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1.
Clin Chim Acta ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061575

RESUMO

The early concentration kinetic profiles of cardiac troponin in patients with non-ST-elevated myocardial infarction (NSTEMI) measured by high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have not been described. In intermediate-to-high-risk of NSTEMI patients we measured serial cTn concentrations on ED arrival, at 1, 2, 3, 6-12, 24 and 48-hours with hs-cTnI and hs-cTnT assays. Log-normal curves were fitted to concentrations from time from symptom onset, and the time to rule-out decision thresholds estimated (hs-cTnI: 2ng/L and 5ng/L; hs-cTnT: 5ng/L). Among 164 patients there were 58 NSTEMI. The hs-cTnI to hs-cTnT ratio increased linearly over the first 6-12 hours following symptom onset. The estimated times from symptom onset to the 2ng/L and 5ng/L thresholds for hs-cTnI were 1.8h (0.1-3.1) and 1.9h (1.1-3.5) hours, and to the 5ng/L threshold for hs-cTnT 1.9h (1.1-3.8). The estimated time to exceed 5ng/L was ≥3 hours in 32.6% (95%CI: 20.0% to 48.1%) cases for hs-cTnI and 33.3% (19.6% to 50.0%) for hs-cTnT. cTnI concentrations increased at a much more rapid rate than cTnT concentrations in patients with NSTEMI. Concentrations of a high proportion of patients took longer than 3 hours from symptom onset to exceed the 5ng/L rule-out decision threshold.

2.
Heart Fail Rev ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062825

RESUMO

Acute decompensated heart failure (ADHF) is associated with a high incidence of acute kidney injury (AKI), an abrupt loss of kidney function associated with a near doubling of mortality at 1 year. In addition to the direct threat acute HF itself poses to kidney function, the beneficial effects of commonly prescribed HF treatments must be weighed against their potentially adverse effects on glomerular perfusion. Consequently, there is an urgent need to identify early markers for AKI in ADHF to facilitate timely implementation of supportive measures to minimize kidney damage and improve outcomes. The recent recognition of the diagnostic potential of circulating microRNAs presents the potential to address this gap if microRNAs specific for AKI can be identified in serial plasma, serum and/or urine samples from well-phenotyped cohorts of ADHF patients, including a proportion with AKI. This review summarizes emerging circulating diagnostic and prognostic microRNA biomarkers (serum, plasma or urine) in HF and AKI.

3.
Eur Heart J Acute Cardiovasc Care ; : 2048872620907539, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067483

RESUMO

BACKGROUND: Undetectable high-sensitivity cardiac troponin (hs-cTn) in a single determination upon admission may rule out acute coronary syndrome. We investigated undetectable hs-cTnT (

4.
Emerg Med J ; 37(1): 2-7, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31719104

RESUMO

BACKGROUND: Emergency physicians frequently assess risk of acute cardiac events (ACEs) in patients with undifferentiated chest pain. Such estimates have been shown to have moderate to high sensitivity for ACE but are conservative. Little is known about the factors implicitly used by physicians to determine the pretest probability of risk. This study sought to identify the accuracy of physician risk estimates for ACE in patients presenting to the ED with chest pain and to identify the demographic and clinical information emergency physicians use in their determination of patient risk. METHODS: This study used data from two prospective studies of consenting adult patients presenting to the ED with symptoms of possible acute coronary syndrome. ED physicians estimated the pretest probability of ACE. Multiple linear regression analysis was used to identify predictors of physician risk estimates. Logistic regression was used to determine whether there was a correlation between physicians' estimated risk and ACE. RESULTS: Increasing age, male sex, abnormal ECG features, heavy/crushing chest pain and risk factors were correlated with physician risk estimates. Physician risk estimates were consistently found to be higher than the expected proportion of ACE from the sampled population. CONCLUSION: Physicians systematically overestimate ACE risk. A range of factors are associated with physician risk estimates. These include factors strongly predictive of ACE, such as age and ECG characteristics. They also include other factors that have been shown to be unreliable predictors of ACE in an ED setting, such as typicality of pain and risk factors.

5.
J Hepatol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31760072

RESUMO

BACKGROUND & AIMS: Acetaminophen-protein adducts are specific biomarkers of toxic acetaminophen (paracetamol) metabolite exposure. In patients with hepatotoxicity (alanine aminotransferase [ALT] >1,000 U/L), an adduct concentration ≥1.0 nmol/ml is sensitive and specific for identifying cases secondary to acetaminophen. Our aim was to characterise acetaminophen-protein adduct concentrations in patients following acetaminophen overdose and determine if they predict toxicity. METHODS: We performed a multicentre prospective observational study, recruiting patients 14 years of age or older with acetaminophen overdose regardless of intent or formulation. Three serum samples were obtained within the first 24 h of presentation and analysed for acetaminophen-protein adducts. Acetaminophen-protein adduct concentrations were compared to ALT and other indicators of toxicity. RESULTS: Of the 240 patients who participated, 204 (85%) presented following acute ingestions, with a median ingested dose of 20 g (IQR 10-40), and 228 (95%) were treated with intravenous acetylcysteine at a median time of 6 h (IQR 3.5-10.5) post-ingestion. Thirty-six (15%) patients developed hepatotoxicity, of whom 22 had an ALT ≤1,000 U/L at the time of initial acetaminophen-protein adduct measurement. Those who developed hepatotoxicity had a higher initial acetaminophen-protein adduct concentration compared to those who did not, 1.63 nmol/ml (IQR 0.76-2.02, n = 22) vs. 0.26 nmol/ml (IQR 0.15-0.41; n = 204; p <0.0001), respectively. The AUROC for hepatotoxicity was 0.98 (95% CI 0.96-1.00; n = 226; p <0.0001) with acetaminophen-protein adduct concentration and 0.89 (95% CI 0.82-0.96; n = 219; p <0.0001) with ALT. An acetaminophen-protein adduct concentration of 0.58 nmol/ml was 100% sensitive and 91% specific for identifying patients with an initial ALT ≤1,000 U/L who would develop hepatotoxicity. Adding acetaminophen-protein adduct concentrations to risk prediction models improved prediction of hepatotoxicity to a level similar to that obtained by more complex models. CONCLUSION: Acetaminophen-protein adduct concentration on presentation predicted which patients with acetaminophen overdose subsequently developed hepatotoxicity, regardless of time of ingestion. An adduct threshold of 0.58 nmol/L was required for optimal prediction. LAY SUMMARY: Acetaminophen poisoning is one of the most common causes of liver injury. This study examined a new biomarker of acetaminophen toxicity, which measures the amount of toxic metabolite exposure called acetaminophen-protein adduct. We found that those who developed liver injury had a higher initial level of acetaminophen-protein adducts than those who did not. CLINICAL TRIAL REGISTRATION: Australian Toxicology Monitoring (ATOM) Study-Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.

6.
Circulation ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31416346

RESUMO

BACKGROUND: Variations in cardiac troponin concentrations by age, sex and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients. METHODS: A machine learning algorithm (myocardial-ischemic-injury-index [MI3]) incorporating age, sex, and paired high-sensitivity cardiac troponin I concentrations, was trained on 3,013 patients and tested on 7,998 patients with suspected myocardial infarction. MI3 uses gradient boosting to compute a value (0-100) reflecting an individual's likelihood of a diagnosis of type 1 myocardial infarction and estimates the sensitivity, negative predictive value (NPV), specificity and positive predictive value (PPV) for that individual. Assessment was by calibration and area under the receiver-operating-characteristic curve (AUC). Secondary analysis evaluated example MI3 thresholds from the training set that identified patients as low-risk (99% sensitivity) and high-risk (75% PPV), and performance at these thresholds was compared in the test set to the 99th percentile and European Society of Cardiology (ESC) rule-out pathways. RESULTS: Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI3 was well calibrated with a very high AUC of 0.963 [0.956-0.971] in the test set and similar performance in early and late presenters. Example MI3 thresholds identifying low-risk and high-risk patients in the training set were 1.6 and 49.7 respectively. In the test set, MI3 values were <1.6 in 69.5% with a NPV of 99.7% (99.5%-99.8%) and sensitivity of 97.8% (96.7-98.7%), and were ≥49.7 in 10.6% with a PPV of 71.8% (68.9-75.0%) and specificity of 96.7% (96.3-97.1%). Using these thresholds, MI3 performed better than the ESC 0/3-hour pathway (sensitivity 82.5% [74.5-88.8%], specificity 92.2% [90.7-93.5%]) and the 99th percentile at any time-point (sensitivity 89.6% [87.4-91.6%]), specificity 89.3% [88.6-90.0%]). CONCLUSIONS: Using machine learning, MI3 provides an individualized and objective assessment of the likelihood of myocardial infarction, which can be used to identify low-risk and high-risk patients who may benefit from earlier clinical decisions. CLINICAL TRIAL REGISTRATION: Unique Identifier: Australian New Zealand Clinical Trials Registry: ACTRN12616001441404. URL: https://www.anzctr.org.au.

7.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
10.
Int J Cardiol ; 274: 66-70, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30297189

RESUMO

BACKGROUND: We studied the association between heart failure with reduced or preserved ejection fraction (EF) and the risk of acute kidney injury (AKI) in patients undergoing coronary artery bypass surgery (CABG). METHODS: We included all patients who underwent isolated CABG in Sweden 2003 to 2013. AKI was defined according to the Kidney Disease Improving Global Outcomes definition, as an increase in postoperative serum creatinine concentration by ≥26 µmol/L or ≥50%, compared to preoperative values. Adjusted odds ratios (OR) for AKI were calculated using logistic regression for patients with and without heart failure, and among patients with heart failure, by EF categories (<30% severely reduced; 30-40% moderately reduced; ≥50% preserved). RESULTS: Included were 36,403 patients of whom 3914 (11%) had heart failure. In patients with heart failure, 26% developed AKI compared with 14% in patients without heart failure. After adjustment for background characteristics, including preoperative kidney function and EF, the OR for AKI was 1.12 (95% CI 1.02-1.23) in patients with heart failure compared with no heart failure. Among patients with heart failure, the adjusted OR for AKI among patients with EF <30% vs. ≥50% was 1.32 (95% CI 1.06-1.65) and for 30-49% vs. ≥50% 1.06 (95% CI 0.87-1.28), respectively. CONCLUSION: Patients with heart failure who underwent CABG had an increased risk for AKI postoperatively even after adjustment for comorbidity such as EF. Among patients with heart failure, having a severely reduced EF was associated with AKI compared to patents with preserved EF.


Assuntos
Lesão Renal Aguda/etiologia , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Insuficiência Cardíaca/complicações , Complicações Pós-Operatórias , Volume Sistólico/fisiologia , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/epidemiologia , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/complicações , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Suécia/epidemiologia , Fatores de Tempo
11.
Eur J Emerg Med ; 26(4): 242-248, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29878922

RESUMO

OBJECTIVE: To describe patients presenting with chest pain to the emergency department (ED) according to acute kidney injury (AKI) status at arrival, with a focus on the most common discharge diagnoses and on long-term mortality. METHODS: All adult patients visiting the Karolinska University Hospital ED between December 2010 and October 2014 with a principal complaint of chest pain were included. AKI at arrival was defined as an increase in presentation serum creatinine concentration of at least 26 µmol/l ( ≥ 0.3 mg/dl) or at least 50% above baseline. Risk ratios (RR) with 95% confidence intervals (CIs) between the AKI and no-AKI groups were calculated for the most common discharge diagnoses in the AKI group. Hazard ratios for long-term mortality were calculated using Cox regression models with adjustment for covariates. RESULTS: In total, 8480 patients were included, of whom 476 (5.6%) had AKI. AKI patients were older and had more comorbidities. It was more common in AKI patients compared to no AKI patients to be diagnosed with heart failure, RR 3.03 (CI: 2.15-4.26) and myocardial infarction RR 1.44 (CI: 1.01-2.04). During a median follow-up of 3.2 years (interquartile range: 2.1-4.3), 37% of the patients with AKI died compared with 16% of patients without AKI. The multivariable adjusted hazard ratio of death for AKI compared with no AKI was 1.30 (95% CI: 1.10-1.53). CONCLUSION: When attending the ED, patients with chest pain and AKI were more likely to be diagnosed with heart failure and myocardial infarction and had an increased long-term mortality compared with patients with no AKI.


Assuntos
Lesão Renal Aguda/diagnóstico , Causas de Morte , Dor no Peito/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Insuficiência Cardíaca/diagnóstico , Infarto do Miocárdio/diagnóstico , Centros Médicos Acadêmicos , Lesão Renal Aguda/mortalidade , Adulto , Idoso , Dor no Peito/mortalidade , Estudos de Coortes , Comorbidade , Intervalos de Confiança , Diagnóstico Diferencial , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Alta do Paciente , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Suécia
12.
Health Informatics J ; 25(4): 1563-1571, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-29905094

RESUMO

Clinical pathways are used to support the management of patients in emergency departments. An existing document-based clinical pathway was used as the foundation on which to design and build a digital clinical pathway for acute chest pain, with the aim of improving clinical calculations, clinician decision-making, documentation, and data collection. Established principles of decision support system design were used to build an application within the existing electronic health record, before testing with a multidisciplinary team of doctors using a think-aloud protocol. Technical authoring was successful, however, usability testing revealed that the user experience and the flexibility of workflow within the application were critical barriers to implementation. Emergency medicine and acute care decision support systems face particular challenges to existing models of linear workflow that should be deliberately addressed in digital pathway design. We make key recommendations regarding digital pathway design in emergency medicine.

13.
JAMA Cardiol ; 3(11): 1108-1112, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30347004

RESUMO

Importance: Emergency department (ED) investigations of patients with suspected acute myocardial infarction (AMI) are time consuming, partly because of the turnaround time of laboratory tests. Current point-of-care troponin assays shorten test turnaround times but lack precision at lower concentrations. Development of point-of-care troponin assays with greater analytical precision could reduce the decision-making time in EDs for ruling out AMI. Objective: To determine the clinical accuracy for AMI of a single troponin concentration measured on arrival to ED with a new-generation, higher precision point-of-care assay with a 15-minute turnaround time. Design, Setting, and Participants: This observational study occurred at a single urban regional ED. Adults presenting acutely from the community to the ED with symptoms suggestive of AMI were included. Troponin concentrations were measured on ED arrival with both a novel point-of-care assay (i-STAT TnI-Nx; Abbott Point of Care) and a high-sensitivity troponin I assay (Architect hs-cTnI; Abbott Diagnostics). Main Outcomes and Measures: The primary outcome was type 1 AMI during index presentation. We compared the discrimination ability of the TnI-Nx assay with the hs-cTnI assay using the area under receiver operator characteristic curve (AUC) and sensitivity, negative predictive value, and the proportion of negative test results at thresholds with 100% sensitivity. Results: Of 354 patients (255 [72.0%] men; mean [SD] age, 62 [12] years), 57 (16.1%) experienced an AMI. Eighty-five patients (24.0%) presented to the ED less than 3 hours after symptom onset. No difference was found between the AUC of the TnI-Nx assay (0.975 [95% CI, 0.958-0.993]) and the hs-cTnI assay (0.970 [95% CI, 0.949 to 0.990]; P = .46). A TnI-Nx assay result of less than 11 ng/L identified 201 patients (56.7%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 98.2%-100%). In comparison, an hs-cTnI assay result of less than 3 ng/L identified 154 patients (43.5%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 97.6%-100%). Conclusions and Relevance: A novel point-of-care troponin assay that can produce a result 15 minutes after blood sampling had comparable discrimination ability to an hs-cTnI assay for ruling out AMI after a single blood test. Use in the ED may facilitate earlier decision making and could expedite the safe discharge of a large proportion of low-risk patients.


Assuntos
Infarto do Miocárdio/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Troponina I/análise , Idoso , Área Sob a Curva , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Nova Zelândia , Sensibilidade e Especificidade , Fatores de Tempo
14.
CMAJ ; 190(33): E974-E984, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127037

RESUMO

BACKGROUND: Testing for high-sensitivity cardiac troponin (hs-cTn) may assist triage and clinical decision-making in patients presenting to the emergency department with symptoms of acute coronary syndrome; however, this could result in the misclassification of risk because of analytical variation or laboratory error. We sought to evaluate a new laboratory-based risk-stratification tool that incorporates tests for hs-cTn, glucose level and estimated glomerular filtration rate to identify patients at risk of myocardial infarction or death when presenting to the emergency department. METHODS: We constructed the clinical chemistry score (CCS) (range 0-5 points) and validated it as a predictor of 30-day myocardial infarction (MI) or death using data from 4 cohort studies involving patients who presented to the emergency department with symptoms suggestive of acute coronary syndrome. We calculated diagnostic parameters for the CCS score separately using high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: For the combined cohorts (n = 4245), 17.1% of participants had an MI or died within 30 days. A CCS score of 0 points best identified low-risk participants: the hs-cTnI CCS had a sensitivity of 100% (95% confidence interval [CI] 99.5%-100%), with 8.9% (95% CI 8.1%-9.8%) of the population classified as being at low risk of MI or death within 30 days; the hs-cTnT CCS had a sensitivity of 99.9% (95% CI 99.2%-100%), with 10.5% (95% CI 9.6%-11.4%) of the population classified as being at low risk. The CCS had better sensitivity than hs-cTn alone (hs-cTnI < 5 ng/L: 96.6%, 95% CI 95.0%-97.8%; hs-cTnT < 6 ng/L: 98.2%, 95% CI 97.0%-99.0%). A CCS score of 5 points best identified patients at high risk (hs-cTnI CCS: specificity 96.6%, 95% CI 96.0%-97.2%; 11.2% [95% CI 10.3%-12.2%] of the population classified as being at high risk; hs-cTnT CCS: specificity 94.0%, 95% CI 93.1%-94.7%; 13.1% [95% CI 12.1%-14.1%] of the population classified as being at high risk) compared with using the overall 99th percentiles for the hs-cTn assays (specificity of hs-cTnI 93.2%, 95% CI 92.3-94.0; specificity of hs-cTnT 73.8%, 95% CI 72.3-75.2). INTERPRETATION: The CCS score at the chosen cut-offs was more sensitive and specific than hs-cTn alone for risk stratification of patients presenting to the emergency department with suspected acute coronary syndrome. Study registration: ClinicalTrials.gov, nos. NCT01994577; NCT02355457.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Técnicas de Laboratório Clínico , Miocárdio/química , Troponina I/análise , Troponina T/análise , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Morte , Serviço Hospitalar de Emergência , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo
15.
Clin Chem ; 64(7): 1044-1053, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29760219

RESUMO

BACKGROUND: Increased cardiac troponin I or T detected by high-sensitivity assays (hs-cTnI or hs-cTnT) confers an increased risk of adverse prognosis. We determined whether patients presenting with putatively normal, detectable cTn concentrations [> limit of detection and < upper reference limit (URL)] have increased risk of major adverse cardiovascular events (MACE) or all-cause mortality. METHODS: A prospective 5-year follow-up of patients recruited in the emergency department with possible acute coronary syndrome (ACS) and cTn concentrations measured with hs-cTnI (Abbott) and hs-cTnT (Roche) assays. Cox regression models were generated with adjustment for covariates in those without MACE on presentation. Hazard ratios (HRs) for hs-cTn were calculated relative to the HRs at the median concentration. RESULTS: Of 1113 patients, 836 were without presentation MACE. Of these, 138 incurred a MACE and 169 died during a median 5.8-year follow-up. HRs for MACE at the URLs were 2.3 (95% CI, 1.7-3.2) for hs-cTnI and 1.8 (95% CI, 1.3-2.4) for hs-cTnT. Corresponding HRs for mortality were 1.7 (95% CI, 1.2-2.2) for hs-cTnI and 2.3 (95 % CI, 1.7-3.1) for hs-cTnT. The HR for MACE increased with increasing hs-cTn concentration similarly for both assays, but the HR for mortality increased at approximately twice the rate for hs-cTnT than hs-cTnI. Patients with hs-cTnI ≥10 ng/L or hs-cTnT ≥16 ng/L had the same percentage of MACE at 5-year follow-up (33%) as patients with presentation MACE. CONCLUSIONS: Many patients with ACS ruled out and putatively normal but detectable hs-cTnI concentrations are at similar long-term risk as those with MACE. hs-cTnT concentrations are more strongly associated with 5-year mortality than hs-cTnI.


Assuntos
Troponina I/sangue , Troponina T/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Humanos , Limite de Detecção , Padrões de Referência , Fatores de Risco
16.
Circulation ; 138(10): 989-999, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-29691270

RESUMO

BACKGROUND: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. METHODS: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. RESULTS: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0-99.9%]; product: NPV 99.4% [95% CI, 98.8-99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2-100%]; NPV validation cohort 99.5% [95% CI, 98.9-99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6-78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7-87.6%]). CONCLUSIONS: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Troponina T/sangue , Austrália , Biomarcadores/sangue , Diagnóstico Precoce , Europa (Continente) , Humanos , Infarto do Miocárdio/sangue , Nova Zelândia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Regulação para Cima
17.
Clin J Am Soc Nephrol ; 13(4): 569-576, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29507005

RESUMO

BACKGROUND AND OBJECTIVES: In patients with CKD, elevated plasma parathyroid hormone (PTH) levels are associated with greater cardiovascular morbidity and mortality. However, the reference method for PTH measurement is disputed. It has been argued that measurement of nonoxidized PTH better reflects biologically active PTH than measurements with conventional assays. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: PTH and nonoxidized PTH levels were measured at study baseline in 535 patients with CKD with an eGFR range between 89 and 15 ml/min per 1.73 m2. Patients were followed over 5.1 years for the occurrence of acute heart failure, atherosclerotic events, CKD progression (doubling of serum creatinine or initiation of RRT), or all-cause death. RESULTS: Atherosclerotic events, acute heart failure, CKD progression, and deaths from any cause occurred in 116, 58, 73, and 85 patients, respectively. In Kaplan-Meier analyses, patients at the highest PTH and nonoxidized-PTH tertile (79-543 and 12-172 pg/ml, respectively) showed a higher rate of atherosclerotic events, acute heart failure, CKD progression, and death from any cause. After adjustment for eGFR and albuminuria, nonoxidized PTH was no longer associated with atherosclerotic events (hazard ratio third versus first tertile, 1.04 [95% confidence intervals, 0.62-1.75]), acute heart failure (hazard ratio third versus first tertile, 1.24 [95% confidence intervals, 0.59-2.62]), CKD progression (hazard ratio third versus first tertile, 0.93 [95% confidence intervals, 0.46-1.90]), and death from any cause (hazard ratio third versus first tertile, 1.23 [95% confidence intervals, 0.66-2.31]), and PTH lost its association with atherosclerotic events (hazard ratio third versus first tertile, 0.80 [95% confidence intervals, 0.46-1.38]) and CKD progression (hazard ratio third versus first tertile, 0.99 [95% confidence intervals, 0.46-2.10]), although it remained associated with acute heart failure (hazard ratio third versus first tertile, 2.76 [95% confidence intervals, 1.11-6.89]) and all-cause death (hazard ratio third versus first tertile, 2.35 [95% confidence intervals, 1.13-4.89]). After further adjustment for cardiovascular and kidney risk factors, PTH remained associated with all-cause death (hazard ratio third versus first tertile, 2.79 [95% confidence intervals, 1.32-5.89]), but with no other end point. CONCLUSIONS: In a cohort of patients with CKD, PTH was associated with all-cause mortality; there was no association of nonoxidized PTH with any of the clinical outcomes examined.


Assuntos
Doenças Cardiovasculares/epidemiologia , Mortalidade , Hormônio Paratireóideo/sangue , Insuficiência Renal Crônica/sangue , Idoso , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oxirredução , Hormônio Paratireóideo/química , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença
18.
J Cardiothorac Vasc Anesth ; 32(5): 2190-2200, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29452878

RESUMO

OBJECTIVE: To evaluate the prognostic utility of multiple novel urinary biomarkers of renal injury when used alone, in pair-wise combination with an early delta serum creatinine (ΔSCr) term, and combined as a broad biomarker panel for the prediction of serious adverse outcomes that may reflect AKI in patients undergoing cardiac surgery. DESIGN: Post-hoc analysis of prospective observational study. SETTING: Academic medical center. PARTICIPANTS: 603 adults undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urinary cystatin-c, kidney injury molecule-1, chemokine (C-C motif) ligand 2 and interleukin-18 were measured at baseline and <1 hour, 3 hours and 18-24 hours after separation from cardiopulmonary bypass (CPB). ΔSCr-initial was defined as the difference in SCr from baseline to first postoperative measure. The primary outcome of hospital mortality or renal replacement therapy occurred in 25 patients. Concordant elevation of any urinary biomarker measured 3 hours after CPB together with ΔSCr-initial ≥0 mg.dL-1 provided excellent early risk stratification for the primary outcome (OR ≥15.1, 95% CI 4.1-55.4). Combining four urinary biomarkers together with ΔSCr-initial and neutrophil gelatinase-associated lipocalin, previously reported from the same cohort, to provide a 6-point AKI risk score enabled early identification of patients reaching the primary outcome (ROCAUC 0.86, 95% CI 0.79-0.92) with potentially useful sensitivity and specificity at varied cut-points. CONCLUSIONS: Combining novel urinary biomarkers of renal injury with a creatinine-based metric soon after cardiac surgery provided excellent prognostic utility for serious adverse outcomes. Future studies are required to confirm these findings and determine optimal biomarker combinations for cost-effective risk stratification.


Assuntos
Lesão Renal Aguda/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Creatinina/sangue , Medição de Risco/métodos , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
19.
Acad Emerg Med ; 25(4): 434-443, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29131477

RESUMO

OBJECTIVES: Early discharge of patients with presentations triggering assessment for possible acute coronary syndrome (ACS) is safe when clinical assessment indicates low risk, biomarkers are negative, and electrocardiograms (ECGs) are nonischemic. We hypothesized that the Emergency Department Assessment of Chest Pain Score (EDACS) combined with a single measurement of high-sensitivity cardiac troponin (hs-cTn) could allow early discharge of a clinically meaningful proportion of patients. METHODS: We pooled data from four patient cohorts from New Zealand and Australia presenting to an emergency department with symptoms suggestive of ACS. The primary outcome was major adverse cardiac events (MACE) within 30 days of presentation. In patients with a nonischemic ECG we evaluated the sensitivity for MACE and percentage low risk of every combination of high-sensitivity cardiac troponin T (hs-cTnT) concentration and high-sensitivity cardiac troponin I (hs-cTnI) concentration with EDACS. We used a standard smoothing technique on the probability density function for hs-cTn and EDACS and applied bootstrapping to determine the optimal threshold combinations, namely, the combination that maximized the percentage low risk with ≥98.5% sensitivity for MACE. RESULTS: From 2,536 patients, 2,258 presented without an ischemic ECG of whom 272 (12.1%) had a MACE within 30 days. The optimal threshold for hs-cTnI was 7 ng/L combined with an EDACS threshold of 16 (36.8% patients low risk). The optimal thresholds for hs-cTnT were 8 ng/L combined with an EDACS threshold of 15 (30.2% patients low risk). CONCLUSION: Single measurements of both hs-cTnI and hs-cTnT at presentation combined with EDACS to identify over 30% of patients as low risk and therefore eligible for safe early discharge after only one blood draw.


Assuntos
Dor no Peito/diagnóstico , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência/organização & administração , Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Biomarcadores , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Alta do Paciente , Estudos Prospectivos , Medição de Risco , Troponina T/sangue , Adulto Jovem
20.
Circulation ; 137(4): 354-363, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29138293

RESUMO

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Serviço Hospitalar de Cardiologia/normas , Procedimentos Clínicos/normas , Serviço Hospitalar de Emergência/normas , Hospitalização , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Tomada de Decisão Clínica , Eletrocardiografia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Troponina/sangue
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