Left-ventricular Scar Pattern in Chagas cardiomyopathy

Corresponding author
Andrés Diaz; Postal address: Cll 135 # 17A—77, Bogotá, Colombia; e-mail: andresdiaz1992@live.com;
phone: +57 3176784894.

Coauthors
Andrés Diaz, Department of Cardiology, Hospital San José, Bogotá, Colombia. Fundación Universitaria de
Ciencias de la Salud, Bogotá, Colombia. Escola de Doctorat, Universitat de Barcelona, Barcelona, Spain.
Hector M. Medina, Department of Diagnostic Imaging, Fundación Cardioinfantil, Bogotá, Colombia
Juan José Diaztagle, Internal Medicine Service, Hospital San José, Bogotá, Colombia. Fundación Universi-
taria de Ciencias de la Salud, Bogotá, Colombia; Department of Medicine, Universidad Nacional de Colom-
bia, Bogotá, Colombia.
Alejandro Olaya, Department of Cardiology, Hospital San José, Bogotá, Colombia; Department of Cardiol-
ogy, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia; Department of Cardiology, Hospi-
tal Cardiovascular del Niño de Cundinamarca.
Guillermo Mora, Department of Medicine, National University of Colombia, Bogotá, Colombia; Cardiology
Unit, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
Ignacio López-Lima, Department of Cardiovascular Imaging, Hospital Dr. Guillermo Rawson, San Juan, Ar-
gentina.
Carolina Ayala, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia. Escola de Doctorat,
Universitat de Barcelona, Barcelona, Spain.
Diana Vargas Vergara. Department of Cardiology, Hospital San José, Bogotá, Colombia. Fundación
Gina Polo, Statistical Analysis and Research Consulting, Bogotá, Colombia.
Néstor Galizio, Department of Electrophysiology and Arrhythmias, Hospital Universitario Fundación Faval-
oro, Buenos Aires, Argentina.
Frida T. Manrique, Department of Diagnostic Imaging, Fundación Cardioinfantil, Bogotá, Colombia
Azucena Martinez Caballero. Coronary Care Unit., Fundación Cardioinfantil, Bogotá, Colombia
Julian F. Forero, Department of Diagnostic Imaging, Fundación Cardioinfantil, Bogotá, Colombia
Josep Brugada, Department of Medicine, Escola de Doctorat, Universitat de Barcelona, Barcelona, Spain;
Department of Arrhythmias, Hospital Clínic de Barcelona, Barcelona, Spain; Escola de Doctorat, Universitat
de Barcelona, Barcelona, Spain.

Word Count
2938
ABSTRACT

Objective: This cross-sectional study established a pattern of the left ventricular scar in Chagas cardiomy-
opathy and its association with parameters of disease severity. Methods: Late gadolinium enhancement im-
ages were obtained from 118 Chagas seropositive patients (57.6% females; age = 59.1 ± 10.7) without is-
chemic heart disease or conditions that cause myocardial fibrosis or dilation. Patients were grouped accord-
ing to the left ventricular ejection fraction (LVEF) as G1 (LVEF ≥ 60%; n=43), G2 (41% > LVEF < 59%;
n=49), and G3 (LVEF ≤40%; n=26). Results: Myocardial fibrosis was present in 76 (64.4%) patients and a
total of 235 scars was identified. Scars were mainly located in the basal inferolateral segment (22.4%; n
=52), followed by the apex (14.7%; n =34) and the mid inferolateral (11.6%; n =27) segment. When LVEF ≥
60%, a greater aggregation of scars in the basal inferolateral and mid inferolateral segments was observed.
Progressively, as LVEF decreased, a greater apex involvement was detected, as well as an expansion towards
neighboring segments. Most of scars had a transmural (28.1%; n =66) or a midwall (21.7%; n =51) exten-
sion. The basal and midventricular regions revealed an evident pattern of the scars, with an apparent midwall
origin, followed by a midwall/subepicardial extension and subsequently transmural involvement. This pat-
tern was not evident in the apical region. Conclusion: A regional non-homogeneous midwall-transmural pat-
tern of left ventricular scar was evidenced in patients with Chagas cardiomyopathy. Apical fibrosis was
strongly associated with major adverse outcomes.

KEY QUESTIONS

What is already known about this subject?

International efforts for controlling Chagas disease have enabled important advances. However, efforts fo-
cused on understanding Chagas cardiomyopathy are still not enough for the avoidance of lethal cases. Previ-
ous attempts focused on determining an accurate pattern of the left ventricular scar have been published,
however, no pattern has been specifically related to these outcomes.

What does this study add?

This study established a pattern of the left ventricular scar in Chagas cardiomyopathy and its association with
markers of disease severity.

How might this impact on clinical practice?

Our findings support decisions regarding therapy, including heart transplantation, based on the best knowl-
edge of the long-term prognosis of the affected patients with Chagas cardiomyopathy. This will allow the op-
timization of resources and prevention of lethality.
INTRODUCTION

Chagas disease is a neglected tropical infection caused by Trypanosoma cruzi,[1] that affects millions of
people in the Americas. It is transmitted mainly by triatomine vectors,[2] but it can also spread via non-vec-
torial routes, such as congenital transmission,[3] blood transfusion,[4] organ transplantation,[5] ingestion of
contaminated food or beverages,[6] laboratory accidents,[7] and by sexual intercourse,[8]. Chagas disease
occurs mainly in the continental part of Latin America, being endemic from Mexico to northern Argentina
and Chile.[1,7] In the past decades, however, because of the high migration of Latin Americans across the
world, it has been increasingly detected in the United States of America, Canada, many European and some
Western Pacific countries.[1, 7, 9-11] In the Americas, the general prevalence goes up to 0.29%, being the
highest seroprevalence found in Bolivia (22.8%), Guatemala (3.9%), and Peru (3.8%).[12] Although inter-
national efforts for controlling the disease have enabled important advances over the past two decades,[12,
13] public policies and strategies focused on the epidemiological surveillance, prevention, detection, treat-
ment and control of this disease are still necessary, mainly in rural areas.
Moreover, efforts focused on the diagnosis, treatment, and understanding of cardiac involvement and its as-
sociation with parameters of disease severity are fundamental for the avoidance of lethal cases. Chronic car-
diomyopathy is the most serious manifestation of Chagas disease, affecting approximately one-third of indi-
viduals with positive serology,[14] which may require heart transplantation in those with severe cardiomy-
opathy.[15] Cardiac magnetic resonance (CMR) is a non-invasive sensitive technique to detect myocardial
fibrosis through contrast delayed enhancement techniques, (LGE)[16-18] which allows a precise delimitation
of scarred areas with high correlation with histological findings,[19] and works as a predictor of poor prog-
nosis in non-ischemic cardiomyopathy.[20] Also, LGE by CMR has merged as a non-invasive tool for risk-
stratifying patients with chronic chagasic cardiomyopathy, since it is currently the in vivo gold standard for
identifying and quantifying myocardial scar.[21] Several clinical studies reported its use in a variety of clini-
cal settings including ischemic disease, amyloidosis, aortic valve disease,[22-24] and Chagas disease.[16-18,
25-29] However, to the best of our knowledge, none of these preceding studies have identified a pattern of
the left ventricular scar related to the outcomes. In this study, a pattern of the left-ventricular scar in patients
with Chagas cardiomyopathy and its association with disease severity is investigated.

METHODS

Study population
This study considered 118 patients with Chagas diseases recruited from the cardiology, electrophysiology,
emergency, and in-hospital services of seven cardiovascular reference centers in Bogota DC, Colombia be-
tween 2018 and 2019. Each patient signed a consent to be part of the study. The inclusion criteria were pa-
tients over 18 years old, positive for Chagas disease according to the CDC criteria, and two positive labora-
tory tests for Chagas disease (immunoenzymatic assay tests ELISA, and indirect immunofluorescence-IFI).
The exclusion criteria included refusal to participate in the study, diagnosis of coronary disease, ischemic or
valvular dilated cardiomyopathy, pregnancy, fever, severe psychiatric disorders, creatinine clearance <30
mL/minute in a 24-hour sample test, contraindication to magnetic resonance, and contraindication to gadolin-
ium.

CMR Examination
CMRs were performed in a Philips Ingenia 1.5 T scanner. Images were post-processed in the Intellispace-
Philips 8.0 Platform. The protocol included localizers for an initial morphological evaluation considering
bright and black-blood gradient-echo sequences in the axial, sagittal and coronal planes. The functional eval-
uation included cine imaging using steady-state free precession (SSFP) sequences for quantitative functional
evaluation. Structural (bi-ventricular end-diastolic and end-systolic volumes, diastolic thickness of the walls,
left atrial diameter and presence of pericardial effusion) and functional measurements (LVEF and presence
and degrees of mitral and tricuspid regurgitation) were obtained from each patient. The intravenous contrast
material used was Gadobutrol (0.15 mmol/kg) and LGR sequences were obtained 10-15 minutes after injec-
tion. The presence, location, and extension of left-ventricular scars were reported.

Data analysis
Patients were grouped according to the LVEF as G1 (LVEF ≥ 60%; n=43), G2 (41% > LVEF < 59%; n=49),
and G3 (LVEF ≤40%; n=26). Well-recognized markers of disease severity (New York Heart Association
(NYHA) functional classification, LV/RV volumes and indexes) and other clinical outcomes were compared
between the groups. Continuous variables were expressed as mean (standard deviation) and values were
compared through the one-way analysis of variance (ANOVA) with the Bonferroni post hoc test for multiple
comparisons. The nonparametric test for discrete variables and non-normal continuous variables was the
Kruskal–Wallis test by ranks. Normality was determined by the Shapiro–Wilk test. Categorical variables
were expressed as total number (percentages) and compared between groups using the Chi-square test or the
Fisher's test as appropriate.
Left ventricular scars were characterized in all patients with myocardial fibrosis detected through LGE by
CMR. Scar localization and extension patterns were classified according to the 17-segment model of the
American Heart Association (AHA) by two experienced cardiac imagers (one cardiologist and one radiolo-
gist). The extension pattern was classified as subendocardial, midwall, subepicardial, or transmural and was
compared between the three groups of patients according to the LVEF through the nonparametric Kruskal–
Wallis test by ranks with the powerful Benjamini and Hochberg adjustment method. An LVEF measurement
under 40% was considered as evidence of heart failure or cardiomyopathy. The extension pattern was related
to the segment involved and it was also associated with an abnormal LVEF. A confidence level of 95% was
used to considered test results statistically significant. All statistical analyses were performed using the R
language.[30]
RESULTS

Table 1 summarizes the clinical features of Chagas cardiomyopathy patients classified by groups according
to the LVEF. The mean age of all patients was 59.1 years (ranging from 31 to 81), 57.6% (n=68) were
women, and the mean body mass index was 25.9 (SD 4.1). Some patients suffered from high blood pressure
(39.8%; n=47), diabetes mellitus (7.6%; n=9), dyslipidemia (11.8%; n=14) or were smokers (2.5%; n=3).
The patients belong to the NYHA functional class I (49.1%: n=58), II (48.3%; n=57), and III (2.5%; n=3).

Table 1. Clinical characteristics of Chagas cardiomyopathy disease patients classified by groups. G1 (LVEF 
≥ 60%; n=43), G2 (41% > LVEF < 59%; n=49), and G3 (LVEF ≤40%; n=26).

Total G1 G2 G3 p-value
n=118 n=43 n=49 n=26
Gender (female) 68 (57.6) 33 (76.7) 21 (42.8) 14 (53.8) 0.01(1-2, 1-3)
Age (years) 59.1 (10.7) 59.1 (11.6) 56.6 (10.3) 63.5 (8.6) 0.02(2-3)
BMI (kg/m2) 25.9 (4.1) 26.6 (3.9) 25.5 (3.5 ) 25.5 (4.8) 0.28
Hypertension 47 (39.8) 21 (48.8) 12 (24.5) 14 (53.8) 0.02(1-2, 2-3)
Type 2 diabetes 9 (7.6) 4 (9.3) 2 (4.1) 3 (11.5) 0.45
DLP 14 (11.8) 8 (18.6) 0 6 (23.1) 0.01(1-2, 2-3)
Smoke 3 (2.5) 0 2 (4.1) 1 (3.8) 0.41
NYHA > I 58 (49.1) 20 (46.5) 17 (34.7) 21 (80.1) 0.01(1-3, 2-3)
CMR
LGE 76 (64.4) 19 (44.2) 34 (69.4) 23 (88.5) 0.01*
RVEF 53.9 (9.5) 58.9 (5.9) 54.0 (6.7) 41.3 (13.6) 0.01*
Edema 16 (13.6) 3 (6.9) 6 (12.2) 7 (26.9) 0.06
Segments with fibrosis 3.3 (2.2) 2.8 (2.7) 2.7 (1.8) 4.1 (1.9) 0.01(1-3, 2-3)
LV Telediastolic volume 170.2 (78.7) 124.1 (31.8) 157.2 (44.1) 272.8 (93.6) 0.01*
LV Telediastolic vol. index 97.6 (46.4) 71.4 (17.0) 87.0 (26.5) 161.6 (51.8) 0.01*
LV Telesystolic volume 92.9 (76.9) 44.2 (15.1) 73.4 (27.8) 210.3 (81.4) 0.01*
LV Telesystolic vol. index 53.1 (45.3) 24.7 (7.8) 40.6 (17.1) 123.7 (45.8) 0.01*
LV Mass 103.4 (36.6) 88.6 (19.5) 98.2 (26.5) 141.4 (70.1) 0.01(1-3, 2-3)
LV Mass index 58.2 (17.4) 49.6 (13.1) 52.8 (15.8) 87.1 (19.9) 0.01(1-3, 2-3)
RV Telediastolic volume 142.9 (58.3) 123.2 (37.6) 146.1 (43.9) 169.1 (91.8) 0.01(1-2, 1-3)
RV Telediastolic vol. index 81.3 (31.8) 70.4 (19.8) 81.2 (24.1) 99.7 (49.1) 0.01(1-2, 1-3)
RV Telesystolic volume 69.9 (46.3) 50.6 (19.1) 69.1 (26.6) 104.1 (78.9) 0.01(1-2, 1-3)
RV Telesystolic vol. index 40.3 (25.8) 29.1 (10.1) 38.1 (14.7) 63.2 (42.1) 0.01*
Laboratory
 Creatinine 0.91 (0.21) 0.86 (0.22) 0.87 (0.16) 1.07 (0.2) 0.01(1-3, 2-3)
BUN 16.8 (5.8) 16.4 (3.1) 15.6 (2.8) 19.4 (10.7) 0.84
Data are expressed as mean (standard deviation) or number (%) for discrete variables. BMI: body mass index; NYHA FC: New York
Heart Association functional class. * indicates statistically significant post hoc comparisons between all groups otherwise indicates
different groups.

Myocardial fibrosis was present in 76 (64.4%) patients, 23 (88.5%) of G3, 34 of G2 (69.4%) and 19 (44.2%)
of G1. G3 and G2 patients had a lower RVEF (p<0.01) and a higher LV telediastolic volume (p<0.01), LV
telediastolic volume index (p<0.01), LV telesystolic volume (p<0.01), LV telesystolic volume index
(p<0.01), RV telesystolic volume index (p<0.01), RV telediastolic volume (p<0.01), RV telediastolic vol-
ume index (p<0.01), and RV telesystolic volume (p<0.01). LV mass and LV mass index were significantly
higher in G3 patients (p<0.01). G3 patients had a greater number of scarred segments compared to the other
groups. Patients with LVEF ≥ 60% had left ventricular fibrosis in up to three cardiac segments, and those
with lower LVEF had up to 10 segments with myocardial fibrosis. Although edema was observed in a
greater proportion in G3 patients, there was no significant difference between the groups.
A total of 235 scars was identified in the 76 patients with myocardial fibrosis. Left ventricular scars location
and distribution patterns classified according to the 17-segment model of the American Heart Association
(AHA) presented in Figure 1 (upper left). The basal region was the most affected (43.8%; n = 103) followed
by the apical (28.9%; n = 68) and the midventricular region (25.9%; n = 61). As depicted in Figure 1, in gen-
eral, left ventricular scars were mainly located in the basal inferolateral segment (segment 5; 22.4%; n = 52),
followed by the apex (segment 17; 14.7%; n = 34), the midventricular inferolateral (segment 11; 11.6%; n =
27), and the neighboring mid anterolateral (segment 12; 6.9%; n = 16), lateral apical (segment 16; 6.5%; n =
15), basal anterolateral (segment 6; 6.5%; n = 15) and basal inferior (segment 4; 6.1%; n = 14) segments.
The least affected were the basal anterior (segment 1; 0.9%; n = 2), midventricular anterior (segment 7;
0.4%; n = 1), apical anterior (segment 13; 2.2%; n = 5), mid anteroseptal (segment 8; 1.7%; n = 4), mid in-
feroseptal (segment 9; 2.2%; n = 5) and apical septal (segment 14; 2.6%; n = 6) segments. As also shown in
Figure 1, a concentration of left ventricle scars in the basal inferolateral (segment 5; 29.2%; n = 14) and mid-
ventricular inferolateral (segment 11; 12.5%; n = 6) segments is observed in patients with LVEF ≥ 60%. A
null involvement of the anterior basal (segment 1), mid anterior (segment 7) and apical anterior (segment
13) segments is also noticed in those patients. Continuously, as the LVEF decreases (LVEF 41%-59%), a
lower proportion of fibrosis is observed in these segments and an expansion to neighboring segments is de-
tected such as in the mid anterolateral (segment 12; 8.0%; n = 7) and the basal anterolateral (segment 6;
9.0%; n = 7) segments, as well as a greater apex involvement (segment 17; 14.8%; n = 13). No involvement
of the basal anterior (segment 1) was detected in these patients. Finally, when there is evidence of heart fail-
ure (i.e. LVEF ≤40%), a further involvement of the apex (segment 17; 17.7%; n = 17) is evident as well as a
greater myocardial fibrosis in other segments such as the basal anteroseptal (segment 2; 8.3%; n = 8), apical
inferior (segment 15; 6.2%; n = 6), mid inferior (segment 10; 4.2%; n = 4), apical anterior (segment 13;
3.1%; n = 3) and septal apical (segment 14; 3.1%; n = 3) segments. In patients with the lowest LVEF
(<40%), no scars were observed in the mid anterior (segment 7) mid anteroseptal (segment 8) and mid infer-
oseptal (segment 9) segments. In the three different groups of LVEF there were always left ventricular scars
in the apical region, these being in a smaller proportion in the group LVEF ≥ 60% and in greater proportion
in the group LVEF ≤40%.
Forty-seven (61.8%) patients with myocardial fibrosis had at least three segments with a left ventricular scar
and just twenty (26.3%) had a left ventricular scar in a unique segment. Two patients (2.6%) had left ventric-
ular scar in six segments, two patients in seven segments and the other two patients in ten segments. Of the
twenty patients with compromise in a single segment, the scar was mainly located in the basal inferolateral
(segment 5; 75%; n=15) segment, followed by the apex (segment 17; 15%; n=3) and the mid inferior (seg-
ment 10; 5%, n=1) segment.
Relating to the extension, most of the reported scars had a transmural pattern (28.1%; n = 66) followed by
midwall (21.7%; n = 51), midwall/subepicardial (16.6%; n = 39), exclusively subendocardial (11.9%; n =
28), exclusively subepicardial (10.6%; n = 25), and midwall/subendocardial (9.4%; n = 22) pattern. A mid-
wall extension was observed more frequently in scars located in the mid anteroseptal (segment 8, 100%, n =
4), basal inferoseptal (segment 3; 85.7%, n = 6), basal anteroseptal (segment 2; 76.9%, n = 10), basal infe-
rior (segment 4; 64.3%, n = 9), mid inferior (segment 10; 62.5%, n = 5), mid inferoseptal (segment 9; 60%, n
= 3), basal inferolateral (segment 5; 57.7%, n = 30), mid inferolateral (segment 11; 56.2%, n = 9) and basal
anterolateral (segment 6; 53.3%, n = 8) segments. In addition, a transmural extension was observed mainly in
scars located in the apex (segment 17, 73.5%, n = 25), apical septal (segment 14, 66.7%, n = 4) and apical
anterior (segment 13, 60.0%, n = 4) segments. There was a subepicardial involvement in all scars found in
the basal anterior segment (segment 1, 100%, n = 2) and a subendocardial involvement in the only scar found
in the mid anterior region (segment 7, 100%, n = 1). Scars located in the apical anterior (segment 13), apical
septal (segment 14), apical inferior (segment 15) and apical lateral (segment 16) segments presented a trans-
mural pattern in more than 40% of the cases. In the segments basal anterior (segment 1), basal inferoseptal
(segment 3), mid anterior (segment 7), mid anteroseptal (segment 8) and mid inferoseptal (segment 9) a
transmural pattern was never reported.
As shown in Figure 1, when the extension of the left ventricle scars was compared between the three groups
of patients according to the LVEF, a clear expansion of the scars was evidenced in the basal and midventric-
ular regions. Thus, a spread with an apparent midwall origin in patients with higher LVEF was observed, fol-
lowed by a midwall/subepicardial expansion and a subsequent transmural involvement in patients with evi-
dence of heart failure. As also shown in Figure 1, this midwall-transmural extension pattern is not evident for
the apical region, where few left-ventricular scars presented a midwall extension pattern in patients with evi-
dence of heart failure or cardiomyopathy, and a large number of scars presented a transmural extension in
patients with high LVEF. This demonstrated that the left-ventricular scar extension in patients with Chagas
cardiomyopathy is not homogenous for all cardiac regions.

DISCUSSION
This cross-sectional design study demonstrates a regional non-homogeneous midwall-transmural pattern of
the left ventricular scar, as detected by the presence of LGE, in patients with Chagas cardiomyopathy. Fur-
ther, it shows the association between the extension pattern and clinical events associated with disease sever-
ity. Myocardial fibrosis was present in 76 (64.4%) patients with Chagas cardiomyopathy, which coincides
with a similar prevalence of fibrosis between 58-73% previously reported.[16, 25, 26, 29] In addition, a total
of 235 scars was identified mainly located in the basal inferolateral segment, followed by the apex and the
mid inferolateral segment. This result corresponds with previous works reporting the presence of wall motion
abnormalities and delayed enhancement more frequently in the inferolateral,[25, 27] apical,[25, 27] lateral,
[26] and inferior segments.[26] Furthermore, as LVEF decreased, a greater apex involvement was detected,
as well as an expansion towards neighboring segments. Although previous efforts focused on determining
an accurate pattern of left ventricular scar extension have been published,[26, 27, 29] no pattern was specifi-
cally related to the outcomes. Volpe et al.[26] reported a transmural, focal, or diffuse scar in approximately
one-third of patients with positive LGE myocardial fibrosis. Likewise, Regueiro et al.[27] described a de-
layed enhancement mainly transmural and subendocardial, in the myocardial and related to larger cardiac
chambers and worse systolic function. We found that most of the reported scars had a transmural or midwall
extension patterns. In addition, it was clearly evidenced a pattern of extension in the basal and midventricular
regions with an apparent midwall origin, followed by a midwall/subepicardial extension and subsequently
exhibiting a transmural involvement. This pattern of the extension was not evident in the apical region, indi-
cating a heterogeneous progression. However, apical fibrosis was strongly associated with major adverse
outcomes.
In relation to disease severity, G3 and G2 patients had a lower RVEF and a higher LV telediastolic volume/
index, LV telesystolic volume/index, RV telesystolic volume/index, RV telediastolic volume/index, and RV
telesystolic volume/index. LV mass and LV mass index were significantly higher in G3 patients. In relation
to the NYHA functional class classification, this was higher in G3 patients. Rochitte et al.[29] similarly
quantified an increase in myocardial fibrosis across disease severity subgroups and NYHA functional
classes. We found that patients with evidence of heart failure had a greater number of scarred segments com-
pared to the other groups.
Some study limitations should be recognized. As the patients were recruited from the cardiology, electro-
physiology, emergency, and in-hospital services of seven reference centers of Bogotá, the results of this non-
probability sampling cannot be generalized to the target population because of the potential bias of the sam-
pling and the consequent under-representation of subgroups in comparison to the population with Chagas
cardiomyopathy. Although this bias of the sample cannot be measured, we found that some variables that
could potentially affect the results were homogeneous between the groups as the body mass index, the pres-
ence of diabetes and the fact of being a smoker. However, albeit its importance in Chagas disease pathophys-
iology is not fully elucidated, other factors such as age, gender, and the presence of high blood pressure were
not homogeneous between the groups.
This study was conducted in Bogotá, Colombia, and there are uncertainties whether our results can be gener-
alized to other parts of the world, as environmental and cultural factors may play a role in the disease dynam-
ics. In addition, this study was carried out in an urban region, and although many people came from rural ar-
eas, the exclusion of a highly vulnerable patient population who do not have access to urban health systems
may underestimate the measure of cardiovascular outcomes in individuals with Chagas cardiomyopathy and
may not be generalizable to the risk population.

CONCLUSION

This study evidenced for the first time a pattern of the left ventricular scar in Chagas cardiomyopathy. We
found that most of the reported scars in patients with Chagas cardimyopathy had a transmural or midwall ex-
tension patterns. In addition, it was clearly evidenced a pattern of extension in the basal and midventricular
regions with an apparent midwall origin, followed by a midwall/subepicardial extension and subsequently
exhibiting a transmural involvement. This pattern of the extension was not evident in the apical region, indi-
cating a heterogeneous progression. However, apical fibrosis was strongly associated with major adverse
outcomes.

ACKNOWLEDGMENTS

Special thanks go to Tania Sanchez Vargas for the support in the constant updating of the database.

FUNDING

This work was supported by the “Departamento Administrativo de Ciencia, Tecnología e Innovación -COL-
CIENCIAS” (Convocatoria 744/2016).

FIGURE LEGEND
Figure 1. Upper Left: Illustration of the 17-segment model of the American Heart Association (upper left)
used to determine the location of scars. Basal (green), mid-ventricular (purple) and apical (orange) regions
are represented as well as LAD - left anterior descending (dark); RCA-right coronary artery (medium trans-
parency) and LCX - left circumflex (light) areas are discriminated. Segments are shown in numbers as 1:
basal anterior; 2: basal anteroseptal; 3: basal inferoseptal; 4: basal inferior; 5: basal inferolateral; 6: basal an-
terolateral; 7: mid anterior; 8: mid anteroseptal; 9: mid inferoseptal; 10: mid inferior; 11: mid inferolateral;
12: mid anterolateral; 13: apical anterior; 14: apical septal; 15: apical inferior; 16: apical lateral; 17: apex.
Left: Location and distribution proportion of scars in each segment according to the three different groups of
LVEF (G1: EF ≥ 60%; G2: 41% > EF < 59%; G3: EF ≤40%). Right: Extension of scars according to mid-
wall, midwall/subendocardial, midwall/subepicardial and transmural patterns. Asterisks represent the results
of the Kruskal–Wallis test by ranks with the powerful BH adjustment method. A different number of aster-
isks represents a statistically significant difference between the groups. Median/standard deviation bars are
shown for basal (green), mid-ventricular (purple) and apical (orange) regions. Orange light ovals represent
left-ventricular scars with apical distribution, where few presented a midwall extension pattern in patients
with evidence of heart failure or cardiomyopathy, and a large number distributed mainly in the apex pre-
sented a transmural extension in patients with high LVEF.

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