. [DOI] [PubMed] [Google Scholar]
- 33.Nunes MC, Barbosa MM, Rocha ES, Rocha MO. Função do atrio esquerdo na miocardiopatia chagásica. Arq Bras Cardiol. 2005;84(6):452–456. doi: 10.1590/s0066-782x2005000600004. [DOI] [PubMed] [Google Scholar]
- 34.Mancuso FJ, Almeida DR, Moisés VA, Oliveira WA, Mello ES, Poyares D, et al. Left atrial dysfunction in Chagas cardiomyopathy is more severe than in idiopathic dilated cardiomyopathy: a study with real-time three-dimensional echocardiography. J Am Soc Echocardiogr. 2011;24(5):526–532. doi: 10.1016/j.echo.2011.01.013. [DOI] [PubMed] [Google Scholar]
- 35.Vinicius Lins Barros M, Otávio Da Costa Rocha M, Luiz Pinho Ribeiro A, Santana Machado F. Tissue Doppler imaging in the evaluation of the regional diastolic function in Chagas' disease. Eur J Echocardiogr. 2001;2(2):94–99. doi: 10.1053/euje.2000.0062. [DOI] [PubMed] [Google Scholar]
- 36.Abhayaratna WP, Seward JB, Appleton CP, Douglas PS, Oh JK, Tajik AJ, et al. Left atrial size: physiologic determinants and clinical applications. J Am Coll Cardiol. 2006;47(12):2357–2363. doi: 10.1016/j.jacc.2006.02.048. [DOI] [PubMed] [Google Scholar]
- 37.Nishimura RS, Abel MD, Hatle LK, Tajiki AJ. Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography: effect of different loading conditions. Circulation. 1990;81(5):1488–1497. doi: 10.1161/01.cir.81.5.1488. [DOI] [PubMed] [Google Scholar]
- 38.Oh JK, Hatle L, Tajik AJ, Little WC. Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography. J Am Coll Cardiol. 2006;47(3):500–506. doi: 10.1016/j.jacc.2005.09.032. [DOI] [PubMed] [Google Scholar]
- 39.Tsang TS, Abhayaratna WP, Barnes ME, Miyasaka Y, Gersh BJ, Bailey KR, et al. Prediction of cardiovascular outcomes with left atrial size: is volume superior to area or diameter? J Am Coll Cardiol. 2006;47(5):1018–1023. doi: 10.1016/j.jacc.2005.08.077. [DOI] [PubMed] [Google Scholar]