This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Acquatella, H. Search for Related Content PubMed PubMed Citation Articles by Acquatella, H. Pubmed/NCBI databases Medline Plus Health Information Cardiomyopathy Chagas Disease Related Collections Other heart failure Congestive Echocardiography

(Circulation. 2007;115:1124-1131.)
© 2007 American Heart Association, Inc.

Heart Disease in Latin America

Echocardiography in Chagas Heart Disease

Harry Acquatella, MD

From the Faculty of Medicine Universidad Central de Venezuela, Hospital Universitario and Centro Medico, Caracas, Venezuela.

Correspondence to Dr Harry Acquatella, 275 Centro Medico, San Bernardino, Caracas 1011, Venezuela. E-mail hacquatella{at}cantv.net

Received March 15, 2006; accepted August 8, 2006.

	Abstract

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
Background— Chagas heart disease is a frequent cause of morbidity and mortality in Latin America. Echocardiography provides useful diagnostic and prognostic information and is an important tool in the management of patients with Chagas disease.

Methods and Results— A search for relevant publications was obtained from MEDLINE, LILACS, and SCIELO sources. Acute Chagas myocarditis is a rare disorder in which pericardial effusion is frequent. Echocardiography may exclude pericardial tamponade in case of heart failure. Chronic Chagas cardiomyopathy evolves for several decades after the infection. Epidemiological history, positive serology, and suggestive clinical and ECG abnormalities establish the diagnosis. About three quarters of chronic Chagas cardiomyopathy subjects remain asymptomatic with normal (indeterminate form) or abnormal ECGs. Early Doppler abnormalities includes prolongation of isovolumic contraction and relaxation times. Systolic function frequently is normal, but dysfunction may be elicited by stress tests. Half or more of symptomatic patients have a left ventricular apical aneurysm and other segmental contractile abnormalities similar to those seen in coronary heart disease. The dilated nonsegmental form is indistinguishable from dilated cardiomyopathy. Results from univariate and multivariate Cox survival analyses indicate that impaired systolic function and increased ventricular dimensions have significant value in predicting cardiac morbidity and mortality. Cardiac ultrasound commonly is used in the follow-up of patients and in the assessment of various therapeutic modalities.

Conclusions— Echocardiographic and Doppler techniques provide useful structural and functional information in the detection of early myocardial damage, risk assessment of prognosis, disease progression, and management of patients with Chagas disease.

Key Words: cardiomyopathy • Chagas disease • echocardiography, Doppler • echocardiography • heart failure • survival

	Introduction

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
Chagas disease remains a public health problem in several countries of Latin America. Prophylactic control programs have diminished substantially the number of infected individuals from 16 to 18 million in the early 1990s to 11 million in a recent estimation, but 100 million persons still continue to be at risk of acquiring the infection.¹ The diagnosis of Chagas disease requires an epidemiological history and 2 positive serologic tests. Cardiac damage is suspected by 1 of the following ECG findings: right bundle-branch block, left anterior fascicular block, AV blocks, multiform ventricular beats, sinus bradycardia, abnormal ST-T segment, and abnormal T and Q waves.^2–7 The decreasing prevalence of the disease in some endemic areas or migration of infected subjects to urban nonendemic places within or outside their original country may result in misdiagnosis of a cardiomyopathy of different origin.^8,9 Two-dimensional and Doppler echocardiography provides additional valuable information on cardiac structure and function that complements information provided by ECG. This review is focused primarily on the utility of cardiac ultrasound in the diagnosis, classification, and detection of early myocardial damage and the prognostic assessment of patients with Chagas disease. Other aspects of epidemiology and pathophysiology are briefly considered.

	Acute Chagas Disease

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
Chagas disease usually is acquired during childhood.^1,3,4,7 Infected forms of Trypanosoma cruzi present in the feces of reduvidae insects penetrate the skin or conjunctiva of people living in poor rural housing. The disease has an acute phase and a chronic phase. Acute Chagas disease may appear as a nonspecific febrile illness lasting for 2 to 8 weeks, becoming clinically manifest in <1% of infected subjects.^3,4 Acute chagasic myocarditis is infrequent, appearing in only 1% to 5% of those having the acute phase (1 to 5 of every 10 000 infected subjects).⁴

The largest published echocardiographic series on acute Chagas disease includes 58 subjects.¹⁰ Abnormal 2-dimensional echocardiograms were present in 52%, and pericardial effusion was seen in 42%. In 10 of 12 patients with heart failure (HF), the effusion was moderate to severe. Of note, mean left ventricular ejection fraction (LVEF) was normal (63%). Apical or anterior dyskinesis was found in 21%, and only 6% had LV dilation. Five patients died, 4 of them in HF. In 2 other reports,^11,12 pericardial effusion was present in 7 of 8 patients, 3 of whom were in tamponade. Figure 1 shows a patient with this complication who improved substantially after pericardiocentesis. These findings demonstrate the need to perform echocardiograms to rule out a rapidly treatable cause of HF (pericardial effusion) and to evaluate systolic dysfunction during the acute phase. More studies are necessary.

View larger version (160K): [in this window] [in a new window]   Figure 1. Four-chamber apical view echocardiogram of a woman with a 1-month history of acute Chagas myocarditis with pericardial effusion and tamponade. Chamber size and systolic function were normal. Notice the compression of the right atrial (RA) wall. LA indicates left atria; PE, pericardial effusion.

	Chronic Chagas Disease

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
In most patients, the initial infection occurs unnoticed, passing to the chronic stage 1 to several decades later. On histology, diffuse and patchy chronic myocarditis, interstitial mononuclear cell infiltrates, and myocardial fiber destruction with fibrotic replacement are commonly present^3,4,13–16 (Figure 2). Most initial autopsy studies performed in subjects dying at the end stage of the disease reported grossly enlarged hearts.^3,4,14,16 A pioneering necropsy work¹⁷ pointed out the high rate of LV chagasic apical aneurysm found in these patients. This result was confirmed by others studies,^14,18 including a large series of 1078 autopsies¹⁹ in which apical aneurysms were found in half of cases, more frequently in male than in female patients, and at similar proportions in all age groups. Eighty-two percent were found at the LV apex, 9% at the right ventricular (RV) apex, and 9% at both. Other series had rates ranging from 30% to 92%.^3,14,17,18 Additional LV segmental lesions such as at the posteroinferior walls ranged from 21%¹⁴ to 33%³ (Figure 2).

View larger version (135K): [in this window] [in a new window]   Figure 2. Echocardiogram and postmortem specimen from a patient who had HF secondary to CCM. A, M-mode long-axis, slow-sweep echocardiogram showing the relatively preserved systolic septal (S) motion and thickening and a thin, noncontractile posterior wall (PW). B, Long-axis autopsy section of the heart. Notice the LV apical and posteroapical fibrotic thinning with relative septal sparing. The coronary arteries were normal. Reproduced from Acquatella et al25, with permission of the publisher. Copyright © 1980, the American Heart Association.

Chronic Chagas cardiomyopathy (CCM) may be detected with or without symptoms. Most investigators combine clinical and ECG findings, cardiomegaly, and systolic dysfunction into 4 groups of progressive heart damage^7,20–23 (Table 1). The recent American College of Cardiology/American Heart Association staging²⁴ of disease progression into A (high risk of HF without structural heart disease), B (structural heart disease without HF), C (structural heart disease with prior or present HF), and D (refractory HF) is incorporated into Table 1. Asymptomatic subjects comprise about three quarters of seropositive persons. Those with a normal ECG are referred as being in the indeterminate phase of the disease (stage A). The appearance of ECG abnormalities implies disease progression (stage B). By definition, no cardiomegaly is present, and LV systolic function is normal. Fewer than 10% may have LV segmental wall motion abnormalities. Symptomatic patients with mild to moderate cardiac damage are in New York Heart Association (NYHA) functional class II or III (stage C) and may present with arrhythmias, embolism, sudden death, and reversible HF.^20–22 The ECG is abnormal in almost all. The heart is dilated, and LV systolic and diastolic functions are usually abnormal. About half of these patients may have LV apical and other segmental wall abnormalities.^21,25–29 Mitral and tricuspid valve regurgitation may be present. Survival at 10 years is 75% to 85%.^21,22,30 Those with HF in NYHA functional class IV (stage D),^13,21,22,30 may, if untreated, have a very high mortality (50%) at 2 years. In all groups, coronary angiography, when performed, is normal or shows nonsignificant lesions.

View this table: [in this window] [in a new window]   TABLE 1. Clinical, ECG, and Echocardiographic Findings in CCM

	Echocardiographic and Doppler Findings

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
Anatomic Abnormalities
In asymptomatic subjects, it may be difficult to differentiate precisely a normal thin apical segment from an early scar. This difficulty may explain the different rates of apical abnormalities published in various reports.^{26–29,31–34} LV cavity opacification with ultrasound contrast and harmonic imaging may help in difficult cases.³¹ The aneurysm may range from as small as a "hollow punch" to large, indistinguishable from a myocardial infarction.

The mean prevalence of LV aneurysm from different 2-dimensional echocardiographic series was 8.5% (range, 1.6% to 8.6%)^26,28,31 among 920 asymptomatic individuals or patients with mild cardiac damage and 55% (range, 47% to 64%)^26–29 in 242 patients with moderate to severe cardiac impairment (Table 1 and Figure 3). In a recent work that included 1053 subjects,³⁴ it was less frequent, 2% in subjects with a normal ECG and 24% in those with an abnormal ECG. In logistic regression analysis, the LV apical aneurysm was an independent predictor of mural thrombus.³⁴ In another work, patients with aneurysms had a significant association with thrombus and stroke during a mean follow-up of 2 years.²⁹

View larger version (85K): [in this window] [in a new window]   Figure 3. Two-dimensional 4-chamber echocardiogram apical view of a patient with CCM with an LV apical aneurysm (AA). There is a distinct limit between the normal contractile myocardium and the dyskinetic apex (arrows). LVEF was moderately decreased (40%).

Segmental LV contractile abnormalities of other walls also may be detected. The most common is at the posteroinferior wall, with a mean prevalence of 20% (range, 5.3% to 22%)^26,28,31,35 in 1164 asymptomatic subjects or patients with mild heart damage and of 23% (range, 16% to 30%)^26–28 in 280 patients having symptoms or with HF (Figure 2).

Endocardial curvature and global shape evaluated by Fourier analysis of LV 2-dimensional echocardiograms³⁶ disclosed a significantly decreased apical curvature with a more spherical LV, resulting in a disruption of the optimal global prolate-ellipsoid shape even in patients with relatively preserved LV volumes. This finding may suggest that early segmental lesions may progress to diffuse hypokinesis and increased LV end-diastolic dimensions as found in advanced disease.

Systolic Function
Subjects presenting with the indeterminate form almost invariably have a normal global systolic function,^{31,33,37–39} but some may have abnormal echocardiograms.³¹ Among 505 subjects with normal ECGs and a mean normal LVEF of 67%, 13% had segmental lesions and 0.8% had systolic dysfunction. In contrast, of 257 persons with abnormal ECGs and a mean LVEF of 68%, 33% had segmental lesions and 8% had systolic dysfunction. Both groups had normal biventricular end-diastolic and end-systolic dimensions.³¹ In patients with abnormal ECGs, global systolic function has prognostic implications. A cohort of 538 patients³⁹ grouped in 4 stages of disease progression (A to D)²⁴ had markedly dissimilar 5-year survival rates of 98%, 91%, 45%, and 13% for those with a normal LVEF, mildly decreased LVEF, reversible HF, or irreversible HF, respectively.

With tissue Doppler imaging (TDI),⁴⁰ myocardial velocity systolic shortening and diastolic lengthening (E' and A') during the cardiac cycle can be estimated (Figure 4). With TDI, subjects with normal ECGs and 2-dimensional echocardiograms have shown prolonged LV^41,42 and RV⁴³ isovolumic contraction times as signs of early contractile abnormalities. Thus, a normal ECG does not rule out myocardial abnormalities, the clinical significance of which is currently unknown.

View larger version (40K): [in this window] [in a new window]   Figure 4. Doppler findings of the patient in Figure 3 (tracings are aligned with the first QRS complex). A, Mitral valve pulsed-wave Doppler displays a decreased E/A ratio of 0.64 and a prolonged E deceleration time of 295 ms, consistent with a diastolic pattern of prolonged relaxation. Mitral regurgitation was mild. B, TDI at the septal mitral annular level shows prolonged isovolumic contraction time (ICT) and relaxation time (IRT) of 130 and 155 ms, respectively. S, E', and A' peak velocities are decreased. Note the prominent apical-directed IRT wave (white arrow on C), probably related to earlier relaxation of the aneurysm. C, Color Doppler M-mode velocity propagation of the LV inflow tract. A diminished slope of the color edge in early diastole (white line) represents a lower velocity of blood flow toward the aneurysmal apex, consistent with loss of apical suction.

In patients with normal EF, systolic dysfunction may become apparent under pharmacological stress. An impairment for chronotropic, global, and regional contractile responses has been seen during standard dobutamine stress echocardiography.⁴⁴ Some patients show a biphasic response (initially augmentation followed by hypocontractility at higher dobutamine doses) predominantly at the LV posteroinferior wall segments, suggestive of viable but dysfunctional myocardium. The possible mechanisms are complex and may include ß-adrenergic dysfunction, endothelial dysfunction, ischemia, and structural myocardial damage.⁴⁴ Others have shown a lower slope of the end-systolic pressure–dimension relation during phenylephrine infusion,⁴⁵ suggestive of a reduction in LV contractility in patients with the indeterminate form, mild cardiac involvement, or the digestive form of the disease.⁴⁵

RV systolic impairment may be the only abnormality detected by biventricular radionuclide angiography.^46,47 In contrast, in a recent group of 74 patients studied by 2-dimensional and Doppler echocardiography, RV dysfunction, when present, was secondary to the severity of LV damage and high levels of pulmonary pressure rather than primary RV depressed function.⁴⁸ These apparently discordant results may be due to the different techniques used.

Diastolic Function
The chronic myocarditic damage^{3,13,14,18,19,49} may impair ventricular relaxation and diastolic filling. Diastolic abnormalities usually precede systolic dysfunction.^50,51 Reduced LV compliance leads to an increase in left atrial pressure, changes in transmitral and pulmonary venous flow velocities, and prolongation of systolic and diastolic time intervals. Early works using simultaneous M-mode echocardiographic, phonocardiographic, and apex cardiographic tracings^50,51 had already shown that significant prolongation of the isovolumic relaxation and ventricular filling times was present in asymptomatic subjects with normal systolic function and in symptomatic patients.

The combination of pulsed Doppler of mitral valve inflow, pulmonary veins, and mitral annular TDI velocities currently is used to classify patients into 4 groups of worsening diastolic function: abnormal relaxation, pseudonormal, reversible, and nonreversible restrictive filling.⁴⁰

In a group of 169 CCM subjects, diastolic dysfunction was found in 20% of the patients.²⁶ There was a strong correlation between worsening diastolic function and increased left atrial and ventricular dimensions and decreased LVEF. A reduced TDI septal E' wave of 11 cm/s and a septal E/E' ratio of >7.2 were highly sensitive and moderately specific and had a high negative predictive value for detecting any kind of diastolic dysfunction (Figure 4). Another group of 89 patients⁵² were classified according to the presence of normal or pseudonormal ventricular filling pattern. Patients with pseudonormal filling pattern had statistically significantly larger LV dimensions, higher LV wall motion score, and lower LVEF. TDI was able to differentiate CCM patients with normal LV diastolic function from those with a pseudonormal filling pattern and increased LV filling pressures.

	Other Echocardiographic Doppler Techniques

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
In color M-mode, early inflow jet velocities across the mitral valve as it moves toward the apex display a slope representing the blood flow velocity propagation⁴⁰ (Figure 4). A group of CCM patients had decreased velocity propagation consistent with relaxation abnormalities, which was more pronounced in those with LV apical aneurysm. LVEF and pulsed-wave Doppler patterns were not significantly different between CCM patients and a control group.⁵³

The myocardial performance index (Tei index) is a global function index combining the time duration of systole and diastole by pulsed-wave Doppler.⁵⁴ A study found abnormally high values of LV myocardial performance index (0.32) in one third of asymptomatic subjects, in all of symptomatic patients, and in 2% of the control subjects.⁵⁵ ECG abnormalities in the asymptomatic chagasic patients were associated with abnormal myocardial performance index, but not in the control subjects with the same ECG changes. Symptomatic patients had markedly increased RV and LV myocardial performance index values, suggestive of severe myocardial dysfunction.

Doppler-derived myocardial strain also has been studied in patients with Chagas disease.⁵⁶ CCM patients had lower radial and longitudinal values compared with normal control subjects. However, strain was not able to differentiate between normal control subjects and subjects with the indeterminate form of the disease. This technique was able to quantify subtle segmental contractile dysfunction not detected visually.

	Echocardiographic Prognostic Variables

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
Echocardiographic series of chronic CCM patients were selected on the basis of having survival analysis performed by the Cox multivariate method (Table 2 and Figure 5). The populations included subjects with a broad expression of disease severity ranging from none^31,38 to none to severe^{31,32,34,57,58} to severe symptoms.^59,60

View this table: [in this window] [in a new window]   TABLE 2. Results of Echocardiographic Survival Analysis

View larger version (65K): [in this window] [in a new window]   Figure 5. Inverse significant correlation between LVEF and mortality among 3138 patients from 6 echocardiographic series. The first letter indicates the author initial; the second, the group. I indicates Ianni et al38; V, Viotti et al,31 groups 0, 1, and 2; S, Salles et al,57,58 groups Y (survived) and N (not survived); B, Bestetti et al,59 groups Y (survived) and N (not survived); R, Rodriguez-Salas et al,32 groups A (asymptomatic) and S (symptomatic); and X, Xavier et al,34 groups Y and N (apical aneurysm, yes or no). See text and Table 2 for other details.

No mortality occurred in 2 series of asymptomatic subjects with normal ECG at entry. In 1 series of 159 subjects, there were no events,³⁸ LVEF remained normal in all subjects, and ECG was unchanged in nearly 80%. In the other series of 505 subjects, 8% had events.³¹ In the same work, among 257 asymptomatic subjects with an initially abnormal ECG, mortality was 1%, and 26% had clinical events. In 87 patients with abnormal ECGs³¹ and cardiomegaly but no HF, 52% had clinical events with 14% mortality. On multivariate analysis, change in clinical group, LV systolic dimension, and LVEF were predictors of mortality. Chagas-related ECG abnormalities, LV diastolic and systolic dimensions, and LVEF were predictors of events.³¹

Four series included mixed populations, from asymptomatic subjects to patients with HF. One consisted of 738 patients.^57,58 QT-interval dispersion and LV end-systolic dimension were the strongest independent predictors of all end points. In another work of 1053 subjects classified according to whether an LV apical aneurysm was present,³⁴ LVEF remained the only significant predictor of mortality. Apical aneurysm was not significant when adjusted for LVEF. In a study of 283 patients³² grouped as asymptomatic and symptomatic, significant mortality risk factors were initial NYHA class, E-point septal separation, and M-mode echo fractional shortening. Finally, 2 series had patients with severe HF. One collected 56 persons in NYHA functional classes III and IV.⁵⁹ The only significant risk factor was LVEF. In a series of 104 male patients⁶⁰ in NYHA functional classes II, III, and IV, statistically significant differences between survivors and nonsurvivors on multivariate analysis were LVEF and maximal O₂ uptake (VO₂max). Thus, systolic dysfunction and increasing heart size emerged as significant predictors of morbidity and mortality (Figure 5).

	Applications in the Management of Patients

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
Echocardiography is used in the routine clinical evaluation of CCM patients to assess disease progression, in survival studies^{31,32,34,38,57–60} to rule out the presence of intraventricular thrombus,^29,34 in the follow-up of pacemakers devices⁶¹ and implanted automatic cardioverter-defibrillators,⁶² and to monitor response to vasodilator therapy in patients with HF (enalapril)⁶³ or to antiparasitic medications (benznidazole),⁶⁴ among others. The last study showed in a long-term follow-up that the only independent predictors of deteriorating clinical status were a lower echocardiographic LVEF and a higher LV end-diastolic diameter.

	Study Limitations

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
The echocardiographic and Doppler findings of CCM are nonspecific and may be similar to those observed in other cardiomyopathies (ischemic and nonischemic). A need exists for comparative studies to estimate the sensitivity and specificity of such abnormalities. The prognostic value of associated mitral regurgitation or RV dysfunction is unknown. LVEF should be preferentially estimated by 2-dimensional instead of M-mode echocardiography because the latter does not evaluate the frequently abnormal ventricular apex of these patients.

	Conclusions

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 
In patients with acute chagasic myocarditis, echocardiograms should be performed almost routinely, especially if HF is present, to exclude pericardial effusion and tamponade. In the chronic phase, subjects with a normal ECG have a good long-term prognosis; most have normal global systolic function, but contractile and diastolic abnormalities may be found, although the significance of these findings in disease progression is unknown. Ventricular involvement in CCM symptomatic individuals may range from an isolated small LV apical aneurysm to a globally dilated heart without segmental scars. A chagasic origin should be considered in the differential diagnosis of a cardiomyopathy patient with a positive epidemiological history and serology, suggestive ECG abnormalities, and apical aneurysm. Depressed LVEF and increased LV internal dimensions emerged in different survival studies as significant risk factors associated with increasing morbidity and mortality.

	Acknowledgments

 
We thank Dr Leonardo Rodriguez (Cleveland Clinic) for his help in editing the manuscript.

Disclosures

None.

	References

Top Abstract Introduction Acute Chagas Disease Chronic Chagas Disease Echocardiographic and Doppler... Other Echocardiographic Doppler... Echocardiographic Prognostic... Applications in the Management... Study Limitations Conclusions References

 

1. Dias JCP, Silveira AC, Schofield CJ. The impact of Chagas disease control in Latin America: a review. Mem Inst Oswaldo Cruz. 2002; 97: 603–612.[Medline] [Order article via Infotrieve]
   
2. Rosenbaum MB, Alvarez AJ. The electrocardiogram in chronic chagasic myocarditis. Am Heart J. 1955; 50: 492–527.[CrossRef][Medline] [Order article via Infotrieve]
   
3. Laranja FS, Dias E, Nobrega G, Miranda A. Chagas disease: a clinical, epidemiologic, and pathologic study. Circulation. 1956; 14: 1035–1060.[Medline] [Order article via Infotrieve]
   
4. Rosenbaum MB. Chagasic myocardiopathy. Prog Cardiovasc Dis. 1964; 7: 199–225.[CrossRef][Medline] [Order article via Infotrieve]
   
5. Storino R. Non-invasive studies. In: Storino R, Milei J, eds. Enfermedad de Chagas. Buenos Aires, Argentina: Doyma Argentina; 1994: 359–454.
   
6. Maguire JH, Hoff R, Sherlock I, Guimaraes AC, Sleigh AC, Ramos NB, Mott KE, Weller TH. Cardiac morbidity and mortality due to Chagas disease: prospective electrocardiographic study of a Brazilian community. Circulation. 1987; 75: 1140–1145.[Abstract/Free Full Text]
   
7. Elizari MV. Chagasic myocardiopathy: historical perspective. Medicina (B Aires). 1999; 59 (suppl 2): 25–40.[Medline] [Order article via Infotrieve]
   
8. Hagar JM, Rahimtoola SH. Chagas heart disease in the United States. N Engl J Med. 1991; 325: 763–768.[Abstract]
   
9. Milei J, Mautner B, Storino R, Sanchez JA, Ferrans VJ. Does Chagas disease exist as an undiagnosed form of cardiomyopathy in the United States? Am Heart J. 1992; 123: 1732–1735.[CrossRef][Medline] [Order article via Infotrieve]
   
10. Parada H, Carrasco HA, Añez N, Fuenmayor C, Inglessis I. Cardiac involvement is a constant finding in acute Chagas disease: a clinical, parasitological and histopathological study. Int J Cardiol. 1997; 60: 49–54.[CrossRef][Medline] [Order article via Infotrieve]
    
11. Carme B, Aune I, Nguyen G, Aznar C, Beaudet B. Four cases of acute chagasic myocarditis in French Guiana. Am J Trop Med Hyg. 2001; 64: 162–163.[Abstract]
    
12. Pinto AY, Valente SA, Valente Vda C. Emerging acute Chagas disease in Amazonian Brazil: case reports with serious cardiac involvement. Braz J Infect Dis. 2004; 8: 454–460.[Medline] [Order article via Infotrieve]
    
13. 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: 716–724.[CrossRef][Medline] [Order article via Infotrieve]
    
14. Suarez JA, Puigbó JJ, Nava-Rhode JR, Valero JA, Gil-Yepez C. Pathological study of 210 cases of cardiomyopathies in Venezuela. Acta Med Venez. 1968; 15: 320–330.
    
15. Higuchi ML. Chronic chagasic cardiopathy: the product of a turbulent host-parasite relationship. Rev Inst Med Trop Sao Paulo. 1997; 39: 53–60.[Medline] [Order article via Infotrieve]
    
16. Hagar JM, Rahimtoola SH. Chagas heart disease. Curr Prob Cardiol. 1995; 20: 825–928.[Medline] [Order article via Infotrieve]
    
17. Moia B, Rosenbaum MB, Hojman D. Ventricular aneurysms in chronic chagasic myocarditis. Rev Arg Cardiol. 1955; 22: 113–150.
    
18. Andrade ZA. Pathologic anatomy of Chagas disease. Rev Goiania Med. 1958; 4: 103–119.
    
19. Oliveira JS, Mello De Oliveira JA, Frederigue U Jr, Lima Filho EC. Apical aneurysm of Chagas heart disease. Br Heart J. 1981; 46: 432–437.[Abstract/Free Full Text]
    
20. Puigbó JJ, Nava-Rhode JR, García-Barrios H, Suárez JA, Gil-Yepes C. Clinical and epidemiologic study of chronic heart involvement in Chagas disease. Bull WHO. 1966; 34: 655–669.[Medline] [Order article via Infotrieve]
    
21. Carrasco HA, Barboza JS, Inglessis G, Fuenmayor A, Molina C. Left ventricular cineangiography in Chagas disease: detection of early myocardial damage. Am Heart J. 1982; 104: 595–602.[CrossRef][Medline] [Order article via Infotrieve]
    
22. Espinosa RA, Carrasco HA, Belandria F, Fuenmayor AM, Molina C, González R, Martinez O. Life expectancy analysis in patients with Chagas disease: prognosis after one decade (1973–1983). Int J Cardiol. 1985; 8: 45–56.[CrossRef][Medline] [Order article via Infotrieve]
    
23. Kuschnir E, Sgammini H, Castro R, Evequoz C, Ledesma R, Brunetto J. Evaluation of cardiac function by radioisotopic angiography, in patients with chronic Chagas cardiopathy. Arq Bras Cardiol. 1985; 45: 249–256.[Medline] [Order article via Infotrieve]
    
24. Hunt SA. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005; 46: e1–e82.[Free Full Text]
    
25. Acquatella H, Schiller NB, Puigbó JJ, Giordano H, Suárez JA, Casal H, Arreaza N, Valecillos R, Hirschhaut E. M-mode and two dimensional echocardiography in chronic Chagas heart disease: a clinical and pathologic study. Circulation. 1980; 62: 787–799.[Free Full Text]
    
26. Migliore RA, Adaniya ME, Tamagusuku H, Lapuente A. Assessment of diastolic function in Chagas disease with pulsed Doppler tissue imaging. Arch Cardiol Mex. 2004; 74: 31–38.[Medline] [Order article via Infotrieve]
    
27. Câmara EJN. Segmental changes in contractility of the left heart ventricle in Chagas cardiomyopathy with and without ventricular dilatation. Arq Bras Cardiol. 1993; 60: 151–155.[Medline] [Order article via Infotrieve]
    
28. Acquatella H. Present situation of Chagas disease in Venezuela and therapeutic management. Gac Med Caracas. 2003; 111: 136–156.
    
29. Nunes MCP, Barbosa MM, Rocha MOC. Peculiar aspects of cardiogenic embolism in patients with Chagas cardiomyopathy: a transthoracic and transesophageal echocardiographic study. J Am Soc Echocardiogr. 2005; 18: 761–767.[CrossRef][Medline] [Order article via Infotrieve]
    
30. Acquatella A, Catalioti F, Gomez-Mancebo JR, Dávalos V, Villalobos L. Long-term control of Chagas disease in Venezuela: effects on serologic findings, electrocardiographic abnormalities, and clinical outcome. Circulation. 1987; 76: 556–562.[Abstract/Free Full Text]
    
31. Viotti RJ, Vigliano C, Laucella S, Lococo B, Petti M, Bertocchi G, Ruiz Vera B, Armenti B. Value of echocardiography for diagnosis and prognosis of chronic Chagas disease cardiomyopathy without heart failure. Heart. 2004; 90: 655–660.[Abstract/Free Full Text]
    
32. Rodriguez-Salas LA, Klein E, Acquatella H, Catalioti F, Dávalos V, Gomez-Mancebo JR, Gonzalez H, Bosch F, Puigbó JJ. Echocardiographic and clinical predictors of mortality in chronic Chagas disease. Echocardiography. 1998; 15: 271–278.[Medline] [Order article via Infotrieve]
    
33. Pereira-Barreto AC, Serro-Azul LG, Mady C, Ianni BM, Vianna CB, Belloti G, Pileggi F. Indeterminate form of Chagas disease: a polymorphic disease. Arq Bras Cardiol. 1990; 55: 347–353.[Medline] [Order article via Infotrieve]
    
34. Xavier SS, de Sousa AS, do Brasil PEAA, Gabriel FG, de Holanda MT, Hasslocher-Moreno A. Apical aneurysm in the chronic phase of Chagas disease: prevalence and prognostic value in an urban cohort of 1053 patients. SOCERJ. 2005; 18: 351–356.
    
35. Ortiz J, Pereira-Barreto AC, Matsumoto AY, Mônaco CAF, Ianni BA, Marotta RHQ, Mady C, Bellotti G, Pileggi F. Segmental contractility changes in indeterminate form of Chagas disease: echocardiographic study. Arg Bras Cardiol. 1987; 49: 217–220.
    
36. Patel AR, Lima C, Parro A, Arsenault M, Vannan MA, Pandian NG. Echocardiographic analysis of regional and global left ventricular shape in Chagas cardiomyopathy. Am J Cardiol. 1998; 82: 197–202.[CrossRef][Medline] [Order article via Infotrieve]
    
37. Maciel BC, de Almeida-Filho OC, Schmidt A, Marin-Neto JA. Ventricular function in Chagas heart disease. Sao Paulo Med J. 1995; 113: 814–820.[Medline] [Order article via Infotrieve]
    
38. Ianni BM, Arteaga E, Frimm CC, Barreto ACP, Mady C. Chagas heart disease: evolutive evaluation of electrocardiographic and echocardiographic parameters in patients with the indeterminate form. Arq Bras Cardiol. 2001; 77: 59–62.[Medline] [Order article via Infotrieve]
    
39. Xavier SS, Sousa AS, Hasslocher-Moreno A. Application of the new classification of cardiac insufficiency (ACC/AHA) in chronic Chagas cardiopathy: a critical analysis of the survival curves. SOCERJ. 2005; 18: 227–232.
    
40. Quiñones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002; 15: 167–184.[CrossRef][Medline] [Order article via Infotrieve]
    
41. Barros MVL, Rocha MOC, Ribeiro ALP, Machado FS. Doppler tissue imaging to evaluate early myocardium damage in patients with undetermined form of Chagas disease and normal echocardiogram. Echocardiography. 2001; 18: 131–136.[CrossRef][Medline] [Order article via Infotrieve]
    
42. Barros MVL, Ribeiro ALP, Santana-Machado F, Rocha MOC. Doppler tissue imaging to assess systolic function in Chagas disease. Arq Bras Cardiol. 2003; 80: 36–40.[Medline] [Order article via Infotrieve]
    
43. Barros MV, Machado FS, Ribeiro AL, Da Costa Rocha MO. Detection of early right ventricular dysfunction in Chagas disease using Doppler tissue imaging. J Am Soc Echocardiogr. 2002; 15: 1197–1201.[CrossRef][Medline] [Order article via Infotrieve]
    
44. Acquatella H, Pérez J, Condado JA, Sánchez I. Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas disease. J Am Coll Cardiol. 1999; 33: 522–529.[Abstract/Free Full Text]
    
45. Almeida-Filho OC, Maciel BC, Schmidt A, Pazin-Filho A, Marin-Neto JA. Minor segmental dyssynergy reflects extensive myocardial damage and global left ventricle dysfunction in chronic Chagas disease. J Am Soc Echocardiogr. 2002; 15: 610–616.[CrossRef][Medline] [Order article via Infotrieve]
    
46. Maciel BC, Almeida-Filho OC, Schmidt A, Marin-Neto JA. Ventricular function in Chagas heart disease. Sao Paulo Med J. 1995; 113: 814–820.[Medline] [Order article via Infotrieve]
    
47. Marin-Neto JA, Bromberg-Marin G, Pazin-Filho A, Simoes MV, Maciel BC. Cardiac autonomic impairment and early myocardial damage involving the right ventricle are independent phenomena in Chagas disease. Int J Cardiol. 1998; 65: 261–269.[CrossRef][Medline] [Order article via Infotrieve]
    
48. Nunes MCP, Barbosa MM, Brum VAA, Rocha MOC. Morphofunctional characteristics of the right ventricle in Chagas dilated cardiomyopathy. Int J Cardiol. 2004; 94: 79–85.[CrossRef][Medline] [Order article via Infotrieve]
    
49. Rochitte CE, Oliveira PF, Andrade JM, Ianni BM, Parga JR, Ávila LF, Kalil-Filho R, MD, Mady C, Meneghetti JC, Lima JAC, Ramires JAF. Myocardial delayed enhancement by magnetic resonance imaging in patients with Chagas disease: a marker of disease severity. J Am Coll Cardiol. 2005; 46: 1553–1558.[Abstract/Free Full Text]
    
50. Combellas I, Puigbó JJ, Acquatella H, Tortoledo F, Gomez JR. Echocardiographic features of impaired left ventricular diastolic function in Chagas heart disease. Br Heart J. 1985; 53: 298–309.[Abstract/Free Full Text]
    
51. Migliore RA, Guerrero FT, Armenti A, Fernández C, Adaniya ME, Iannariello J, Tamagusuku H, Mouzo G, Baudino C, Posse R. Diastolic function in Chagas disease. Medicina (B Aires). 1990; 50: 537–542.[Medline] [Order article via Infotrieve]
    
52. Barros MVL, Rocha MOC, Ribeiro ALP, Machado FS. Tissue Doppler imaging enables the identification of diastolic dysfunction of pseudonormal pattern in Chagas disease. J Am Soc Echocardiogr. 2001; 14: 353–359.[CrossRef][Medline] [Order article via Infotrieve]
    
53. Adaniya ME, Migliore RA, Miramont G, Barranco M, Guerrero FT, Tamagusuku H. Influence of apical segmental dysfunction in the spatio-temporal velocity propagation of mitral inflow: a color M-mode Doppler study. J Am Soc Echocardiogr. 2000; 13: 473. Abstract.
    
54. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, Tajik AJ, Seward JB. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function study in normals and dilated cardiomyopathy. J Cardiol. 1995; 26: 357–366.[Medline] [Order article via Infotrieve]
    
55. Yacoub S, Birks EJ, Slavik Z, Henein M. Early detection of myocardial dysfunction in Chagas disease using novel echocardiographic indices. Trans R Soc Trop Med Hyg. 2003; 97: 528–534.[CrossRef][Medline] [Order article via Infotrieve]
    
56. Silva CE, Ferreira LD, Peixoto LB, Monaco CG, Gil MA, Ortiz J, Ianni BM, Andrade JL, Mathias W Jr, Barretto AC. Evaluation of segmentary contractility in Chagas disease by using the integral of the myocardial velocity gradient (myocardial strain) obtained through tissue Doppler echocardiography. Arq Bras Cardiol. 2005; 84: 285–291.[Medline] [Order article via Infotrieve]
    
57. Salles G, Xavier S, Sousa A, Hasslocher-Moreno A, Cardoso C. Prognostic value of QT interval parameters for mortality risk stratification in Chagas disease: results of a long-term follow-up study. Circulation. 2003; 108: 305–312.[Abstract/Free Full Text]
    
58. Salles GF, Cardoso CLR, Xavier SS, Sousa AS, Hasslocher-Moreno A. Electrocardiographic ventricular repolarization parameters in chronic Chagas disease as predictors of asymptomatic left ventricular systolic dysfunction. Pacing Clin Electrophysiol. 2003; 26: 1326–1335.[CrossRef][Medline] [Order article via Infotrieve]
    
59. Bestetti RB, Dalbo CM, Freitas OC, Teno LA, Castilho OT, Oliveira JS. Noninvasive predictors of mortality for patients with Chagas heart disease: a multivariate stepwise logistic regression study. Cardiology. 1994; 84: 261–267.[Medline] [Order article via Infotrieve]
    
60. Mady C, Cardoso RH, Barretto AC, da Luz PL, Bellotti G, Pileggi F. Survival and predictors of survival in patients with congestive heart failure due to Chagas cardiomyopathy. Circulation. 1994; 90: 3098–3102.[Abstract/Free Full Text]
    
61. da Silva Menezes A. Outcome of right ventricular bifocal pacing in patients with permanent atrial fibrillation and severe dilated cardiomyopathy due to Chagas disease: three years of follow-up. J Interv Card Electrophysiol. 2004; 11: 193–198.[CrossRef][Medline] [Order article via Infotrieve]
    
62. Cardinalli-Neto A, Greco OT, Bestetti RB. Automatic implantable cardioverter-defibrillators in Chagas heart disease patients with malignant ventricular arrhythmias. Pacing Clin Electrophysiol. 2006; 26: 467–470.
    
63. Szajnbok FE, Barretto AC, Mady C, Parga Filho J, Gruppi C, Alfieri RG, da Luz PL, Pileggi F. Beneficial effects of enalapril on the diastolic function in Chagas cardiomyopathy. Arq Bras Cardiol. 1993; 60: 273–278.[Medline] [Order article via Infotrieve]
    
64. Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, Postan M, Armenti A. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Int Med. 2006; 144: 724–734.[Abstract/Free Full Text]
    

This article has been cited by other articles:

				C. Bern, S. P. Montgomery, B. L. Herwaldt, A. Rassi Jr, J. A. Marin-Neto, R. O. Dantas, J. H. Maguire, H. Acquatella, C. Morillo, L. V. Kirchhoff, et al. Evaluation and Treatment of Chagas Disease in the United States: A Systematic Review JAMA, November 14, 2007; 298(18): 2171 - 2181. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar