The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas’ Disease: A Study Using Magnetic Resonance

Noya-Rabelo, Marcia Maria; Macedo, Carolina The; Larocca, Ticiana; Machado, Admilson; Pacheco, Thais; Torreão, Jorge; Souza, Bruno Solano de Freitas; Soares, Milena B. P.; Ribeiro-dos-Santos, Ricardo; Correia, Luis Claudio Lemos

doi:10.5935/abc.20180016

Brasil

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Original Article • Arq. Bras. Cardiol. 110 (2) • Feb 2018 • https://doi.org/10.5935/abc.20180016 linkcopy

The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas’ Disease: A Study Using Magnetic Resonance

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background: Previous data has shown that patients in the indeterminate form of Chagas disease may present myocardial fibrosis as shown on through magnetic resonance imaging (MRI). However, there is little information available regarding the degree of severity of myocardial fibrosis in these individuals. This variable has the potential to predict the evolution of Chagas’ disease into its cardiac form.

Objectives: To describe the frequency and extent of myocardial fibrosis evaluated using an MRI in patients in the indeterminate form, and to compare it with other forms of the disease.

Methods: Patients were admitted one after another. Their clinical history was collected and they were submitted to laboratory exams and an MRI.

Results: Sixty-one patients with Chagas’ disease, with an average age of 58 ± 9 years old, 17 patients in the indeterminate form, 16 in the cardiac form without left ventricular (LV) dysfunction and 28 in the cardiac form with LV dysfunction were studied. P <0.05 was considered to be statistically significant. Late enhancement was detected in 37 patients (64%). Myocardial fibrosis was identified in 6 individuals in indeterminate form (41%; 95% CI 23-66) in a proportion similar to that observed in cardiac form without LV dysfunction (44%); p = 1.0. Among the individuals with fibrosis, the total area of the affected myocardium was 4.1% (IIQ: 2.1 - 10.7) in the indeterminate form versus 2.3% (IIQ: 1-5) in the cardiac form without LV (p = 0.18). The left ventricular fraction ejection in subjects in the indeterminate form was similar to that of the individuals in the cardiac form without ventricular dysfunction (p = 0.09).

Conclusion: The presence of fibrosis in the indeterminate form of Chagas’ disease has a frequency and extension similar to that of in the cardiac form without dysfunction, suggesting that the former is part of a subclinical disease spectrum, rather than lacking cardiac involvement.

Keywords: Chagas Disease; Chagas Cardiomyopathy; Fibrosis; Magnetic Resonance Imaging

Variables	Subjects (n = 61)	Indeterminate form (n = 17)	Cardiac form without ventricular dysfunction (n = 16)	Cardiac form with ventricular dysfunction (n = 28)
Demographic characteristics
Age (years), mean ± standard deviation	58 ± 8	59 ± 11	59 ± 9	58 ± 7
Female, n (%)	36 (59)	12 (70)	12 (75)	12 (43)
Lived in a mud house, n (%)	50 (82)	15 (88)	15 (94)	20 (71)
Family members with positive serology, n (%)	39 (64)	11 (65)	14 (88)	14 (50)
Digestive form, n (%)	4 (6.6)	-	2 (12)	2 (7)
Body mass index (kg/m²), mean ± standard deviation	25 ± 4	26 ± 4	27 ± 4	26 ± 3
Comorbidities, n (%)
Arterial hypertension	44 (72)	14 (82)	12 (75)	18 (64)
Diabetes mellitus	9 (15)	4 (23)	-	5 (18)
Syncope	6 (7)	1 (6)	1 (6)	2 (7)
Smoking	16 (26)	3 (18)	3 (18)	10 (36)
Congestive heart failure NYHA III/IV	16 (26)	-	-	16 (57)^* * p < 0.001, Fisher's exact text.
Laboratory characteristics
Creatinine (mg/dL)	0.88 (0.7 - 0.99)	0.84 (0.7 - 0.98)	0.78 (0.6 - 0.91)	0.94 (0.7 - 1.0)
Sodium (mmoL/dL)	140 ± 3	138 ± 2	139 ± 2	139 ± 2
Hemoglobin (g/dL)	13.9 ± 0.9	14.2 ± 1.3	13.4 ± 0.7	14.2 ± 1.0
Total Cholesterol (mg/dL)	193 ± 38	202 ± 40	194 ± 42	200 ± 45
Reactive C protein (mg/dL)	1.15 (0.63 - 4.02)	1.71 (0.35 - 6.54)	1.24 (0.51 - 4.74)	1.09 (0.73 - 3.62)
NT-ProBNP (pg/mL)	686 (66 - 816)	60.5 (34 - 108)	96.0 (73 - 181)	839.5^ p < 0.001, Kruskal-Wallis one-way analysis of variance. (189 - 2271)
Troponin I (ng/mL)	0.684 (0.012 - 0.04)	0.012 (0.012 - 0.012)	0.012 (0.012 - 0.028)	0.038 (0.019 - 0.06)
LVEF (%)	54 ± 15	64 ± 3	64 ± 4	43 ± 10^* * p < 0.001, Fisher's exact text.
METS	9 ± 2.5	12 ± 3	9 ± 2	8 ± 2

Variables	Indeterminate form (n = 17)	Cardiac form without ventricular dysfunction (n = 16)	p value
Rassi Score	2 (0 - 2)	6 (1 - 8)	0.30^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
Area of fibrosis from the CMR (%)	4.1 (2.1 - 10.7)	2.3 (1 - 5)	0.18^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
LV ejection fraction (%)	72 ± 8	67 ± 6	0.09^† † Student's t test;
Ventricular Tachycardia (%)	-	20	0.001^* * Fisher's exact test;
METS	10 ± 3	9.4 ± 2	0.60^† † Student's t test;
Maximum VO₂	35 ± 10	33 ± 7	0.47^† † Student's t test;
NT-ProBNP (pg/mL)	125 (34 - 108)	171 (73 - 181)	0.61^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
Ultrasensitive PCR (mg/L)	1.7 (0.35 - 6.5)	1.2 (0.51 - 4.7)	0.40^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
Troponin I (ng/mL)	0.012 (0.0 - 0.012)	0.012 (0.012 - 0.028)	0.31^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
IL-2 (pg/mL)	0.21 (0.03 - 0.55)	0.27 (0.03 - 0.96)	0.14^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
IL-4 (pg/mL)	0.62 (0.00 - 1.6)	0.37 (0.2 - 2.2)	0.83^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
IL-6 (pg/mL)	2.26 (1.39 - 4.35)	3.98 (2.01 - 6.22)	0.50^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
IL-10 (pg/mL)	0.44 (0.19 - 1.06)	0.63 (0.50 - 1.61)	1.47^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
TNF-alfa (pg/mL)	0.48 (0.14 - 1.15)	0.72 (0.58 - 2.71)	1.16^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.
IFN-gama (pg/mL)	2.07 (1.30 - 4.35)	2.15 (1.69 - 6.73)	0.51^‡ ‡ Mann-Whitney's test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.

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[TFN1] NYHA: New York Heart Association; NT-ProBNP: N-terminal pro B-type natriuretic peptide; LVEF: left ventricular ejection fraction; METS: metabolic equivalent of task. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution.

[TFN2] ^*
p < 0.001, Fisher's exact text.

[TFN3] ^**
p < 0.001, Kruskal-Wallis one-way analysis of variance.