European Journal of Echocardiography Advance Access published July 19, 2011 European Journal of Echocardiography doi:10.1093/ejechocard/jer096

Is atrial function in Chagas dilated cardiomyopathy more impaired than in idiopathic dilated cardiomyopathy? Marcia M. Barbosa 1, Manoel Ota´vio C. Rocha 2, Fernando Antoˆnio Botoni 2, Antoˆnio Luiz Pinho Ribeiro 2, and Maria Carmo Pereira Nunes 2* 1 ECOCENTER, Hospital Socor, Belo Horizonte, MG, Brazil; and 2Post-Graduate Course of Infectology and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil

Received 14 March 2011; accepted after revision 6 May 2011

Aims

----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords

Chagas cardiomyopathy † Dilated cardiomyopathy † Atrial function † Strain † Strain rate

Introduction Atrial function can be primarily or secondarily affected in cardiac diseases. Although there are several methods to assess ventricular function, quantitative evaluation of atrial function remains limited. Non-invasive study of left atrial (LA) function has been attempted using Doppler echocardiography, scintigraphic methods, computed tomography and magnetic resonance. Two-dimensional echocardiography and Doppler are the most practical methods to analyse the LA in routine clinical practice.1 – 5 In a previous study, our group has shown that LA volume is an independent predictor of mortality in Chagas cardiomyopathy.6 However,

atrial mechanical function cannot be assessed directly by conventional Doppler echocardiography, since transmitral Doppler velocity is more dependent on the atrioventricular pressure gradient than on the intrinsic atrial contractility. Recently, tissue Doppler imaging (TDI), Doppler-based strain rate (SR), and its integral strain, have been employed as efficient tools to evaluate atrial function.1 – 5 Left ventricular (LV) fibrosis seems to be more prevalent in Chagas dilated cardiomyopathy (CDC) than in other forms of non-ischaemic dilated cardiomyopathies.7 – 9 However, atrial fibrosis and its consequence in atrial function has not been established in CDC. Atrial fibrosis has been described in dilated

* Corresponding author: Departamento de Clı´nica Me´dica – UFMG, Av Professor Alfredo Balena, 190, Santa Efigeˆnia, 30130 100 – Belo Horizonte, MG, Brazil. Tel: +55 31 34099746; fax: +5531 34099437. Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2011. For permissions please email: [email protected]

Downloaded from by guest on January 17, 2017

Atrial function is an important component in overall cardiovascular performance. However, information on atrial function in dilated cardiomyopathy is limited. This study aimed to assess atrial function in dilated cardiomyopathy and to investigate if parameters of atrial function are more impaired in Chagas dilated cardiomyopathy (CDC) than in idiopathic dilated cardiomyopathy (IDC). ..................................................................................................................................................................................... Methods Seventy-two patients with dilated cardiomyopathy (36 with CDC and 36 with IDC) and 32 healthy controls were and results evaluated by tissue Doppler, Doppler-based strain and strain rate (SR) imaging of the left atrium (LA) and right atrium (RA). Peak atrial strain during systole and SR during systole, early and late diastolic SR, were measured at the interatrial septum, LA inferior wall and at the lateral wall of the RA. The clinical characteristics and the parameters of LV function were similar between patients with CDC and IDC. Myocardial deformation indices during the reservoir phase of both RA and LA were lower in patients with dilated cardiomyopathy than in controls, suggesting atrial dysfunction in cardiomyopathies. However, LA and RA deformation parameters did not differ between CDC and IDC patients (interatrial septal strain during the reservoir phase: 225.2 + 14.8 vs. 224.9 + 16.0%, P ¼ NS; strain rate during the reservoir phase: 21.3 + 0.7 vs. 21.5 + 0.9/s, P ¼ NS). ..................................................................................................................................................................................... Conclusions Atrial myocardial deformation properties are abnormal in patients with dilated cardiomyopathy. CDC does not seem to have more atrial involvement than IDC.

Page 2 of 5

M.M. Barbosa et al.

cardiomyopathy10,11 but information on atrial myopathy in dilated cardiomyopathy is limited because methods for non-invasive analysis of the atrial function have only now been introduced. LA dysfunction in dilated cardiomyopathy may be related not only to abnormal LV filling pressures, but also to intrinsic atrial involvement in the myopathic process. Since fibrosis can interfere with atrial function and Chagas disease has been described as a dilated cardiomyopathy where fibrotic changes are common, the present study aimed to assess atrial function by TDI, strain and strain rate, and to investigate if these parameters are more impaired in CDC than in idiopathic dilated cardiomyopathy (IDC).

Methods Study group

Conventional Doppler echocardiogram A comprehensive Doppler echocardiogram, with TDI and Dopplerbased strain and strain rate measurements, was performed using commercially available equipment (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway) with an electronic high-resolution multifrequency transducer. Measurements were performed by one experienced cardiologist who was blinded to other data from the patients. LV measurements were obtained according to the European Association of Echocardiography and the American Society of Echocardiography standards, and LVEF was calculated by the Simpson’s method.13 Left atrial volume (LAV) was assessed by the biplane area-length method from apical four- and two-chamber views and indexed to body surface area.14 In all patients in whom an adequate tricuspid regurgitation spectral Doppler profile could be obtained, pulmonary artery pressure was estimated as previously described.15 Diastolic function was assessed by pulsed Doppler of the mitral inflow: E, A and the deceleration time of the mitral inflow (DT) were measured. TDI measurements (systolic velocity – S, early – e′ and late – A′ diastolic velocities) were obtained at the medial and lateral border of the mitral annulus in the apical four-chamber view. The ratio of the mitral E velocity to the mean e’ was calculated (E/e′ ).16

TDI of the atria Atrial peak velocities in systole (Sat), and early (E′ at) and late (A′ at) velocities in diastole were measured using pulsed wave Doppler tissue imaging. The pulsed wave Doppler sample volume (size of

the interatrial septum. Narrowed sector enables maximum yield in frame rate, optimizing image clarity and data acquisition.

4 mm) was placed on the mid-segment of the interatrial septum in the apical four-chamber view and in the mid-segment of the right atrial (RA) free wall. An average of three beats was measured. Special attention was paid to align the Doppler beam as parallel to the interatrial septum as possible.3

Atrial strain and strain rate Doppler-based atrial strain and strain rate were obtained from the apical views for the medial segment of the interatrial septum (Figure 1), inferior wall of the LA and the RA-free wall during the reservoir phase (during ventricular systole, the atria function as reservoirs to store blood when the atrioventricular valves are closed). Images were obtained using a narrow sector (frame rate .110 fps), and attempts were made to align the Doppler beam as parallel as possible to the atrial wall. The recorded wall was positioned at the centre of the sector to minimize the interference of any angle between the longitudinal motion and the interrogating beam. Since the atrial wall is very thin, a narrow sample volume (10 × 2 mm) was used. The interatrial septum and the inferior wall were chosen based on data presented by Thomas et al.,4 who demonstrated that a better alignment was obtained on these walls. Peak positive systolic strain curves for both atria were measured in the middle segment of all three atrial walls.17 Strain rate measurements were obtained during systole (S-aSR) and during early (E-aSR) and late (A-aSR) diastoles. An average from three consecutive beats was obtained.

Statistical analysis Categorical data were presented as numbers and percentages, and continuous data were expressed as means + SD. Clinical and echocardiographic variables of patients with CDC and IDC were compared using x2 test, unpaired Student’s t-test or Mann – Whitney test, as appropriate. Atrial strain and SR in patients with dilated cardiomyopathies and healthy controls were compared by Kruskal – Wallis or one-way ANOVA, as appropriate, followed by Bonferroni correction. A value of P , 0.05 was considered significant. SPSS version 17 (SPSS, Inc. Chicago, IL, USA) was used for all analyses.

Downloaded from by guest on January 17, 2017

Seventy-two patients from a tertiary centre for treatment of dilated cardiomyopathy were consecutively selected and compared with 32 healthy controls. The study protocol was approved by the institutional ethic committee and all enrolled patients gave an informed written consent to participate. Inclusion criteria were the diagnosis of dilated cardiomyopathy characterized by LV diastolic diameter/body surface area .31 mm/m2 and LV ejection fraction (EF) ,55%.12 Patients were grouped into two categories according to the underlying cause of cardiomyopathy: (i) CDC, characterized by dilated cardiomyopathy secondary to Chagas disease confirmed by at least two positive serologic tests for antibodies against Trypanosoma cruzi; (ii) IDC, defined by the presence of LV dilatation and LV systolic dysfunction in the absence of significant coronary artery disease or other specific valvar or muscle heart diseases. Patients who had other associated heart diseases, including atrial fibrillation or pacemakers, were excluded. All patients were on optimized treatment for heart failure, according to current practice.

Figure 1 Peak atrial strain obtained at the medial segment of

Page 3 of 5

Atrial function in Chagas dilated cardiomyopathy

Results

Table 1 Baseline clinical characteristics of the patients according to the aetiology of dilated cardiomyopathy CDC (n 5 36)

Discussion The present study demonstrated that patients with dilated cardiomyopathy had decreased atrial function when compared with healthy controls. However, atrial involvement in CDC was not more significant than in IDC, when LA and RA were analysed by atrial TDI, strain and strain rate.

Non-invasive analysis of the atrial function Strain and strain rate imaging of LV myocardium have been reported both in normal and in diseased patients. However, there are few data on strain and strain rate imaging of the atria.

Table 2 Echocardiographic baseline characteristics according to the underlying cause of cardiomyopathy CDC (n 5 36) IDC (n 5 36) P-value

................................................................................ LVDd (mm)

65.8 + 7.6

71.0 + 13.5 0.052

LVDd/BSA (mm/m2)

39.3 + 5.7

39.8 + 6.9

LVSd (mm) LVEF (%)

54.9 + 8.2 32.1 + 8.4

61.5 + 14.9 0.025 28.2 + 11.9 0.098

LA dimension (mm)

43.9 + 8.5

45.9 + 9.6

LA volume index (ml/m2) E (cm/s)

50.6 +23.7 82.2 + 27.1

48.7 + 20.6 0.725 88.4 + 33.8 0.396

A (cm/s)

58.9 + 28.5

55.1 + 29.5 0.594

E/A ratio DT (ms)

1.7 + 1.0 201.7 + 72.5

1.9 + 1.2 0.371 166.7 + 50.1 0.025

35.2 + 8.8

39.1 + 11.6 0.125

SPAP (mmHg)

IDC (n 5 36) P-value

................................................................................ Clinical parameters

Moderate or severe MR Moderate or severe TR

6.5 + 2.7

6.1 + 3.4

0.610

6.1 + 2.4 4.7 + 1.7

0.637 0.171

44.3 + 10.6

42.5 + 11.7

0.494

22 (61) 1.7 + 0.14

21 (58) 1.8 + 0.27

0.810 0.029

E/e′

NYHA functional class III/IV

10 (28)

Heart rate (bpm)

60.5 + 7.5

SBP (mmHg) DBP (mmHg)

108.7 + 11.8 72.1 + 11.6

0.122

81.5 + 14.1 ,0.001 108.9 + 17.2 73.1 + 12.9

0.956 0.737

Medication ACE inhibitor Digoxin

33 (92) 13 (36)

32 (89) 25 (69)

0.635 0.004

Diuretics

29 (81)

33 (92)

0.211

Beta-blockers Amiodarone

17 (47) 21 (58)

33 (92) 5 (14)

,0.001 ,0.001

Data are expressed as the mean value + SD or number (percentage) patients. ACE, angiotensin-converting enzyme inhibitor; CDC, Chagas dilated cardiomyopathy; DBP, diastolic blood pressure; IDC, idiopathic dilated cardiomyopathy; NYHA, New York Heart Association; SBP, systolic blood pressure.

0.042 0.736

6.3 + 2.1 5.2 + 1.3

Male gender Body surface area (m2)

5 (14)

17 (47) 6 (17)

0.332

e′ (cm/s) A′ (cm/s) S (cm/s)

Age (years)

9 (25) 6 (17)

0.714

15.2 + 8.1

18.5 + 10.7 0.140

Atrial TDI myocardial velocities (cm/s) IAS-S 3.1 + 1.3

3.0 + 1.2

0.910

IAS-E

3.3 + 2.1

3.5 + 2.1

0.371

IAS-A RA-S

3.4 + 1.8 6.0 + 2.1

4.3 + 1.8 5.4 + 1.9

0.067 0.230

RA-E

5.2 + 2.5

5.0 + 2.4

0.872

RA-A

7.0 + 3.1

6.7 + 2.9

0.435

BSA, body surface area; CDC, Chagas dilated cardiomyopathy patients; DT, deceleration time; E, early diastolic transmitral flow velocity; e′ , early diastolic mitral annular velocity, E/e′ , ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity; IAS-A, interatrial septum late diastolic velocity; IAS-E, interatrial septum early diastolic velocity; IAS-S, interatrial septum systolic velocity; IDC, idiopathic dilated cardiomyopathy patients; LA, left atrial; LVDd, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVSd, left ventricular end-systolic diameter; MR, mitral regurgitation; SPAP, systolic pulmonary artery pressure; RA, right atrium; RV, right ventricular; S, systolic tissue Doppler velocity; TDI, tissue Doppler imaging; TR, tricuspid regurgitation.

Downloaded from by guest on January 17, 2017

Thirty-six patients with CDC (22 males; mean age, 42 + 11 years) and 36 with IDC (20 males; mean age, 44 + 10 years) were enrolled. Patients from both groups were compared with 32 healthy individuals. Clinical data and conventional Doppler echocardiographic parameters comparing the two groups of patients with dilated cardiomyopathy are presented in Tables 1 and 2, respectively. There was substantial homogeneity between the groups with regard to age, gender, and functional class. Most patients were clinically stable, in NYHA functional classes I and II. Chagas patients had lower heart rate. Amiodarone was more used by CDC patients, while b-blockers was more used by the IDC group. Doppler echocardiographic parameters of systolic function were similar between the two groups with dilated cardiomyopathy, with similar LV diameters indexed to body surface area and EF (P ¼ 0.714 and 0.098, respectively). Echocardiographic LV filling pressure parameters were similar between the groups, although deceleration time was significantly shorter in the IDC group. Although moderate-to-severe mitral regurgitation was more frequent in the IDC group, LA volume was similar between the two groups. Atrial myocardial deformation indices for both RA and LA are described in Table 3. When these indices in CDC and IDC were compared with healthy individuals (CG), they were found to be significantly lower in patients with dilated cardiomyopathy than

in control patients, indicating atrial dysfunction in both forms of cardiomyopathies. However, when these indices were compared between CDC and IDC patients, there was no difference.

Page 4 of 5

Table 3

M.M. Barbosa et al.

Atrial strain and strain rate in patients with dilated cardiomyopathies and healthy controls CDC (n 5 36)

IDC (n 5 36)

P*

Controls (n 5 32)

P

RA wall strain (%)

43.5 + 22.6

47.9 + 26.2

0.616

81.4 + 40.7*

,0.001†

Inter atrial septum Strain (%)

25.2 + 14.8

24.9 + 16.0

0.909

36.2 + 24.6*

0.011†

S SR (/s)

1.3 + 0.7

1.5 + 0.9

0.490

2.3 + 1.0*

0.003†

E SR (/s) A SR (/s)

1.2 + 0.4 1.7 + 0.6

1.5 + 0.9 2.2 + 1.3

0.204 0.169

2.1 + 1.0* 1.9 + 0.7

0.003† 0.395

Strain (%) Peak S SR (/s)

27.1 + 14.9 1.4 + 0.8

25.9 + 20.4 1.5 + 0.9

0.166 0.551

42.4 + 15.4* 2.3 + 0.9*

,0.001† ,0.001†

Peak E SR (/s)

1.2 + 0.8

1.5 + 1.1

0.242

2.7 + 1.2*

,0.001†

Peak A SR (/s)

1.9 + 1.0

1.6 + 0.7

0.293

2.5 + 1.2

...............................................................................................................................................................................

Left atrial inferior wall

0.003

*P: CDC vs. IDC (Mann –Whitney test). † P: cardiomyopathy patients vs. controls. A-SR, peak atrial strain rate in late diastole; CDC, Chagas dilated cardiomyopathy patients; E-SR, peak atrial strain rate in early diastole; IDC, idiopathic dilated cardiomyopathy; LA, left atrium; RA, right atrium; Strain: peak atrial strain in systole; SR, peak systolic strain rate.

Atrial involvement in dilated cardiomyopathy Ventricular function does not seem to be the only factor influencing atrial function, and intrinsic atrial characteristics, such as atrial myopathy and fibrosis, might also play a role. In favour of this hypothesis, decreased LA contractility has been shown to be greater in dilated cardiomyopathy than in aortic valvar disease with similar loading conditions.10

Ohtani et al.,11 comparing dilated cardiomyopathy with LV dysfunction secondary to myocardial infarct, showed that atrial fibrosis was more extensive in patients with dilated cardiomyopathy. The possibility of ischaemia as a possible mechanism involved in atrial function is controversial. Atrial chambers are low-pressure reservoirs. Thus, some advocate that they are not susceptible to ischaemia.11 In fact, atrial infarct is extremely rare.21 However, the role of ischaemia in atrial function is still controversial and LA mechanical dysfunction has been shown in ischaemia.1,22 LA myopathy may contribute to a decrease in LA function in dilated cardiomyopathies. In these entities, LA myopathy may precede LV myopathy and evaluation of LA function in dilated cardiomyopathy may contribute to earlier detection of the disease and better stratification of patients. Thus, LA function may be a prognostic factor in dilated cardiomyopathy10 and in Chagas disease.6 Indeed, LA systolic function has been shown to be predictive of exercise tolerance in heart failure.23 Although fibrosis has been suggested as a prominent finding in CDC,9 evidence of atrial fibrosis is still lacking and its possible repercussion in atrial function has not been evaluated. In Chagas disease, although the histological characteristics of the left atrium have not been well defined, it can be inferred that they may be similar to those observed in the LV. Severe myocardial inflammation and fibrosis can involve the atrial myocardium in different clinical stages of the disease, similar to patients with dilated cardiomyopathy.10 Therefore, atrial myopathy could lead to atrial dysfunction independent of the haemodynamic load. In addition, the accumulation of interstitial collagen fibres in chronic myocarditis of Chagas disease may be expected to decrease myocardial compliance, which leads to an increase in LA pressure.7,9 In a previous study from our group, BNP levels in patients with Chagas disease correlated with LAV, but not with other echocardiographic indices of diastolic dysfunction.24 The main differential diagnosis of CDC is idiopathic cardiomyopathy.12 Although fibrosis is thought to be common in Chagas cardiomyopathy, the subject is still controversial. A recent biopsy

Downloaded from by guest on January 17, 2017

LA function is an important component in overall cardiovascular performance, not only because of its contractile function during ventricular diastole, but also because of its function as a reservoir and as a conduit. However, a major limitation in analysing atrial involvement has been the lack of gold standard for the measurement of LA function. Recently, with the advent of new techniques, such as TDI, strain rate and strain, and the establishment of normal values for the LA wall,18 these new tools have been utilized to analyse atrial function.2 – 5 Since peak values of SR and strain during the late reservoir period occur during LV ejection, the influence of ventricular systole in this reservoir phase can be inferred. During the conduit period, LA volume flows to the LV and the LA is refilled by the pulmonary veins. This causes the LA to decrease in the early conduit phase, which happens after LA stretching during the preceding reservoir phase. Thus, LA expansion during the reservoir phase may be an important factor for maintaining adequate LV filling.18 If peak atrial strain and SR provide an estimation of the reservoir function of the LA, their measurement can provide insights on atrial function and on the haemodynamic repercussion of the LV function on the LA. The same rationale can be applied to the RA. In fact, some papers have recently come out analysing atrial function in several conditions.19,20 Moustafa et al.19 have shown reduced LA strain in moderate-and-severe mitral regurgitation, even in the presence of normal systolic function, emphasizing early atrial dysfunction in this group of patients.

Page 5 of 5

Atrial function in Chagas dilated cardiomyopathy

study showed no difference in the amount of myocardial fibrosis between patients with Chagas and IDC.25 Perhaps the persistence of the activity of myocarditis, somehow contributes to an accelerated progression of the disease in Chagas cardiomyopathy patients.25,26 Indeed, myocardial fibrosis has been shown to correlate inversely with LVEF and clinical status.9 Increased LA volume is a consequence of chronic abnormalities in LV filling pressures. However, studies analysing LA volumes have not evaluated atrial function itself. It may be that instantaneous analysis of the atrial contractility and filling properties by TDI, SR and strain imaging will provide some insights into a better understanding of the role of atrial function in dilated cardiomyopathy. However, in the present study, when patients with CDC and IDC with similar degrees of ventricular dysfunction were compared using these parameters, atrial dysfunction was not more prevalent in CDC patients.

6.

7.

8.

9.

10. 11.

12.

Conclusion 13. 14. 15.

Conflict of interest: none declared.

16.

Funding

17.

This work was supported by CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnolo´gico, Brası´lia, Brazil), FAPEMIG (Fundac¸a˜o de Apoio a` Pesquisa do Estado de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil), and CAPES (Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior, Brası´lia, Brazil).

References 1. Yu CM, Fung JWH, Zhang Q, Kum LCC, Lin H, Yip GWK et al. Tissue Doppler echocardiographic evidence of atrial mechanical dysfunction in coronary artey disease. Int J cardiol 2005;105:178 – 85. 2. Wang T, Fung JWH, Yip GWK, Zhang Y, Ho PPY, Tse DMK et al. Atrial strain rate echocardiography can predict success or failure of cardioversion for atrial fibrillation: a combined transthoracic tissue Doppler and transesophageal imaging study. Int J Cardiol 2007;114:202 –9. 3. Thomas L, Levett K, Boyd A, Leung DYC, Schiller NB, Ross DL. Changes in regional left atrial function with aging: evaluation by Doppler tissue imaging. Eur J Echocardiogr 2003;4:92 –100. 4. Thomas L, Mckay T, Byth K, Marwick TH. Abnormalities of left atrial function after cardioversion: an atrial strain rate study. Heart 2007;93:89 –95. 5. Di Salvo G, Caso P, lo Piccolo R, Fusco A, Martiniello AR, Russo MG et al. Atrial myocardial deformation properties predict maintenance of sinus rhythm after external cardioversion of recent-onset lone atrial fibrillation. A color Doppler

18. 19.

20. 21. 22.

23.

24.

25.

26.

Downloaded from by guest on January 17, 2017

This study demonstrated that atrial myocardial deformation properties were abnormal in patients with dilated cardiomyopathy, regardless of the aetiology. Atrial function in Chagas disease does not seem to be more impaired than in IDC with similar degree of LV dysfunction, when new atrial deformation parameters are used.

myocardial imaging and transthoracic echocardiographic study. Circulation 2005; 112:387–95. Nunes MC, Barbosa MM, Ribeiro AL, Colosimo EA, Rocha MOC. Left atrial volume provides independent prognostic value in patients with chagas cardiomyopathy. Am Soc Echocardiogr 2009;22:82– 8. Carrasco H, Palacios E, Scorza C, Molina C, Inglessis G, Mendoza R. Clinical, histochemical and ultrastructural correlations in septal endomyocardial biopsies from chronic chagasic patients. Am Heart J 1987;113:716 –24. Higuchi ML, Benvenuti LA, Reis MM, Metzger M. Pathophysiology of the heart in Chagas’ disease: current status and new developments. Cardiovasc Res 2003;60: 96 – 107. Rochitte CE, Oliveira PF, Andrade JM, Ianni BM, Parga JR, Avila LF et al. Myocardial delayed enhancement by magnetic resonance imaging in patients with Chagas disease: a marker of disease severity. J Am Coll Cardiol 2005;46:1553 –8. Triposkiadis F, Pitsavos C, Boudoulas H, Trikas A, Toutouzas P. Left atrial myopathy in idiopathic dilated cardiomyopathy. Am Heart J 1994;28:308 –15. Ohtani K, Yutani C, Nagata S, Koretsune Y, Hori M, Kamada T. High prevalence of atrial fibrosis in patients with dilated cardiomyopathy. J Am Coll Cardiol 1995;25: 1162 –9. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807 – 16. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA et al. Recommendations for chamber quantification. Eur J Echocardiogr 2006;7:79– 108. Wang Y, Gutman J, Heilbron D, Wahr D, Schiller N. Atrial volume in a normal adult population by two-dimensional echocardiography. Chest 1984;86:595 – 601. McQuillan BM, Picard MH, Leavitt M, Weyman AE. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation 2001;104:2797 – 802. 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. Eur J Echocardiogr 2009;10:165 –93. Sirbu C, Herbots L, D’hooge J, Claus P, Marciniak A, Langeland T et al. Feasibility of strain and strain rate imaging for the assessment of regional left atrial deformation: a study in normal subjects. Eur J Echocardiogr 2006;7:199 –208. Matsumori A, Kawai C. An experimental model for congestive heart failure after encephalomyocarditis in mice. Circulation 1982;65:1230 –5. Moustafa SE, Alharthi M, Kansal M, Deng Y, Chandrasekaran K, Mookadam F. Global left atrial dysfunction and regional heterogeneity in primary chronic mitral insufficiency. Eur J Echocardiogr 2011;12:384 –93. OÇonnor K, Magne J, Rosca M, Pie´rard LA, Lancelllotti P. Left atrial function and remodelling in aortic stenosis. Eur J Echocardiogr 2011;12:299 –305. James TN, Burch GE. The atrial coronary arteries in man. Circulation 1958;17: 90 – 8. Stefanidis C, Dernellis J, Tsiamis E, Toutouzas P. Effects of pacing induced and balloon coronary occlusion ischemia on left atrial function in patients with coronary artery disease. J Am Coll Cardiol 1999;33:687 –96. Triposkiadis F, Trikas A, Pitsavos T, Papadopoulos P, Toutouzas P. Relation of exercise capacity in dilated cardiomyopathy to left atrial size and systolic dysfunction. Am J Cardiol 1992;70:825 –7. Barbosa MM, Nunes MC, Ribeiro AL, Barral MM, Rocha MO. N-terminal proBNP levels in patients with Chagas disease: a marker of systolic and diastolic dysfunction of the left ventricle. Eur J Echocardiogr 2007;8:204 –12. Nunes VL, Ramires FJA, Pimentel WS, Fernandes F, Ianni BM, Mady C. The role of storage of interstitial myocardial collagen on the overlife rate of patients with idiopathic and Chagasic dilated cardiomyopathy. Arq Bras Cardiol 2006;87:693 – 8. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simo˜es MV. Pathogenesis of chronic Chagas heart disease. Circulation 2007;115:1109 –23.