Accuracy of chest radiographs in the emergency diagnosis of heart failure

The purpose of this study was to determine the diagnostic accuracy of chest radiographic findings of heart failure (HF) in current patients presenting with dyspnea in the emergency department. In a secondary analysis of the BASEL study, initial chest radiographs of 277 patients with acute dyspnea were evaluated by two radiologists blinded to the adjudicated diagnosis (56% had the final diagnosis of HF). Predefined radiographic criteria of HF were used. Statistical analysis included receiver-operating characteristic (ROC) analysis and calculation of a logistic regression model including B-type natriuretic peptide (BNP) levels. The reader's overall impression showed the highest area under the ROC curve for the diagnosis of HF in both supine and erect patient positions (0.855 and 0.857). Among individual radiographic findings, peribronchial cuffing in the supine position (0.829) showed the highest accuracies. The lowest accuracy was found for the vascular pedicle width in the supine position (0.461). Logistic regression analysis showed no significant differences between the reader's overall impression, the radiographic model, and BNP testing. In our study, the combination of radiographic features provided valuable information and was of comparable accuracy as BNP-testing for the diagnosis of H

Uremic cardiomyopathy is characterised by loss of the cardioprotective effects of insulin

Chronic kidney disease is associated with a unique cardiomyopathy, characterised by a combination of structural and cellular remodelling, and an enhanced susceptibility to ischaemia-reperfusion injury. This may represent dysfunction of the reperfusion injury salvage kinase pathway, due to insulin resistance. Aims: The susceptibility of the uraemic heart to ischaemia-reperfusion injury and the cardioprotective effects of insulin and rosiglitazone were investigated. Methods and Results: Uraemia was induced in Sprague-Dawley rats by subtotal nephrectomy. Functional recovery from ischaemia was investigated in vitro in control and uraemic hearts ±insulin ±rosiglitazone. The response of myocardial oxidative metabolism to insulin was determined by 13C NMR spectroscopy. Activation of reperfusion injury salvage kinase pathway intermediates (Akt and GSK3β) were assessed by SDS-PAGE and immuno-precipitation. Insulin improved post-ischaemic rate pressure product in control but not uraemic hearts, (recovered rate pressure product (%), control 59.6±10.7 vs 88.9±8.5, p<0.05; uraemic 19.3±4.6 vs 28.5±10.4, p=ns). Rosiglitazone resensitised uraemic hearts to insulin-mediated cardio-protection (recovered rate pressure product (%) 12.7±7.0 vs. 61.8±15.9, p<0.05). Myocardial carbohydrate metabolism remained responsive to insulin in uraemic hearts. Uraemia was associated with increased phosphorylation of Akt (1.00±0.08 vs. 1.31±0.11, p<0.05) in normoxia, but no change in post-ischaemic phosphorylation of Akt or GSK3β. Akt2 isoform expression was decreased post-ischaemia in uraemic hearts (p<0.05). Conclusion: Uraemia is associated with enhanced susceptibility to ischaemia-reperfusion injury and a loss of insulin-mediated cardio-protection, which can be restored by administration of rosiglitazone. Altered Akt2 expression in uraemic hearts post ischaemia-reperfusion and impaired activation of reperfusion injury salvage kinase pathway may underlie these findings

Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial

Aims The most effective regimen for the prevention of contrast-induced nephropathy (CIN) remains uncertain. Our purpose was to compare two regimens of sodium bicarbonate with 24 h sodium chloride 0.9% infusion in the prevention of CIN. Methods and results We performed a prospective, randomized trial between March 2005 and December 2009, including 258 consecutive patients with renal insufficiency undergoing intravascular contrast procedures. Patients were randomized to receive intravenous volume supplementation with either (A) sodium chloride 0.9% 1 mL/kg/h for at least 12h prior and after the procedure or (B) sodium bicarbonate (166 mEq/L) 3 mL/kg for 1h before and 1 mL/kg/h for 6h after the procedure or (C) sodium bicarbonate (166 mEq/L) 3 mL/kg over 20min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). The primary endpoint was the change in estimated glomerular filtration rate (eGFR) within 48h after contrast. Secondary endpoints included the development of CIN. The maximum change in eGFR was significantly greater in Group B compared with Group A {mean difference −3.9 [95% confidence interval (CI), −6.8 to −1] mL/min/1.73 m2, P = 0.009} and similar between Groups C and B [mean difference 1.3 (95% CI, −1.7-4.3) mL/min/1.73 m2, P = 0.39]. The incidence of CIN was significantly lower in Group A (1%) vs. Group B (9%, P = 0.02) and similar between Groups B and C (10%, P = 0.9). Conclusion Volume supplementation with 24 h sodium chloride 0.9% is superior to sodium bicarbonate for the prevention of CIN. A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen. ClinicalTrials.gov Identifier: NCT0013059

Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Aims Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI. Methods and results This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. Conclusion Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. Clinical Trial Registration Information: ClinicalTrials.gov, NCT0047058

Value of arterial blood gas analysis in patients with acute dyspnea: an observational study

ABSTRACT: INTRODUCTION: The diagnostic and prognostic value of arterial blood gas analysis (ABGA) parameters in unselected patients presenting with acute dyspnea to the Emergency Department (ED) is largely unknown. METHODS: We performed a post-hoc analysis of two different prospective studies to investigate the diagnostic and prognostic value of ABGA parameters in patients presenting to the ED with acute dyspnea. RESULTS: We enrolled 530 patients (median age 74 years). ABGA parameters were neither useful to distinguish between patients with pulmonary disorders and other causes of dyspnea nor to identify specific disorders responsible for dyspnea. Only in patients with hyperventilation from anxiety disorder, the diagnostic accuracy of pH and hypoxemia rendered valuable with an area under the receiver operating characteristics curve (AUC) of 0.86. Patients in the lowest pH tertile more often required admission to Intensive Care Unit (28% vs 12% in the first tertile, P >0.001) and had higher in-hospital (14% vs 5%, P =0.003) and 30-day mortality (17% vs 7%, P =0.002). Cumulative mortality rate was higher in the first (37%), than in the second (28%), and the third tertile (23%, P =0.005) during 12 months follow-up. pH at presentation was an independent predictor of 12-month mortality in multivariable Cox proportional hazard analysis both for patients with pulmonary (P =0.043) and non-pulmonary disorders (P =0.038). CONCLUSIONS: ABGA parameters provide limited diagnostic value in patients with acute dyspnea, but pH is an independent predictor of 12 months mortality

Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU study

Acute respiratory failure (ARF) is responsible for about one-third of intensive care unit (ICU) admissions and is associated with adverse outcomes. Predictors of short- and long-term outcomes in unselected ICU-patients with ARF are ill-defined. The purpose of this analysis was to determine predictors of in-hospital and one-year mortality and assess the effects of oral beta-blockers in unselected ICU patients with ARF included in the BASEL-II-ICU study. The BASEL II-ICU study was a prospective, multicenter, randomized, single-blinded, controlled trial of 314 (mean age 70 (62 to 79) years) ICU patients with ARF evaluating impact of a B-type natriuretic peptide- (BNP) guided management strategy on short-term outcomes. In-hospital mortality was 16% (51 patients) and one-year mortality 41% (128 patients). Multivariate analysis assessed that oral beta-blockers at admission were associated with a lower risk of both in-hospital (HR 0.33 (0.14 to 0.74) P = 0.007) and one-year mortality (HR 0.29 (0.16 to 0.51) P = 0.0003). Kaplan-Meier analysis confirmed the lower mortality in ARF patients when admitted with oral beta-blocker and further shows that the beneficial effect of oral beta-blockers at admission holds true in the two subgroups of patients with ARF related to cardiac or non-cardiac causes. Kaplan-Meier analysis also shows that administration of oral beta-blockers before hospital discharge gives striking additional beneficial effects on one-year mortality. Established beta-blocker therapy appears to be associated with a reduced mortality in ICU patients with acute respiratory failure. Cessation of established therapy appears to be hazardous. Initiation of therapy prior to discharge appears to confer benefit. This finding was seen regardless of the cardiac or non-cardiac etiology of respiratory failure. ClinicalTrials.gov Identifier: NCT00130559

Midregional pro-Adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study

The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea.; We conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea.; MR-proADM levels were elevated in non-survivors (n = 77) compared to survivors (median 1.9 (1.2 to 3.2) nmol/L vs. 1.1 (0.8 to 1.6) nmol/L; P > 0.001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.81 (95% CI 0.73 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for MR-proADM, NT-proBNP and BNP, respectively (MRproADM vs. NTproBNP P = 0.38; MRproADM vs. BNP P = 0.009). For one-year mortality the AUC were 0.75 (95% CI 0.69 to 0.81), 0.75 (95% CI 0.68 to 0.81), 0.69 (95% CI 0.62 to 0.76) for MR-proADM, NT-proBNP and BNP, respectively without any significant difference. Using multivariate linear regression analysis, MR-proADM strongly predicted one-year all-cause mortality independently of NT-proBNP and BNP levels (OR = 10.46 (1.36 to 80.50), P = 0.02 and OR = 24.86 (3.87 to 159.80) P = 0.001, respectively). Using quartile approaches, Kaplan-Meier curve analyses demonstrated a stepwise increase in one-year all-cause mortality with increasing plasma levels (P > 0.0001). Combined levels of MR-proADM and NT-proBNP did risk stratify acute dyspneic patients into a low (90% one-year survival rate), intermediate (72 to 82% one-year survival rate) or high risk group (52% one-year survival rate).; MR-proADM alone or combined to NT-proBNP has a potential to assist clinicians in risk stratifying patients presenting with acute dyspnea regardless of the underlying disease

Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays

Aims To examine the diagnostic accuracy of sensitive cardiac troponin (cTn) assays in elderly patients, since elevated levels with sensitive cTn assays were reported in 20% of elderly patients without acute myocardial infarction (AMI). Methods and results In this multi-centre study, we included 1098 consecutive patients presenting with symptoms suggestive of AMI, 406 (37%) were >70 years old. Measurement of three investigational sensitive cTn assays [Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, and Abbott-Architect cTnI) and the standard assay (Roche cTnT) was performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the adjudicated final diagnosis in 24% of elderly patients. Among elderly patients without AMI, baseline cTn levels were elevated above the 99th percentile in 51% with Roche hs-cTnT, in 17% with Siemens TnI-Ultra, and 13% with Abbott-Architect cTnI. The diagnostic accuracy as quantified by the area under the receiver operating characteristic (ROC) curve (AUC) was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.94; Siemens cTnI-Ultra, 0.95; and Abbott-Architect cTnI, 0.95 vs. AUC for the standard assay, 0.90; P < 0.05 for comparisons). The best cut-offs for the sensitive cTn-assays determined by the ROC-curve in elderly patients differed clearly from those in younger patients. Furthermore, the prognostic value regarding 90-day mortality varied among the sensitive cTn assays. Conclusion Sensitive cTn assays have high diagnostic accuracy also in the elderly. Mild elevations are common in elderly non-AMI patients, therefore the optimal cut-off levels are substantially higher in elderly as compared with younger patients. Furthermore, sensitive cTn assays yielded different prognostic value (ClinicalTrials.gov number, NCT00470587

Imaging the kidney using magnetic resonance techniques: structure to function

Purpose of review Magnetic resonance imaging (MRI) offers the possibility to non-invasively assess both the structure and function of the kidney in a single MR scan session. This review summarises recent advancements in functional renal MRI techniques, with a particular focus on their clinical relevance. Recent findings A number of MRI techniques have been developed that provide non-invasive measures of relevance to the pathophysiology of kidney disease. Diffusion-weighted imaging (DWI) has been used in chronic kidney disease (CKD) and renal transplantation, and appears promising as a measure of renal impairment and fibrosis. Longitudinal relaxation time (T1) mapping has been utilised in cardiac MRI to measure fibrosis and oedema; recent work suggests its potential for assessment of the kidney. Blood oxygen level dependent (BOLD) MRI to measure renal oxygenation has been extensively studied, but a number of other factors affect results making it hard to draw definite conclusions as to its utility as an independent measure. Phase contrast and arterial spin labelling (ASL) can measure renal artery blood flow and renal perfusion respectively without exogenous contrast, in contrast to dynamic contrast enhanced (DCE) studies. Current data on clinical use of such functional renal MR measures is largely restricted to cross-sectional studies. Summary Renal MRI has seen significant recent interest and advances. Current evidence demonstrates its potential, and next steps include wider evaluation of its clinical application

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas