Clinical assessment, neuroimaging and immunomarkers in Chagas disease study (CLINICS): rationale, study design and preliminary findings / Avaliação clínica, neuroimagem e imunomarcadores na doença de Chagas (CLINICS): fundamentação teórica, desenho do estudo e resultados preliminares

Chagas disease (CD) is an important cause of cardiomyopathy and stroke in Brazil. Brain infarcts and atrophy seem to occur independently of cardiomyopathy severity and cognitive impairment is under studied. Objective: Compare the prevalence of brain magnetic resonance imaging abnormalities between patients with or without CD; determine if inflammatory biomarkers are increased in CD; and determine the efficacy of aspirin in reducing the rate of microembolization in these patients. Methods: 500 consecutive patients with heart failure will undergo a structured cognitive evaluation, biomarker collection and search for microembolic signals on transcranial Doppler. The first 90 patients are described, evaluated with cognitive tests and brain magnetic resonance imaging to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI) and creatine (Cr). Results: Mean age was 55±11 years, 51% female, 38 (42%) with CD. Mean NAA/Crratio was lower in patients with CD as compared to other cardiomyopathies. Long-term memory and clock-drawing test were also significantly worse in CD patients. In the multivariable analysis correcting for ejection fraction, age, sex and educational level, reduced NAA/Cr (p=0.006) and cognitive dysfunction (long-term memory, p=0.023; clock-drawing test, p=0.015)remained associated with CD. Conclusion: In this preliminary sample, CD was associated with cognitive impairment and decreased NAA/Cr independently of cardiac function or educational level.

A doença de Chagas (DC) é causa importante de cardiomiopatia e acidente vascular cerebral no Brasil. Os infartos e atrofia cerebral na DC parecem ocorrer independente da gravidade da cardiomiopatia, sendo o comprometimento cognitivo pouco estudado. Objetivo: Determinar a prevalência de alterações na ressonância magnética entre chagásicos e não chagásicos; determinar se os níveis de marcadores inflamatórios estão aumentados na DC e determinar a eficácia da aspirina em reduzir a taxa de microembolização nestes pacientes. Métodos: Quinhentos pacientes consecutivos com diagnóstico de insuficiência cardíaca serão submetidos a uma avaliação cognitiva estruturada, coleta de biomarcadores e pesquisa de sinais de microembolia por Doppler transcraniano. Os primeiros 90 pacientes são descritos, avaliados por testes cognitivos e ressonância magnética cerebral, com medida de N-acetil aspartato (NAA), colina (Cho), mioinositol (MI)e creatina (Cr). Resultados: A idade média foi de 55±11 anos, 51% eram do sexo feminino, 38 (42%) tinha DC. A médiada relação NAA/Cr foi mais baixa em pacientes com DC quando comparada com outras miocardiopatias. O desempenho nos testes de memória de longo prazo e desenho do relógio foi significativamente pior nos portadores de DC. Na análise multivariada, corrigindo para fração de ejeção, idade, gênero e nível educacional, redução da relação NAA/Cr (p=0.006) e disfunção cognitiva (memória de longo prazo, p=0.023; teste do desenho do relógio, p=0.015) permaneceram associados a DC. Conclusão: Nesta amostra preliminar, a doença de Chagas esteve associada a disfunção cognitiva e redução dos níveis de NAA/Cr, independente da função cardíaca e nível educacional.

Clinical assessment, neuroimaging and immunomarkers in Chagas disease study (CLINICS): Rationale, study design and preliminary findings.

Chagas disease (CD) is an important cause of cardiomyopathy and stroke in Brazil. Brain infarcts and atrophy seem to occur independently of cardiomyopathy severity and cognitive impairment is understudied. OBJECTIVE: Compare the prevalence of brain magnetic resonance imaging abnormalities between patients with or without CD; determine if inflammatory biomarkers are increased in CD; and determine the efficacy of aspirin in reducing the rate of microembolization in these patients. METHODS: 500 consecutive patients with heart failure will undergo a structured cognitive evaluation, biomarker collection and search for microembolic signals on transcranial Doppler. The first 90 patients are described, evaluated with cognitive tests and brain magnetic resonance imaging to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI) and creatine (Cr). RESULTS: Mean age was 55±11 years, 51% female, 38 (42%) with CD. Mean NAA/Cr ratio was lower in patients with CD as compared to other cardiomyopathies. Long-term memory and clock-drawing test were also significantly worse in CD patients. In the multivariable analysis correcting for ejection fraction, age, sex and educational level, reduced NAA/Cr (p=0.006) and cognitive dysfunction (long-term memory, p=0.023; clock-drawing test, p=0.015) remained associated with CD. CONCLUSION: In this preliminary sample, CD was associated with cognitive impairment and decreased NAA/Cr independently of cardiac function or educational level.

A doença de Chagas (DC) é causa importante de cardiomiopatia e acidente vascular cerebral no Brasil. Os infartos e atrofia cerebral na DC parecem ocorrer independente da gravidade da cardiomiopatia, sendo o comprometimento cognitivo pouco estudado. OBJETIVO: Determinar a prevalência de alterações na ressonância magnética entre chagásicos e não chagásicos; determinar se os níveis de marcadores inflamatórios estão aumentados na DC e determinar a eficácia da aspirina em reduzir a taxa de microembolização nestes pacientes. MÉTODOS: Quinhentos pacientes consecutivos com diagnóstico de insuficiência cardíaca serão submetidos a uma avaliação cognitiva estruturada, coleta de biomarcadores e pesquisa de sinais de microembolia por Doppler transcraniano. Os primeiros 90 pacientes são descritos, avaliados por testes cognitivos e ressonância magnética cerebral, com medida de N-acetil aspartato (NAA), colina (Cho), mioinositol (MI) e creatina (Cr). RESULTADOS: A idade média foi de 55±11 anos, 51% eram do sexo feminino, 38 (42%) tinha DC. A média da relação NAA/Cr foi mais baixa em pacientes com DC quando comparada com outras miocardiopatias. O desempenho nos testes de memória de longo prazo e desenho do relógio foi significativamente pior nos portadores de DC. Na análise multivariada, corrigindo para fração de ejeção, idade, gênero e nível educacional, redução da relação NAA/Cr (p=0.006) e disfunção cognitiva (memória de longo prazo, p=0.023; teste do desenho do relógio, p=0.015) permaneceram associados a DC. CONCLUSÃO: Nesta amostra preliminar, a doença de Chagas esteve associada a disfunção cognitiva e redução dos níveis de NAA/Cr, independente da função cardíaca e nível educacional.

Stroke history and Chagas disease are independent predictors of silent cerebral microembolism in patients with congestive heart failure.

BACKGROUND: Chagas disease is endemic in South and Central America, where 18 million individuals are infected by Trypanosoma cruzi, causing congestive heart failure (CHF) and cardioembolic stroke. Transcranial Doppler (TCD) is able to detect real-time microembolic signals (MES) to the brain vessels and may represent a surrogate marker of stroke risk. We aimed to determine predictors of MES in a population of patients with CHF. METHODS: Consecutive CHF patients from a university-based cardiomyopathy clinic underwent TCD recording of the middle cerebral artery for 60 min by a single investigator who was blinded to all clinical data including cardiomyopathy etiology. Predictors of MES were sought by multivariable logistic regression analysis. RESULTS: From April 2004 to February 2009, 144 patients were studied, including 62 (44.6%) patients with Chagas disease. MES were detected in 9 (6.2%) patients and were more frequent in patients with Chagas disease than in patients with other causes of CHF (12.9 vs. 1.2%, p = 0.005). In multivariate analysis corrected for age and left-ventricular ejection fraction, predictors of MES were Chagas disease (odds ratio = 1.15, 95% confidence interval = 1.05-1.26, p = 0.004) and stroke history (odds ratio = 1.27, 95% confidence interval = 1.08-1.50, p = 0.005). CONCLUSIONS: Chagas disease and stroke history are risk factors for MES independent of cardiac disease severity. Other mechanisms besides structural cardiac disease may be operative, increasing embolic risk in Chagas disease.

Cognitive dysfunction in chronic Chagas disease cardiomyopathy.

Chagas disease (CD) remains a major cause of stroke in developing countries, but cognitive repercussion of CD has not been well studied. OBJECTIVE: To compare the frequency and pattern of cognitive dysfunction in patients with CD cardiomyopathy (CDC) and other cardiomyopathies (OC). METHODS: We studied 37 patients with CDC and 42 patients with OC with similar age, educational level and cardiac systolic function. Cognitive tests were applied to both groups by a single examiner blinded to CD status. Logistic regression multivariable models were constructed to ascertain predictors of cognitive dysfunction for each test. RESULTS: Cognitive dysfunction was detected in 9 (24%) CDC patients and 6 (14%) OC patients by Mini Mental State Exam (MMSE) corrected for educational level. Independent predictors of abnormal MMSE (p<0.05) included stroke history (OR=5.51; 95% CI=1.27-24.01) and digoxin use (OR=0.23, 95% CI=0.06-0.89), while CD showed a trend toward statistical significance (OR=4.63; 95% CI=0.87-24.73, p=0.07). Delayed recall of Rey's Complex Figure Test was significantly worse in CD patients, where this remained a significant predictor in the multivariable analysis (OR=4.67; 95% CI=1.23-17.68). CONCLUSIONS: Cognitive dysfunction is frequent in Chagas disease and should be considered as an outcome measure in Chagas disease studies.

A doença de Chagas (DC) permanence uma causa importante de acidente vascular cerebral em países em desenvolvimento, mas a repercussão cognitiva dessa doença não tem sido bem estudada. OBJETIVO: Comparar a frequência e padrão de disfunção cognitiva em pacientes com cardiomiopatia associada à DC (CDC) em comparação com outras cardiomiopatias (OC). MÉTODOS: Foram estudados 37 pacientes com CDC e 42 portadores de OC com idade, nível de instrução e função sistólica cardíaca semelhantes. Testes cognitivos foram realizados em ambos os grupos por um único investigador cegado quanto ao diagnóstico de DC. Modelos de regressão logística multi-variável foram construídos para detectar preditores de disfunção cognitiva para cada teste. RESULTADOS: Disfunção cognitiva foi detectada em 9 (24%) pacientes com CDC e 6 (14%) com OC pelo Mini Exame do Estado Mental (MEEM) corrigido pelo nível de instrução. Preditores independentes de MEEM anormal (p<0,05) foram: história de AVC (OR=5,51; IC 95%=1,27­24,01) e uso de digoxina (OR=0,23, IC 95%=0,06­0,89); DC mostrou tendência a significância estatística (OR=4,63; IC 95%=0,87­24,73, p=0,07). Pacientes com CDC apresentaram pior desempenho na evocação tardia da figura complexa de Rey. Neste teste, a DC se manteve um preditor significante de disfunção cognitiva na análise multivariável (OR=4,67; IC 95%=1,23­17,68). CONCLUSÕES: Disfunção cognitiva é frequente na doença de Chagas e deve ser considerada como desfecho quantificado nos estudos da doença de Chagas.

Prevalence of hepatitis C and B virus infection in patients with idiopathic dilated cardiomyopathy in Brazil: a pilot study.

The idiopathic dilated cardiomyopathy (IDMC) is a disease of the cardiac muscle characterized by systolic dilation and/or dysfunction of one or both ventricles, symptoms of congestive heart failure and risk of early death. Several studies in animal models and in humans have supported the hypothesis of the viral infection as initial event in the immunopathogenesis of the ventricular dilation. The objective of this study was to correlate the presence of hepatitis C virus chronic infection and idiopathic dilated cardiomyopathy, comparing samples of cases with IDCM with paired controls with Chagas-type specific dilated cardiomyopathy and ischemic-type specific dilated cardiomyopathy. Only 2.9% (1/34) of IDCM patients were HCV carriers, which strongly argue against this hypothesis. Therefore, based on our results, there is no justification for investigating HCV in patients with idiopathic dilated cardiomyopathy diagnosis.

Prevalence of hepatitis C and B virus infection in patients with idiopathic dilated cardiomyopathy in Brazil: a pilot study

The idiopathic dilated cardiomyopathy (IDMC) is a disease of the cardiac muscle characterized by systolic dilation and/or dysfunction of one or both ventricles, symptoms of congestive heart failure and risk of early death. Several studies in animal models and in humans have supported the hypothesis of the viral infection as initial event in the immunopathogenesis of the ventricular dilation. The objective of this study was to correlate the presence of hepatitis C virus chronic infection and idiopathic dilated cardiomyopathy, comparing samples of cases with IDCM with paired controls with Chagas-type specific dilated cardiomyopathy and ischemic-type specific dilated cardiomyopathy. Only 2.9 percent (1/34) of IDCM patients were HCV carriers, which strongly argue against this hypothesis. Therefore, based on our results, there is no justification for investigating HCV in patients with idiopathic dilated cardiomyopathy diagnosis.

Cognitive dysfunction in congestive heart failure: transcranial Doppler evidence of microembolic etiology.

Cognitive symptoms are common in patients with congestive heart failure (CHF) and are usually attributed to low cerebral blood flow. In the present study, we aimed to evaluate global cognitive function (Mini Mental State Exam MMSE) in relation to both cardiac function (evaluated by echocardiogram) and cerebrovascular hemodynamics (evaluated by transcranial Doppler TCD) in CHF patients. In 83 patients studied, no correlation was found between echocardiographic parameters and MMSE scores. In contrast, a significant correlation was found between right middle cerebral artery (RMCA) mean flow velocity and MMSE score (r=0.231 p=0.039), as well as between RMCA pulsatility index and MMSE score (rs= -0.292 p=0.015). After excluding patients with a previous history of stroke, only RMCA pulsatility index correlated with MMSE score (rs=-0,314 p=0,007). The relationship between high cerebrovascular resistance and worse cognitive scores suggest that microembolism may be responsible for a significant proportion of cognitive symptoms in CHF patients.

Cognitive dysfunction in congestive heart failure: transcranial Doppler evidence of microembolic etiology

Sintomas cognitivos são comuns em pacientes com insuficiência cardíaca congestiva (ICC) e são geralmente atribuídos a um regime de baixo fluxo sanguíneo cerebral. Neste estudo, objetivamos avaliar a função cognitiva global (Mini Exame do Estado Mental MEEM) em pacientes com ICC e sua relação com o grau de disfunção cardíaca (avaliada pelo ecocardiograma) e a hemodinâmica cerebral (avaliada pelo Doppler transcraniano DTC). Em 83 pacientes estudados, nenhuma correlação foi encontrada entre a pontuação no MEEM e parâmetros ecocardiográficos. Em contraste, uma correlação significativa foi encontrada entre a velocidade média na artéria cerebral média direita (ACMD) e a pontuação no MEEM (r=0,231 p=0,039), assim como entre o índice de pulsatilidade na ACMD e a pontuação no MEEM (rs=–0,292 p=0,015). Após excluir pacientes com histórico prévio de acidente vascular encefálico, somente o índice de pulsatilidade na ACMD manteve uma correlação com a pontuação no MEEM (rs=–0,314 p=0,007). A relação entre maior resistência vascular cerebral e pior desempenho cognitivo sugere que microembolia pode ser responsável por uma proporção significativa de sintomas cognitivos em pacientes com ICC.

Chagas disease is an independent risk factor for stroke: baseline characteristics of a Chagas Disease cohort.

BACKGROUND AND PURPOSE: Chagas disease (CD) is frequently associated with cardioembolic stroke in South America. Our objective was to identify the predictors of stroke in a region where CD is endemic. METHODS: We screened 305 consecutive cardiopathy patients. Significant predictors of stroke in univariable analyses were included in a multivariable model. RESULTS: Stroke was more frequent in CD (15.0%) compared with other cardiopathies (6.3%; P=0.015). Other predictors of stroke in univariable analyses were previous diabetes or cardioversion and use of amiodarone, antiplatelet agents, and warfarin. In multivariable analysis, remaining predictors of stroke were CD (odds ratio [OR], 1.09; 95% CI, 1.02 to 1.17), cardioversion (OR, 1.07; 95% CI, 1.02 to 1.13), and diabetes (OR, 1.12; 95% CI, 1.01 to 1.24). CONCLUSIONS: In conclusion, CD is a risk factor for stroke, independent of systolic dysfunction or presence of cardiac arrhythmias.