Determinants of circulating asymmetric and symmetric dimethylarginines in patients evaluated for acute dyspnea.

BACKGROUND: The relationship between asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) plasma concentrations and acute heart failure is unknown. We evaluated ADMA and SDMA in patients with acute dyspnea. METHODS: We studied 57 dyspneic subjects (50-95 years), with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m², presenting to the emergency department. Troponin I, N terminal-proBNP (NT-proBNP), ADMA, and SDMA were measured. Electrocardiogram, chest X-ray and lung ultrasound were performed. Patients were classified into cardiogenic dyspnea and non-cardiogenic dyspnea, and were also classified on the basis of renal function according to their eGFR. RESULTS: Two-way analysis of variance demonstrated that ADMA and SDMA did not differ for type of dyspnea, but increased in renal dysfunction. NT-proBNP significantly increased both in cardiogenic dyspnea and renal dysfunction. Multiple regression analysis demonstrated that after adjustment for troponin and dyspnea, the only variables which significantly correlated with SDMA plasma concentrations were renal function (ß = -0.47, p < 0.001) and NT-proBNP (ß = 0.28, p = 0.02). CONCLUSIONS: Neither type of dimethylarginine showed cardiogenic dyspnea to be a determinant for plasma concentrations. Renal dysfunction was a confounder for both ADMA and SDMA.

Effect of a dialysis session on the prognostic values of NT-proBNP, troponins, endothelial damage and inflammation biomarkers.

BACKGROUND: In hemodialysis, the relationship between the increased concentration of natriuretic peptides and volume overload, inflammatory activity, endothelial dysfunction, left ventricular function and mass, and silent ischemic events is not clear. To investigate the relationship, a 3-year prospective cohort study was conducted in 50 adult hemodialysis patients in NYHA class I-II who were free from diabetes and ischemic heart events. METHODS: Doppler echocardiogram, plasma NT-proBNP, troponin T and I, CRP, TNF alpha, big-endothelin 1, and cystatin-C, were determined both before and after a dialysis session. The outcome was all-cause death. RESULTS: 13 out of 50 patients died. Survival curves significantly differed by age (above vs. below the median 68 yrs), NT-proBNP (9719 pg/mL), troponin T (0.03 ng/mL), C-reactive protein (4.8 mg/L), left atrial volume index (51 mL/sqm), ejection fraction (61%), and diastolic pattern. In the Cox model only NT-proBNP (cutoff 10000 pg/mL) had a significant hazard ratio (4.1). Post-HD measurements of NT-proBNP, troponin T, and CRP maintained their prognostic value. The high correlation between pre and post values of NT-proBNP, and the lack of correlation with ultrafiltration volume excluded a role for acute fluid removal on its regulation. CONCLUSIONS: The increased level of NT-proBNP is the most important prognostic factor even in the absence of severe heart dysfunction and myocardial ischemic events, without any relationship with endothelial dysfunction, inflammatory biomarkers, or with acute fluid removal. A cutoff value of NT-proBNP of 10000 pg/mL could be used to identify hemodialysis patients with a higher risk of death.

Multidimensional Prognostic Index and pro-adrenomedullin plasma levels as mortality risk predictors in older patients hospitalized with community-acquired pneumonia: a prospective study.

BACKGROUND: To evaluate the prognostic accuracy of proadrenomedullin (proADM) in comparison with and in addition to the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a comprehensive geriatric assessment (CGA) to predict one-month mortality risk in older patients hospitalized with community-acquired pneumonia (CAP). METHODS: All patients aged 65 years and older, consecutively admitted to an acute geriatric ward with a diagnosis of CAP from February to July 2012. At admission and at discharge they were submitted to a standard CGA in order to calculate MPI. Moreover, plasma samples were taken at baseline and after one, three and five days of hospitalization for the analysis of pro-ADM. RESULTS: Fifty patients (mean age 86.2±7.5 years), with 31 at high risk of mortality (MPI-3) were enrolled. ProADM and MPI, both at admission and at discharge, were significant predictor of mortality. As expected, MPI at admission showed lower predictive accuracy than MPI at discharge (survival C-statistic 0.667 vs. 0.851). The addition of proADM to the MPI at admission significantly increased accuracy in predicting one-month mortality (C-statistics from 0.667 to 0.731, P=0.018 at baseline; from 0.667 to 0.733, P=0.008 at 1 day; from 0.633 to 0.724; P=0.019 at 3 days; from 0.667 to 0.828; P=0.003 at 5 days). Conversely, adding pro-ADM to the MPI at discharge did not significantly improve the model's prognostic accuracy. CONCLUSIONS: ProADM may significantly improve the prognostic accuracy of the MPI at admission in hospitalized elderly patients with CAP.

Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest.

BACKGROUND: Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest. METHODS: As a subcohort analysis of a prospective, observational, multicenter study "FINNRESUSCI," we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models. RESULTS: Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68-0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65-0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome. CONCLUSIONS: Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.

Analytical and clinical performance of a fully automated cardiac multi-markers strategy based on protein biochip microarray technology.

OBJECTIVES: The analytical and clinical performance of the Evidence Cardiac Panel were evaluated. DESIGN AND METHODS: The Evidence Cardiac Panel, an automated protein biochip microarray system, allows the simultaneous determination of creatine kinase MB (CK-MB), myoglobin (MYO), glycogen phosphorylase BB (GPBB), heart-type fatty acid-binding protein (H-FABP), carbonic anhydrase III (CA III), cardiac troponin I (cTnI). Precision: 3 levels of quality control (QC) and 2 in house pools (P) were assayed. Method comparison: MYO and cTnI concentrations measured on Evidence (E) and on Dimension RxL (D) analyzers were compared. Clinical study: 132 non-consecutive patients admitted to the Emergency Department for chest pain were enrolled. RESULTS AND CONCLUSIONS: The between-day imprecision was CK-MB=6.80-10.08%; MYO=5.36-16.50%; GPBB=6.51-12.12%; H-FABP=6.26-12.63%; CA III=6.98-13.61%; cTnI=6.02-9.80%. Method comparison: E-MYO vs. D-MYO, Bias=-29.22, 95% CI from -40.25 to -18.18; E-cTnI vs. D-cTnI, Bias=-2.75, 95% CI from -4.04 to -1.46. In patients studied (at discharge: AMI, acute myocardial infarction n=42; non-AMI, n=90) H-FABP showed the highest accuracy (ROC analysis, AUC=0.92) and "cTnI+H-FABP" the greatest diagnostic efficacy (89.4%) in AMI diagnosis.

Prognostic value of decreased peripheral congestion detected by Bioelectrical Impedance Vector Analysis (BIVA) in patients hospitalized for acute heart failure: BIVA prognostic value in acute heart failure.

OBJECTIVES: The objective of this study was to investigate the prognostic role of quantitative reduction of congestion during hospitalization assessed by Bioelectrical Impedance Vector Analysis (BIVA) serial evaluations in patients admitted for acute heart failure (AHF). BACKGROUND: AHF is a frequent reason for patients to be admitted. Exacerbation of chronic heart failure is linked with a progressive worsening of the disease with increased incidence of death. Fluid overload is the main mechanism underlying acute decompensation in these patients. BIVA is a validated technique able to quantify fluid overload. METHODS: a prospective, multicentre, observational study in AHF and no AHF patients in three Emergency Departments centres in Italy. Clinical data and BIVA evaluations were performed at admission (t0) and discharge (tdis). A follow-up phone call was carried out at 90 days. RESULTS: Three hundred and thirty-six patients were enrolled (221 AHF and 115 no AHF patients). We found that clinical signs showed the most powerful prognostic relevance. In particular the presence of rales and lower limb oedema at tdis were linked with events relapse at 90 days. At t0, congestion detected by BIVA was observed only in the AHF group, and significantly decreased at tdis. An increase of resistance variation (dR/H) >11 Ω/m during hospitalization was associated with survival. BIVA showed significant results in predicting total events, both at t0 (area under the curve (AUC) 0.56, p<0.04) and at tdis (AUC 0.57, p<0.03). When combined with clinical signs, BIVA showed a very good predictive value for cardiovascular events at 90 days (AUC 0.97, p<0.0001). CONCLUSIONS: In AHF patients, an accurate physical examination evaluating the presence of rales and lower limbs oedema remains the cornerstone in the management of patients with AHF. A congestion reduction, obtained as a consequence of therapies and detected through BIVA analysis, with an increase of dR/H >11 Ω/m during hospitalization seems to be associated with increased 90 day survival in patients admitted for AHF.

The C-reactive protein levels in left ventricular dysfunction of different etiology.

BACKGROUND: We have investigated variations in the C-reactive protein levels in groups of patients with left ventricular dysfunction of various causes. MATERIALS AND METHODS: We have studied 59 patients (ranging from 40 to 80 years, mean age of 64, SD 9) with left ventricular dysfunction caused by dilated cardiomyopathy, valvular heart disease, chronic ischemic cardiomyopathy. These patients have been compared to 30 healthy subjects and to 15 others with acute myocardial infarction. The C-reactive protein levels have been analyzed and correlated to echocardiographic index of the left ventricular function as well as to the clinical parameters. RESULTS: The levels of C-reactive protein show a statistically significant difference between healthy controls and patients with chronic left ventricular dysfunction (0.95mg/l +-0.9 vs 10.17+-13.77; p <0.0001); a statistically significant difference between patients with chronic left ventricular dysfunction and patients with acute myocardial infarction (10.17mg/l+-13.7 vs 30.78+-22.53, p<0.0001), and a statistically significant difference between the group of patients with chronic left ventricular dysfunction of both ischemic and non ischemic origin (15.39mg/l +-18.19 vs 6.83+-8.77, p = 0.0095). When all chronic patients were analyzed together, the levels of C-reactive protein correlated with the New York Heart Association class (r = 0.282, p = 0.015), age (r = 0.231, p = 0.039) and with the end diastolic volume of left ventricle (r = -0.230, p = 0.040). CONCLUSIONS: As shown by increment of C-reactive protein values, the immune system is activated in patients with the chronic left ventricular dysfunction. The patients with the chronic left ventricular dysfunction of an ishemic origin have higher levels of C-reactive protein than those of a non-ischemic origin. This difference could depend on the atherosclerotic process present presumably only in the first group.