Patients

This study included 60 patients: 30 patients with documented CCM (at least two positive serologic tests for antibodies against Trypanosoma cruzi ) and 30 patients with DCM (idiopathic was defined as absence of coronary artery disease, by coronary angiography or epidemiology, and absence of secondary forms of heart muscle disease) who were recruited in a tertiary center for HF and cardiomyopathy at the Federal University of Sao Paulo, Brazil. The inclusion criteria were age ≥ 18 years, functional class ≤ III (New York Heart Association [NYHA]), optimized clinical treatment for HF, sinus rhythm, LV ejection fraction ≤ 0.40 (modified Simpson’s rule), and good image quality. We excluded patients with primary valve disease, end-stage renal failure, or chronic obstructive pulmonary disease. We also studied 20 normal subjects as a control group. All participants gave written informed consent, which was approved by the institutional review board.

Echocardiography

All individuals underwent a comprehensive two-dimensional echocardiography with an IE33 (Philips Medical Systems, Andover, MA) echocardiography system with a 2- to 5-MHz transducer under continuous electrocardiographic monitoring. Patients were studied in the left lateral decubitus position and always by the same single level 3 physician. The quantification of the cardiac chambers was performed according to American Society of Echocardiography guidelines, and the LV ejection fraction was calculated according to a modified Simpson’s rule. Mitral regurgitation was assessed by effective regurgitant orifice area by the proximal isovelocity surface area method. Diastolic function was evaluated by pulsed Doppler analysis of early (E) and late (A) transmitral diastolic flow velocities and by tissue Doppler recording of peak early (e’) mitral annular septal velocity. These data were used to calculate the E/e’ ratio as an estimation of LV filling pressures ( Figure 1 ).

Mitral inflow pulsed Doppler and septal annulus tissue Doppler in a patient with CCM. The E/e’ ratio is 17.1, suggesting an elevated filling pressure.

The same equipment, with a fully sampled X3 matrix array transducer (1–3 MHz), was used for the acquisition of “full-volume,” real-time pyramidal volumetric data sets for four consecutive cardiac cycles. To ensure inclusion of the entire LV volume within the pyramidal scan volume, data sets were acquired using the wide-angled mode, thus acquiring four wedge-shaped subvolumes during a single 5- to 7-second breath-hold. The RT3DE data sets were digitally stored and analyzed using QLab-Philips software (version 5.0; Philips Medical Systems). Analysis of three-dimensional echo imaging was based on a two-dimensional approach relying on the echo images obtained from the apical views and on a semiautomated tracing of endocardial border. This was performed by marking five points in the atrial surfaces of the mitral annulus: at anterior, inferior, lateral, and septal annuli and the fifth point at apex of LA. Once this was completed, the endocardial surface was automatically delineated and could be visualized from different points of views and the LAV calculation was obtained. Manual modification was made to correct the automatic tracings if needed ( Figure 2 ).

LA volume calculation by RT3DE in a patient with CCM. The LA volume variation throughout the cardiac cycle is shown ( bottom ).

LA volumes were measured at the following three phases of the cardiac cycle, as previously described: 1) the maximum volume (maxLAV): at end systole, the time at which atrial volume was largest, just before mitral valve opening; 2) the minimum volume (minLAV): at end diastole, the time at which the atrial volume was at its nadir before mitral valve closure; and 3) volume before atrial contraction (pre-A LAV): the last frame before the P wave on the electrocardiogram. From these volumes, the following measurements were selected as indexes of LA function: 1) total LA emptying fraction: (maxLAV–minLAV)/maxLAV; and 2) active LA emptying fraction: (pre-A LAV–minLAV)/pre-A LAV.

Statistical Analysis

Statistical analysis was performed with SPSS 13.0 software (SPSS Inc., Chicago, IL). Continuous data were reported as mean ± SD, and categoric data were described as a percentage. Continuous data of CCM, DCM, and control groups were compared using analysis of variance, and Bonferroni’s post hoc test was applied as necessary. A Student t test was used to compare continuous data between CCM and DCM groups. Categoric data were compared with the chi-square test or Fisher exact test. In the CCM group, the Pearson’s coefficient was used to identify the correlation of maxLAV, indexed for body surface area, with the heart rate, E/e’, and mitral regurgitation effective regurgitant area, and the correlation of active LA emptying fraction with the heart rate, maxLAV indexed for body surface area, mitral regurgitation effective regurgitant area, and E/e’ ratio. A multiple linear regression model was developed that included maxLAV indexed for body surface area as the dependent variable and heart rate, E/e’, and mitral regurgitation effective regurgitant area as predictive variables in the CCM group. Another multiple linear regression model was developed with active LA emptying fraction as the dependent variable and heart rate, max LAV, and E/e’ ratio as predictive variables in the CCM group.

The coefficient of variation was used to assess the intra- and interobserver variabilities for all LA volumes assessed by RT3DE in a sample of 20 patients (10 with CCM and 10 with DCM). The observers were blinded to previous measurements of LA volumes.

Clinical Data

The baseline clinical characteristics of the CCM and DCM groups and the control group are listed in Table 1 . There were no significant differences among groups in age, sex proportion, body surface area, heart rate, or mean NYHA functional class. Systolic and diastolic blood pressures were higher in the control group than in the CCM group, but did not differ between the CCM and DCM groups. All patients were taking beta-blockers (carvedilol 47 ± 11 mg vs. 50 ± 10 mg; P = .27 and metoprolol 150 ± 86 mg vs. 175 ± 50 mg; P = .65 in the CCM and DCM groups, respectively), angiotensin-converting enzyme inhibitors (captopril 127 ± 33 mg/day vs. 112 ± 42 mg and enalapril 28 ± 11 mg vs. 26 ± 10 mg; P = .75 in the CCM and DCM groups, respectively), and furosemide (110 ± 65 mg vs. 91 ± 65 mg; P = .25 in the CCM and DCM groups, respectively) at similar doses. The percentage of patients taking spironolactone (86% vs. 86%; P = 1.0) and digoxin (23% vs. 17%; P = .74) was equivalent in the CCM and DCM groups.

Two-Dimensional Doppler Echocardiographic Findings

The two-dimensional and Doppler echocardiographic data are shown in Table 2 . The LA anteroposterior diameter was similar in the CCM and DCM groups, both of which were significantly larger than in the control group. Also, the LV volumes and ejection fraction did not differ significantly between the CCM and DCM groups, although they were significantly different from the control group, as expected. A restrictive filling pattern occurred in an equivalent proportion of the CCM and DCM groups. The mitral regurgitation regurgitant effective orifice area was not significantly different between the CCM and DCM groups. E, A, and e’ velocities, and the E/A ratio were also similar between the CCM and DCM groups. The E/e’ ratio and pulmonary systolic arterial pressure were both significantly higher in the CCM group compared with the DCM group, and both groups had values greater than those in the control group.

Real-time Three-Dimensional Echocardiographic Findings

MaxLAV, pre-A LAV, and min-LAV, indexed for body surface area, were significantly larger in the CCM group than in the DCM group, and all of these measurements were also significantly greater than found in the control group ( Table 3 ). In CCM, MaxLAV indexed for body surface area correlated significantly with E/e’ ( r = 0.532; P < . 01) and mitral regurgitation effective regurgitant area ( r = 0.307; P = .05). Multivariate analysis showed the E/e’ ratio as the only predictor of larger maxLAV indexed for body surface area ( P < . 01) ( Table 4 ).

Table 3

Three-dimensional echocardiographic data of patients and control group

	CCM	DCM	CG	P
maxLAV (mL)	76.9 ± 21.9 ∗	59.1 ± 26.0 ∗	29.0 ± 5.7	<.01
max LAV indexed BSA (mL/m 2 )	44.7 ± 13.1 ∗	34.4 ± 13.6 ∗	16.7 ± 4.3	<.01
Pre-A LAV (mL)	67.8 ± 20.5 ∗	50.6 ± 26.1 ∗	24.2 ± 9.2	<.01
Pre-A LAV (mL) indexed BSA (mL/m 2 )	38.74 ± 12.59 ∗	29.59 ± 13.82 ∗	14.24 ± 5.63 ∗	<.01
minLAV (mL)	53.6 ± 18.9 ∗	37.7 ± 23.2 ∗	15.4 ± 5.8	<.01
minLAV (mL) indexed BSA (mL/m 2 )	30.63 ± 11.61 ∗	22.05 ± 12.27 ∗	9.06 ± 3.72 ∗	<.01
TLAEF (%)	30.5 ± 10.5 †	39.9 ± 11.8 †	46.9 ± 4.2	<.01
ALAEF (%)	21.9 ± 9.5 †	28.2 ± 11.1 †	36.3 ± 4.2	<.01

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