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Risk of death due to chronic chagasic cardiopathy

Dr. Enrique C. Manzullo

Centro de Investigaciones Epidemiológicas
Academia Nacional de Medicina
Argentina

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Introduction
Materials and methods
Results
Discussion
Abstract
References

Introduction

In this longitudinal study 5710 people were included .The inclusion criteria were 2 positive serological results for Trypanosoma Cruzi infection, 15 and 50 years old and no other demostrable diesease at the time of study. In the five year follow up 1117 patients were lost. The follow up involved yearly evaluation of serology, clinical examination, Xray of torax, and ECG, for 4593 patients and 263 were contacted at home because they did not assist for their clinical consultant.Time average of follow up was 5.3 years.

Eighty nine (1.5%) of the 4593 patients died during the follow up period., 63 (71%) by Cardiac Insufiency (CI) and 26 (29%) by severe ventricular arrithmias. Diagnosis of Cardiomegaly was present in all the patients with diagnosis of CI and in 15 (5%) of the patients with diagnosis of arrithmias.The E.C.G. alterations of these pacients show : 61 RBBB, associated or not with LAHB, 47 patological Q wave and 70 primary repolarization alterations; 61 had polifocal Ventricular arrithmia. The death rate was similar in the sexes and was more frequent between 40 and 50 years of age. Information on 1380 recuperated patients shows that 15 died with no previous symptoms and without medical assistance and were interpretate as sudden death. The latest ECG in thre follow up of these pacients indicate (before death) that only one had normal study and 14 presented: 12 RBBB; 9 LAHB ; 7 isolated ventricular arrithmia ; 10 Repolariz. Trastorns ; 2 Patolgical Q wave . 10 patients of them with RBBB and Repolariz. Trastorns. In all the cases we had people between 35 and 43 years old, 9 men and 6 women.

This study shows that in Chagas disease is possible to differenciate two risk groups.A low risk death goup that have normal ECG.and clinical evaluation during the follow up, and a high risk group associate E.C.G with RBBB and primary alterations of repolarization and/or inactivation zones with not anual clinical evaluation. Despite numerous studies examining the parasite vector host and environmental factors involved in Chagas disease ( Prata 1983, Alderete 1982) our knowledge of this condition is not yet completed .

Taking in account the longitudinal study is the best method to make apports to the aknowledge of this sickness, of it´s risks, evolutive tendences and way of manisfestation,we have done it in the Cátedra de Enfermedades Infecciosas , de la Facultad de Ciencias Médicas de la Universidad de Buenos Aires ( UBA), Argentina, this study about chagasic cardiopathy. The investigation was due to the aknowlegde of chronic chagasic evolution cardiopathy , for residents outside the endemic zone with the following studies: clinical medical, X- ray, and E.C.G. after a follow-up of 10 years.

It was considered that a longitudinal study out side an endemic zone was possible and useful , because it can address the issue of "urbanization " of this sickness and possibly give us more information to confront it, in combination with the knowledge we have from endemic zone. To make possible this purpose , we should start with the basic questions that makes definition by itself and its escence, they were already considered when the project was made and were respected during the development. They are the following :

1)sample characterization.
2) Definition and application of criteria for inclusion and exclusion
3) Details of the techinique utilized and criteria for the interpretation
4) Presentation of advanced stage
5) Periodic evaluation of the results from the different National and International Organizations vinculated with these subject. In this case we can mention the Instituto Nacional de Investigaciones Cardiovasculares, la secretaría de Ciencia y Técnica de la Nación, HWO y OPS.

The Doctors. Romeu Cancando, ( Profesor Catedratico de Terapeútica Clínica, Facultad de Medicina, Universidad Federal de Minas Gerais) y Vanize Macedo (Profesora de Medicina Tropical , Universidad de Brasilia) agreed to assess us because of an OPS request. Their presence made us scientifically stronger, permiting us to make corrections on time and they gave us their talent and friendship until today.

In the present report we only consider those patients who died during the study.

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Materials and methods

Two cardiologic consultories were installed with a secretary looking after them five hours per day from Monday till Friday. Two specialities were required from the professionals: Specialist in Cardiology and in Infection sickness. The technical operation staff were trained to: obtain information, obtain E.C.G. and back up. Clinical histories and cards were designed and numerated as complementary information. This number was given to the patient. We had books with double entries: by correlative number, by date of entrance and surname of father and mother of the patients.

1) People came in, by blood bank diagnosis, because they were familiar of the people assisted and had positive serology for Chagas disease confirmed by our center. They did not assist by cardiological derivation. All of them had at least two positive serological reaction for Chagas disease: One of them was Inmunofluorescence.

2) They were asked: 2a: sex; 2b: age 2c: birth place (country, province, department, city ); 2d: other resident place (three years or more in the same place); 2e: employee functions; 2f: personal and family backgrounds specially with relation to Triatoma Infestans; 2g: Epidemiologic, cardiologic, neurologic, endrocrinologic and digestive background; 2h: Home characteristics and ecological aspects; 2i: other sickness.

3) General clinical examination with relationship to the points 2g: background.

4) Basal E.C.G of 12 derivations.For the electrocardiographic diagnosis we began using Minessota (Rose 1968) code adding to it hemiblocks (Rosembaum 1965). For the final analisys of these E.C.G. the parameters became from Nomenclatura y criterios de diagnóstico electrocardiográfico - Programa de Salud Humana (Rosembaum 1982).

5) Chest X Ray (1.80 mt distance) Maximum cardiac silohuette accepted as normal was the relation cardiothoraccic less than 0.5

6) Electroencefalogram when headache was present

7) Oesophagus transit, gastrointestinal or colon in dysphagia, regurgitation and constipation of 3 or 4 days with interval egest as minimun.

8) Everybody was called for consultant at least once in a period of six months, even those who have non demonstrable disease.

9) Serological and electrocardiographical studies were done twice. The first yearly, the second one at each consultation.

With periodicity the results were statistically validated. Data that were not in the original project (new technique, concommitant sickness, new therapeutic) were the basis for other investigations without modifying the original scheme of this study. To have a better characterization of the population sample, a social study of it was done, with predesigned interviews that were done by a Doctor in Sociology with experience in Chagas disease.

In the larger follow-up of an open population, movement of the population is a reality we can not dismiss. It`s level increases over time, putting in danger the success of the study.

Trying to have less people lost and obtain more information from them we had several strategies, for example, giving them whole health attention in the same hospital, and not only the follow-up of their Chagas disease, not generate more difficulties giving them dates too further in time for their assistance, giving them all the medicine they needed free of charge, and making for them some cerficates of their assistance in hospital, dating them by letter to their homes or to their working place, therefore obtaining more effective attention on all the familiar group. This let us have more information on patients that abandoned follow-up, to each person we insisted to bring with him living family members with Chagas disease or to do the serological study when they were born in endemic zones, teaching them the importance of a periodic control.We asked them at each opportunity about the people they know in the follow-up, giving dates to those who did not assist or at least having information about people that move out of the study.

1) We studied the evolution of electrocardiografic trastorns of those infected people that began with normal E.C.G and those that presented alterations in their first consult.

2) They were identified by sex and age, the groups of highest risk by electrocardiographical evolution and risk of death.. We've done a study of hospitalized dead people in our center, and in other institutions too and we elaborate a sudden death hypothesis.

3) The death results of our population were compared with those of the Programa Nacional de Salud para la Argentina.

4) Evolutive similarity was established between the group of positive people treated with parasitological medicine and the group without treatment.

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Results

5710 persons were included that should have completed the five years of follow-up.4330 among those did it and 1117 did not ( see Fig. 1)

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From the total of the follow- up 89 hospitilied patients died with the etarea distribution shown in figure 2. Of them among those 26 died by

fig2.jpg (37116 bytes)

arrhythmias and in 63 the cause was cardiac insufiency refractory to the conventional treatments. All of them had cardiomegaly in chest X-ray and patological E.C.G. (Fig. 3)

fig3.jpg (32194 bytes)

In figure 4 we distinguish that 89 patients dead represent the 1.5%of the total study population. Indeed 23 persons died during the follow-up by causes not imputable to Chagas disease .(accidents , tumours, and several identified causes) These add 0.4% to the general mortality of the group. (Fig.4)

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As we had said in methodology, we made every effort to ensure that patients attended their consultaries or at least to determine the reasons for their abandonment.

1117 did not complete the five years follow-up (19,5%). Of 263 we know the causes of their abandonment : change of geographical place, non intereste, attended in other places and 15 died , we were told by their familiars. They did not needed medical assistance during the previous 24 hours before death and is interpretated as sudden death.

The analysis of the last studies of dead people by sudden death give us results: one had normal E.C.G. and this represents the 0.0017 of the sample and a year rate mortality of 0.004%year. Another patient with Pacemaker indication refused to do treatment. The rest of the 13 patients left had in their last obtained E.C.G: Right Bundle Branch Block (RBBB) Left Anterior HemiBlock (LAHB), Repolarization primary trastorns, inactivation zones, and in some cases isolated ventricular arrhythmias and low voltage.All of them died between 35 and 45 years old (see figure 5)

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Discussion

Infected people with normal E.C.G. presented a low risk of death (0.0045).We believe that this electrocardiographical result is a good prediction indicator . But periodic controls must be done.

Indicator of bad prediction resulted to be for the people with the following associated E.C.G. alterations RBBB,LAHB, repolarization primary trastorns, inactivations , with or without arrhythmias having or not low voltage, This group of patients had a yearly mortality rate of 10% and is defined as a high risk group.

We permit ourselves to expose our Sudden Death Hypotesis .(see figure 6). We try to obtain information about the 1380 people that abandon follow-up with Social visitors, by letter, by information given by their parents.

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Of 1117 we received our letters back because destination was not found, whole families change of place, largest places with precary homes that were thrown away, and other ones we could not reach because we did not have enough monney. If we consider this group had similar destination as the 263 of which we obtain information we arrive to , that the possible sudden death is of 78 persons (1.2 *1000/year). In figure 7 to have better exposition of our samples of mortality and letality we compare them with Rep.Argentine total mortality in people between 20 and 60 years old sunistred by the Programa Nacional de Estadìsticas de Salud .

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In figure number 8 we compare the mortality in the Argentine population (2.6 * 1000/year) with our study (4 *1000/year). This signifies that Chagas infected people have a greater risk of death than the rest of the population 53.8%.

fig8.jpg (62435 bytes)

We made a comparison of our results wtih longitudinal studies of: Dra. Macedo (1980), Dr. Pinto Dias (1982) and Dr. Puigbò (1969). We found coincidance in age of death cause by Chagas disease is between 35 and 45 years old, also, by Cardiac Insufiency or Sudden death. And that a normal E.C.G. is indicator of good prediction in Chagasic Infected people but always needs a additional periodic control.

The group that we show of high risk have severe trastorns in E.C.G. that we might consider of danger.Comes uppon Dr. Reis Lopes (1981) question: Sudden death expected or unexpected? We believe these patients should be dectected by population studies because many of them are oligosymtomatic . They can be found in the perypheria of great cities where they had migrated from rural zones. Perhaps under such circumstances, our study in non-endemic zone could be useful.

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Abstract

In this longitudinal study 5710 people were included. The inclusion criteria was 2 positive serological results for Trypanosoma Cruzi infection, 15 and 50 years old and other demostrable diesease at the time of study. In the five years follow up 1117 patients were lost. The follow up was year evaluation of serology, clinical examination, Xray of torax, and ECG, for 4593 patients and 263 were contacted at home because they did not assist for their clinical consultant.Time average of follow up was 5.3.
89 pacients from 4593 died hospitalized during the follow up , (1.5%), of them 63 (71%) by Cardiac Insufiency (CI) and 26 (29%) by severe ventricular arrithmias. Diagnosis of Cardiomegaly was present in all the pacients with diagnosis of CI and in 15 (5%) of the pacients with diagnosis of arrithmias.The E.C.G. alterations of these pacients show : 61 RBBB, associated or not with LAHB, 47 patological Q wave and 70 primary repolarization alterations; 61 had polifocal Ventricular arrithmia.
Death rate was similar in the sexes and was more frecuent between 40 and 50 years old of age.
Information of 1380 recuperated pacients shows that 15 died with not previous symptoms and without medical assistance and were interpretate as sudden death.
The latest ECG in thre follow up of these pacients indicate (before death) that only one had normal study and 14 presented: RBBB (12); LAHB (9); isolated ventricular arrithmia (7); Repolariz. Trastorns (10); Patolgical Q wave.(2) . 10 of them with RBBB and Repolariz. Trastorns. In all the cases we had people between 35 and 43 years old, 9 men and 6 women.
This study shows that in Chagas disease is possible to differenciate two risk groups. A low risk death goup that have normal ECG and clinical evaluation during the follow up, and a high risk group associate E.C.G with RBBB and primary alterations of repolarization and/or inactivation zones with not anual clinical evaluation.

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References

ALDERETE NIETO PILAR DE.1982 Versión preliminar de Bibliografía Argentina sobre Enfermedad de Chagas. Programa de Formación de Recursos Humanos Arg.
MACEDO VANISE, O 1980.Forma indeterminada de doenca de Chagas. JBM,
PINTO DIAS JUAN C, 1982. Doenca de Chagas en Bambui, Minas Gerais, Brasil. Estudo clinico epidemiologico a partir da fase aguda entre 1940 e 1982. Tesis 1982, Belo Horizonte.
PRATA A., PIRES E, DE SANT ANNA.1983 Bibliografía Brasileira sobre Doença de Chagas Brasil
PUIGBO JUAN R. Et al .1969 Cuatro años de estudio longitudinal de una comunidad rural con endimicidad chagasica. Bol Oficina Sanitaria Panam.. 66:112.
REIS LOPEZ E.: 1981. Morte súbita em área endêmica da doença de Chagas. Sua importância Médico-Legal. Tesis presentada para o concurso de Professor Titular de Medicina Legal e Deontología Médica de Facultade de Medicina do Triângulo Mineiro. Uberaba. M.G. Brasil.
ROSE G. A., BLACKBURNE H.1968 Cardio-vascular Survey Methods. Geneve O.M.S. Ser monografias. Nº 56.
ROSENBAUM M B., ELIZARI M., LAZZARI J. 1965 Los Hemibloqueos. Ed. Paidos, Bs. As.-
ROSENBAUM M.Y COL. 1995 Criterios de lectura electrocardiográficos. Programa de Formación en Recursos Humanos- Ministerio de Salud Pública Argentina. 1982. Reedición Consejo Arg de Chagas. Sociedad Arg . de Cardiología-

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Update
Mar/02/2000