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Magnetic Resonance Imaging of
Chagas' Disease

Carlos Eduardo Rochitte, MD; Ricardo de Hollanda, MD;
Paulo Fabiani de Oliveira, MD; Maria de Lourdes Higuchi, MD;
José Rodrigues Parga, MD;
Luiz Francisco Rodrigues de Ávila, MD;
José Antonio F. Ramires, MD

Cardiovascular Magnetic Resonance Laboratory, Heart Institute (InCor),
University of São Paulo Medical Scholl, São Paulo, Brazil

INTRODUCTION
   Chagas' disease is a chronic infectious disease endemic in the Americas, and is found from the south of the United States to the south of Argentina and Chile. The World Health Organization estimates that 25 % of Latin America population (90 million people) is at risk of acquiring the disease and 16 million individuals are infected. (1)

   Despite of this high prevalence, not all infected individuals develop heart disease. Dias (2) reports that between 25% to 35% of patients with Chagas disease suffer from cardiac involvement, and most of them present only minor symptoms. Only 10 % of patients have significant heart disease. (2, 3)

   Early studies by Carlos Chagas showed that roughly 60 % of patients with this disease present the undetermined form. This phase of the disease is characterized by positive serologic reactions for T. cruzi, lack of symptoms, normal electrocardiogram (ECG), normal chest x-ray, and normal barium studies of esophagus and colon. (4)

   Our knowledge about the cardiac involvement of this disease evolved parallel to the development of new methods of investigation in cardiology. Some studies, which employed new modalities of diagnosis, showed abnormalities in many patients with the undetermined form, most of the time mild. (5, 6)

   Fortunately most patients classified as with the undetermined form do not progress to symptomatic disease. (7) Many prognostic factors have been identified, but the determinants of the evolution of the disease are not fully known.

   Magnetic resonance imaging (MRI) is a non-invasive method that does not use ionizing radiation. Its versatility and spatial resolution allows us to study multiple aspects of cardiac anatomy and function. One of the most important goals of MRI investigations on Chagas' disease is to identify early signs of the heart involvement and new prognostic factors. To achieve these goals MRI will need to use its high spatial resolution and tissue contrast capabilities. In the following sections we will talk about different MRI techniques and their use in patients with Chagas' disease.

STANDARD MRI TECHNIQUES
   ECG-gated spin echo images give us good anatomical images of the heart and are within the capabilities of most MRI equipment. Enlargement of the ventricles and thinning of their walls can be adequately detected by this technique. Other pulse sequences, like double inversion recovery and triple inversion recovery fast spin-echo produce even better anatomical images, and are currently used in our laboratory. These new techniques allow for high-resolution multiplane short and long axis of the heart with blood suppression (double IR) and fat saturation (Triple IR). With these techniques we can see myocardial thinning clearly (Figure 1 - Note the distinct wall thinning on the inferior basal left ventricle wall (arrows))

Figure 1

   ECG-gated fast gradient echo sequences (cine-MRI) are traditionally used for the study of cardiac function. These images allow the analysis of global ventricular function with accurate measurement of ventricular volumes, ejection fraction and stroke volumes, and are nowadays considered the gold standard for global cardiac function. The reproducibility of function indices is better than with echocardiography, allowing better follow-up of patients. Regional function can be analyzed subjectively (visual analysis of wall motion) or quantitatively (quantification of wall thickening). In addition one can easily detect aneurysms and wall thinning. Valvar insufficiency or stenosis may also be detected with this technique, particularly if associated with phase contrast imaging, allowing for flow velocity measurements.

   The technique of myocardial tissue tagging is particularly useful to the detection and analysis of regional dysfunction. This technique allows the visualization of the deformation of tag lines within the myocardium, making possible visualization and measurement of the deformation of discrete myocardium segments through the cardiac cycle. Beyond the subjective analysis of the images, dedicated software (e.g. Findtags, HARP) has been successfully developed and used for quantitative analysis of systolic function in two and three-dimensional modes. In our laboratory, the protocol for myocardium tagging includes 6 to 8 slices in the short axis of the heart and 4 slices in the long axis, and the tagging lines are 7 mm apart. The entire examination takes no longer than 20 minutes.

FINDINGS OF MRI IN CHAGAS' DISEASE
   Cardiac involvement is the main determinant of prognosis in Chagas' disease. Thus the accurate evaluation of the heart is fundamental for the care of the individual patient.

   Approximately 30 to 40 % (8) of infected persons will develop cardiac abnormalities during their lifetimes, but only 10 to 20 % will present symptomatic cardiac involvement. Thus, most patients with cardiac involvement can be identified only through ECG or other studies.

   Classically, Chagas' disease is divided in three phases: acute, undetermined, and chronic. The distinction between the undetermined and chronic phase is based in the absence or presence of symptoms, ECG abnormalities, augmented heart size detected by chest x-ray, and overt cardiac failure. A large percentage of patients in the undetermined phase have definite evidence of cardiac involvement detected only by detailed noninvasive evaluation. (4) Based on this fact, a newer and more detailed classification, that takes into account more subtle abnormalities, was proposed in 1992 (see table1). (9)

Table 1


   Recently, our group at Heart Institute has seriously studied Chagas's disease pathophysiology. We clearly demonstrated differences between Chagas' heart disease and idiopathic dilated cardiomyopathy. We have shown that hearts with Chagas' disease exhibited severe diffuse fibrosis and arteriolar dilatation with organized thrombi. (10) Those findings led to the hypothesis that ischemic myocardial lesions could explain the severity of diffuse fibrosis and lesions like the aneurysm of left ventricle apex and inferior-basal LV wall ( Figure 2, note the hachures denoting the ischemic areas in watershed myocardial regions). (11)

Figure 2

   Bocchi et al and Kalil et al studied the correlation among cardiac magnetic resonance imaging (MRI), gallium-67 myocardial uptake, and right ventricular endomyocardial biopsy results in chronic Chagas' disease. (12, 13) They found that myocarditis is frequently found in Chagas' disease.

   The findings at MRI studies are dependent on the extent of myocardial involvement, and may help the classification of individual patients.

   Heart disease caused by T. cruzi may have a wide variety of clinical manifestations, but all are the result of segmental myocardial damage. When myocardial damage is small, ventricular abnormalities may be absent by less accurate methods. With more extensive damage, small areas of wall motion abnormalities may be evident. Patients with this finding would be classified as Stage IB. MRI can visualize these areas, and the intensity of the abnormalities can be quantified. Myocardial tagging seems particularly suitable for detection of subtle segmental abnormalities. It is important to notice that segmental wall motion abnormalities precede symptoms, heart enlargement, and even ECG abnormalities, being henceforth the first detectable manifestation of heart involvement in Chagas' disease. Of patients with normal ECG, 40 % who would be classified as in undetermined phase had mild apical wall-motion abnormalities. (14)

   Progressive myocardial damage leads to more severe segmental abnormalities with localized areas of thinning, hypokinesis or akinesis frequently present, and to aneurysm formation. The capability of showing wall thinning and wall motion abnormalities enables the easy visualization of the typical narrow-neck aneurysm at the apex of the left ventricle, and of aneurysms at other locations as well (see Figure 1). An example of left ventricle apical aneurysm (the vortex lesion) is shown on the movie (see movie showing a cine-MRI sequence with two long axis planes, in which we can clearly see an aneurysm at left ventricle apex). The apical aneurysm is a common place of formation of thrombi, although they may occur at other sites. MRI clearly depicts thrombi in both ventricles.

Movie

   More extensive myocardial involvement leads to global ventricular dysfunction, which can be detected and quantified by fast cine MRI techniques. The good reproducibility of ejection fraction measured by MRI allows follow-up of the progression of the disease. The detection of an abnormal ejection fraction is an ominous finding, since left ventricle global function is one of the main determinants of prognosis. Mady et al 15 found ejection fraction as one of the main determinants of death in a group of patients with the chronic form of the disease. Pereira Barreto et al (16) attributed the worst prognosis in men at least partially to LV dysfunction, which is more common among males.

   Congestive heart failure and enlargement of left ventricle are late manifestations of Chagas' disease. The development of congestive heart failure signals a poor prognosis, with survival around 47 % two years after its beginning. (17) At this stage of the disease cine images show global dysfunction and wall thinning, and may show valve regurgitation caused by the severe enlargement of ventricles.

NEW MRI PERSPECTIVES
   At our MRI laboratory, we have been working in new techniques to enhance evaluation of Chagas' heart disease. Recently a new dynamic pulse sequence, using extremely short TRs in a steady state acquisition is being used in our institution (FIESTA), allowing for cine MRI with high signal to noise ratio and contrast to noise ratio between myocardium and blood pool. The new technique is faster and has increased temporal resolution, leading to the possibility of diastolic function evaluation. This also allowed for more precise and automatic detection of left ventricle volumes and ejection fraction. On the function evaluation, our laboratory just start to investigate the use of three dimensional cine acquisitions in just one breath-hold for Chagas' disease.

   Beyond the function evaluation, we started to investigate the myocardial tissue characterization by MRI using new developed techniques, which we believe will further improve our understanding of the complex pathophysiology of Chagas' disease.

CONCLUSIONS
   Therefore, recent developments on cardiac MRI technology should and is being used to detect and quantify early signs of cardiac involvement that can be of prognostic information. This is already being routinely done by detailed evaluation of cardiac function, using myocardial tagging and high-resolution cine-MRI. New techniques are now being developed to investigate other facets of Chagas' disease by MRI.

   Our opinion is that MRI can be in the future a screening for very early myocardial involvement by Chagas' disease. This would allow the investigation of new therapeutic methods to change the natural history of Chagas' disease.

REFERENCES

1. WHO Expert Committee: World Health Organization. Control of Chagas' disease. WHO technical report series 1991;811:1-95

2. Dias JCP: Profilaxia e impacto médico-social da Doença de Chagas na região mineira do polígono das secas. Rev Goiana Med 1982;28:97-102

3. Elizari MV, Chiale PA: Cardiac arrhythmias in Chagas' heart disease. J Cardiovasc Electrophysiol 1993;4:596-608

4. Pereira Barreto AC, Serro Azul LG, Mady C, Ianni BM, Vianna CB, Bellotti G, Pileggi F: Forma indeterminada da doença de Chagas: uma doença polimórfica. Arq Bras Cardiol 1990;55:347-353

5. Ortiz J, Pereira Barreto AC, Matsumoto AY, Monaco CAF, Ianni BM, Marotta RHQ, Mady C, Bellotti G, Pileggi F: Alteração contrátil segmentar na forma indeterminada da Doença de Chagas. Estudo ecocardiográfico. Arq Bras Cardiol 1987;49:217-220

6. Mady C, Moraes AV, Galiano N, Décourt L: Estudo hemodinâmico na forma indeterminada da Doença de Chagas. Arq Bras Cardiol 1982;38:271-275

7. Ianni BM, Mady C: A forma indeterminada da doença de Chagas. Mitos versus fatos. Arq Bras Cardiol 1997;68:147-148

8. Laranja FS, Dias E, Nobrega G, Miranda A: Chagas' disease: a clinical, epidemiologic, and pathologic study. Circulation 1956;14:1035-1059

9. Puigbo JJ, Giordano H, Suarez C, Acquatella H, Combellas I: Clinical aspects in Chagas' disease, in Madoery RJ, Madoery C, Camera MI (eds): Actualizaciones en la enfermedade de Chagas. Buenos Aires, Organismo oficial del congreso nacional de medicina, 1992, pp 27-38

10. Higuchi MdL, Fukasawa S, De Brito T, Parzianello LC, Bellotti G, Ramires JAF: Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas' disease: a three dimensional confocal microscopy study. Heart 1999;82:279-285

11. Higuchi MdL: Human chronic chagasic cardiopathy: participation of parasite antigens, subsets of lymphocytes, cytokines nd microvascular abnormalities. Mem Inst Oswaldo Cruz 1999;94:263-267

12. Bocchi EA, Kalil R, Bacal F, Higuchi MdL, Meneghetti C, Magalhães A, Bellotti G, Ramires JAF: Magnetic Resonance Imaging in Chronic Chagas' Disease: Correlation with Endomyocardial Biopsy Findings and Gallium-67 Cardiac Uptake. Echocardiography 1998;15:279-288

13. Kalil R, Bocchi EA, Ferreira BM, Higuchi MdL, Lopes NH, Magalhães A, Mady C, Pereira Barreto AC, Albuquerque CP, Bellotti G: Magnetic resonance imaging in chronic Chagas cardiopathy. Correlation with endomyocardial biopsy findings. Arq Bras Cardiol 1995;65:413-416

14. Carrasco H, Barboza JS, Inglessis G, Fuenmayor AM, Molina C: Left ventricular cineangiography in Chagas' disease: detection of early myocardial damage. Am Heart J 1982;104:595-602

15. 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;90:3098-3101

16. Pereira Barreto AC, Arteaga E, Mady C, Ianni BM, Bellotti G, Pileggi F: Sexo masculino. Fator prognóstico na doença de Chagas. Arq Bras Cardiol 1993;60:225-227

17. Espinosa R, Carrasco H, Belandria F, Fuenmayor AM, Molina C, Gonzalez R, Martinez O: Life expectancy analysis in patients with Chagas' disease: prognosis after one decade (1973-1983). Int J Cardiol 1985;8:45-56

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
President
Dr. Raúl Bretal
Scientific Committee
President
Dr. Armando Pacher
Technical Committee - CETIFAC
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