International Journal of Cardiology 176 (2014) 1352–1354
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Assessment of the source of ischemic cerebrovascular events in patients with Chagas disease☆ José Olímpio Dias Junior a, Manoel Otávio da Costa Rocha a, Aline Cristina de Souza a, Lucas Jordan Kreuser b, Laura Alves de Souza Dias a, Timothy C. Tan c, Antônio Lúcio Teixeira a, Maria Carmo P. Nunes a,⁎ a b c
Post-Graduate Program in Infectious Diseases and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil University of Minnesota Medical School, Minneapolis, MN, USA Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 7 July 2014 Received in revised form 27 July 2014 Accepted 28 July 2014 Available online 6 August 2014 Keywords: Chagas disease Stroke Ischemic cerebrovascular events Echocardiography Carotid intima-media thickness
Chagas disease (ChD) remains a major public health problem in Latin America and it is an emerging disease in non-endemic countries [1]. ChD is an important cause of ischemic cerebrovascular events (ICE), which result in a substantial long-term disability [2–5] and risk of death [6]. Cardioembolic source for thrombi is considered to be the main pathophysiological mechanism, related to apical aneurysms, heart failure and arrhythmias [2]. However, ChD also compromises microvasculature function, which may contribute to the risk of ischemic events [7]. The vascular dysfunction in Chagas disease is multifactorial, involving infection-associated microvascular spasm, reduction in blood flow, increased platelet aggregation, and increased myocardial inflammation and fibrosis [7]. Although vascular inflammatory injuries have been associated with Trypanosoma cruzi infection in animal experimental studies [8], the association between the vasculopathy in Chagas disease and ischemic events has not been studied in a clinical setting. ☆ This study was partly supported by grants from Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasília, Brazil, and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Belo Horizonte, Brazil. ⁎ Corresponding author at: Department of Internal Medicine, School of Medicine of the Federal University of Minas Gerais, Av. Professor Alfredo Balena, 190, Santa Efigênia, 30130 100 Belo Horizonte, MG, Brazil. Tel.: +55 31 34099746; fax: +55 31 34099437. E-mail address: [email protected] (M.C.P. Nunes).
http://dx.doi.org/10.1016/j.ijcard.2014.07.266 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Vascular ultrasound allows noninvasive quantitative assessment of arterial properties by quantification of parameters linked to wall stiffness. Increased arterial stiffness and carotid intima–media thickness (IMT) are considered independent predictors of cardiovascular events including cerebrovascular ischemic events [9]. Therefore, this study was design to assess the potential source of ischemic events in patients with ChD disease who had ICE by comprehensively evaluating cardiac chambers, and the morphology and function of the carotid arteries, especially focusing on carotid stiffness and IMT. Patients were recruited prospectively from a tertiary center for Infectious and Parasitic Diseases at Federal University of Minas Gerais, Brazil. The study enrolled 26 ChD patients with ICE who were matched by age, sex, NYHA functional class, left ventricular ejection fraction and cardiovascular risk factors for ICE and 26 randomly selected ChD patients who did not have any ICE. Patients with other cardiac or systemic disease that could independently affect morphological and functional properties of carotid arteries were excluded. In addition, patients with atrial fibrillation were also excluded. All enrolled patients underwent clinical and neurological examination, electrocardiogram (ECG), standard transthoracic echocardiogram and carotid ultrasound. Ultrasound assessment of intima–media thickness and carotid stiffness was performed as previously reported using an Esaote My Lab 60 ultrasound machine and a high multifrequency (3 or 11 MHz) linear array transducer (Fig. 1). The indices of carotid stiffness were estimated by measuring the diameter (D) and its change during the heart cycle (stroke change in diameter, or distension [ΔD]) from ultrasound data in conjunction with the local pulse pressure [10]. All ultrasound measurements were performed by a single investigator blinded to the clinical evaluation of the patients. The values presented are an average of three measurements over three cardiac cycles. Categorical variables, expressed as numbers and percentages, were compared by a chi-square test, whereas continuous data, expressed as mean ± SD and median (interquartile range) were compared using unpaired t-test or the Mann–Whitney U test, when appropriate. Statistical analysis was performed using the Statistical Package for Social Sciences for Windows, version 18.0 (SPSS Inc., Chicago, Illinois). The classification of the ICE is shown in Table 1. There was a predominance of cardioembolic stroke (89%), largely compromising the anterior circulation (70%) with low frequency of long term disabling sequelae.
J.O. Dias Junior et al. / International Journal of Cardiology 176 (2014) 1352–1354
1353
Fig. 1. A: Measurement of right carotid intima–media thickness; B: Quantitative measurement of right common carotid artery stiffness.
Demographic and clinical features of ChD patients with and without ICE are shown in Table 2. Mean age of the patients with ICE was 49 ± 14 years with 54% being male, similar to the patients without ICE. Diastolic blood pressure was higher in patients with ICE compared to those without ICE, although still within the normal range. Pharmacological treatment differed only in the use of oral anticoagulants, which was increased in the case group, based on a clinical indication. Echocardiographic parameters were similar between the groups, with the exception of the presence of an apical aneurysm, which was more frequent in the patients with ICE. Eight patients had LV apical thrombus, all of whom had ICE. Atherosclerotic plaques in the carotids were detected in 22 patients, including 39% of cases and 46% of controls (p = 0.390). There was no difference between the groups in relation to the distribution and morphological characteristics of the atherosclerotic plaques, as well as in carotid IMT. Local systolic and diastolic blood pressures calculated from the exploration of the right and left common carotid arteries differed between groups, being higher in ICE patients. There was no difference between the case and control groups in relation to the variation in diameter, coefficient of compliance and pulse wave velocity. The local BP readings obtained from the exploration of the right and left common carotid arteries were higher in patients with ICE. These values, however, were within normal limits. The present study explores the potential contribution of vascular disease to ischemic events in patients with ChD. The results demonstrate that in a cohort of ChD patients with and without ICE matched for age, gender, and severity of myocardial dysfunction, a cardiac source of thrombi was the main cause of ICE. The carotid IMT was similar between cases and controls, suggesting that a carotid vascular atherosclerotic event did not contribute significantly in the genesis of ICE in ChD. In this study, the main pathophysiological mechanism of stroke in the setting of Chagas disease was a cardiac source of embolism.
Table 1 Classification of ischemic cerebrovascular events according to Rankin scale, Barthel indices, Bamford and TOAST classification of the ChD patients. Rankin scalea
Barthel index Oxfordshire classification
TOAST classification a
Class 0 — asymptomatic Class 1 — symptoms without disability Class 2 — mild disability Class 3 — moderate disability Fully independent Mildly dependent Lacunar syndromes Total anterior circulation syndromes Partial anterior circulation syndromes Cardioembolism Small-vessel occlusion
Values are expressed as absolute numbers (percentage).
10 (39) 3 (11) 9 (34) 4 (14) 18 (72) 8 (18) 3 (14) 3 (14) 14 (70) 23 (89) 3 (11)
Accordingly, the presence of an apical aneurysm and thrombi were more frequent in patients with ICE than in matched-controls. This result is consistent with other studies [2,4,11]. Apical aneurysms are characteristic lesions of ChD, and besides the potential impairment of ventricular systolic (LV) function, is associated with thromboembolic events, and may constitute an arrhythmogenic focus. Therefore, this study reinforces the significance of apical aneurysms and LV thrombi in the genesis of ischemic cerebrovascular events in patients with ChD. Atherosclerotic lesions have been described as a potential cause of ICE in patients with ChD, with a prevalence of atherosclerotic cerebrovascular disease reported at 8.5% and hemodynamically significant carotid stenosis in 1.1% of patients [4]. Carotid IMT is recognized as a surrogate marker of atherosclerosis and has been shown implicated in the prediction of future cardiovascular events in asymptomatic individuals [12]. In the present study, no differences were seen between groups suggesting that atherosclerotic cerebral events are an unlikely cause of ischemic stroke in these patients. Other vascular measures such as decreased elasticity and increased stiffness in large and medium caliber arteries have also been shown to be associated with cardiovascular risk factors [10]. In our cohort, there was no significant difference in the tensile properties of the carotid arterial walls, between the groups. Our results are comparable to Villacorta et al., which also did not support changes in the elasticity properties of blood vessels in ChD patients compared to healthy subjects [13]. Regarding carotid arterial stiffness, patients with ICE had higher carotid arteries' local systolic and diastolic blood pressures. In our study, brachial diastolic blood pressure differed between the two groups, whereas systolic blood pressure was similar. The difference in the values of the diastolic blood pressure between the two groups may partly explain why the local diastolic carotid pressure was higher in patients compared to controls. Although Chagas disease patients who have suffered ICE have a highrisk of cardiogenic embolism, the precise mechanism is often difficult to determine. The determinants of increased arterial stiffness are complex and we cannot rule out the possibility of endothelial cell changes caused by ChD to be potentially relevant in the etiopathogenesis of ischemic events. Apical aneurysm and intracavitary thrombi are the main factors associated with cerebrovascular ischemic events in Chagas disease patients. Subclinical atherosclerosis assessed by carotid IMT did not appear to have a major role in the genesis of ischemic events in Chagas disease. Carotid blood pressures were higher in patients with ICE compared to matched-controls, and further studies to identify the determinants of increased arterial stiffness are needed. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
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J.O. Dias Junior et al. / International Journal of Cardiology 176 (2014) 1352–1354
Table 2 Characteristics of the Chagas disease patients with ischemic cerebrovascular events compared to those without events. Variablesa Clinical data Age (years) Male Smoking Hyperlipidemia NYHA functional class I/II III/IV Heart rate (bpm) Systolic arterial pressure (mm Hg) Diastolic arterial pressure (mm Hg) Electrocardiographic parameters RBBB plus LAFB LBBB PVC ST–T abnormalities Echocardiographic parameters LVDd (mm) LVSd (mm) LVEF (%) LA volume index (ml/m2) Apical aneurysm E/e′ ratio
Patients with ICE
Patients without ICE
P value
49 ± 14 14 (54) 3 (12) 10 (38) 17 (65) 9 (35) 68 ± 2 119 ± 17
51 ± 11 14 (54) 3 (12) 5 (19) 22 (85) 4 (14) 66 ± 2 111 ± 19
0.465 0.303
77 ± 9
70 ± 10
0.043
13 (50) 3 (12) 4 (14) 8 (31)
11 (42) 2 (8) 6 (23) 9 (35)
0.803 0.500 0.517 0.893
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References
57.9 44.0 49.7 36.6
± ± ± ±
9.1 11.0 12.9 18.9
57.4 43.0 49.9 38.3
± ± ± ±
8.4 10.3 13.5 18.6
0.192 1.000 0.666 0.110 0.100
0.817 0.547 0.909 0.756 b0.001 0.618
22 (85) 7.7 ± 2.7
5 (19) 7.3 ± 2.4
Carotid intima–media thickness (IMT) RCC mean LCC mean
0.62 ± 0.18 0.64 ± 0.18
0.64 ± 0.17 0.67 ± 0.13
0.694 0.589
Carotid stiffness parametersb RCC D (μm) CC (m2 kPa−1) PWV (m/s) LSP (mm Hg) LDP (mm Hg) LCC D (μm) CC (m2 kPa−1) PWV (m/s) LSP (mm Hg) LDP (mm Hg)
255 [178–378] 0.65 [0.4–1.3] 7.3 [5.4–9.8] 107 [94–119] 80 [70–80] 267 [198–378] 0.80 [0.6–1.4] 7.0 [5.4–8.6] 107 [94–116] 80 [70–80]
253 [171–341] 0.78 [0.5–1.2] 7.9 [5.7–9.2] 98 [91–109] 65 [60–80] 271 [183–350] 0.72 [0.5–0.9] 7.5 [6.3–8.3] 97 [89–110] 65 [60 –80]
0.721 0.993 0.528 0.049 0.007 0.469 0.318 0.552 0.048 0.008
CC = compliance coefficient; D = distensibility; E/e′ = ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity; ICE = ischemic cerebrovascular events; LA = left atrial; LVDd = left ventricular end-diastolic diameter; LVEF = left ventricular ejection fraction; LVSd = left ventricular end-systolic diameter; NYHA = New York Heart Association; PVC = premature ventricular contraction; RBBB = right bundle-branch block; LAFB = left anterior fascicular block; LBBB = left bundle-branch block; LCC = left common carotid. LDP = local diastolic pressure; LSP = local systolic pressure; PWV = pulse-wave velocity; RCC = right common carotid. a Values are expressed as absolute numbers (percentage); mean value ± SD or median [interquartile range]. b Compliance coefficient expresses absolute change in lumen area during systole for a given pressure change, calculated by the ratio between diastolic lumen area and local pulse pressure (CC = ΔA/ΔP), m2 kPa−1.
[1] Schmunis GA, Yadon ZE. Chagas disease: a Latin American health problem becoming a world health problem. Acta Trop Jul-Aug 2010;115(1-2):14–21. [2] Nunes MC, Barbosa MM, Ribeiro AL, Barbosa FB, Rocha MO. Ischemic cerebrovascular events in patients with Chagas cardiomyopathy: a prospective follow-up study. J Neurol Sci Mar 15 2009;278(1–2):96–101. [3] Paixao LC, Ribeiro AL, Valacio RA, Teixeira AL. Chagas disease: independent risk factor for stroke. Stroke Dec 2009;40(12):3691–4. [4] Carod-Artal FJ, Vargas AP, Horan TA, Nunes LG. Chagasic cardiomyopathy is independently associated with ischemic stroke in Chagas disease. Stroke May 2005;36(5): 965–70. [5] Souza AC, Rocha MO, Teixeira AL, Dias Junior JO, Sousa LA, Nunes MC. Depressive symptoms and disability in chagasic stroke patients: impact on functionality and quality of life. J Neurol Sci Jan 15 2013;324(1–2):34–7. [6] Lima-Costa MF, Matos DL, Ribeiro AL. Chagas disease predicts 10-year stroke mortality in community-dwelling elderly: the Bambui cohort study of aging. Stroke Nov 2010;41(11):2477–82. [7] Hassan GS, Mukherjee S, Nagajyothi F, et al. Trypanosoma cruzi infection induces proliferation of vascular smooth muscle cells. Infect Immun Jan 2006;74(1):152–9. [8] Tanowitz HB, Kaul DK, Chen B, et al. Compromised microcirculation in acute murine Trypanosoma cruzi infection. J Parasitol Feb 1996;82(1):124–30. [9] Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima–media thickness: a systematic review and meta-analysis. Circulation Jan 30 2007;115(4):459–67. [10] Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J Nov 2006; 27(21):2588–605. [11] Nunes Mdo C, Barbosa MM, Rocha MO. Peculiar aspects of cardiogenic embolism in patients with Chagas' cardiomyopathy: a transthoracic and transesophageal echocardiographic study. J Am Soc Echocardiogr Jul 2005;18(7):761–7. [12] Polak JF. Carotid intima–media thickness: an early marker of cardiovascular disease. Ultrasound Q Jun 2009;25(2):55–61. [13] Villacorta H, Bortolotto LA, Arteaga E, Mady C. Aortic distensibility measured by pulse-wave velocity is not modified in patients with Chagas' disease. J Negat Results Biomed 2006;5:9.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Assessment of the source of ischemic cerebrovascular events in patients with Chagas disease☆ José Olímpio Dias Junior a, Manoel Otávio da Costa Rocha a, Aline Cristina de Souza a, Lucas Jordan Kreuser b, Laura Alves de Souza Dias a, Timothy C. Tan c, Antônio Lúcio Teixeira a, Maria Carmo P. Nunes a,⁎ a b c
Post-Graduate Program in Infectious Diseases and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil University of Minnesota Medical School, Minneapolis, MN, USA Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 7 July 2014 Received in revised form 27 July 2014 Accepted 28 July 2014 Available online 6 August 2014 Keywords: Chagas disease Stroke Ischemic cerebrovascular events Echocardiography Carotid intima-media thickness
Chagas disease (ChD) remains a major public health problem in Latin America and it is an emerging disease in non-endemic countries [1]. ChD is an important cause of ischemic cerebrovascular events (ICE), which result in a substantial long-term disability [2–5] and risk of death [6]. Cardioembolic source for thrombi is considered to be the main pathophysiological mechanism, related to apical aneurysms, heart failure and arrhythmias [2]. However, ChD also compromises microvasculature function, which may contribute to the risk of ischemic events [7]. The vascular dysfunction in Chagas disease is multifactorial, involving infection-associated microvascular spasm, reduction in blood flow, increased platelet aggregation, and increased myocardial inflammation and fibrosis [7]. Although vascular inflammatory injuries have been associated with Trypanosoma cruzi infection in animal experimental studies [8], the association between the vasculopathy in Chagas disease and ischemic events has not been studied in a clinical setting. ☆ This study was partly supported by grants from Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasília, Brazil, and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Belo Horizonte, Brazil. ⁎ Corresponding author at: Department of Internal Medicine, School of Medicine of the Federal University of Minas Gerais, Av. Professor Alfredo Balena, 190, Santa Efigênia, 30130 100 Belo Horizonte, MG, Brazil. Tel.: +55 31 34099746; fax: +55 31 34099437. E-mail address: [email protected] (M.C.P. Nunes).
http://dx.doi.org/10.1016/j.ijcard.2014.07.266 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Vascular ultrasound allows noninvasive quantitative assessment of arterial properties by quantification of parameters linked to wall stiffness. Increased arterial stiffness and carotid intima–media thickness (IMT) are considered independent predictors of cardiovascular events including cerebrovascular ischemic events [9]. Therefore, this study was design to assess the potential source of ischemic events in patients with ChD disease who had ICE by comprehensively evaluating cardiac chambers, and the morphology and function of the carotid arteries, especially focusing on carotid stiffness and IMT. Patients were recruited prospectively from a tertiary center for Infectious and Parasitic Diseases at Federal University of Minas Gerais, Brazil. The study enrolled 26 ChD patients with ICE who were matched by age, sex, NYHA functional class, left ventricular ejection fraction and cardiovascular risk factors for ICE and 26 randomly selected ChD patients who did not have any ICE. Patients with other cardiac or systemic disease that could independently affect morphological and functional properties of carotid arteries were excluded. In addition, patients with atrial fibrillation were also excluded. All enrolled patients underwent clinical and neurological examination, electrocardiogram (ECG), standard transthoracic echocardiogram and carotid ultrasound. Ultrasound assessment of intima–media thickness and carotid stiffness was performed as previously reported using an Esaote My Lab 60 ultrasound machine and a high multifrequency (3 or 11 MHz) linear array transducer (Fig. 1). The indices of carotid stiffness were estimated by measuring the diameter (D) and its change during the heart cycle (stroke change in diameter, or distension [ΔD]) from ultrasound data in conjunction with the local pulse pressure [10]. All ultrasound measurements were performed by a single investigator blinded to the clinical evaluation of the patients. The values presented are an average of three measurements over three cardiac cycles. Categorical variables, expressed as numbers and percentages, were compared by a chi-square test, whereas continuous data, expressed as mean ± SD and median (interquartile range) were compared using unpaired t-test or the Mann–Whitney U test, when appropriate. Statistical analysis was performed using the Statistical Package for Social Sciences for Windows, version 18.0 (SPSS Inc., Chicago, Illinois). The classification of the ICE is shown in Table 1. There was a predominance of cardioembolic stroke (89%), largely compromising the anterior circulation (70%) with low frequency of long term disabling sequelae.
J.O. Dias Junior et al. / International Journal of Cardiology 176 (2014) 1352–1354
1353
Fig. 1. A: Measurement of right carotid intima–media thickness; B: Quantitative measurement of right common carotid artery stiffness.
Demographic and clinical features of ChD patients with and without ICE are shown in Table 2. Mean age of the patients with ICE was 49 ± 14 years with 54% being male, similar to the patients without ICE. Diastolic blood pressure was higher in patients with ICE compared to those without ICE, although still within the normal range. Pharmacological treatment differed only in the use of oral anticoagulants, which was increased in the case group, based on a clinical indication. Echocardiographic parameters were similar between the groups, with the exception of the presence of an apical aneurysm, which was more frequent in the patients with ICE. Eight patients had LV apical thrombus, all of whom had ICE. Atherosclerotic plaques in the carotids were detected in 22 patients, including 39% of cases and 46% of controls (p = 0.390). There was no difference between the groups in relation to the distribution and morphological characteristics of the atherosclerotic plaques, as well as in carotid IMT. Local systolic and diastolic blood pressures calculated from the exploration of the right and left common carotid arteries differed between groups, being higher in ICE patients. There was no difference between the case and control groups in relation to the variation in diameter, coefficient of compliance and pulse wave velocity. The local BP readings obtained from the exploration of the right and left common carotid arteries were higher in patients with ICE. These values, however, were within normal limits. The present study explores the potential contribution of vascular disease to ischemic events in patients with ChD. The results demonstrate that in a cohort of ChD patients with and without ICE matched for age, gender, and severity of myocardial dysfunction, a cardiac source of thrombi was the main cause of ICE. The carotid IMT was similar between cases and controls, suggesting that a carotid vascular atherosclerotic event did not contribute significantly in the genesis of ICE in ChD. In this study, the main pathophysiological mechanism of stroke in the setting of Chagas disease was a cardiac source of embolism.
Table 1 Classification of ischemic cerebrovascular events according to Rankin scale, Barthel indices, Bamford and TOAST classification of the ChD patients. Rankin scalea
Barthel index Oxfordshire classification
TOAST classification a
Class 0 — asymptomatic Class 1 — symptoms without disability Class 2 — mild disability Class 3 — moderate disability Fully independent Mildly dependent Lacunar syndromes Total anterior circulation syndromes Partial anterior circulation syndromes Cardioembolism Small-vessel occlusion
Values are expressed as absolute numbers (percentage).
10 (39) 3 (11) 9 (34) 4 (14) 18 (72) 8 (18) 3 (14) 3 (14) 14 (70) 23 (89) 3 (11)
Accordingly, the presence of an apical aneurysm and thrombi were more frequent in patients with ICE than in matched-controls. This result is consistent with other studies [2,4,11]. Apical aneurysms are characteristic lesions of ChD, and besides the potential impairment of ventricular systolic (LV) function, is associated with thromboembolic events, and may constitute an arrhythmogenic focus. Therefore, this study reinforces the significance of apical aneurysms and LV thrombi in the genesis of ischemic cerebrovascular events in patients with ChD. Atherosclerotic lesions have been described as a potential cause of ICE in patients with ChD, with a prevalence of atherosclerotic cerebrovascular disease reported at 8.5% and hemodynamically significant carotid stenosis in 1.1% of patients [4]. Carotid IMT is recognized as a surrogate marker of atherosclerosis and has been shown implicated in the prediction of future cardiovascular events in asymptomatic individuals [12]. In the present study, no differences were seen between groups suggesting that atherosclerotic cerebral events are an unlikely cause of ischemic stroke in these patients. Other vascular measures such as decreased elasticity and increased stiffness in large and medium caliber arteries have also been shown to be associated with cardiovascular risk factors [10]. In our cohort, there was no significant difference in the tensile properties of the carotid arterial walls, between the groups. Our results are comparable to Villacorta et al., which also did not support changes in the elasticity properties of blood vessels in ChD patients compared to healthy subjects [13]. Regarding carotid arterial stiffness, patients with ICE had higher carotid arteries' local systolic and diastolic blood pressures. In our study, brachial diastolic blood pressure differed between the two groups, whereas systolic blood pressure was similar. The difference in the values of the diastolic blood pressure between the two groups may partly explain why the local diastolic carotid pressure was higher in patients compared to controls. Although Chagas disease patients who have suffered ICE have a highrisk of cardiogenic embolism, the precise mechanism is often difficult to determine. The determinants of increased arterial stiffness are complex and we cannot rule out the possibility of endothelial cell changes caused by ChD to be potentially relevant in the etiopathogenesis of ischemic events. Apical aneurysm and intracavitary thrombi are the main factors associated with cerebrovascular ischemic events in Chagas disease patients. Subclinical atherosclerosis assessed by carotid IMT did not appear to have a major role in the genesis of ischemic events in Chagas disease. Carotid blood pressures were higher in patients with ICE compared to matched-controls, and further studies to identify the determinants of increased arterial stiffness are needed. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
1354
J.O. Dias Junior et al. / International Journal of Cardiology 176 (2014) 1352–1354
Table 2 Characteristics of the Chagas disease patients with ischemic cerebrovascular events compared to those without events. Variablesa Clinical data Age (years) Male Smoking Hyperlipidemia NYHA functional class I/II III/IV Heart rate (bpm) Systolic arterial pressure (mm Hg) Diastolic arterial pressure (mm Hg) Electrocardiographic parameters RBBB plus LAFB LBBB PVC ST–T abnormalities Echocardiographic parameters LVDd (mm) LVSd (mm) LVEF (%) LA volume index (ml/m2) Apical aneurysm E/e′ ratio
Patients with ICE
Patients without ICE
P value
49 ± 14 14 (54) 3 (12) 10 (38) 17 (65) 9 (35) 68 ± 2 119 ± 17
51 ± 11 14 (54) 3 (12) 5 (19) 22 (85) 4 (14) 66 ± 2 111 ± 19
0.465 0.303
77 ± 9
70 ± 10
0.043
13 (50) 3 (12) 4 (14) 8 (31)
11 (42) 2 (8) 6 (23) 9 (35)
0.803 0.500 0.517 0.893
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References
57.9 44.0 49.7 36.6
± ± ± ±
9.1 11.0 12.9 18.9
57.4 43.0 49.9 38.3
± ± ± ±
8.4 10.3 13.5 18.6
0.192 1.000 0.666 0.110 0.100
0.817 0.547 0.909 0.756 b0.001 0.618
22 (85) 7.7 ± 2.7
5 (19) 7.3 ± 2.4
Carotid intima–media thickness (IMT) RCC mean LCC mean
0.62 ± 0.18 0.64 ± 0.18
0.64 ± 0.17 0.67 ± 0.13
0.694 0.589
Carotid stiffness parametersb RCC D (μm) CC (m2 kPa−1) PWV (m/s) LSP (mm Hg) LDP (mm Hg) LCC D (μm) CC (m2 kPa−1) PWV (m/s) LSP (mm Hg) LDP (mm Hg)
255 [178–378] 0.65 [0.4–1.3] 7.3 [5.4–9.8] 107 [94–119] 80 [70–80] 267 [198–378] 0.80 [0.6–1.4] 7.0 [5.4–8.6] 107 [94–116] 80 [70–80]
253 [171–341] 0.78 [0.5–1.2] 7.9 [5.7–9.2] 98 [91–109] 65 [60–80] 271 [183–350] 0.72 [0.5–0.9] 7.5 [6.3–8.3] 97 [89–110] 65 [60 –80]
0.721 0.993 0.528 0.049 0.007 0.469 0.318 0.552 0.048 0.008
CC = compliance coefficient; D = distensibility; E/e′ = ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity; ICE = ischemic cerebrovascular events; LA = left atrial; LVDd = left ventricular end-diastolic diameter; LVEF = left ventricular ejection fraction; LVSd = left ventricular end-systolic diameter; NYHA = New York Heart Association; PVC = premature ventricular contraction; RBBB = right bundle-branch block; LAFB = left anterior fascicular block; LBBB = left bundle-branch block; LCC = left common carotid. LDP = local diastolic pressure; LSP = local systolic pressure; PWV = pulse-wave velocity; RCC = right common carotid. a Values are expressed as absolute numbers (percentage); mean value ± SD or median [interquartile range]. b Compliance coefficient expresses absolute change in lumen area during systole for a given pressure change, calculated by the ratio between diastolic lumen area and local pulse pressure (CC = ΔA/ΔP), m2 kPa−1.
[1] Schmunis GA, Yadon ZE. Chagas disease: a Latin American health problem becoming a world health problem. Acta Trop Jul-Aug 2010;115(1-2):14–21. [2] Nunes MC, Barbosa MM, Ribeiro AL, Barbosa FB, Rocha MO. Ischemic cerebrovascular events in patients with Chagas cardiomyopathy: a prospective follow-up study. J Neurol Sci Mar 15 2009;278(1–2):96–101. [3] Paixao LC, Ribeiro AL, Valacio RA, Teixeira AL. Chagas disease: independent risk factor for stroke. Stroke Dec 2009;40(12):3691–4. [4] Carod-Artal FJ, Vargas AP, Horan TA, Nunes LG. Chagasic cardiomyopathy is independently associated with ischemic stroke in Chagas disease. Stroke May 2005;36(5): 965–70. [5] Souza AC, Rocha MO, Teixeira AL, Dias Junior JO, Sousa LA, Nunes MC. Depressive symptoms and disability in chagasic stroke patients: impact on functionality and quality of life. J Neurol Sci Jan 15 2013;324(1–2):34–7. [6] Lima-Costa MF, Matos DL, Ribeiro AL. Chagas disease predicts 10-year stroke mortality in community-dwelling elderly: the Bambui cohort study of aging. Stroke Nov 2010;41(11):2477–82. [7] Hassan GS, Mukherjee S, Nagajyothi F, et al. Trypanosoma cruzi infection induces proliferation of vascular smooth muscle cells. Infect Immun Jan 2006;74(1):152–9. [8] Tanowitz HB, Kaul DK, Chen B, et al. Compromised microcirculation in acute murine Trypanosoma cruzi infection. J Parasitol Feb 1996;82(1):124–30. [9] Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima–media thickness: a systematic review and meta-analysis. Circulation Jan 30 2007;115(4):459–67. [10] Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J Nov 2006; 27(21):2588–605. [11] Nunes Mdo C, Barbosa MM, Rocha MO. Peculiar aspects of cardiogenic embolism in patients with Chagas' cardiomyopathy: a transthoracic and transesophageal echocardiographic study. J Am Soc Echocardiogr Jul 2005;18(7):761–7. [12] Polak JF. Carotid intima–media thickness: an early marker of cardiovascular disease. Ultrasound Q Jun 2009;25(2):55–61. [13] Villacorta H, Bortolotto LA, Arteaga E, Mady C. Aortic distensibility measured by pulse-wave velocity is not modified in patients with Chagas' disease. J Negat Results Biomed 2006;5:9.
