A FOUR-YEAR FOLLOW-UPSURVEY OF CHAGASIC CARDIOPATHY IN CHILE1

Arturo Arribada C., 2 Werner Apt B.,3 and J. MantieZ Ugartti

I NTRODUCTION of Chagas’ disease in endemic areas and its cardiac implications. This study re- The natural history of Chaga- vealed that all previous assessmentshad sic cardiopathy is still not well-known, underestimated both the incidence of mainly because innumerable clinical pic- the disease and its socioeconomic reper- tures develop without symptoms, and cussions for the country (1-G). Respond- the casesseen at hospitals are merely the ing to these findings, health authorities most overtly serious. This circumstance may tend to create a false impression that took up the problem and adopted a this cardiopathy is relatively benign, be- number of health measures-including periodic disinsection of accessible areas cause of the small demand it generates for hospital beds in comparison with and health education at community cen- other pathologies. Hence, if it were pos- ters and primary schools. (A simple ex- sible to elucidate what happens to the planatory leaflet was produced for these great majority of asymptomatic cases, education campaigns that informed that would constitute an important for- readers about the dangers of the disease ward step in understanding a diseasethat and about ways to prevent household in- afflicts millions of people in the Ameri- festations of triatomid vectors.) We also promoted parallel C&S. In 1977 we launched a long- studies seeking to elucidate epidemio- term project in Chile that was directed at logic relationships between humans, as- investigating the epidemiologic picture sociated animals, and vector insects (7- 8); to detect different types of vectors and examine their interrelationships; %it\ and to define the structures of zymo- 1 ’ This article will also be published in Spanish in the Bo- /ehi de la Ojcina Sanitaria Panamen~ana, Volume demes in various Tgpanosoma crzzi 3 101. 1986. The work reported was financed by a grant strains found in different endemic areas % from the University of Chile and by Grant No. 820599 (9-10). x from the UNDPlWorld Bank/WHO Tropical Diseases Research Program. This article reports our experi- 3 * Associate Professor of Medicine, Paula Jaraquemada ence with long-term field followup of Hospital, Faculty of Medicine, University of Chile, cardiac pathologies observed during the 2 Southern Division, Santiago, Chile. 3 Professor of Parasitology, Department of Experimental first survey, specifically regarding 2 Medicine, Faculty of Medicine, University of Chile, a, Southern Division, Santiago, Chile. ’ Professor of Biostatistics, Faculty of Medicine, Univer- sity of Chile, Northern Division, Santiago, Chile. 245 changes in the subjects’ clinical, sero- All members of these three logic, and electrocardiographic pictures groups were given serologic tests for 1: after a lapse of four years. It also reports crzlzi antibodies at the beginning of the findings concerning the risk that people original study and again after four years exposed to chagasic infection but show- (12-15). On both occasions each serum ing a normal ECG in the original survey sample was tested by two of three sero- would subsequently develop cardiopa- logic methods, the three being indirect thy. hemagglutination (IHA), complement futation (CF), and indirect immuno- fluorescence (IIF). IHA titers above 1: 16, CF titers above 1: 5, and IFF titers above M ATERIALS 1: 20 were considered positive. AND METHODS During the fourth year after the initial survey, the year depending Our original survey begun in upon when the first survey had been car- 1977, whose data were employed in the ried out, a clinical study was conducted work reported here, involved 2,938 sub- of 481 people in the three groups; this jects who were given serologic tests and study was similar to that conducted dur- ECGs. Nearly two-thirds of these sub- ing the original survey. In addition, these jects (1,932) yielded serologic results subjects were given a twelve-lead ECG negative for chagasic infection. Four with an extended II lead for the study of hundred and two (22%) of these 1,932 . These ECGs were analyzed showed significant ECG alterations, and independently of the serologic results ac- these 402 were considered to constitute a cording to the following parameters: spa- control group hereafter referred to as tial P, QRS, and T axes; PR, RR, RS, and “Group A.” The other 1,006 subjects QT intervals; amplitude of R in Vi and yielded serologic results positive for cha- V,; intrinsecoid deflection in Vi and V6; gasic infection. Three hundred and ST-T segment; and T-wave items (Soko- ninety-one (39 % ) of these 1,006 showed low index). The electrocardiographic di- significant ECG alterations, and 298 of agnoses developed in this manner were the latter yielded findings suggesting grouped according to the guidelines pro- chagasic cardiopathy (G,ll). These 298 posed by Maguire and colleagues (IT), constituted a group designated “Group and a statistical analysis was made of the B.” As the foregoing implies, 615 (61%) differences between the groups. In addi- of the 1,006 subjects with positive sero- tion, the diagnoses were analyzed ac- logic findings had normal ECGs; these cording to the age and sex of the persons % 615 were considered to be at risk of con- 2 surveyed in the three groups during the -. tracting chagasic cardiopathy at any initial ECG. When no significant differ- 3 time. For purposes of our study, 67 of ences were found, we used the method z these 615 were selected at random, des- of diagnosis employed in the original .$ ignated “Group C,” and subjected to work (5) to which Student’s t test was u further examination. These three groups B applied. were selected in 1981 when we began the We also studied the trend of 2 followup work reported here. ECG abnormalities in groups A and B by means of time-correlation graphs, and in this manner evaluated the origins of new abnormalities. By definition, there were 246 initially no normal ECGs in groups A and B, and normalization of an abnor- mality that had been recorded on the ini- SULTS tial ECG was regarded as a change for RE purposes of statistical analysis. However, Followup of Groups A and B because we were dealing with multiple abnormalities in many ECGs, normaliza- Table 1 shows the reasons for tion of a specific condition did not neces- reduction in the numbers of subjects in sarily constitute normalization of the groups A and B during the study period. whole tracing. Of the 402 original Group A subjects All of the studies reported (people with negative serology but ab- here-performed in 1981, 1982, 1983, normal ECGs), nine (2.2 % ) died from and 1984-were carried out in the 36 vil- causes indicated below; 168 (41.8%) lages where the original sample survey moved to other areas in search of better was conducted. For reasons to be dis- financial prospects; seven (1.7%) de- cussed, by the end of four years Group A clined to be surveyed; and two (0.5%) had been reduced to 216 subjects and showed a serologic conversion from nega- Group B to 198 subjects, and so it was tive to positive for 1: C~ZLZZ’antibodies. these subjects who provided the basis for Of the 298 original Group B the comparison reported here. subjects (people with positive serology, The members of all three abnormal ECGs, and findings suggesting groups lived in rural, mostly semi-desert Chagas’ disease), 22 (7.4%) died of cha- areas of northern Chile. All were en- gasic cardiopathy; one (0.3 % ) died of gaged in farming arable land found stomach cancer; 48 (16.1% ) moved to along the courses of small rivers flowing other areas; and 29 were eliminated for down from the Andes Mountains, and in the following reasons: Four were hospi- general all had very similar working con- talized in other areas at the time of the ditions. Apart from a few people over 80 survey; one was away in the mountains years of age who were excluded from looking after livestock; four underwent Group B in order to eliminate arterioscle- serologic conversion from positive to rotic pathologies (11), the age distribu- negative; two exhibited symptoms of tion of subjects in Group A and Group B aortic insuffrciency; one showed symp- was similar. The members of Group C toms of obstructive ; 12 shared essentially the same socioeco- had diastolic pressure readings over 100 nomic conditions as members of the mmHg; and five had been over 80 years other two groups, but they tended to be old when initially surveyed. somewhat younger. The ages of the dif- Causes of death. All deaths in ferent subjects correspond to those re- Chile must be certified by the responsi- corded in the years mentioned above ble physician of the main provincial hos- (1981-1984), so that the recorded agesof pital. Because of this requirement, we all subjects were four years greater than were able to obtain reliable data about those recorded at the time of the original all of the study subjects who died during study. the study period. Four of the nine Group A fatalities (see Table 1) were caused by bronchopneumonial conditions, one by stomach cancer, one by a cerebrovascular accident, and three by refractory cardiac insufficiency. In contrast, nearly all the Group B fatalities appeared attributable 247 TABLE1. Changesin the sizes of groups A and 6 over the four-yearstudy period.

GroupA Group6

No. % No. %

Size of original group 402 fW 298 fW Deathsdue to chagasic cardiopathy 0 KY 2; (7.4)a Deathsdue to other causes 9 (2.2)a (0.3) Left the area 168 (41.8) 48 (16.1) other status (2.2) 29 (9.7) Size after four years (53.7) 198 (66.4)

a The differencein overall mortali (2.2% in Group A, 7.7% in Group 8) is highly signifint (P

to chagasic cardiomyopathy. Specifically, that most of the Group A fatalities oc- 12 Group B subjects suffered “instanta- curred among women, while most of the neous death” (two of these people were Group B fatalities occurred among men. wearing pacemakers to counteract total The specific ages of the nine Group A auriculoventricular block), 10 died of subjects at the time of death were as fol- congestive cardiac insuff%ziency,and only lows: men-63, 78, and 82 years; one died of another cause (stomach can- women-50, 67, 72, 77, 80, and 80 cer). years. The specific ages of the 22 Group These four-year data show B subjects apparently dying of Chagas’ that the Group B subjects (with chagasic disease were as follows: men-45, 46, cardiopathy) had an appreciably higher 54, 56, 58, 59, 60(2), 61, 62(2), 63, 65, annual risk of dying than did the control and 76 years; women-47, 48, 50, 55, subjects with abnormal ECGs in Group 56(2), 58, and 65 years. As these figures A, the annual risks being 0.6% in Group show, most of the Group A fatalities oc- A and 1.9% in Group B. The differ- curred after age 60, while most of the ence between these mortality figures was Chagas’-related Group B fatalities oc- found to be highly significant curred in younger subjects. (P< 0.001). Age and sex of the decedents. Regarding age and sex, Table 2 shows

TABLE2. Sex and age of the nine GroupA subjects dying of all causes and the 22 GroupB subjjcts apparenttydytng of Chagas’ diseaseduring the four-yearstudy period.

GroupA GroupB Age at death (in years) Women Men Total Women Men Total

41-5051-60 -1 - i!m 34 62 lo” 61-70 1 1 2 1 5 6 71-80 4 1 5 - 1 1 81-90 - 1 1 - - - Total 6 3 9 8 14 22 Electrocardiographic findings found in a woman of 50, and two casesof (decedents). As Table 3 indicates, the total A-V block corrected by fured-rate Group B decedents with chagasic cardi- pacemakers were observed in men of 60 opathy showed more auriculoventricular and 76. and intraventricular conduction disor- The eight casesof unifascicu- ders than did the Group A (control lar block included four complete right group) decedents. branch blocks (in two women of 48 and Specifically, the nine Group A 65 and two men of 61 and 63). There decedents exhibited no A-V or bifascicu- were also three cases of left anterior lar block. Two Group A women (72 and hemiblock (in three men of 62, 62, and 77 years old) exhibited arrhythmias (1 65) and one case of left posterior auricular extrasystole and 1 ventricular hemiblock (in a man of 46). extrasystole). Two Group A men (63 and The four casesof bifascicular 78 years old) exhibited left anterior block involved left anterior hemiblock hemiblock, and a Group A woman (80 associated with complete right branch years old) exhibited complete left branch block (in two men of 59 and 60 and two block. Left was women of 56 and 58). observed in two Group A women 50 and One case of anterior-face is- 67 years old. An image indicating necro- chemia occurred in a man of 45, and two sis of the diaphragmatic wall of the caseswith an inactivation or QS image of myocardium was found in one Group A the anterior wall were observed in two woman 80 years old, and another indi- women of 55 and 56. cating necrosis of the anterior wall was found in one Group A man 82 years old. Analysis of Followup Data on In Group B, the four casesof Groups A, B, and C included two casesof polyfo- 2 cal ventricular extrasystole (one in a man The distribution by age and $ sex of all subjects remaining in the three of 56 and the other in a woman of 47) s and two of auricular extrasystole (in men study groups after four years is shown in of 54 and 58). First degree A-V block was Table 4. As may be seen, women pre- dominated in all three groups, presum- tE ably because the survey was conducted % on week-days during hours when the 2 TABLE3. ECGabnormalities obsenred in the nine Group male head of the household was gener- A and 22 GroupB decedents. ally at work. The age distribution of 3 Group A and Group B subjects was gen- 2 Conditions GroupA GroupB erally similar; it should be noted, how- 2 Arrhythmias 2 4 ever, that five Group B subjects over 81 % A-V block, first degree 0 1 years old were excluded from the study in 5 A-V block, third degree 0 2 order to reduce arteriosclerosis as a factor Unifascicularblock 3 8 . Biiascicularblock 0 4 in assessingchagasic cardiopathy. < lschemia 0 1 QS image 2 2 Clinical Cardiopathic Findings ’ Cavity hypertrophy 2 0 In the original survey it was 2 Total 9 22 noted that both the Group A and Group 3 B subjects showed few clinical symp- toms, and the same circumstance pre- vailed in the survey reported here. 249 TABLE4. Distributionby age and sex of all GroupA, B, and C subjectsremaining in their respective study groups four years after the initial survey.

GroupA GroupB GroupC Age group (in years) Men Women Total Men Women Total Men Women Total 11-20 10 9 19 2 3 5 4 1 5 21-30 14 23 37 9 11 20 4 6 10 31-40 13 26 39 9 28 37 4 16 20 41-50 15 24 39 19 31 50 7 24 31 51-60 13 16 29 10 24 34 - 1 1 61-70 IO 18 28 14 20 34 - - - 71-80 9 9 18 9 9 18 - - - 81-90 2 5 7 0 oo--- Total 86 130 216 72 126 198 19 48 67

Group A clinical histories re- block (left posterior hemiblock plus com- vealed symptoms of congestive cardiac plete right branch block). insufficiency in 10 subjects (4.6%). Also, 10 Group B subjects ex- These included six men 52 to 89 years old hibited symptoms of congestive cardiac and four women 52 to 80 years old. (The insufficiency. (Four were among those ECGs showed previous necrosis in five of with bifascicular block and Adams- the 10 cases-in three men of 52, 62, Stokes syndrome.) The ECGs of three and 89 and two women of 55 and 63.) women of 45,48, and 50 showed altera- Group B clinical histories re- tion of ventricular repolarization, while vealed symptoms of chagasic cardiopathy those of the other three subjects (two in 21 subjects (10.8%), seven of these women of 60 and 62 and a man of 63) having multiple complaints. Nine sub- showed images. Neither acute- jects presented ;vith irregular precordial phase antecedents nor portal of entry palpitations and sharp precordial pain, (Romaiia’s sign) antecedents were ob- the latter most often located on the left served in any members of the group. side. (The subjects involved were four Physical examinations re- men of 23 to 40 and five women of 19 to vealed arrhythmias in five Group A and 50; three of these also exhibited casesof nine Group B subjects. Mesosystolic Adams-Stokes crisis.) murmurs without an organic character In all, there were 10 Group B were observed in three Group A subjects subjects with Adams-Stokes crisis, but (two men 45 and 70 years old and a only one of these (a man of 60) had woman of 72) and in six Group B sub- third-degree A-V block. Of the other jects (three men 35, 48, and 56 years old nine, three women of 38, 39, and 42 and three women of 56, 60, and 65). showed wandering of the auricular pace- This latter finding did not coincide with maker; one man of 38 had auricular symptomatic Chagas’ disease cases. ; three men of 49, 53, and 65 and a woman of 52 exhibited bifascicular block (left anterior hemiblock plus com- plete right branch block), while one man of 33 showed another type of bifascicular Electrocardiogram Results number of ECGs normalized. Overall, 5 1 Group A final tracings (23 % ) were Table 5 shows the changes found to be normal, as were 16 Group B found in the control group (A) and the final tracings (8%). The number of ab- chagasic group (B) when the first ECGs normalities that became normalized were compared with those obtained four were 99 in Group A and 137 in Group B. years later. As may be seen, there was a Table 5 also shows that the higher proportion of ECG abnormalities prevalences of observed abnormalities in per tracing among the chagasic group on the two groups were fairly similar in most both occasions. Initially, by definition, cases,and that there were only a few in- there were no normal ECGs in either stanceswhen the Group A and Group B group. A considerable number of these data showed differences that were statis- abnormalities (28.4% in the control tically very significant (P < 0.01). More group, 3 1.7 % in the chagasic group) specifically, initial abnormalities very sig- were found to have normalized them- nificantly more prevalent in Group B selves as of the final tracing. However, than Group A (P < 0.01) included bifas- because some subjects had multiple ab- cicular block, subepicardial damage normalities, the number of abnormali- (which was not found in Group A), and ties normalized was greater than the the presence of a prolonged QT interval on the initial tracing. The greater fre- quency of QS images in Group A related to coronary cardiopathy (a history of in-

TABLE5. ECGabnormaliies found in the 216 Gmup A and 198 Group8 study subjects.

GroupA Group B

Initial ECG Final ECG Initial ECG Final ECG

Abnormal ECGfindings No. (%) No. VW No. (%) No. (%I 1. Normalized 99 (28.4) (0) 137 (31.7) 2. Auriculararrhythmia 6: $3) 47 (13.5) 4: (14.3) 55 (12.7) 3. Ventriculararrhythmia 4. A-V block, 1st degree 5. A-V block, 2nd degree 6. A-V block, 3rd degree (0.7) 7. Unifascicularblock (21.7) 62 (14.4) 8. Bifascicularblock (11.81” 47 (10.9)” 9. lschemia image (2.3) 10. Subepicardialdamage (0.9)b Il. Subendocardialdamage (4.4)a 12. QS image 13. Repolartzationchange 14. Cavity hyper-trophy 27 (10.7) 32 (4.9) 15. ProlongedQT 1 (0.4) 29 (8.3) 45 (4.4) Total No. of abnormalities 253 (100) 349 (100) 322 (100) 432 (100) Total No. of ECGs 216 216 198 198

a Diierence between data for Gmup A (initial) and Group B (initial) or between GroupA (final) and Group B (final) is highly significant (PC 0 01) b Differencebetween data for GroupA (initial) and Gmup B (initial) or between Group A (fural)and Group B (final) is not highly significant (P> 0 01). farct) in seven Group A subjects. In con- served much more frequently (P < 0.01) trast, the three Group B subjects initially in the Group B subjects included wan- showing QS images had no history of an- dering of the auricular pacemaker, auric- gina. Regarding the final ECGs, the only ular tachycardia, and auricular fibrilla- abnormalities very significantly more fre- tion. Of these, the only one sufficiently quent in Group B than Group A more frequent in Group B than Group A (P

TABLE6. ECGabnormalities associated with arrhythmiasobserved in the 216 GroupA and 198 GroupB study subjects.

GroupA Group B

Initial ECG Final ECG Initial ECG Final ECG

Abnormalities No. (%I No. (%I No. (%I No. (%I Short PR syndrome 28 (40.6) 33 (70.2) 13 (28.3) 14 Wolff-Parkinson-Whitesyndrome 4 (0) 0 ‘S5’ Wanderingauricular pacemaker 2 ;;q 8 1:; i (19.6)” 1 (1.8)b Auricular extrasystole 17 (24:6) 6 (12.8) 8 (17.4) 13 (23.6)b Auriculartachycardia 1 (1.4) y (0) 6 (13.0)” 10 (18.2)” Auricular bradycardia 8 (11.6) (2.1) ; (0) 5 Auricularfibrillation 1 (1.4) 5 (13.0)” 5 1i.i; b PulmonaryP wave 3 (4.3) 0 ‘l?’ 0 (0) 2” (4 Nodal rhythm 1 (1.4) y (0) 2 (3.6) lsorhythmicA-V dissociation 1 (2.1) ; lt3’ 2 (3.6) Nodaltachycardia 1 1i.i; 0 (0) (0) y (0) Sick sinus syndrome 0 (0) 0 (0) 1 (2.2) (1.8) Nodalextrasystole 1 (1.4) y (0) 0 (0) ‘: (0) Sinus arrest 0 (0) (2.1) ; (1.8) 2/l flutter (1.4) 0 (0) 1:; 0 (0) Left auricular rhythm il 04 0 (0) y (0) (1.8) Pacemakerdefect with arrhythmia 0 (0) cl 03 (2.2) :, (0) Total 69 (100) 47 (100) 46 (100) 55 (100)

a Mference between data for GroupA (inltlal) and Group 6 (imhal) or betmen GroupA (fmal) and Group B (fmal) is highly slgnlfmnt (PC 0.01) b Differencebelween data for Group A (sitial) and Group B (Mai) or between GroupA (fsal) and Group B (final) IS not highly significant (P> 0.01) categories of findings reflected the fe- Unifascicular blocks. Table 8 male predominance seen previously in provides information about the unifasci- the two study groups, there were more cular intraventricular blocks observed in Group A men than women with first de- Group A and Group B subjects. As may gree A-V block, and about equal num- be seen, the initial ECG showed com- bers of Group A men and women with plete right branch block to be three times unifascicular block and bifascicular as prevalent in the Group B (chagasic) block, aswell as more Group B men than subjects (P

TABLE7. Abnormalinitial EGGfindings amongthe 216 GroupA and 198 GroupB subjjcts, showingthe numbersand age ranges of the affectedsubjects, by sex.

GroupA Group B

Men Women Men Women

Age range Age range Age range Age range Abnormal ECGfindings No. (years) No. (years) Total No. (years) No. (years) Total 1. Normalized 0 0 0 0 0 0 0 0 0 0 2. Auriculararrhythmia 26 11-82 43 16-70 69 23 24-73 23 19-73 46 3. Ventriculararrhythmia 4 20-82 8 11-86 12 8 23-76 9 36-80 17 4. A-V block, 1st degree 6 32-59 2 30-63 8 5 24-49 6 34-49 11 5. A-V block, 2nd degree 0 0 0 0 0 0 0 0 6. A-V block, 3rd degree 1 65 0 8 1 1 6: 0 0 1 7. Unifascicularblock 39 11-83 37 15-86 76 30 20-30 40 II-80 70 8. Bifascicularblock 5 15-83 4 24-64 9 21 21-80 17 22-68 38 9. lschemia image 53 9 43-71 IO IO 32-80 8 22-67 18 IO. Subepicardialdamage :, 0 0 0 0 2 32-48 5 25-63 7 11. Subendocardialdamage 0 0 4 30-63 4 2 65-71 13 33-49 15 12. QS image 4 41-89 3 52-63 7 2 56-76 1 73 3 13. Repolarfzationchange 5 23-63 24 32-83 29 4 27-56 24 30-73 28 14. Cavity hypertrophy 12 22-73 15 16-78 27 20 24-80 3 22-60 23 15. ProlongedQT 1 67 0 0 1 14 23-80 31 23-80 45 Total No. of abnormatiiies 104 149 253 142 180 322 TABLE8. Unifascicularblocks observedin the 216 GroupA and 198 GroupB study subjects.

Initial EGG Final ECG

GroupA GroupB GroupA Group B Type of unifascicularblock No. (%) No. WI No. (%I No. WI Incompleteright branch block 30 (39.5) 7 (10.0) 30 (42.9) 10 (16.1) Completeright branch block 7 (9.2) 21 (30.0)” 6 (8.6) 16 (25.8)b Left anterior hemiblock 29 (38.2) 36 (51.4)a 26 (37.1) 32 (51.6)b Left posteriorhemiblock 8 (10.5) 4 (5.7) 4 (5.7) 2 Completeleft branch block 2 (2.6) 2 (2.9) 4 (5.7) 2 I?$. Total 76 (100) 70 (100) 70 (100) 62 (100)

a Differencebetween data for Group A and Group B (mltial) is highly signkant (PC 0.01). b Differencebetween data for Group A and Group B (final) IS not highly sigmflcani (P> 0 01).

TbLE 9. Numbersand age rangesof the 216 GroupA and 198 Group6 subjectswhose initial ECGsshowed unifascicular blocks, by sex.

GroupA GroupB

Men Women Men Women

Age range Age range Age range Age range Type of unifascicularblock No. (years) No. (years) Total No. (years) No. (years) Total Incompleteright branch block 15 11-77 15 2158 30 3 20-47 4 19-65 Completeright branch block 4 34-83 3 31-62 2; 1: 26-57 13 21-81 2: Left anterior hemiblock 16 15-74 13 15-75 23-80 20 29-75 36 Left posteriorhemiblock 4 30-47 4 18-43 8 2 42-49 2 II-34 4 Completelefl branch block 0 0 2 42-54 2 1 65 1 61 2 Tota 39 37 76 30 40 70

block. Regarding the ages of subjects statistical analysis failed to reveal any with unifascicular blocks, it is worth not- very significant (P < 0.01) differences in b ing that in Group B both incomplete the distribution of particular types of bi- and complete right branch block was fascicular blocks within the groups. This 3 . found to occur predominantly in young- suggests that a quantitative rather than a 53 er men. qualitative difference is involved. % Bifasciculat blocks. Table 10 Regarding distribution of bi- .j$ shows data on bifascicular blocks found fascicular blocks by sex, the data in Table 9, in both initial and final ECGs of Group 11 show that roughly equal numbers of a3 A and Group B subjects. The quantita- Group B men and women experienced 2 tive differences involved demonstrate blocks of the types found. The numbers that these blocks predominated among 2 Group B (chagasic) subjects. Regarding distribution of the various types of blocks 254 within Group A and Group B, however, TABLE10. Bifascicularblocks observedin the 216 GroupA and 198 Group6 study subjects.

Initial ECG Final EGG

GroupA Group B GroupA Group B Type of bifascicularblocka No. (%I No. (%I No. w No. (%I L4HB + IRBB 2 (22) (21) IAHB + CRBB 4 (44) 1: LPHB + IRBB 2 (22) (0) LPHB + CRBB 1 (11) 1: (26)b 2 (14) 1: (23)b Total 9 (100) 38 (100) 14 (100) 47 WV

a L4HB = left anterior hemiblcck: LPHB = left posterior hemiblock: IRBB = incompleteright branch block, and CRBB = complete right branch black b Ddferencesbetween the indicated Group A and Group B data are not highly significant (P>O 01)

TABLE11. Numbersand age ranges of GroupA and GroupB subjectswhose initial ECGsshowed bifascicularbloc@, by sex.

GroupA Group B

Men Women Men Women

Age range Age range Age range Age range Type of bifascicularblocka No. (years) No. (years) Total No. (years) No. (years) Total LAHB + IRBB 1 15 1 64 2 5 37-62 4 32-63 9 LAHB + CRBB 3 26-83 1 4 10 29-80 8 22-69 18 LPHB + IRBB 0 0 2 2&I 2 1 54 0 0 1 LPHB + CRBB 1 38 0 0 1 5 21-80 5 42-54 IO Total 5 4 9 21 17 38 a LAHB = left anterior hemibkck; LPHB = left posterior hemlblock; IRBB = incompleteright branch block, and CRBE = complete right branch block of Group A subjects with such blocks the second tracing are listed horizontally were too small for conclusions to be by number. The place where the two list- drawn. ings for a given abnormality cross shows ECG changes. So far we have the number of casesin which that abnor- examined numerical data that establish mality appeared on both ECGs, while certain differences between the two other entries on the same horizontal line groups studied but do not express the show the number of casesin which the variation in ECG abnormalities over initial abnormality became normalized time. To assessthis variation we have or in which it was associated on the later used cross-indexed tables in which the 15 ECG with other abnormalities. For ex- ECG abnormalities diagnosed from the ample, Table 12 shows that of 12 subjects first tracing are listed vertically, and with ventricular arrhythmia on the initial the same abnormalities diagnosed from ECG, nine did not show this abnormal- ity four years later; three did show it; and the final ECGs of these 12 subjects also showed unifascicular block (in one case), QS image (in one case), repolarization of the initial QS image abnormalities as- change (in one case), and cavity hyper- sociated with myocardial necrosis ap- trophy (in three cases).In addition, look- peared on the final ECG. In addition, ing down column three it may be seen 105 new abnormalities appeared on the that five other subjects (for a total of final ECG, these being as follows: eight) exhibited ventricular arrhythmia on the final ECG. (4 10 new auricular arrhythmias-five cases of short P-R syndrome (in men 17 to 54) four Table 12, which lists only data :asesof auricular fibrillation (in women 70 to for Group A (the control group), shows 78) and one case of sinus arrest (in a woman that 99 of the 25 3 abnormalities found in Id 58); the initial 216 ECGs had normalized on (b) Iive new casesof ventricular arrhythmia (all of the final ECG. Those abnormalities that ventricular extrasystole in men 54 to 73); (c) one new case of first-degree A-V block (in a disappeared were as follows: man of 68 whose ECG also showed a picture of left ventricular hypertrophy); (a) 32 auricular arrhythmias-four casesof Wolff- (4 one new case of third-degree A-V block (in a Parkinson-White syndrome (in men given the man of 68 with an image indicating subendo- final ECG when they were 35 to 54 years old), cardial damage); two cases of wandering auricular pacemaker (4 13 new cases of unifascicular block-three (in women of 23 and 35) one caseof auricular cases in which a bifascicular block had re- tachycardia (in a woman of 25) 11 casesof au- verted to a unifascicular form (left posterior ricular extrasystole (in five men 16 to 54 and hemiblock plus incomplete right branch block six women 17 to 68) seven casesof auricular becoming left posterior hemiblock in a bradycardia (in four men 28 to 35 and three woman of 38; left anterior hemiblock plus in- women 18 to 40), three casesof pulmonary P complete right branch block becoming in- wave (in women 27 to 49) one case of nodal complete right branch block in a boy of 15; tachycardia (in a woman of 27) one case of and left anterior hemiblock plus complete nodal extrasystole (in a woman of 70). one right branch block becoming complete right case of nodal rhythm (in a man of 35), and branch block in a woman of 21); five casesof one case of 2:l auricular flutter (in a man of incomplete right branch block (in three men 61); 15 to 56 and two women 36 and 47); three (b) nine ventricular arrhythmias (all of ventricular cases of complete left branch block (in two extrasystole in three men 20 to 82 years old men 54 and 79 and one woman of 70); and and sh women 38 to 61 years old); two cases of left anterior hemiblock (in men (4 five cases of first-degree A-V block (in four 56 and 75); men 32 to 59 and one woman of 30); (0 eight new cases of bifascicular block, six of (4 13 casesof unifascicular block-six casesof in- which developed in subjects whose initial complete right branch block (in three men 31 ECGs showed unifascicular blocks (three cases to 42 and three women 21 to 39), four casesof of incomplete right branch block changed to left posterior hemiblock (in two men 35 and left anterior hemiblock plus complete right 56 and two women 30 and 43), and three cases branch block in men of 22, 37, and 57, and of left anterior hemiblock (in two males 15 three other cases of incomplete right branch and 24 and a girl of 15); block changed to left anterior hemiblock plus six ischemia images (in women 43 to 71 years incomplete right branch block in women of old); 29, 39, and 47); in addition, two new casesof all four images indicating subendocardial left anterior hemiblock plus incomplete right damage (in women 30 to 50); branch block appeared in women of 48 and d k) 19 cases of repolarization alterations (in four 74; 3 men 23 to 55 and 15 women 17 to 68); (g) two new casesof subendocardial damage (in a (h) 11 images of cavity hypertrophy (in three men man of 50 and a woman of 63); z 45 to 56 and eight women 17 to 76). 3 The remaining Group A ab- normalities persisted over time. In this 256 regard, it should be noted that all seven TABLE12. GroupA abnormalitiesfound by analysisof the initialand final ECGsof the 216 GroupA study subjects. The numbersof abnormalities foundinitially, by type, are shownin column2. The numbersof subjectswith particularabnormalffes found on the final ECG,by type, are shownat the bottomof the table (e.g., four subjects showed first-degreeA-V block on their final ECGs).The numbers of subjects in whom the initially observedabnormality persisted are shown by the dark numbersrunning diagonallythrough the table. And the numbersof subjects who initially had a particular abnormalitythat disappearedon the final ECGor who showed other abnormalitieson the final ECGmay be seen by reading horizontallyacross the table (e.g., of eight subjectswith first-degreeA-V block on the initial ECG,five did not show this abnormali on the final ECG,three did show it, and one showedanother abnormality, prolonged GT).

TotalNo. of initial Final ECGfindings (l-15) abnormalities Initial ECGfindings (I-15) observed 1 23 4 5 6 7 8 9 IO 11 12 13 14 15 I. Abnormalitynormalized ____------2. Auriculararrhythmia 69 32 37 1 - - - 2- 3-- I- 2 6 3. Ventriculararrhythmia 12 g-3--- l---- 1 13- 4. A-V block, 1st degree 8 5--3------l 5. A-V block, 2nd degree - _____------6. A-V block, 3rd degree 1 ---all------7. Unifascicularblock 76 13 1 1 - - - 49 6 4-- 2 3 5 9 8. Bifascicularblock g ------3 6----- 13 9. lschemiaimage 10 6-j--- l- 4--- 111 10. Subepicardialdamage - _------_----- 11. Subendocardialdamage 4 4----l-.- 1 - - - 1 - - 12. QS image 7 - 4---- I---- 7 I-- 13. Repolarizationchange 29 19 - 1 - - - 2 l-- 1 1 10 4 5 14. Cavity hypertrophy 27 11 5 1 1 - - 3 1 l- 1 - - 16 3 15. ProlongedCIT , -~------.---~~~l Total abnormalities or normalized 99 47 8 4 - 2 62 14 13 - 2 12 17 32 29 events observedon final ECG s: G Anibada et al. l CHAGASIC CARDIOPATHY IN CHILE 04 five new images of myocardial necrosis-QS 6) 11 casesof ischemia image (in six men of 36 to image (in two men of 53 and 82 and three 71 and five women of 37 to 66); women of 29, 61, and 68, the last two being (g) six images of subepicardial damage (all in the associated with left anterior hemiblock; the apical region, in two men of 32 and 48 and woman of 29 had no history of ); four women of 25 to 63); (9 seven new cases of repolarization alterations (h) 11 images of subendocardial damage (in two (in two men of 31 and 82 and five women of men of 65 and 71 and nine women of 33 to 38 to 62); 49); (j) 16 new images of cavity hypertrophy-three (9 two cases of myocardial necrosis-QS image cases of hypertrophy of the left auricle (in a (in a man of 76 and a woman of 73); man of 47 and two women of 67 and 74) and (i) 21 casesof repolarization change (in two men 13 casesof left ventricular hypertrophy (in five of 51 and 56 and 19 women of 30 to 73); men of 55 to 82 and eight women of 58 to (k) 13 images of cavity hypertrophy (in nine men 78); of 29 to 77 and four women of 60 to 80); (kj 28 new casesof prolonged QT (in seven men (1) 36 cases of prolonged QT syndrome (in 12 of 43 to 83 and 21 women of 21 to 66). men of 29 to 80 and 24 women of 20 to 60).

Table 13, which presents the The remaining Group B ab- data for Group B, shows that 137 of the normalities persisted over the four-year 322 abnormalities found in the initial study period. In addition, 130 new ab- 198 ECGs had normalized on the final normalities appeared on the final ECG, ECG. Those abnormalities that disap- these being as follows: peared were as follows: (4 19 new auricular arrhythmias-one case of (4 10 auricular arrhythmias-eight casesof wan- short P-R syndrome (in a man of 47), five cases dering auricular pacemaker (in three men of of auricular extrasystole (in a man of 47 and 38, 44, and 73 and five women of 46 to 73), four women of 47 to 57), four casesof auricu- one case of auricular fibrillation (in a woman lar tachycardia (in women of 30 to 43), one of 65) and one caseof arrhythmia in a man 68 case of left auricular rhythm (in a woman of years old with a fLued-rate pacemaker that was 46) two casesof isorrhythmic A-V dissociation complicated by multiple extrasystole; (in a man of 52 and a woman of 73) one case (b) nine ventricular arrhythmias (all of ventricular of sinus arrest (in a woman of 44), and five extrasystole in four men of 23 to 76 and five cases of (in four men of 37 women of 36 to 63); to 76 and a woman of 53); (4 five cases of first-degree A-V block (in four (b) 11 new casesof ventricular arrhythmia (all of men of 26 to 49 and a woman of 34); ventricular extrasystole in six men,of 36 to 60 (4 11 cases of unifascicular block-four casesof and five women of 36 to 60); six of these cases incomplete right branch block (in a man of 47 were multifocal; and three women of 19 to 38), five casesof left (cl four new cases of first-degree A-V block (in anterior hemiblock (in two men of 47 and 49 two men of 47 and 77 and two women of 39 and three women of 29,’ 35, and 66), one case and 61); all four were associated with in- of left posterior hemiblock (in a man of 49), traventricular conduction blocks; and one case of complete right branch block (4 two new casesof third-degree A-V block (in a (in a man of 30); man of 66 whose first ECG had shown a bifas- (4 two casesof bifascicular block (both left ante- cicular block and a woman of 5 1 without prior rior hemiblock plus incomplete right branch evidence of an intraventricular conduction block, in a man of 37 and a woman of 38); disorder); (4 18 new casesof unifascicular block-four cases in which a bifascicular block had reverted to a unifascicular form (left posterior hemiblock I ECG tracingsobtained from this subject are shown in plus complete right branch block becoming Figure 1. complete right branch block in a man of 60; left posterior hemiblock plus incomplete right branch block becoming incomplete right branch block in a man of 54; and left anterior hemiblock plus complete right branch block TABLE13. GroupB abnormaliis found by analysisof the initial and final ECGsof the 198 GroupB study subjects.The numbersof abnormalities foundinitially, by type, are shownin column2. The numbersof subjectswith particularabnormalities found on the final ECG,by type, are shownat the bottomof the table (e.g., 10 subjects showed first-degreeA-V block on their final ECGs).The numbers of subjects in whom the initially obsenredabnormality persisted are shown by the dark numbersrunning diagonallythrough the table. And the numbersof subjectswho initially had a particular abnormali that disappearedon the final ECGor who showed other abnormalitieson the final ECGmay be seen by reading horizontallyacross the table (e.g., of 11 subjectswith first-degreeA-V block on the initial ECG,five did not show this abnormalityon the final ECG, six did show it, and one showedanother abnormalii, unifascicularblock).

TotalNo. of initial Final ECGfindings (1-15) abnormalities Initial ECGfindings (I-15) observed 12 3 45 6 7 8 9 10 11 12 13 14 15 1. Abnormalitynormalized - _------2. Auriculararrhythmia 46 IO 36 i--i 3 - - - l--- 2 3. Ventriculararrhythmia 92 8--- 1 - - I--- I- 4. A-V block, 1st degree i: 5-B 6-A l------.e.m 5. A-V block, 2nd degree - ----_------_-- 6. A-V block, 3rd degree 1 -- ~--l------~~- 7. Unifascicularblock 70 11 8 3 3 - - 44 15 1 - 4 3 4 2 2 8. Bifascicularblock 38 2341-l 4 31 I- 1 2 1 2 2 9. lschemiaimage 18 11 I------7 - 3- 2 11 10. Subepicardialdamage 6 1 1 - - - 2--11-i-i ’ 11. Subendocardialdamage 1: 11 1- - - - 2 - - - 4 - 4 - 2 12. QS image 3 2------1 - - - 13. Repolarizationchange 28 21 1 I--- 4- 1- 5- 7 4- 14. Cavity hypertrophy 23 13 1 ------1 - - - 10 - 15. ProlongedQT 45 36 1 - - - - 1 1 - I-- 119 Total abnormalities or normalized 137 55 19 10 - 3 62 47 10 4 19 6 20 21 19 events observedon final EGG h, s Arribada et al, 9 CHAGASIC CARDIOPATHY IN CHILE FIGURE1. In 1978 the ECGtracings of a Group B woman 25 years old revealedan evident left anteriorhemiblrxk. Aboutfour years laterthe samesubject yielded normaltracings with no evidence of any itiraventricular conductiondefect. aVR aVL aVF

becoming complete right branch block in two hemiblock plus incomplete right branch block women of 60 and 68); nine casesof left ante- in a woman of 34) was associated with a pro- rior hemiblock (in four men of 37 to 65 and longed QT syndrome; five women of 38 to 68); one caseof left poste- (g) three new images of ischemia (in a man of 49 rior hemiblock (in a man of 54); two casesof and two women of 36 and 66); complete right branch block (in two men of (h) three new images of subepicardial damage (in 47); and two casesof incomplete right branch two men of 36 and 66 and a woman of 63); block (in a man of 43 and a woman of 33); (i) 15 new images of subendocardial damage (in (f) 16 new casesof bifascicular block, 15 of which two men of 49 and 67 and 13 women of 26 to developed in subjects whose initial ECGs 66); showed unifascicular blocks (four casesof left (j) five new images of myocardial necrosis-QS anterior hemiblock changed to left anterior image (in two men of 36 and 54 and three hemiblock plus incomplete right branch block women of 44, 47, and 55); these images ap- in two men of 55 and 58 and two women of 54 peared to involve the interior wall of the left and 68; another two cases of left anterior ventricle and were associated in all caseswith hemiblock changed to left anterior hemiblock uni- or bifascicular block; plus complete right branch block in a man of (k) 13 new cases of repolarization alteration (in b 66 and a woman of 47; three casesof complete three men of 49 and 10 women, six of them 5 right branch block changed to left anterior under age 50, who were 32 to 67 years old); - hemiblock plus complete right branch block (1) 11 new images of cavity hypertrophy-four 3 in two men of 57 and 66 and a woman of 5 1; casesof left ventricle hypertrophy (in a man of % another three cases of complete right branch 21 and three women of 58, 67, and 73) and .g block changed to left posterior hemiblock plus seven casesof left auricle hypertrophy (in two complete right branch block in one man of 66 men of 23 and 60 and five women of 43 to $ and two women of 3 1 and 34; two casesof left 67); posterior hemiblock changed to left posterior (m) 10 cases of prolonged QT syndrome (in two 2 hemiblock plus complete right branch block men of 40 and 49 and eight females, seven in a man of 42 and a woman of 2 1; and a case under age 50, who were 11 to 73 years old). 2 of incomplete right branch block changed to left anterior hemiblock plus incomplete right branch block in a man of 20); the sixteenth 260 new case of bifascicular block (left posterior A comparison of Tables 12 but two were 50 or under), received the and 13 indicates that Group B (the cha- same final tests and examinations as gasic group) exhibited more changes in groups A and B. Because this group was its abnormalities over the four-year pe- selected at the time of the final survey, its riod between ECGs. Also, in comparison size was naturally unaffected by deaths or with Group A, fewer of the Group B au- migrations during the study period. ricular arrhythmias disappeared, while However, as Table 14 shows, the final more indications of ischemia, subepicar- ECGs revealed abnormalities in 26 of the dial damage, subendocardial damage, 67 study subjects. These abnormalities, and prolonged QT syndrome disap- 28 in all, included one case of auricular peared. In addition, it should be noted arrhythmia (corresponding to a nodal that in comparison to Group A, Group rhythm problem in a woman of 48) five B exhibited larger numbers of new auric- cases of incomplete right branch block ular arrhythmias ( 19 versus lo), ventricu- (in two men of 16 and 26 and three lar arrhythmias (11 versus 5) unifasci- women of 41, 46, and 47) one case cular blocks (18 versus 13), bifascicular of bifascicular block (left anterior blocks (16 versus 8), images of subendo- hemiblock plus complete right branch cardial damage (15 versus 2), and repo- block in a man of 37), two images of is- larization alterations (13 versus 7). Also, chemia (in women of 27 and 43) three the ages of the Group B subjects experi- casesof repolarization change (in a man encing new abnormalities tended to be of 35 and two women of 3 1 and 47)) and younger, overall, than the ages of their 16 casesof prolonged QT (in four men of Group A counterparts. 38 to 48 and 12 women of 37 to 47). Another important point is not merely that auricular and ventricular arrhythmias were associated with many Group B diagnoses, but that a relatively TABLE14. ECGabnormaliies indicated on the final ECGs high proportion of them were associated of the 67 Group C subjects with chagasic infections, with intraventricular conduction blocks. whose initial ECGshad shown no abnormalities. It is also clear that many of the bifascicu- lar blocks developed from previously es- ECGfindings No. % tablished unifascicular blocks. 1. Abnormalitynormalized N/As N/As 2. Auricular arrhythmia 1 3.6 Development of ECG 3. Ventriculararrhythmia - - 4. A-V block, first degree - - Abnormalities in Infected 5. A-V block, seconddegree - - Subjects 6. A-V block, third degree - - 7. Unifascicularblock 5 17.9 This matter was studied by ex- 8. Bifascicularblock 1 3.6 amining the 67 Group C subjects, whose 9. lschemiaimage 2 7.1 serologic responses to the initial survey IO. Subepicardialdamage - - had indicated chagasic infection but 11. Subendocardialdamage - - - - whose initial ECGs had shown no abnor- 12. CS image 13. Repolarizationchange 3 10.7 malities. This group, comprised of 19 14. Cavity hypertrophy - - men and 48 women not over 60 years of 15. ProlongedQT 16 57.1 age at the time of the initial survey (all TotalNo. of abnormalities 28 100.0 TotalNo. of ECGswith abnormal&s 26

a N/A = noi applicable. 261 The number of abnormalities The study also indicates that arising in this group of relatively young the Chagas’ disease picture in Chile dif- subjects (all those afflicted were under fers from that found in a number of the age of 50 at the time of their initial other countries in the Americas. Specifi- ECGs) is quite striking. Except for the cally, we did not see the acute phase with two women with ischemia images, who characteristic , nor did we complained of sharp precordial pain find caseswith Romaiia’s sign (16-19), or without the characteristics of angina, chronic caseswith bradycardia (20). In- none of the Group C subjects involved deed, the overt symptoms exhibited were showed any overt symptoms. scant, disproportionately so considering On the basis of these data, it the highly abnormal ECGs obtained appears that the risk of contracting cardi- from many of the same subjects and the opathy for a population of persons with severemyocardial compromise evidenced chagasic infections is on the order of by high mortality, including a large pro- 38.8 % over a period of four years, or portion of sudden deaths. (The fact that about 9.7% per annum. many of the fatalities were sudden sug- gests that death was caused by profound changes in myocardial rhythm and elec- trical conduction-21 .) D ISCUSSION In general, comparison of the AND CONCLUSIONS ECG data on Group A (control subjects with cardiopathy) and Group B (chagasic This longitudinal study subjects with cardiopathy) showed the yielded a number of findings about the latter to have a higher frequency of bifas- natural history of chagasic cardiopathy cicular block, subepicardial damage, and that seem significant. To begin with, the prolonged QT syndrome. This finding, data indicate that mortality was four which attracted our attention because it times higher among infected subjects does not agree with the classical descrip- and that the disease threatens a much tions of chagasic cardiopathy (I I, 17,21- younger population than is threatened 23), can be explained by two circum- by nonchagasic cardiopathy. Also, it ap- stancesthat distinguish this investigation pears noteworthy that cardiopathy devel- from other epidemiologic studies. First, oped among the infected Group C sub- this study employed a control group jects at a rate of 9.7 % per year, and that (Group A) with nonchagasic cardiopa- the ECG abnormalities involved were thies residing in the same endemic area similar to those found in Group B, the as the other study subjects. And second, % chagasic group with initial cardiopathy 2 findings for subjects with chagasic cardi- . This 9.7 % rate is considerably higher opathies are customarily compared to 3 than that cited by Puigb6 (I 1) in his lon- results obtained with negative controls. s gitudinal study. In addition, these find- Our data thus provided a basis for com- .,g ings point up the fact that caseswith car- 9, paring chagasic and nonchagasic cardiop- a3 diopathologic problems can be detected. athies, unlike other available data, and This is significant, becausecases in which so a different picture was obtained : lesions have only begun to appear lend (24,25). Because of these differing cir- themselves to timely treatment, and so 3 ECG findings of the sort described could serve as criteria for selecting patients to 262 receive therapeutic treatment (16). cumstances, there seems no reason to and bifascicular blocks appear together doubt that if the work described here with repolarization alterations, ischemia were repeated, a similar result would be images, and prolonged QT syndromes as obtained. Another investigation, con- the first manifestations of abnormality in ducted by Schenone and coworkers (26) previously normal ECGs. It is possible and carried out on 9,990 subjects in that the apparent disappearance of some Chile, describes ECG abnormalities in of these abnormalities in our study sub- the control group that were similar but jects was only temporary, a point that re- less frequent than those seen in the cha- quires further investigation. gasic subjects. Unfortunately, no detailed Regarding our serologic fmd- report of these findings is available. ings, the low rate of conversion from Another point worth noting is negative to positive for chagasic infection that for many Group B (chagasic) sub- (in only two of 218 Group A subjects jects, the abnormalities seen on the final tested in the followup study) is not con- ECG differed from those seen on the ini- sistent with the situation generally ob- tial ECG. This is in accord with available served in endemic areas (11). It seems information indicating that the electrical likely that this finding derives from the tracing can “blank out,” i.e., pass effectiveness of government anti-vector through periods of normality, a circum- efforts that have reduced public exposure stance described by Anis Rassi in report- to triatomid bugs. The conversion in ing on his cases (27). As time goes by, some subjects from positive to negative is many more changes occur, and occur in a harder to explain. However, the four much higher proportion of the subjects, subjects involved showed minimum pos- than is true in the control group; the ar- itive titers to begin with, and so the rhythmias are associated with a larger results could have represented errors 2 number of other events and are more se- (false positive findings in the initial sur- 2 rious; and intraventricular blocks are vey or false negative findings in the fmal b much more frequent. survey), or else could have arisen from s In our own study, if the immunologic depression, a phenome- Group B intraventricular (unifascicular non observed by Breniere and coworkers s and bifascicular) blocks that disappeared that could explain periodic conversions 2 are added to those that did not change in subjects with marginally positive or 8 and to the new ones, the total obtained is negative sera (28, 29). 5 122 intraventricular blocks as compared In conclusion, our study has to 89 in the control group. The number sought to probe the “great silent group” of unifascicular and bifascicular blocks described by Laranja (17), and has ob- % disappearing in Group B was less than tained from it findings that represent no 3 the number appearing, so the total ap- more than a tiny fraction of the informa- parent number increased, with many of tion needed about the pathology of Cha- z the abnormalities appearing in relatively gas’ disease. In the process, by selecting a l young subjects, In general, these find- control group with ECG abnormalities, 4;Q ings tend to confirm the classicpicture of we have also dealt with the broader 2 the disease. group of pathologies described by Black- 2 This longitudinal study also burn (30). As a result of this investiga- demonstrated that both unifascicular tion, we have learned that it is relevant, 2 indeed necessary,to study the problem of chagasic cardiopathy over an extended period of time; we have also gained a 263 heightened awareness of the fact that tality was four times higher among the many matters remain to be resolved and infected subjects and that the disease that a great deal of work must still be tended to threaten a much younger pop- done. ulation than was threatened by noncha- gasic cardiopathy. Also, cardiopathy ap- peared to develop among the infected Group C subjects at a rate of about 9.7% A CKNOWLEDGMENTS per year, considerably faster than indi- cated by a previous longitudinal study The authors wish to thank Dr. (II). In addition, the results point up Luis Cabrera, Dr. Fernando Arab, and the ability to detect developing chagasic Dr. Ricardo Estela for assisting with the cardiopathy on ECGs, an ability that clinical work described herein. suggests ECGs could prove useful in se- lecting patients to receive therapeutic treatment. The findings also suggest that SUMMARY the clinical picture of Chagas’ disease in In 1977 the authors launched Chile differs from that found in certain a long-term investigation of the epide- other parts of the Americas, in that overt miology of Chagas’ disease and its car- symptoms are scant despite the fact that diac implications in Chile. During this the disease gives every appearance of do- work, clinical examinations were per- ing severe damage. formed, blood samples were drawn for Another point worth men- serologic tests, and electrocardiograms tioning is that Group B subjects exhib- were obtained using a study population ited higher frequencies of bifascicular of 2,938 subjects residing in rural settle- blocks, images indicative of subepicar- ments of northern Chile; and this was dial damage, and prolonged QT syn- done again four years later with 481 dromes than did their Group A counter- study subjects remaining in the area. parts. This finding is at variance with the This article reports on the latter four-year classical descriptions of chagasic car- followup study. diomyopathy. It also appears that unifas- To begin with, the study sub- cicular and bifascicular blocks, together jects were divided into three specific with repolarization changes, ischemia groups: those with no evidence of Cha- images, and prolonged QT syndromes, gas’ disease but with cardiopathy (as in- were the first manifestations of abnor- mality in previously normal ECGs. The bco dicated by abnormal ECGs) were desig- aC‘I nated Group A; those with positive apparent appearance and disappearance - chagasic serology and cardiopathy were of some of these abnormalities in our G3 designated Group B; and 67 subjects study suggests some could be only tem- G randomly selected from those with posi- .$ porarY* 9, tive chagasic serology and normal ECGs Seroconversion of four study % were designated Group C. At the time of subjects from positive to negative over the followup work, 216 subjects were re- the followup period is hard to explain; it 2 tained in Group A and 198 in Group B. could indicate immunologic depression 2 Comparison of the initial and final Group A and Group B data yielded a number of results that seem significant. 264 To begin with, they indicated that mor- or erroneous (false positive or false nega- 8 Rios, A. Enfermedad de Chagas en animales tive) serologic findings. The seroconver- sinantropicos de1 Norte de Chile. Thesis for Master of Veterinary Sciences. Escuela de Me- sion of only a few (two) study subjects dicina Veterinaria, Universidad de Chile, San- from negative to positive during this pe- tiago, 1980. riod may have been due to the effective- 9 Miles, M., W. Apt, C. Widmer, C. Schofield, ness of a government disinsection cam- M. Povda, and R. Cibulskis. Isozyme hetero- paign designed to cut public exposure to geneity and numerical taxonomy of Tvpano- the triatomid bugs that carry the disease. soma cmzi from Chile. 5an.r R Sot Eop Med Hyg (in press).

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25 Schenone, H., and G. Niedmann. Nuevos 30 Blackburn, H., A. Keys, S. Simonson, P. Ran- aportes al estudio de la cardiopatia chag;isica taharvn. and S. Punsar. The electrocardioeram en Chile. Bol’ Chd Parasitoll2:2-7, 1957. in po’puiation studies: A classification sysyem. Circdation 21:1160-1175, 1960.

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