Left-ventricular scar progression in Chagas cardiomyopathy

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Corresponding author
Andrés Diaz; Postal address: Cll 135 # 17A - 77, Bogotá, Colombia; e-mail: andresdiaz1992@live.com;
phone: +57 3176784894.
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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.
Juan José Diaztagle, Internal Medicine Service, Hospital San José, Bogotá, Colombia. Fundación
Universitaria de Ciencias de la Salud, Bogotá, Colombia; Department of Medicine, Universidad Nacional de
Colombia, Bogotá, Colombia.
Alejandro Olaya, Department of Cardiology, Hospital San José, Bogotá, Colombia; Fundación Universitaria
de Ciencias de la Salud, Bogotá, Colombia.
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,
Argentina.
Carolina Ayala, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia. Escola de Doctorat,
Universitat de Barcelona, Barcelona, Spain.
Gina Polo, Statistical Analysis and Research Consulting, Bogotá, Colombia.
Néstor Galizio, Department of Electrophysiology and Arrhythmias, Hospital Universitario Fundación
Favaloro, Buenos Aires, Argentina.
Frida T. Manrique, Department of Diagnostic Imaging, Fundación Cardioinfantil, Bogotá, Colombia
Julian F. Forero, Department of Diagnostic Imaging, Fundación Cardioinfantil, Bogotá, Colombia
Hector M. Medina, 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.
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ABSTRACT
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Objective: This cross-sectional study established a pattern of left ventricular scar progression in Chagas
cardiomyopathy and its association with parameters of disease severity. Methods: Late gadolinium
enhancement images were obtained from 118 Chagas seropositive patients (57.6% females; age = 59.1 ± 
10.7) without ischemic heart disease or conditions that cause myocardial fibrosis and dilation. Patients were
grouped according to the left ventricular (LV) ejection fraction (EF) as G1 (EF ≥ 60%; n=43), G2 (41% > EF 
< 59%; n=49), and G3 (EF ≤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) extension
pattern. The basal and midventricular regions revealed an evident pattern of scar progression, with an
apparent midwall origin, followed by a midwall/subepicardial extension and subsequently exhibiting a
transmural involvement. This pattern of progression was not evident in the apical region. Conclusion: A
regional non-homogeneous midwall-transmural pattern of left ventricular scar progression was evidenced in
patients with Chagas cardiomyopathy. Apical fibrosis was strongly associated with major adverse outcomes.
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KEY QUESTIONS
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What is already known about this subject?
International efforts for controlling Chagas disease have enabled important advances. However, efforts to
understand Chagas cardiomyopathy progression are still not enough for the avoidance of lethal cases.
Previous attempts focused on determining an accurate pattern of left ventricular scar progression have been
published, however, no pattern has been specifically related to these outcomes.
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What does this study add?
This study established a pattern of left ventricular scar progression in Chagas cardiomyopathy and its
association with markers of disease severity.
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How might this impact on clinical practice?
Our findings support decisions regarding therapy, including heart transplantation, based on a best knowledge
of the long-term prognosis of the affected patients with Chagas cardiomyopathy. This will allow optimization
of resources and prevention of lethality.
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INTRODUCTION
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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-
vectorial 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 transmission,[8]. Chagas
disease occurs chiefly 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 movement of people 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 has been calculated in 0.29%,
being the highest seroprevalence found in Bolivia (22.8%), Guatemala (3.9%), and Peru (3.8%).[12]
Although international 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, treatment and control of this disease are still necessary, mainly in rural areas.
Moreover, efforts focused on the diagnosis, treatment, and understanding of the cardiac involvement
progression, and its association with parameters of disease severity are fundamental for the avoidance of
lethal cases. Chronic cardiomyopathy is the most serious manifestation of Chagas disease, affecting
approximately one-third of individuals with positive serology for Chagas,[14] and in severe cases, the only
treatment option is heart transplantation.[15] Cardiac magnetic resonance (CMR) is a non-invasive sensitive
technique to detect myocardial necrosis or fibrosis through contrast delayed enhancement techniques,[16-18]
which allows a precise delimitation of scar areas according to histological findings,[19] and works as a
predictor of poor prognosis in nonischemic cardiomyopathy.[20] In addition, late gadolinium enhancement
(LGE) by CMR is promising as a diagnostic and risk-stratifying tool in chronic chagasic cardiomyopathy,
since it is currently the in vivo gold standard for identifying and quantifying myocardial infarction,[21] and
several clinical studies reported its use in a variety of clinical settings, such as ischemic disease, amyloidosis,
aortic valve disease,[22-24] and Chagas disease.[16-18, 25-29] To the best of our knowledge, none of these
preceding studies has identified a pattern of the left ventricular scar progression related to the outcomes. In
this study, the pattern of progression in terms of presence, location, and extension of the left-ventricular scar
in patients with Chagas cardiomyopathy and its association with parameters that comprehend disease
severity is investigated.
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METHODS
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Study population
This study was performed with 118 patients with Chagas diseases recruited from the cardiology,
electrophysiology, emergency, and hospitalization services of seven cardiovascular reference hospitals of
Bogota DC, Colombia between 2018 and 2019. Each patient signed a consent to be part of the study. The
inclusion criteria were patients over 18 years old, positive for Chagas disease according to the CDC criteria,
and two positive laboratory tests for Chagas diseases (immunoenzymatic assay tests ELISA, and indirect
immunofluorescence-IFI). The exclusion criteria considered refusal to participate in the study, diagnosis of
coronary disease, presence of dilated cardiomyopathy of ischemic origin and/or significant valvular disease,
contraindications to magnetic resonance, pregnancy, fever, severe psychiatric disorders, creatinine <30 mL/
minute in a 24-hour depuration test, and contraindication to gadolinium as a contrast medium.
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CMR Examination
CMRs were carried out by specialists in radiology and diagnostic images employing a Philips Ingenia 1.5 T
scanner. The exploration protocol comprised an initial morphological evaluation considering bright and
black-blood gradient-echo sequences in the axial and coronal planes. The functional evaluation considered
maps of T1 and T2 sequences of cine resonance with the technique of steady-state free precession (SSFP).
Additionally, a quantitative functional evaluation was carried out. Structural measures (diastolic and systolic
diameter of the left ventricle, diastolic thickness of the walls, anterior systolic left atrial diameter, volume of
the left atrium in two dimensions, mean lateral diameter of the right ventricle, and presence of pericardial
effusion) and functional measures (ejection fraction of the left ventricle, estimation of pulmonary arterial
pressure, and presence and degrees of mitral and tricuspid regurgitation) were obtained from each patient.
Images of LGE were obtained specifying the presence, location, and extension of left-ventricular scars. The
intravenous contrast material used was Gadobutrol (0.1 mmol/kg), a gadolinium-based MRI contrast agent.
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Data analysis
Patients were grouped according to the left ventricular (LV) ejection fraction (EF) as G1 (EF ≥ 60%; n=43),
G2 (41% > EF < 59%; n=49), and G3 (EF ≤40%; n=26). Well-recognized markers of disease severity (New
York Heart Association (NYHA) functional classification, LVEF, 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
nonnormal 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 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 three experienced radiologists and a cardiologist. 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 percent
was considered as evidence of heart failure or cardiomyopathy. The extension pattern was related to the
segment involved and it was also associated with changes in the LVEF. A confidence level of 95% was used
to considered test results statistically significant. . All statistical analyses were performed using the R
language.[30]
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RESULTS
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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), class II (48.3%; n=57), and class III
(2.5%; n=3).
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Table 1. Clinical characteristics of Chagas cardiomyopathy disease patients classified by groups according to
the LVEF as G1 (EF ≥ 60%; n=43), G2 (41% > EF < 59%; n=49), and G3 (EF ≤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
Age (years) 59.1 (10.7) 59.1 (11.6) 56.6 (10.3) 63.5 (8.6) 0.02
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
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
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
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
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
LV Mass index 58.2 (17.4) 49.6 (13.1) 52.8 (15.8) 87.1 (19.9) 0.01
RV Telediastolic volume 142.9 (58.3) 123.2 (37.6) 146.1 (43.9) 169.1 (91.8) 0.01
RV Telediastolic vol. index 81.3 (31.8) 70.4 (19.8) 81.2 (24.1) 99.7 (49.1) 0.01
RV Telesystolic volume 69.9 (46.3) 50.6 (19.1) 69.1 (26.6) 104.1 (78.9) 0.01
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
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.
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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
volume 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 scar segments 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 general, 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 inferoseptal (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 midventricular 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 detected 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 also detected in these patients. Finally, when there is
evidence of heart failure (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 inferoseptal (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
ventricular 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 (segment 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) patterns. A
midwall extension pattern 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 inferior (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 pattern 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 transmural 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 pattern of the left ventricle scars was compared between the three
groups of patients according to the LVEF, a clear progression of Chagas cardiomyopathy was evidenced for
the basal and midventricular regions. Thus, a spread with an apparent midwall origin in patients with higher
LVEF, followed by a midwall/subepicardial extension and a subsequent transmural involvement in patients
with evidence of heart failure was observed. As also shown in Figure 1, this midwall-transmural progression
pattern is not evident for the apical region, where few left-ventricular scars presented a midwall extension
pattern in patients with evidence 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 progression
in patients with Chagas cardiomyopathy is not homogenous for all cardiac regions.
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DISCUSSION
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This cross-sectional design study demonstrates a regional non-homogeneous midwall-transmural pattern of
left ventricular scar progression, as detected by the presence of LGE, in patients with Chagas
cardiomyopathy. Further, it shows the association between the progression pattern and clinical events
associated with disease severity. Myocardial fibrosis was present in 76 (64.4%) patients with Chagas
cardiomyopathy, which coincides with 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 progression have been
published,[26, 27, 29] no pattern was specifically 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 delayed 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 progression 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 progression was not evident in the apical region, indicating a heterogeneous regional
progression. However, apical fibrosis was strongly associated with major adverse outcomes.
In relation to disease severity factors, G3 and G2 patients had a lower RVEF and a higher LV Telediastolic
volume, LV Telediastolic volume index, LV Telesystolic volume, LV Telesystolic volume index, RV
Telesystolic volume index, RV Telediastolic volume, RV Telediastolic volume index, and RV Telesystolic
volume. LV Mass and LV Mass index were significantly higher in G3 patients. In relation to the NYHA
functional class classification, this was higher in the G3. 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 compared to the other
groups.
Some study limitations should be recognized. As the patients were recruited from the cardiology,
electrophysiology, emergency, and hospitalization services of seven cardiovascular reference hospitals, the
results of this non-probability sampling cannot be generalized to the target population because of the
potential bias of the sampling technique and the consequent to under-representation of subgroups in the
sample 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 presence of diabetes and the fact of being a smoker.
However, albeit its importance in Chagas disease pathophysiology 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 Colombia, and there are uncertainties whether our results can be generalized to
other parts of the world, as environmental and cultural factors may play a role in the disease dynamics. In
addition, this study was carried out in an urban region, and although many people came from rural areas, 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.
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CONCLUSION
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This study evidenced a pattern of left ventricular scar progression 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 progression was not evident in the apical region, indicating a non-
homogeneous regional progression.

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ACKNOWLEDGMENTS
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Special thanks go to Tania Sanchez Vargas, Dr. Lorena Gonzalez Russi, Dr. Juan Sebastián Salcedo, Dr.
Camilo Calvache, and Dr. Leonor Mariño.
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FUNDING
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This work was supported by the “Departamento Administrativo de Ciencia, Tecnología e Innovación -
COLCIENCIAS” (Convocatoria 744/2016).
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FIGURE LEGEND
Figure 1. Left: Localization progression according to the 17-segment model of the American Heart
Association (upper left). Basal (green), mid-ventricular (purple) and apical (orange) regions as well as LAD -
left anterior descending (dark); RCA-right coronary artery (medium transparency) and LCX - left circumflex
(light) areas are discriminated. 1: basal anterior; 2: basal anteroseptal; 3: basal inferoseptal; 4: basal inferior;
5: basal inferolateral; 6: basal anterolateral; 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. The location and distribution pattern of 235 left ventricular scars in patients with
myocardial fibrosis detected through LGE by CMR is shown as the percentage of scar in each segment
according to three different groups of LVEF (G1: EF ≥ 60%; G2: 41% > EF < 59%; G3: EF ≤40%). Right:
Extension progression of the Chagas cardiomyopathy according to midwall, midwall/subendocardial,
midwall/subepicardial and transmural patterns, showing p-values obtained from the nonparametric Kruskal–
Wallis test by ranks with the powerful BH adjustment method. 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, presented a
transmural extension in patients with high LVEF.
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