The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Tissue Inhibitor of Metalloproteinase-1 Is Increased in Chagasic Cardiomyopathy.

Chagas disease (CD) mainly conveys stroke risk through structural cardiac disease. However, stroke and cognitive impairment are seen in CD independently of cardiac disease severity. Chronic inflammation may be an explanation for this association, because inflammation plays an important role in the pathogenesis of acute ischemic stroke and dementia. In the present study, we selected five candidate biomarkers for Chagas disease: interleukin-6, membrane metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP1), orosomucoid, and neprilysin. We sought to determine if mean levels of proinflammatory biomarkers are higher in patients with heart failure (HF) associated with Chagas disease when compared with other etiologies of HF. Patients were consecutively enrolled from subspecialty HF outpatient clinics at two university-based hospitals. Serum biomarker levels from blood samples were analyzed by ELISA. Severity of HF on echocardiography was worse in non-CD when compared with CD patients. No significant difference was observed in the levels of candidate biomarkers between the CD and non-CD groups. We found a significantly 2.2 ng/mL higher level of TIMP1 in CD when compared with non-CD patients with HF after adjustment for age and gender (95% confidence interval = 0.1 to 4.5, P = 0.037). In patients with heart failure, serum TIMP1 is increased in Chagas patients despite a lower myocardial disease severity on echocardiography when compared with non-Chagas patients. TIMP1 is probably one of multiple mediators of inflammatory injury.

Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography.

IMPORTANCE: Limited data exist regarding the natural history of proximal intracranial arterial occlusions. OBJECTIVE To investigate the outcomes of patients who had an acute ischemic stroke attributed to an anterior circulation proximal intracranial arterial occlusion. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study at 2 university-based hospitals from 2003 to 2005 in which nonenhanced computed tomography scans and computed tomography angiograms were obtained at admission of all adult patients suspected of having an ischemic stroke in the first 24 hours of symptom onset. EXPOSURE: Anterior circulation proximal intracranial arterial occlusion. MAIN OUTCOMES AND MEASURES: Frequency of good outcome (defined as a modified Rankin Scale score of ≤ 2) and mortality at 6 months. RESULTS: A total of 126 patients with a unilateral complete occlusion of the intracranial internal carotid artery (ICA; 26 patients: median National Institutes of Health Stroke Scale [NIHSS] score, 11 [interquartile range, 5-17]), of the M1 segment of the middle cerebral artery (MCA; 52 patients: median NIHSS score, 13 [interquartile range, 6-16]), or of the M2 segment of the MCA (48 patients: median NIHSS score, 7 [interquartile range, 4-15]) were included. Of these 3 groups of patients, 10 (38.5%), 20 (38.5%), and 26 (54.2%) with ICA, MCA-M1, and MCA-M2 occlusions, respectively, achieved a modified Rankin Scale score of 2 or less, and 6 (23.1%), 12 (23.1%), and 10 (20.8%) were dead at 6 months. Worse outcomes were seen in patients with a baseline NIHSS score of 10 or higher, with a modified Rankin Scale score of 2 or less achieved in only 7.1% (1 of 14), 23.5% (8 of 34), and 22.7% (5 of 22) of patients and mortality rates of 35.7% (5 of 14), 32.4% (11 of 34), and 40.9% (9 of 22) among patients with ICA, MCA-M1, and MCA-M2 occlusions, respectively. Age (odds ratio, 0.94 [95% CI, 0.91-0.98]), NIHSS score (odds ratio, 0.73 [95% CI, 0.64-0.83]), and strength of leptomeningeal collaterals (odds ratio, 2.37 [95% CI, 1.08-5.20]) were independently associated with outcome, whereas the level of proximal intracranial arterial occlusion (ICA vs MCA-M1 vs MCA-M2) was not. CONCLUSIONS AND RELEVANCE: The natural history of proximal intracranial arterial occlusion is variable, with poor outcomes overall. Stroke severity and collateral flow appear to be more important than the level of proximal intracranial arterial occlusion in determining outcomes. Our results provide useful data for proper patient selection and sample size calculations in the design of new clinical trials aimed at recanalization therapies.

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.