Predictive Accuracy of the Quick Sepsis-related Organ Failure Assessment Score in Brazil. A Prospective Multicenter Study.

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

Clinical Utility of Procalcitonin in the Diagnosis of Pneumonia.

BACKGROUND: The clinical utility of procalcitonin in the diagnosis and management of pneumonia remains controversial. METHODS: We assessed the clinical utility of procalcitonin in 2 prospective studies: first, a multicenter diagnostic study in patients presenting to the emergency department with acute dyspnea to directly compare the diagnostic accuracy of procalcitonin with that of interleukin 6 and C-reactive protein (CRP) in the diagnosis of pneumonia; second, a randomized management study of procalcitonin guidance in patients with acute heart failure and suspected pneumonia. Diagnostic accuracy for pneumonia as centrally adjudicated by 2 independent experts was quantified with the area under the ROC curve (AUC). RESULTS: Among 690 patients in the diagnostic study, 178 (25.8%) had an adjudicated final diagnosis of pneumonia. Procalcitonin, interleukin 6, and CRP were significantly higher in patients with pneumonia than in those without. When compared to procalcitonin (AUC = 0.75; 95% CI, 0.71-0.78), interleukin 6 (AUC = 0.80; 95% CI, 0.77-0.83) and CRP (AUC = 0.82; 95% CI, 0.79-0.85) had significantly higher diagnostic accuracy (P = 0.010 and P < 0.001, respectively). The management study was stopped early owing to the unexpectedly low AUC of procalcitonin in the diagnostic study. Among 45 randomized patients, the number of days on antibiotic therapy and the length of hospital stay were similar (both P = 0.39) in patients randomized to the procalcitonin-guided group (n = 25) and usual-care group (n = 20). CONCLUSIONS: In patients presenting with dyspnea, diagnostic accuracy of procalcitonin for pneumonia is only moderate and lower than that of interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected. SUMMARY: Pneumonia has diverse and often unspecific symptoms. As the role of biomarkers in the diagnosis of pneumonia remains controversial, it is often difficult to distinguish pneumonia from other illnesses causing shortness of breath. The current study prospectively enrolled unselected patients presenting with acute dyspnea and directly compared the diagnostic accuracy of procalcitonin, interleukin 6, and CRP for the diagnosis of pneumonia. In this setting, diagnostic accuracy of procalcitonin for pneumonia was lower as compared to interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected. CLINICALTRIALSGOV IDENTIFIER: NCT01831115.

Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the Institution's Main Source of Income Influence the Results? An Analysis of 21,103 Patients.

OBJECTIVE: We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions' main source of income (public or private). DESIGN: Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014. SETTINGS: Brazilian public and private institutions. PATIENTS: Patients with sepsis admitted in the participant institutions. INTERVENTIONS: The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle. MEASUREMENTS AND MAIN RESULTS: We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the public institutions (p < 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32-0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods. CONCLUSION: This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.

Sepsis in Brazilian emergency departments: a prospective multicenter observational study.

We aimed to assess the prevalence, patient allocation adequacy, and mortality of adults with sepsis in Brazilian emergency departments (ED) in a point-prevalence 3-day investigation of patients with sepsis who presented to the ED and those who remained there due to inadequate allocation. Allocation was considered adequate if the patient was transferred to the intensive care unit (ICU), ward, or remained in the ED without ICU admission requests. Prevalence was estimated using the total ED visit number. Prognostic factors were assessed with logistic regression. Of 33,902 ED visits in 74 institutions, 183 were acute admissions (prevalence: 5.4 sepsis per 1000 visits [95% confidence interval (CI): 4.6-6.2)], and 148 were already in the ED; totaling 331 patients. Hospital mortality was 32% (103/322, 95% CI 23.0-51.0). Age (odds ratio (OR) 1.22 [95% CI 1.10-1.37]), Sequential Organ Failure Assessment (SOFA) score (OR 1.41 [95% CI 1.28-1.57]), healthcare-associated infections (OR 2.59 [95% CI 1.24-5.50]) and low-resource institution admission (OR 2.65 [95% CI 1.07-6.90]) were associated with higher mortality. Accredited institutions (OR 0.42 [95% CI 0.21-0.86]) had lower mortality rates. Allocation within 24 h was adequate in only 52.8% of patients (public hospitals: 42.4% (81/190) vs. private institutions: 67.4% (89/132, p < 0.001) with 39.2% (74/189) of public hospital patients remaining in the ED until discharge, of whom 55.4% (41/74) died. Sepsis exerts high burden and mortality in Brazilian EDs with frequent inadequate allocation. Modifiable factors, such as resources and quality of care, are associated with reduced mortality.

The association of myocardial strain with cardiac magnetic resonance and clinical outcomes in patients with acute myocarditis.

Introduction: The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients. Material and methods: This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction. Results: The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858-0.982, p = 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046-1.325, p = 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031-1.334, p = 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022-1.524, p = 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed. Conclusion: Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients.

Diagnostic Performance of Coronary Tomography Angiography and Serial Measurements of Sensitive Cardiac Troponin in Patients With Chest Pain and Intermediate Risk for Cardiovascular Events. / Desempenho Diagnóstico da Angiotomografia Computadorizada e da Avaliação Seriada de Troponina Cardíaca Sensível em Pacientes com Dor Torácica e Risco Intermediário para Eventos Cardiovasculares.

BACKGROUND: Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk. OBJECTIVE: To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients. METHODS: A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05. RESULTS: Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%). CONCLUSION: CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

FUNDAMENTO: A angiotomografia coronária (ATC) tem sido usada para avaliação de dor torácica principalmente em pacientes de baixo risco, e poucos dados existem com pacientes em risco intermediário. OBJETIVO: Avaliar o desempenho de medidas seriadas de troponinas sensíveis e de ATC em pacientes de risco intermediário. MÉTODOS: Um total de 100 pacientes com dor torácica, TIMI score 3 ou 4 e troponina negativa foram prospectivamente incluídos. Todos os pacientes foram submetidos à ATC, e aqueles com obstruções ≥ 50% foram encaminhados à cineangiocoronariografia. Pacientes com lesões < 50% recebiam alta hospitalar, receberam alta e foram contatados 30 dias depois por telefonema para avaliação dos desfechos clínicos. Os desfechos foram hospitalização, morte, e infarto agudo do miocárdio em 30 dias. A comparação entre os métodos foi realizada pelo teste de concordância kappa. O desempenho das medidas de troponina e da ATC na detecção de lesões coronárias significativas e desfechos clínicos foi calculado. Os resultados foram considerados estatisticamente significativos quando p <0,05. RESULTADOS: Estenose coronária ≥ 50% na ATC foi encontrada em 38% dos pacientes e lesões coronárias significativas na angiografia coronária foram encontradas em 31 pacientes. Dois eventos clínicos foram observados. A análise de concordância Kappa mostrou baixa concordância entre as medidas de troponina e ATC na detecção de lesões coronárias significativas (kappa = 0,022, p = 0,78). O desempenho da ATC para detectar lesões coronárias significativas na angiografia coronária ou para prever eventos clínicos em 30 dias foi melhor que as medidas de troponina sensível (acurácia de 91% versus 60%). CONCLUSÃO: ATC teve melhor desempenho que as medidas seriadas de troponina na detecção de doença coronariana significativa em pacientes com dor torácica e risco intermediário para eventos cardiovasculares.

Adenosine deaminase inhibition prevents Clostridium difficile toxin A-induced enteritis in mice.

Toxin A (TxA) is able to induce most of the classical features of Clostridium difficile-associated disease in animal models. The objective of this study was to determine the effect of an inhibitor of adenosine deaminase, EHNA [erythro-9-(2-hydroxy-3-nonyl)-adenine], on TxA-induced enteritis in C57BL6 mice and on the gene expression of adenosine receptors. EHNA (90 µmol/kg) or phosphate-buffered saline (PBS) was injected intraperitoneally (i.p.) 30 min prior to TxA (50 µg) or PBS injection into the ileal loop. A(2A) adenosine receptor agonist (ATL313; 5 nM) was injected in the ileal loop immediately before TxA (50 µg) in mice pretreated with EHNA. The animals were euthanized 3 h later. The changes in the tissue were assessed by the evaluation of ileal loop weight/length and secretion volume/length ratios, histological analysis, myeloperoxidase assay (MPO), the local expression of inducible nitric oxide synthase (NOS2), pentraxin 3 (PTX3), NF-κB, tumor necrosis factor alpha (TNF-α), and interleukin-1ß (IL-1ß) by immunohistochemistry and/or quantitative reverse transcription-PCR (qRT-PCR). The gene expression profiles of A1, A(2A), A(2B), and A3 adenosine receptors also were evaluated by qRT-PCR. Adenosine deaminase inhibition, by EHNA, reduced tissue injury, neutrophil infiltration, and the levels of proinflammatory cytokines (TNF-α and IL-1ß) as well as the expression of NOS2, NF-κB, and PTX3 in the ileum of mice injected with TxA. ATL313 had no additional effect on EHNA action. TxA increased the gene expression of A1 and A(2A) adenosine receptors. Our findings show that the inhibition of adenosine deaminase by EHNA can prevent Clostridium difficile TxA-induced damage and inflammation possibly through the A(2A) adenosine receptor, suggesting that the modulation of adenosine/adenosine deaminase represents an important tool in the management of C. difficile-induced disease.

The epidemiology of sepsis in paediatric intensive care units in Brazil (the Sepsis PREvalence Assessment Database in Pediatric population, SPREAD PED): an observational study.

BACKGROUND: Data on the prevalence and mortality of paediatric sepsis in resource-poor settings are scarce. We aimed to assess the prevalence and in-hospital mortality of severe sepsis and septic shock treated in paediatric intensive care units (PICUs) in Brazil, and risk factors for mortality. METHODS: We performed a nationwide, 1-day, prospective point prevalence study with follow-up of patients with severe sepsis and septic shock, using a stratified random sample of all PICUs in Brazil. Patients were enrolled at each participating PICU on a single day between March 25 and 29, 2019. All patients occupying a bed at the PICU on the study day (either admitted previously or on that day) were included if they were aged 28 days to 18 years and met the criteria for severe sepsis or septic shock at any time during hospitalisation. Patients were followed up until hospital discharge or death, censored at 60 days. Risk factors for mortality were assessed using a Poisson regression model. We used prevalence to generate national estimates. FINDINGS: Of 241 PICUs invited to participate, 144 PICUs (capacity of 1242 beds) included patients in the study. On the day of the study, 1122 children were admitted to the participating PICUs, of whom 280 met the criteria for severe sepsis or septic shock during hospitalisation, resulting in a prevalence of 25·0% (95% CI 21·6-28·8), with a mortality rate of 19·8% (15·4-25·2; 50 of 252 patients with complete clinical data). Increased risk of mortality was associated with higher Pediatric Sequential Organ Failure Assessment score (relative risk per point increase 1·21, 95% CI 1·14-1·29, p<0·0001), unknown vaccination status (2·57, 1·26-5·24; p=0·011), incomplete vaccination status (2·16, 1·19-3·92; p=0·012), health care-associated infection (2·12, 1·23-3·64, p=0·0073), and compliance with antibiotics (2·38, 1·46-3·86, p=0·0007). The estimated incidence of PICU-treated sepsis was 74·6 cases per 100 000 paediatric population (95% CI 61·5-90·5), which translates to 42 374 cases per year (34 940-51 443) in Brazil, with an estimated mortality of 8305 (6848-10 083). INTERPRETATION: In this representative sample of PICUs in a middle-income country, the prevalences of severe sepsis or septic shock and in-hospital mortality were high. Modifiable factors, such as incomplete vaccination and health care-associated infections, were associated with greater risk of in-hospital mortality. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Científico e Tecnológico. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Sensitive Troponin I Assay in Patients with Chest Pain - Association with Significant Coronary Lesions with or Without Renal Failure.

INTRODUCTION: Despite having higher sensitivity as compared to conventional troponins, sensitive troponins have lower specificity, mainly in patients with renal failure. OBJECTIVE: Study aimed at assessing the sensitive troponin I levels in patients with chest pain, and relating them to the existence of significant coronary lesions. METHODS: Retrospective, single-center, observational. This study included 991 patients divided into two groups: with (N = 681) and without (N = 310) significant coronary lesion. For posterior analysis, the patients were divided into two other groups: with (N = 184) and without (N = 807) chronic renal failure. The commercial ADVIA Centaur® TnI-Ultra assay (Siemens Healthcare Diagnostics) was used. The ROC curve analysis was performed to identify the sensitivity and specificity of the best cutoff point of troponin as a discriminator of the probability of significant coronary lesion. The associations were considered significant when p < 0.05. RESULTS: The median age was 63 years, and 52% of the patients were of the male sex. The area under the ROC curve between the troponin levels and significant coronary lesions was 0.685 (95% CI: 0.65 - 0.72). In patients with or without renal failure, the areas under the ROC curve were 0.703 (95% CI: 0.66 - 0.74) and 0.608 (95% CI: 0.52 - 0.70), respectively. The best cutoff points to discriminate the presence of significant coronary lesion were: in the general population, 0.605 ng/dL (sensitivity, 63.4%; specificity, 67%); in patients without renal failure, 0.605 ng/dL (sensitivity, 62.7%; specificity, 71%); and in patients with chronic renal failure, 0.515 ng/dL (sensitivity, 80.6%; specificity, 42%). CONCLUSION: In patients with chest pain, sensitive troponin I showed a good correlation with significant coronary lesions when its level was greater than 0.605 ng/dL. In patients with chronic renal failure, a significant decrease in specificity was observed in the correlation of troponin levels and severe coronary lesions.

Is There Any Relationship between TSH Levels and Prognosis in Acute Coronary Syndrome?

BACKGROUND: Some small studies have related higher levels of thyrotropin (TSH) to potentially worse prognosis in acute coronary syndromes. However, this relationship remains uncertain. OBJECTIVE: To analyze the outcomes of patients with acute coronary syndromes in relation to the value of TSH at admission. METHODS: Observational and retrospective study with 505 patients (446 in group I [TSH ≤ 4 mIU/L] and 59 in group II [TSH > 4 mIU/L]) with acute coronary syndromes between May 2010 and May 2014. We obtained data about comorbidities and the medications used at the hospital. The primary endpoint was in-hospital all-cause death. The secondary endpoint included combined events (death, non-fatal unstable angina or myocardial infarction, cardiogenic shock, bleeding and stroke). Comparisons between groups were made by one-way ANOVA and chi-square test. Multivariate analysis was determined by logistic regression. Analyses were considered significant when p < 0.05. RESULTS: Significant differences between groups I and II were observed regarding the use of enoxaparin (75.2% vs. 57.63%, p = 0.02) and statins (84.08% vs. 71.19%, p < 0.0001), previous stroke (5.83% vs. 15.25%, p = 0.007), combined events (14.80% vs. 27.12%, OR = 3.05, p = 0.004), cardiogenic shock (4.77% vs. 6.05%, OR = 4.77, p = 0.02) and bleeding (12.09% vs. 15.25%, OR = 3.36, p = 0.012). CONCLUSIONS: In patients with acute coronary syndromes and TSH > 4 mIU/L at admission, worse prognosis was observed, with higher incidences of in-hospital combined events, cardiogenic shock and bleeding.

Prognostic Differences between Men and Women with Acute Coronary Syndrome. Data from a Brazilian Registry.

BACKGROUND: Gender-related differences have been reported in patients with acute coronary syndrome. The description of this comparative finding in a Brazilian registry has not yet been documented. OBJECTIVE: To compare male vs. female patients regarding the baseline characteristics, coronary findings, treatment and in-hospital and long-term prognosis. METHODS: This is a retrospective, multicenter and observational study that included 3,745 patients (2,437 males and 1,308 females) between May 2010 and May 2015. The primary in-hospital outcome was all-cause mortality. The secondary outcome consisted of combined events (cardiogenic shock, reinfarction, death, stroke and bleeding). The comparison between groups was performed using the chi-square and the t test, considering p < 0.05 as significant. In the long term, mortality and combined events were assessed using the Kaplan-Meier method, with a mean follow-up of 8.79 months. RESULTS: The mean age was 60.3 years for males and 64.6 for females (p < 0.0001). The most prevalent risk factor was systemic arterial hypertension in 72.9% of the women and 67.8% of the men (p = 0.001). Percutaneous coronary intervention was carried out in 44.9% of the males and 35.4% of the females (p < 0.0001), and coronary artery bypass grafting (CABG) was performed in 17% of the males and 11.8% of females (p < 0.0001), with a higher prevalence of three-vessel coronary artery disease in males (27.3% vs. 16.2%, p < 0.0001). Approximately 79.9% of the female patients received a diagnosis of acute coronary syndrome without ST-segment elevation, while in the male patients, this diagnosis was attained in 71.5% (p < 0.0001). No significant differences were observed between the groups in the short and long term, regarding both mortality and the combined events. CONCLUSION: Several gender-related differences were observed in patients with acute coronary syndrome regarding the demographic characteristics, coronary artery disease pattern and implemented treatment. However, the prognostic evolution was similar between the groups.

Desempenho Diagnóstico da Angiotomografia Computadorizada e da Avaliação Seriada de Troponina Cardíaca Sensível em Pacientes com Dor Torácica e Risco Intermediário para Eventos Cardiovasculares / Diagnostic Performance of Coronary Tomography Angiography and Serial Measurements of Sensitive Cardiac Troponin in Patients With Chest Pain and Intermediate Risk for Cardiovascular Events

Resumo Fundamento A angiotomografia coronária (ATC) tem sido usada para avaliação de dor torácica principalmente em pacientes de baixo risco, e poucos dados existem com pacientes em risco intermediário. Objetivo Avaliar o desempenho de medidas seriadas de troponinas sensíveis e de ATC em pacientes de risco intermediário. Métodos Um total de 100 pacientes com dor torácica, TIMI score 3 ou 4 e troponina negativa foram prospectivamente incluídos. Todos os pacientes foram submetidos à ATC, e aqueles com obstruções ≥ 50% foram encaminhados à cineangiocoronariografia. Pacientes com lesões < 50% recebiam alta hospitalar, receberam alta e foram contatados 30 dias depois por telefonema para avaliação dos desfechos clínicos. Os desfechos foram hospitalização, morte, e infarto agudo do miocárdio em 30 dias. A comparação entre os métodos foi realizada pelo teste de concordância kappa. O desempenho das medidas de troponina e da ATC na detecção de lesões coronárias significativas e desfechos clínicos foi calculado. Os resultados foram considerados estatisticamente significativos quando p <0,05. Resultados Estenose coronária ≥ 50% na ATC foi encontrada em 38% dos pacientes e lesões coronárias significativas na angiografia coronária foram encontradas em 31 pacientes. Dois eventos clínicos foram observados. A análise de concordância Kappa mostrou baixa concordância entre as medidas de troponina e ATC na detecção de lesões coronárias significativas (kappa = 0,022, p = 0,78). O desempenho da ATC para detectar lesões coronárias significativas na angiografia coronária ou para prever eventos clínicos em 30 dias foi melhor que as medidas de troponina sensível (acurácia de 91% versus 60%). Conclusão ATC teve melhor desempenho que as medidas seriadas de troponina na detecção de doença coronariana significativa em pacientes com dor torácica e risco intermediário para eventos cardiovasculares.

Abstract Background Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk. Objective To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients. Methods A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05. Results Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%). Conclusion CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

Complete Treatment Versus Residual Lesion - Long-Term Evolution After Acute Coronary Syndrome.

INTRODUCTION: A recently published study raised doubts about the need for percutaneous treatment of nonculprit lesions in patients with acute coronary syndromes (ACS). METHODS: Retrospective, unicentric, observational study. OBJECTIVE: To analyze the long-term outcomes in patients undergoing treatment of the culprit artery, comparing those who remained with significant residual lesions in nonculprit arteries (group I) versus those without residual lesions in other coronary artery beds (group II). The study included 580 patients (284 in group I and 296 in group II) between May 2010 and May 2013. We obtained demographic and clinical data, as well as information regarding the coronary treatment administered to the patients. In the statistical analysis, the primary outcome included combined events (reinfarction/angina, death, heart failure, and need for reintervention). The comparison between groups was performed using the chi-square test and ANOVA. The long-term analysis was conducted with the Kaplan-Meier method, with a mean follow-up of 9.86 months. RESULTS: The mean ages were 63 years in group I and 62 years in group II. On long-term follow-up, there was no significant difference in combined events in groups I and II (31.9% versus 35.6%, respectively, p = 0.76). CONCLUSION: The strategy of treating the culprit artery alone seems safe. In this study, no long-term differences in combined endpoints were observed between patients who remained with significant lesions compared with those without other obstructions.

Fondaparinux versus Enoxaparin - Which is the Best Anticoagulant for Acute Coronary Syndrome? - Brazilian Registry Data.

BACKGROUND:: Recent studies have shown fondaparinux's superiority over enoxaparin in patients with non-ST elevation acute coronary syndrome (ACS), especially in relation to bleeding reduction. The description of this finding in a Brazilian registry has not yet been documented. OBJECTIVE:: To compare fondaparinux versus enoxaparin in in-hospital prognosis of non-ST elevation ACS. METHODS:: Multicenter retrospective observational study. A total of 2,282 patients were included (335 in the fondaparinux group, and 1,947 in the enoxaparin group) between May 2010 and May 2015. Demographic, medication intake and chosen coronary treatment data were obtained. Primary outcome was mortality from all causes. Secondary outcome was combined events (cardiogenic shock, reinfarction, death, stroke and bleeding). Comparison between the groups were done through Chi-Square test and T test. Multivariate analysis was done through logistic regression, with significance values defined as p < 0.05. RESULTS:: With regards to treatment, we observed the performance of a percutaneous coronary intervention in 40.2% in the fondaparinux group, and in 35.1% in the enoxaparin group (p = 0.13). In the multivariate analysis, we observed significant differences between fondaparinux and enoxaparin groups in relation to combined events (13.8% vs. 22%. OR = 2.93, p = 0.007) and bleeding (2.3% vs. 5.2%, OR = 4.55, p = 0.037), respectively. CONCLUSION:: Similarly to recently published data in international literature, fondaparinux proved superior to enoxaparin for the Brazilian population, with significant reduction of combined events and bleeding. FUNDAMENTO:: Estudos recentes têm apresentado superioridade do fondaparinux em relação à enoxaparina em pacientes com síndrome coronariana aguda (SCA) sem supradesnivelamento de ST, principalmente relacionada à redução de sangramentos. A descrição desse achado em registro brasileiro ainda não foi documentada. OBJETIVO:: Comparar fondaparinux versus enoxaparina no prognóstico intrahospitalar em SCA sem supradesnivelamento de ST. MÉTODOS:: Estudo retrospectivo, multicêntrico e observacional. Foram incluídos 2.282 pacientes (335 no grupo fondaparinux e 1.947 no grupo enoxaparina) entre maio de 2.010 e maio de 2.015. Foram obtidos dados demográficos, medicações utilizadas e tratamento coronariano adotado. O desfecho primário foi mortalidade por todas as causas. O desfecho secundário foi eventos combinados (choque cardiogênico, reinfarto, morte, acidente vascular cerebral e sangramentos). A comparação entre os grupos foi realizada por meio de Q-quadrado e teste-T. A análise multivariada foi realizada por regressão logística, sendo considerado significativo p < 0,05. RESULTADOS:: Em relação ao tratamento, observou-se realização de intervenção coronária percutânea em 40,2% no grupo fondaparinux e 35,1% no grupo enoxaparina (p = 0,13). Na análise multivariada, observaram-se diferenças significativas entre os grupos fondaparinux e enoxaparina em relação a eventos combinados (13,8% vs. 22%, OR = 2,93, p = 0,007) e sangramentos (2,3% vs. 5,2%, OR = 4,55, p = 0,037), respectivamente. CONCLUSÃO:: Semelhante aos dados recentemente publicados na literatura mundial, fondaparinux mostrou-se superior à enoxaparina para a população brasileira, com redução significativa de eventos combinados e sangramentos.

Mortality reduction with use of oral beta-blockers in patients with acute coronary syndrome.

OBJECTIVES:: Recent studies have revealed a relationship between beta-blocker use and worse prognosis in acute coronary syndrome, mainly due to a higher incidence of cardiogenic shock. However, the relevance of this relationship in the reperfusion era is unknown. The aim of this study was to analyze the outcomes of patients with acute coronary syndrome that started oral beta-blockers within the first 24 hours of hospital admission (group I) compared to patients who did not use oral beta-blockers in this timeframe (group II). METHODS:: This was an observational, retrospective and multicentric study with 2,553 patients (2,212 in group I and 341 in group II). Data regarding demographic characteristics, coronary treatment and medication use in the hospital were obtained. The primary endpoint was in-hospital all-cause mortality. The groups were compared by ANOVA and the chi-square test. Multivariate analysis was conducted by logistic regression and results were considered significant when p<0.05. RESULTS:: Significant differences were observed between the groups in the use of angiotensin-converting enzyme inhibitors, enoxaparin, and statins; creatinine levels; ejection fraction; tabagism; age; and previous coronary artery bypass graft. Significant differences were also observed between the groups in mortality (2.67% vs 9.09%, OR=0.35, p=0.02) and major adverse cardiovascular events (11% vs 29.5%, OR=4.55, p=0.02). CONCLUSIONS:: Patients with acute coronary syndrome who underwent early intervention with oral beta-blockers during the first 24 hours of hospital admission had a lower in-hospital death rate and experienced fewer major adverse cardiovascular events with no increase in cardiogenic shock or sustained ventricular arrhythmias compared to patients who did not receive oral beta-blockers within this timeframe.

Plasma cytokine profile in tropical endomyocardial fibrosis: predominance of TNF-a, IL-4 and IL-10.

BACKGROUND: The participation of immune/inflammatory mechanisms in the pathogenesis of tropical endomyocardial fibrosis (EMF) has been suggested by the finding of early blood and myocardial eosinophilia. However, the inflammatory activation status of late-stage EMF patients is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated pro- and anti-inflammatory cytokine levels in plasma samples from late stage EMF patients. Cytokine levels of Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-γ, Interleukin (IL)-2, IL-4, IL-6, and IL-10 were assayed in plasma samples from 27 EMF patients and compared with those of healthy control subjects. All EMF patients displayed detectable plasma levels of at least one of the cytokines tested. We found that TNF-α, IL-6, IL-4, and IL-10 were each detected in at least 74% of tested sera, and plasma levels of IL-10, IL-4, and TNF-α were significantly higher than those of controls. Plasma levels of such cytokines positively correlated with each other. CONCLUSIONS/SIGNIFICANCE: The mixed pro- and anti-inflammatory/Th2circulating cytokine profile in EMF is consistent with the presence of a persistent inflammatory stimulus. On the other hand, the detection of increased levels of TNF-α may be secondary to the cardiovascular involvement observed in these patients, whereas IL-4 and IL-10 may have been upregulated as a homeostatic mechanism to buffer both production and deleterious cardiovascular effects of pro-inflammatory cytokines. Further studies might establish whether these findings play a role in disease pathogenesis.

Is There Safety in the Use of Clopidogrel Loading Dose in Patients Over 75 Years of Age with Acute Coronary Syndrome?

There is limited evidence in the literature regarding the administration of clopidogrel to acute coronary syndrome (ACS) in patients over 75 years of age. Most studies excluded this age group, making the subject controversial due to the increased risk of bleeding in this population. Objective: This is a retrospective, unicentric, and observational study aimed at assessing whether the administration of clopidogrel loading dose increases bleeding rates in patients over 75 years of age. Methods: Patients were divided into two groups: group I: 75 mg of clopidogrel; group II: 300-to 600-mg loading dose of clopidogrel. A total of 174 patients (129 in group I and 45 in group II) were included between May 2010 and May 2015. Statistical analysis: The primary outcome was bleeding (major and/or minor). The secondary outcome was combined events (cardiogenic shock, reinfarction, death, stroke and bleeding). The comparison between groups was performed through Q-square and T-test. The multivariate analysis was performed by logistic regression, being considered significant p < 0.05. Results: Comparisons between groups I and II showed differences in the prevalence of diabetes (46.5% vs. 24.4%, p = 0.01), arterial hypertension (90.7% vs. 75, p = 0.01), dyslipidemia (62% vs. 42.2%, p = 0.021), ST segment elevation (11.6% vs. 26.6%, p = 0.016) and coronary intervention percutaneous (16.5% vs. 62.2%, p < 0.0001), respectively. In the multivariate analysis, significant differences were observed between groups I and II in relation to the occurrence of bleeding (8.5% vs. 20%, OR = 0.173, 95% CI: 0.049 - 0.614, p = 0.007). Conclusion: A loading dose of 300 mg or more of clopidogrel

Is There Any Relationship between TSH Levels and Prognosis in Acute Coronary Syndrome? / Existe Alguma Relação entre Níveis de TSH e Prognóstico em Síndrome Coronariana Aguda?

Abstract Background: Some small studies have related higher levels of thyrotropin (TSH) to potentially worse prognosis in acute coronary syndromes. However, this relationship remains uncertain. Objective: To analyze the outcomes of patients with acute coronary syndromes in relation to the value of TSH at admission. Methods: Observational and retrospective study with 505 patients (446 in group I [TSH ≤ 4 mIU/L] and 59 in group II [TSH > 4 mIU/L]) with acute coronary syndromes between May 2010 and May 2014. We obtained data about comorbidities and the medications used at the hospital. The primary endpoint was in-hospital all-cause death. The secondary endpoint included combined events (death, non-fatal unstable angina or myocardial infarction, cardiogenic shock, bleeding and stroke). Comparisons between groups were made by one-way ANOVA and chi-square test. Multivariate analysis was determined by logistic regression. Analyses were considered significant when p < 0.05. Results: Significant differences between groups I and II were observed regarding the use of enoxaparin (75.2% vs. 57.63%, p = 0.02) and statins (84.08% vs. 71.19%, p < 0.0001), previous stroke (5.83% vs. 15.25%, p = 0.007), combined events (14.80% vs. 27.12%, OR = 3.05, p = 0.004), cardiogenic shock (4.77% vs. 6.05%, OR = 4.77, p = 0.02) and bleeding (12.09% vs. 15.25%, OR = 3.36, p = 0.012). Conclusions: In patients with acute coronary syndromes and TSH > 4 mIU/L at admission, worse prognosis was observed, with higher incidences of in-hospital combined events, cardiogenic shock and bleeding.

Resumo Fundamento: Estudos pequenos têm relacionado níveis mais elevados de hormônio tireoestimulante (TSH) a pior prognóstico em pacientes com síndrome coronariana aguda (SCA). Tal relação, no entanto, permanece incerta. Objetivo: Analisar os desfechos de pacientes com SCA, relacionando-os aos níveis de TSH medidos no setor de emergência. Métodos: Estudo retrospectivo observacional incluindo 505 pacientes com SCA (446 no grupo I: TSH ± 4 mUI/L; 59 no grupo II: TSH > 4 mUI/L) entre maio de 2010 e maio de 2014. Dados sobre comorbidades e medicamentos usados foram obtidos. O desfecho primário foi mortalidade intra-hospitalar por todas as causas. O desfecho secundário incluiu eventos combinados (morte, angina instável não fatal ou infarto do miocárdio, choque cardiogênico, sangramento e acidente vascular encefálico). A comparação entre grupos foi realizada através de ANOVA de uma via e teste do qui-quadrado. A análise multivariada foi realizada por regressão logística, adotando-se o nível de significância de p < 0,05. Resultados: Diferenças significativas foram observadas entre os grupos I e II relacionadas ao uso de enoxaparina (75,2% vs. 57,63%; p = 0,02) e estatinas (84,08% vs. 71,19%; p < 0,0001), acidente vascular encefálico prévio (5,83% vs. 15,25%; p = 0,007), eventos combinados (14,80% vs. 27,12%, OR = 3,05; p = 0,004), choque cardiogênico (4,77% vs. 6,05%, OR = 4,77; p = 0,02) e sangramento (12,09% vs. 15,25%, OR = 3,36; p = 0,012). Conclusão: Em pacientes com SCA e TSH > 4 mUI/L à admissão hospitalar, observou-se pior prognóstico associado à maior incidência de eventos combinados intra-hospitalares, choque cardiogênico e sangramentos.