Table 1 Overview of studies on the association between Chagas disease and stroke. This table summarizes the authors, year of publication, type of study conducted, the number of participants involved, the primary objective of each study, and the key findings. The studies range from cohort and case-control designs to case reports and cross-sectional analyses, providing insights into the prevalence of encephalic infarction, the occurrence of stroke episodes, and the predictive variables for stroke in patients with Chagas Disease

Aras et al. [10]

2003

Cohort

5447

To determine the frequency of encephalic infarction and its contribution to lethality in patients with Chagas’ disease and heart failure.

In 524 patients with Chagas disease, brain infarction was identified in 92 (17.5%) patients. The distribution of brain infarctions according to the affected region was as follows: cerebral infarction, 89.1%; cerebellar infarction, 8.7%; and pituitary infarction, 2.17%.

Barbosa-Ferreira et al. [11]

2010

Case report

1

NA

Report of a stroke episode in a chronic chagasic patient native to the Brazilian Amazon

Bestetti [12].

2000

Cohort

79

To determine the prevalence of stroke in a hospital-derived cohort of patients with chronic Chagas’ disease.

One patient (1%) suffered a fatal stroke during the study period; he was in sinus rhythm on resting ECG and had mild mitral regurgitation, normal left ventricular function, and no intracavitary thrombus on Doppler echocardiography.

Calle-Escobar et al. [13]

2009

Case report

1

NA

Patient with ischemic stroke of probable cardioembolic origin, secondary to grade II cardiomyopathy secondary to untreated symptomatic chronic chagas disease.

Carod Artal et al. [14]

2001

Case report

2

NA

Report on 2 patients exhibiting the chronic cardiac form of Chagas disease, who experienced cardioembolic strokes.

Carod Artal et al. [15]

2003

Case series

136

To describe a group of patients with chronic or latent Chagas Disease affected by ischemic stroke and identify predictive variables for stroke in Chagas Disease patients.

Cardiomyopathy was significantly more prevalent in stroke patients with Chagas disease (45.58% vs. 24.69%; p = 0.00005). The diagnosis of Chagas disease was established after the presentation of a stroke in 38.23% of patients.

Carod Artal et al. [16]

2011

Case-Control

86

To identify associated vascular risk factors and stroke subtypes in ischemic stroke patients with asymptomatic T. cruzi infection and no clinical evidence of heart failure.

38.4% of chagasic stroke patients had asymptomatic T. cruzi infection. Small-vessel infarction (15.6% vs. 3.8%) and large-vessel atherosclerosis (9.4% vs. 3.8%) were significantly more frequent in asymptomatic than in symptomatic T. cruzi-infected stroke patients (p = 0.001).

Cerqueira-Silva et al. [9]

2022

Cohort

565

To determine the incidence of stroke and death in patients with HF, comparing Chagas and non-Chagas etiologies.

Stroke incidence was higher in Chagas compared to non-Chagas patients, with 20.2 vs. 13.9 events per 1000 patient-years, respectively. However, the death rate was similar between groups, with 41.6 for Chagas and 43.1 deaths per 1000 patient-years for non-Chagas patients.

de Matta et al. [17]

2012

Cross-sectional

chagasic (329) and non-chagasic (461) cardiomyopathies

To describe the frequency of stroke correlates in a population presenting with a cardiomyopathy, representative of a tertiary center in northeastern Brazil with a specific focus on the chagasic etiology.

In the study, there were 108 stroke cases, with a significantly higher occurrence in the Chagas group (17.3%) compared to the non-Chagas group (11.1%; p < 0.01). In a multivariable analysis of the entire cohort, Chagas etiology (OR = 1.79), the presence of a pacemaker (OR = 2.49), atrial fibrillation (OR = 3.03), and coronary artery disease (OR = 1.92) emerged as significant predictors of stroke.

Guedes et al. [18]

2016

Cohort

65

To evaluate the association between inflammatory markers and the risk of death and risk of stroke in patients with different clinical forms of chronic Chagas disease.

An imbalance in the inflammatory response among patients with chronic Chagas disease is linked to an elevated risk of mortality and a heightened likelihood of stroke occurrences.

Halaseh et al. [19]

2021

Case report

1

NA

An acute cerebrovascular accident, compounded by multiple prior infarctions affecting various vascular territories, was documented in a patient diagnosed with Chagas disease.

Jesus et al. [20]

2011

Cohort

144

To determine predictors of congestive heart failure in a population of patients with congestive heart failure (CHF)

Microembolic signals (MES) were identified in 9 patients (6.2%), occurring more frequently in those with Chagas disease compared to those with other causes of congestive heart failure (CHF) (12.9% vs. 1.2%, p = 0.005). Multivariate analysis, adjusted for age and left ventricular ejection fraction, identified Chagas disease (OR = 1.15, 95% CI: 1.05–1.26, p = 0.004) and a history of stroke (OR = 1.27, 95% CI: 1.05–1.26, p = 0.004) as predictors of MES.

Leon-Sarmiento et al. [21]

2004

Case-Control

82 cases

102 controls

To demonstrated a link between Chaga disease and symptomatic cerebrovascular disease.

In stroke cases, T. cruzi infection was significantly more prevalent (24.4%) compared to controls (1.9%), as evidenced by statistical analysis (Chi-square: 21.72; OR : 16.13; 95% CI: 3.64–71.4; p < 0.00001).

Lima-Costa et al. [22]

2010

Cohort

1398

To investigate the relationship between Chagas disease and long-term stroke mortality in a large community-based cohort of older adults.

Among T. cruzi-infected participants, the risk of death from stroke was twice as high as that in noninfected individuals (adjusted hazard ratio: 2.36; 95% CI: 1.25–4.44).

Melo et al. [23]

2024

Case-Control

678

To discern factors linked to stroke in Chagas disease by contrasting patients with and without a history of ischemic stroke.

Logistic regression analysis in this study identified that congestive heart failure, right bundle branch block, left anterosuperior divisional block, and atrial fibrillation are factors independently associated with an increased risk of stroke in patients with Chagas disease.

Montanero et al. [24]

2018

Cohort

279

To determine factors associated with mortality and recurrence of ischemic stroke in patients with ischemic stroke and Chagas disease.

In this study, the authors conducted a multivariate analysis to assess factors associated with mortality in stroke patients. The analysis identified several key factors: age at the time of stroke (hazard ratio [HR] 1.04), the severity of disability as measured by the initial modified Rankin Scale score (HR 20.91), the presence of bladder dysfunction (HR 2.51), diabetes mellitus (HR 3.64), and alcoholism (HR 3.37). Each of these variables was significantly associated with an increased risk of mortality, highlighting the complex interplay of health conditions that contribute to outcomes in stroke patients.

Montanero et al. [25]

2016

Cohort

86

To evaluate the etiology of stroke in patients with ischemic stroke and Chagas disease using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) and Stop Stroke Study/Causative Classification System (SSS/CCS TOAST) classification criteria.

In this study, stroke etiology was classified using two different systems, revealing significant findings. The Trial of Org 10,172 in Acute Stroke Treatment (TOAST) Classification showed that 45% of strokes had an undetermined etiology and 45% were of cardioembolic origin. In contrast, the Stop Stroke Study/Causative Classification System (SSS/CCS) TOAST results differed slightly, indicating that 34% of strokes were undetermined, while 50% were identified as cardioembolic (p < 0.01). This discrepancy underscores the complexity of diagnosing stroke origins and the importance of employing multiple classification systems for a comprehensive understanding.

Montanero et al. [26]

2019

Cohort

279

To describe the epidemiological and geographical distribution of IS in Chagas disease in patients attending multicenter, open access, quaternary rehabilitation hospital network spread across four of the five regions of Brazil.

In this investigation, a stark contrast was observed in the distribution of stroke cases across different socio-economic settings. Cities characterized by lower income levels and diminished access to healthcare facilities reported the highest incidence of stroke cases. Furthermore, the study highlighted a variable distribution of vascular risk factors and outcomes post-stroke among the units, suggesting that socio-economic factors significantly influence stroke prevalence and patient recovery trajectories.

Montanero et al. [27]

2021

Cohort

499

To describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS.

In this study, the development of a predictive model for the etiological classification of stroke in Chagas disease revealed a close correlation with the number of abnormalities detected on echocardiography and electrocardiography. Additionally, the model demonstrated a significant association with vascular risk factors, underscoring the importance of these indicators in predicting the likelihood of stroke in patients with Chagas disease.

Montanero et al. [28]

2024

Cohort

499

To describe the largest cohort of patients with Chagas disease and ischemic stroke and determining variables associated with stroke recurrence and cardioembolic cause.

In the investigation, it was discovered that there was a 29.7% recurrence rate of stroke, notably higher within the cardioembolic subgroup. Furthermore, 56% of the patients experienced embolic strokes of undetermined origin. The study also identified specific electrocardiogram (EKG) abnormalities that were linked to an increased risk of a stroke having a cardioembolic etiology.

Nunes et al. [29]

2009

Cohort

213

To describe the incidence and to evaluate the effect of LV ejection fraction on the risk for ICE in patients with Chagas cardiomyopathy.

The study reported an overall incidence of ischemic cerebrovascular events (ICE) at 2.67 events per 100 patient-years. Analysis revealed independent risk factors for ICE to include left ventricular (LV) ejection fraction (HR = 0.95, 95% CI 0.91 to 0.99, p = 0.009) and left atrial volume corrected for body surface area (HR = 1.04, 95% CI 1.01 to 1.07, p = 0.007).

Nunes et al. [30]

2015

Cohort

330

To assess the prevalence of ischemic cerebrovascular events (ICE) among

patients with Chagas heart disease and to identify the risk factors associated with cardioembolism in this population.

In this study, multivariate analysis identified apical aneurysm (aOR 2.19, 95% CI 1.11 to 4.34; p = 0.024) and LV thrombus (aOR 2.43, 95% CI 1.09 to 5.42; p = 0.030) as significant determinants of ischemic cerebrovascular events (ICE), even after adjusting for anticoagulation therapy.

Nussenzveig et al. [31]

1953

Case report

8

NA

In this study, eight cases of Chagas’ heart disease were documented, all confirmed by a positive Machado-Guerrero reaction. These patients experienced cerebrovascular accidents during their disease.

Oliveira-Filho et al. [32]

2005

Cohort-

305

To identify the predictors of stroke in a region where Chagas Disease is endemic.

In this investigation, the occurrence of stroke was significantly higher in patients with CD, at 15.0%, compared to those with other cardiac conditions, which had a stroke rate of 6.3% (p = 0.015).

Paixão et al. [33]

2009

Case-Control

101 cases

100 controls

To investigate Chagas Disease, defined by positive serology, as an independent risk factor for stroke.

In this study, the authors demonstrated that after conducting a multivariable analysis using a backward elimination procedure, a history of previous stroke/transient ischemic attack (OR = 6.98; 95% CI, 2.99 to 16.29), atrial fibrillation (OR = 4.52; 95% CI, 1.45 to 14.04), and positive serology for CD (OR = 7.17; 95% CI, 1.50 to 34.19) remained as independent risk factors associated with stroke.