Patients discharged with elevated baseline high-sensitive cardiac troponin T from the emergency department.

BACKGROUND: Elevated levels of high-sensitive cardiac troponin T (hs-cTnT) are linked to poor prognosis among emergency department (ED) patients. OBJECTIVE: Examine the effect of our ED risk assessment among patients with suspected acute coronary syndrome (ACS) and elevated baseline hs-cTnT levels. DESIGN: Observational cohort study of 16776 ED patients with chest pain or dyspnoea and a hs-cTnT sample analyzed at the time of the ED visit. Of these 1480 patients were sent home with elevated hs-cTnT levels (>14 ng/L). METHODS: Analysis of clinical and laboratory data from the local hospital and data from the National Board of Health and Welfare. RESULTS: Admitted patients had 11% and discharged patients had 1.2% 90-day mortality indicating effective risk assessment of patients with suspected ACS. However, if the suspected ACS patient presented with hs-cTnT between 14 and 22 ng/L, the 90-day mortality was 4.1% among discharged and 6.7% among admitted patients. Among discharged patients, an hs-cTnT level above 14 ng/L was a higher independent risk factor for 90-day mortality (HR 3.3, 95% CI 2.9-3.7, p < 0.001) than if the patient was triaged as a high-risk patient (HR 1.6, 95% CI 1.1-1.8, p < 0.001). CONCLUSIONS: Our ED risk assessment was less effective among patients presenting with elevated hs-cTnT levels.

Cardiac troponin T concentrations and patient-specific risk of myocardial infarction using the novel PALfx parameter.

BACKGROUND: Myocardial infarction (MI) is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample from a patient with chest pain. There is no conventional method to estimate the risk of MI at a specific cTnT concentration. The purpose of this study was to evaluate the performance of a novel method that converts cTnT concentrations to patient-specific risks of MI. METHODS: Admission cTnT measurements in 15,425 ED patients from three hospitals with a primary complaint of chest pain, with or without a clinical diagnosis of MI, were Box-Cox-transformed to normality density functions to calculate the percentage with MI among patients with a given cTnT concentration, the parametric predictive value among lookalikes (PALfx). The ability of the PALfx to generate stable risk estimates of MI was examined by bootstrapping and expressed as the coefficient of variation (CV). RESULTS: Four age and sex-specific subgroups above or below 60 years of age with distinct cTnT distributions were identified among patients without MI. The cTnT distributions across subgroups with MI were similar, allowing us to use all admissions with MI to calculate the PALfx in the four subgroups. For instance, at a baseline cTnT concentration of 7 ng/L, a female patient <60 years would have a 0.5% risk of MI whereas a male patient >60 years would have a 1.9% risk of MI. To assess the stability of the PALfx method we bootstrapped smaller and smaller subsets of the 15,422 ED visits. We found that 1950 patients without MI and 50 patients with MI were sufficient to limit the variation of the PALfx with a CV of 0.8-5.4%, close to the CV using the entire dataset. The MI risk estimates were similar when data from the three hospitals were used separately to derive the PALfx equations. CONCLUSIONS: The PALfx can be used to estimate the risk of MI at patient-specific cTnT concentrations with acceptable margins of error. The patient-specific risk of disease using the PALfx could complement decision limits.

[Assessment of troponin levels on the emergency ward]. / Troponinnivåer ger nu bättre hjälp vid misstänkt hjärtinfarkt - Låga nivåer kan med hög säkerhet utesluta hjärtinfarkt ­ nya analysmetoder ökar den medicinska säkerheten.

Assessment of troponin levels on the emergency ward  Patients with myocardial infarction are at a high risk of sudden death and new cardiovascular events. For this reason, it is important to identify these patients and device treatment to reduce the risk. Patients who seek care with symptoms indicative of myocardial infarction, mainly chest pain, constitute a large proportion of patients at our emergency departments. However, only 5-10 % of these patients have myocardial infarction, whereas the majority has benign causes of their symptoms. This means that it is important not only to identify patients with myocardial infarction quickly, but also to rule out myocardial infarction and other serious disease as fast and safely as possible. With the aid of assays capable of measuring low levels of the cardiac damage biomarker troponin, so-called high-sensitive troponin assays, and several large high-quality clinical studies, myocardial infarction can now be ruled out safely and quickly. If the patient presents with a troponin T level below 5 ng/L and has a normal ECG, myocardial infarction can normally be ruled out without the need for further investigation. In this way, about 30 % of all patients who present with a suspected myocardial infarction can leave the emergency room quickly with a high degree of medical security. On the other hand, when patients present with troponin T levels above 40 ng/L, the patient should normally be admitted to the hospital. These patients are a high-risk group and constitute only 6 % of those who seek medical attention with a suspected myocardial infarction.

Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile.

BACKGROUND: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources. METHODS: Clinical and laboratory data from patients with chest pain or dyspnea at the emergency de¬partment (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient. RESULTS: Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions. CONCLUSIONS: At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.

Clearance of cardiac troponin T with and without kidney function.

OBJECTIVE: The extent of kidney-dependent clearance of the cardiac damage biomarker cardiac troponin T (cTnT) is not known. METHODS AND RESULTS: We examined clearance of cTnT after injection of heart extracts in rats with or without clamped kidney vessels. The extent of degradation of cTnT to fragments able to pass the glomerular membrane and the kidney extraction index of cTnT was examined in human subjects. After a bolus injection of rat cardiac extract, simulating a large myocardial infarction, there was no significant difference in clearance of cTnT with or without kidney function. However, a slower clearance was observed late in the clearance process, when cTnT levels were low. When low levels of rat cardiac extract were infused at a constant rate to steady state, clamping of the renal vessels resulted in significant 2-fold reduction in clearance of cTnT. Over 60% of the measured cTnT in human subjects had a molecular weight below 17kDa, expected to have a relatively free passage over the glomerular membrane. The extraction index of cTnT in three heart failure patients undergoing renal vein catheterization was 8-19%. Kidney function adjusted cTnT levels increased the area under the ROC curve for diagnosis of myocardial infarction of the cTnT analysis in an emergency room cohort. CONCLUSIONS: At high concentrations, often found after a large myocardial infarction, extrarenal clearance of cTnT dominates. At low levels of cTnT, often found in patients with stable cTnT elevations, renal clearance also contribute to the clearance of cTnT. This potentially explains why stable cTnT levels tend to be higher in patients with low kidney function.

Risk of myocardial infarction at specific troponin T levels using the parameter predictive value among lookalikes (PAL).

BACKGROUND: Myocardial infarction is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample, indicating that cardiac damage has occurred. No method allows the clinician to estimate the risk of myocardial infarction at a specific cTnT level in a given patient. METHODS: Predictive value among lookalikes (PAL) uses pre-test prevalence, sensitivity and specificity at adjacent cTnT limits based on percentiles. PAL is the pre-test prevalence-adjusted probability of disease between two adjacent cTnT limits. If a chest pain patient's cTnT level is between these limits, the risk of myocardial infarction can be estimated. RESULTS: The PAL based on percentiles had an acceptable sampling error when using 100 bootstrapped data of 18 different biomarkers from 38,945 authentic lab measurements. A PAL analysis of an emergency room cohort (n=11,020) revealed that the diagnostic precision of a high-sensitive cTnT assay was similar among chest pain patients at different ages. The higher incidence of false positive results due to non-specific increases in cTnT in the high-age group was counterbalanced by a higher pre-test prevalence of myocardial infarction among older patients, a finding that was missed when using a conventional ROC plot analysis. CONCLUSIONS: The PAL was able to calculate the risk of myocardial infarction at specific cTnT levels and could complement decision limits.

High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease.

BACKGROUND: Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers. OBJECTIVE: To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers. METHODS: Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomarkers Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid-Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90mL/min/1.73m(2). RESULTS: Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a GFR of 15mL/min/1.73m(2) varied from 2-fold to 15-fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured GFR and increased more at low GFR compared to hs-cTnI. For hFABP and NTproBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations). CONCLUSION: The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations.

Assessment of a multi-marker risk score for predicting cause-specific mortality at three years in older patients with heart failure and reduced ejection fraction.

BACKGROUND: Due to increasing co-morbidity associated with aging, heart failure (HF) has become more prevalent and heterogeneous in older individuals, and non-cardiovascular (CV) mortality has increased. Previously, we defined a multi-marker modality that included cystatin C (CysC), troponin T (TnT), and age. Here, we validated this multi-marker risk score by evaluating its predictions of all-cause mortality and CV mortality in an independent population of older individuals with HF and reduced ejection fraction (HFrEF). METHODS: This prospective cohort study included 124 patients, median age 73 years, that had HFrEF. We determined all-cause mortality and CV mortality at a 3-year follow-up. We compared the risk score to the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) for predicting all-cause mortality and CV mortality. RESULTS: High risk scores were associated with both all-cause mortality (HR 4.2, 95% CI 2.2-8.1, p < 0.001) and CV mortality (HR 3.6, 95% CI 1.7-8.0, p = 0.0015). Receiver operating characteristics showed similar efficacy for the risk score and NT-proBNP in predicting all-cause mortality (HR 0.74, 95% CI 0.65-0.81 vs. HR 0.74, 95% CI 0.65-0.81, p = 0.99) and CV mortality (HR 0.68, 95% CI 0.59-0.76 vs. HR 0.67, 95% CI 0.58-0.75, p = 0.95). When the risk score was added to the NT-proBNP, the continuous net reclassification improvement was 56% for predicting all-cause mortality (95% CI 18-95%, p = 0.004) and 45% for predicting CV mortality (95% CI 2-89%, p = 0.040). CONCLUSIONS: In HFrEF, a risk score that included age, TnT, and CysC showed efficacy similar to the NT-proBNP for predicting all-cause mortality and CV mortality in an older population.

Small changes in troponin T levels are common in patients with non-ST-segment elevation myocardial infarction and are linked to higher mortality.

OBJECTIVES: The purpose of this study was to examine the extent of change in troponin T levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Changes in cardiac troponin T (cTnT) levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20% to 230% and an absolute change of 7 to 9 ng/l have been suggested as cutoff points. METHODS: In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitivity cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1,178 patients with a final diagnosis of NSTEMI presenting <24 h after symptom onset. RESULTS: After 6 h of observation, the relative change in the hs-cTnT level remained <20% in 26% and the absolute change <9 ng/l in 12% of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p = 0.002) and in multivariate analyses (hazard ratio: 1.61 [95% confidence interval: 1.17 to 2.21], p = 0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change. CONCLUSIONS: Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.

Assessment of a multimarker strategy for prediction of mortality in older heart failure patients: a cohort study.

OBJECTIVE: Primarily to develop a multimarker score for prediction of 3-year mortality in older patients with decompensated heart failure (HF). DESIGN: Prospective cohort study. SETTING: Secondary care. Single centre. PATIENTS AND BIOMARKERS: 131 patients, aged ≥65 years, with decompensated HF were included. Assessment of biomarkers was performed at discharge. PRIMARY OUTCOME MEASURE: 3-year mortality. RESULTS: Mean age was 73±11 years; mean left ventricular ejection fraction , 43±14%; 53% were male. The 3-year mortality was 53.4%. The following N-terminal brain natriuretic peptide (NTproBNP) levels could optimally stratify mortality: <2000 ng/l (n=39), 30.8% mortality; 2000-8000 ng/l (n=58), 51.7% mortality; and >8000 ng/l (n=34), 82.4% mortality. However, in the 2000-8000 ng/l range, NTproBNP levels had low-prognostic capacity, based on the area under the receiver operating characteristic curve (AUC=0.53; 95% CI 0.40 to 0.67). In this group, multivariate analysis identified age, cystatin C (CysC), and troponin T (TnT) levels as independent risk factors. A risk score based on these three risk factors separated a high-risk and low-risk groups within the NTproBNP range of 2000-8000 ng/l. The score exhibited a significantly higher AUC (0.75; 95% CI 0.62 to 0.86) than NTproBNP alone (p=0.03) in this NTproBNP group and had similar prognostic capacity as NTproBNP in patients below or above this NTproBNP range (p=0.57). Net reclassification improvement and integrated discriminatory improvement in the group with NTproBNP levels between 2000 and 8000 ng/l was 54% and 23%, respectively, and in the whole cohort 22% and 11%, respectively. CONCLUSIONS: Our results suggested that, to assess risk in HF, older patients required significantly higher levels of NTproBNP than younger patients. Furthermore, a risk score that included TnT and CysC at discharge, and age could improve risk stratification for mortality in older patients with HF in particular when NTproBNP was moderately elevated.

Cystatin C in a composite risk score for mortality in patients with infective endocarditis: a cohort study.

OBJECTIVE: To develop a multimarker prognostic score for infective endocarditis (IE). DESIGN: Retrospective case-control. SETTING: Secondary care. Single centre. PARTICIPANTS: 125 patients with definite IE. PRIMARY OUTCOME MEASURES: 90-day and 5-year mortality. RESULTS: Mean age was 62.7±17 years. The 90-day and 5-year mortality was 10.4% and 33.6%, respectively. CysC levels at admission and over 20% increases in CysC levels during 2 weeks of treatment were prognostic for 90-day and 5-year mortality independent of creatinine estimated glomerular filtration rate. In multivariate analyses, CysC (OR 5.42, 95% CI 1.90 to 15.5, p=0.002) and age (OR 1.06, 95% CI 1.02 to 1.10, p=0.002) remained prognostic for 5-year mortality. NT-proBNP, TnT, C reactive protein and interleukin 6 were also linked to prognosis. A composite risk scoring system using levels of CysC, NT-proBNP, age and presence of mitral valve insufficiency was able to separate a high-risk and a low-risk group. CONCLUSIONS: CysC levels at admission and increase in CysC after 2 weeks of treatment were independent prognostic markers for both 90-day and 5-year mortality in patients with IE. A multimarker composite risk scoring system including CysC identified a high-risk group.

Prognostic values of NTpro BNP/BNP ratio in comparison with NTpro BNP or BNP alone in elderly patients with chronic heart failure in a 2-year follow up.

BACKGROUND: Plasma BNP and NT-proBNP are often used as interchangeable parameters in heart failure care in clinical practice. In our previous study we have shown that inflammation was able to induce increased NT pro BNP in a hospital cohort with chronic heart failure in the elderly, indicating that NT-proBNP/BNP ratio should be evaluated concomitantly with inflammatory status to avoid overestimation of heart failure severity. The present study was aimed to evaluate the clinical significance of NT-proBNP/BNP ratio in comparison with NTpro BNP or BNP alone as a prognostic indicator in a 2-year follow up of elderly heart failure population. MATERIALS AND METHODS: One hundred and eight-nine elderly heart failure patients (72 ± 11 years, male 52%, LVEF 46 ± 14%) were enrolled consecutively during 2006 and 2007 and followed up during 2 years. NTpro BNP and BNP were measured routinely. RESULTS: We have found that NTpro BNP/BNP ratio provides no additional prognostic information during follow up as compared to NTpro BNP or BNP alone in an elderly population with chronic heart failure. By the use of ROC curves, for total mortality predictive accuracy during 2 years, the cut-off values are NTproBNP ≥ 800 pg/ml, BNP > 60 pg/ml and NTpro BNP/BNP ratio>6.4 respectively. In terms of NTpro BNP, as long as its serum level is above 2000 pg/ml it indicates poor prognosis. However there is an overlap between serum concentration range 2000-8000 pg/ml and >8000 pg/ml in terms of prognostic indicator. Similarly for BNP, as long as its serum level is above 100 pg/ml, it indicates poor prognosis. However there is an overlap between serum concentration range 100-800 pg/ml and >800 pg/ml in terms of prognostic indicator. There was significant correlation between survival and NTpro BNP, BNP and Cystatin-C but not with NTpro BNP/BNP ratio. Such correlation exists irrespective of subgroups regardless of less than or older than 70 years old. CONCLUSIONS: Our results demonstrated that in elderly heart failure population NTpro BNP/BNP ratio may provide diagnostic help in the presence of acute infection but no additional prognostic information in the long run as compared with NTpro BNP or BNP alone. Furthermore, both NTpro BNP and BNP are useful prognostic biomarkers indeed but they need to be interpreted with caution when it is used as a single biomarker and in the meantime concomitant diseases exist because patients may die due to non-cardiac causes.

A single-centre experience of over one thousand lead extractions.

AIMS: The aim of the study was to present a single-centre experience of pacemaker and implantable cardioverter defibrillator (ICD) lead extraction using different methods, mainly laser-assisted extraction. METHODS AND RESULTS: Data from 1032 leads and 647 procedures were gathered. A step-by-step approach using different techniques while performing an ongoing risk-benefit analysis was used. The most common indications were local infection, systemic infection, non-functional lead, elective lead replacement, and J-wire fracture. Mean implantation time for all leads was 69 months and for laser-extracted leads 91 months. Laser technique was used to extract 60% of the leads, 29% were manually extracted, 6% extracted with mechanical tools, 4% were surgically removed, and 0.6% extracted by a femoral approach. Failure rate was 0.7%, and major complication rate was 0.9%. No extraction-related mortality occurred. Median time for laser extraction was 2 min. Long implantation time was not a risk factor for failure or for complication. CONCLUSION: Pacing and ICD leads can safely, successfully, and effectively be extracted. Leads can often be extracted by a superior transvenous approach; however, open-chest and femoral extractions are still required. Laser-assisted lead extraction proved to be a useful technique to extract leads that could not be removed by manual traction. The results indicate that the paradigm of abandoning redundant leads, instead of removing them, may have to be reconsidered.