Usefulness of combining admission brain natriuretic peptide (BNP) plus hospital discharge bioelectrical impedance vector analysis (BIVA) in predicting 90 days cardiovascular mortality in patients with acute heart failure.

Heart failure is a disease characterized by high prevalence and mortality, and frequent rehospitalizations. The aim of this study is to investigate the prognostic power of combining brain natriuretic peptide (BNP) and congestion status detected by bioelectrical impedance vector analysis (BIVA) in acute heart failure patients. This is an observational, prospective, and a multicentre study. BNP assessment was measured upon hospital arrival, while BIVA analysis was obtained at the time of discharge. Cardiovascular deaths were evaluated at 90 days by a follow up phone call. 292 patients were enrolled. Compared to survivors, BNP was higher in the non-survivors group (mean value 838 vs 515 pg/ml, p < 0.001). At discharge, BIVA shows a statistically significant difference in hydration status between survivors and non-survivors [respectively, hydration index (HI) 85 vs 74, p < 0.001; reactance (Xc) 26.7 vs 37, p < 0.001; resistance (R) 445 vs 503, p < 0.01)]. Discharge BIVA shows a prognostic value in predicting cardiovascular death [HI: area under the curve (AUC) 0.715, 95% confidence interval (95% CI) 0.65-0.76; p < 0.004; Xc: AUC 0.712, 95% CI 0.655-0.76, p < 0.007; R: AUC 0.65, 95% CI 0.29-0.706, p < 0.0247]. The combination of BIVA with BNP gives a greater prognostic power for cardiovascular mortality [combined receiving operating characteristic (ROC): AUC 0.74; 95% CI 0.68-0.79; p < 0.001]. In acute heart failure patients, higher BNP levels upon hospital admission, and congestion detected by BIVA at discharge have a significant predictive value for 90 days cardiovascular mortality. The combined use of admission BNP and BIVA discharge seems to be a useful tool for increasing prognostic power in these patients.

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.

Copeptin decrease from admission to discharge has favorable prognostic value for 90-day events in patients admitted with dyspnea.

BACKGROUND: With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients' risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea. METHODS: We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed. RESULTS: A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum-minimum): 31 (0-905) versus 8 (0-13) pmol/L. Median copeptin value at admission was 42 (0-905) pmol/L in acute heart failure patients and 20 (0-887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001). CONCLUSIONS: In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.

Combined evaluation of nutrition and hydration in dialysis patients with bioelectrical impedance vector analysis (BIVA).

BACKGROUND & AIMS: Body hydration changes continuously in hemodialysis patients. The Subjective Global Assessment (SGA) is used for the nutritional evaluation but it does not allow a direct evaluation of hydration. Bioelectrical impedance vector analysis (BIVA) is very sensitive to hydration. The potential of the combined evaluation of hydration and nutrition with SGA and BIVA is still lacking. METHODS: Observational cross-sectional study on 130 (94 Male) uremic patients undergoing chronic hemodialysis three times a week. Nutritional status was evaluated with the SGA. Each subject was classified as SGA-A (normal nutritional status), SGA-B (moderate malnutrition), or SGA-C (severe malnutrition). Body hydration was evaluated with BIVA. The two vector components resistance (R) and reactance (Xc) were normalized by the subject's height and standardized as bivariate Z-score, i.e. Z(R) and Z(Xc). RESULTS: Undernutrition influenced impedance vector distribution both before and after a dialysis session. In pre-dialysis, the mean vector of SGA A was inside the 50% tolerance ellipse. In SGA B and C, Z(R) was increased and Z(Xc) decreased, indicating a progressive loss of soft tissue mass. Fluid removal with dialysis increased both Z(R) and Z(Xc) in SGA A and B but not in C. With ROC curve analysis on the slope of increase, we found the cutoff value of 27.8° below which undernutrition was present, either moderate or severe. The area under the ROC curve was 77.7° (95% CI 69.5-84.5, P < .0001) with sensitivity 75.9%, specificity 78.6%, positive predicted value 74.6%, and negative predicted value 79%. CONCLUSIONS: The distribution of impedance vectors is associated with the SGA classification of patients. The change in body hydration in each SGA category can be detected with BIVA.

Differentiation of cardiac and noncardiac dyspnea using bioelectrical impedance vector analysis (BIVA).

BACKGROUND: There is no gold standard for the differential diagnosis of acute dyspnea despite the usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and lung ultrasound. No study has evaluated the contribution of bioelectrical impedance vector analysis (BIVA) in discriminating between cardiac and noncardiac dyspnea. We sought to determine whether a relationship exists between ultrasound detection of lung congestion, NT-proBNP, and BIVA in patients with acute dyspnea. METHODS AND RESULTS: Eligible patients were between 50 and 95 years, with an estimated glomerular filtration rate of ≥30 mL min(-1) 1.73 m(-2), who presented to an emergency department with dyspnea. Dyspnea was classified by reviewers blinded to BIVA as cardiac or noncardiac based on physical examination, electrocardiogram, chest X-ray, NT-proBNP, and B-lines of lung congestion on ultrasound. Overall, 315 patients were enrolled (median age 77 years, 48% male). An adjudicated diagnosis of cardiac dyspnea was established in 169 (54%). Using BIVA, vector positions below -1 SD of the Z-score of reactance were associated with peripheral congestion (χ(2) = 115; P < .001). BIVA measures were reasonably accurate in discriminating cardiac and noncardiac dyspnea (69% sensitivity, 79% specificity, 80% area under the receiver operating characteristic curve). CONCLUSIONS: In patients presenting with acute dyspnea, the combination of BIVA and lung ultrasound may provide a rapid noninvasive method to determine the cause of dyspnea.

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.

Influence of tonsillectomy on the progression of mesangioproliferative glomerulonephritis.

BACKGROUND: Little information is available about the efficacy of tonsillectomy on long-term renal survival of patients with primary IgA nephropathy (IgAN). METHODS: In this retrospective cohort study, we considered 61 patients with IgAN who had tonsillectomy (n = 15) or not (n = 46) and compared them with 121 control patients with mesangioproliferative glomerulonephritis (MesGN) free of IgA deposits, who had tonsillectomy (n = 49) or not (n = 72). We evaluated the progression from a normal function [estimated glomerular filtration rate 60-220 mL/min/1.73 m(2), chronic kidney disease (CKD) stage 1 and 2] to a moderate renal dysfunction in CKD stage 3, which was considered the outcome. RESULTS: The mean duration of follow-up was 250 months (12-300 months) in the whole group of 182 patients. The survival to progression to stage 3 was 88% after 10 years, 71% after 20 years and 53% after 25 years. It was 72% after 20 years in both groups. Tonsillectomy was not significantly associated with CKD progression. Significant prognostic factors were age (P = 0.01), initial CKD stage (P = 0.03), proteinuria (P = 0.03), persistent proteinuria (P < 0.001) and diastolic blood pressure (P = 0.01). In the multivariate analysis (Cox model), there was no significant effect of tonsillectomy adjusted for the type of glomerulonephritis, initial CKD stage, persistent proteinuria, diastolic blood pressure and age. Only persistent proteinuria adjusted for the other factors was significantly associated with CKD progression (hazard ratio of 6.2, 95% confidence interval 3.1-12.7, P < 0.001). CONCLUSIONS: Tonsillectomy was not associated with a different progression rate of IgAN nor of MesGN after 20 years of follow-up.

Influence of localized edema on whole-body and segmental bioelectrical impedance.

OBJECTIVE: Tetrapolar whole-body (hand-foot) bioelectrical impedance (Z-body) is used in body composition analysis assuming homogeneous soft tissue hydration. Limbs and trunk contribute to Z-body by 90% and 10%, respectively. We determined the effect on Z-body of an edema localized in one leg. METHODS: Resistance (R) and reactance (Xc) components of Z vector were measured at 50 kHz (BIA-101, RJL Systems, Akern, Italy) in 20 adult male patients without edema, before and 3 d after a femoropopliteal bypass that induced pitting edema in the leg. Z-body was measured from hand to foot on the right and left sides. Z from the leg (Z-leg) was measured from the pair of electrodes on the foot and the other pair on the trochanter. Data were analyzed with the vector bioelectric impedance analysis (Vector BIA) method (Piccoli's RXc graph with 95% confidence ellipses). RESULTS: Before surgery, the positions of the mean Z-body and Z-leg vectors from either side of the body were not significantly different (overlapping 95% confidence ellipses). After surgery, the mean Z-leg and Z-body vectors from the side without edema did not change position in the RXc plane with respect to the presurgery position. In contrast, the mean Z-leg and Z-body vectors of the body side with edema significantly (P < 0.05) shortened according to the Vector BIA patterns of fluid accumulation. CONCLUSION: Z-body in the side of the body without edema is not sensitive to the edema localized in the leg on the opposite side and therefore can be used in the assessment of body composition in patients with edema in one leg.

Renal dysfunction is a confounder for plasma natriuretic peptides in detecting heart dysfunction in uremic and idiopathic dilated cardiomyopathies.

BACKGROUND: The diagnostic value of natriuretic peptides in uremic cardiomyopathy has not been defined, nor has the effect of a hemodialysis (HD) session on peptides. METHODS: We performed an observational study of 100 white adult outpatients in New York Heart Association class I-II, with neither diabetes nor ischemic heart disease, 50 of whom had idiopathic dilated cardiomyopathy (DCM) and 50 of whom had uremic cardiomyopathy and were undergoing HD. We measured plasma N-terminal proB-type natriuretic peptide (NT-proBNP), BNP, and atrial natriuretic peptide (ANP) both before and after a dialysis session. Doppler echocardiograms were evaluated. We performed multiple regression analysis on the logarithm of peptide concentrations using clinical, laboratory, and echocardio-Doppler data as explanatory variables. RESULTS: Mean peptide concentrations were higher in the HD group, with an HD:DCM ratio of 25 for NT-proBNP and 5 for BNP and ANP. Peptides were correlated with each other (r > 0.85). After HD, NT-proBNP significantly increased by 14%, BNP decreased by 17%, and ANP decreased by 56%. Predialysis concentrations correlated with postdialysis values (r > 0.85). A multiple regression equation significantly fitted the observed peptide concentrations, both pre- and postdialysis, using the same set of 4 variables: disease group (DCM or HD), diastolic pattern, left atrial volume, and body mass index. CONCLUSIONS: Renal dysfunction was a confounder for natriuretic peptides, which were present in higher concentrations in the uremic patients with milder cardiac dysfunction than in those with idiopathic DCM without renal dysfunction. Left diastolic function pattern and atrial volume were cardiac determinants of peptide concentrations in DCM and HD.

Cystatin C in heart failure is nothing more than a bystander of glomerular filtration.

BACKGROUND: Cystatin is an ubiquitous protease inhibitor involved in degradation of cellular proteins and has recently been associated with increased risk of cardiovascular disease and heart failure independent of renal function. We tested whether cystatin in heart failure is only associated with renal function or also with echocardio-Doppler parameters and factors of myocardial remodeling (C-reactive protein, endothelin, and natriuretic peptides). METHODS: This was an observational study conducted in 100 adult Caucasian outpatients with NYHA class I-II heart function without diabetes and ischemic heart, 50 with idiopathic dilated cardiomyopathy (DCM) and 50 with uremic cardiomyopathy undergoing hemodialysis (HD). Multiple linear regression analysis was performed on cystatin concentration using clinical, laboratory (creatinine, high sensitivity C-reactive protein, endothelin, B-type natriuretic peptide [BNP]) and echocardio-Doppler data as explanatory variables. RESULTS: The heart was more severely involved in DCM patients (worse ejection fraction, diastolic volume index, index of myocardial performance, left ventricular mass index). Mean values of cystatin, creatinine, BNP and C-reactive protein in HD compared with DCM patients were 6, 9, 5 and 3 times higher, respectively. Mean values of endothelin were comparable in both groups. Cystatin significantly correlated with creatinine in both groups (r=0.50 in DCM and r=0.37 in HD, and r=0.95 in pooled groups). In the multiple regression analysis, only disease group and creatinine within groups were significant independent factors that accounted for 94% of the variability of cystatin. CONCLUSION: Renal function was the determinant of cystatin in a concentration range of 6 times regardless of severity of heart involvement.

Evidence for decreased circulating apelin beyond heart involvement in uremic cardiomyopathy.

BACKGROUND: Plasma apelin concentration in heart failure has been described in small studies reporting conflicting results. In hemodialysis (HD) patients, apelin decreased more in those with more severe heart involvement. It is unclear if uremia is connected to this reduction irrespective of heart failure. We compared apelin in two cardiomyopathies with different renal function. METHODS: Observational study conducted in 30 adult Caucasian outpatients in class I NYHA not affected by diabetes or ischemic heart, 15 with idiopathic dilated cardiomyopathy (DCM) and 15 with uremic dilated cardiomyopathy undergoing HD. Plasma apelin, creatinine, high-sensitivity C-reactive protein, endothelin, NT proB-type natriuretic peptide (NT-proBNP), and Doppler echocardiogram were evaluated. RESULTS: Heart involvement was more severe in the DCM patients (lower ejection fraction, greater diastolic volume index, and worse index of myocardial performance). Median value of apelin in HD patients (19.1 pg/ml) was one third of that in DCM patients (58.2 pg/ml) whereas creatinine, NT-proBNP, and C-reactive protein were 11, 80, and 9 times higher respectively in HD than in DCM patients. Median values of endothelin were comparable in both groups. Apelin was not significantly correlated with any variable. CONCLUSION: Uremic status was the determinant for decreased plasma apelin in HD patients regardless of the severity of heart involvement.

Equivalence of information from single frequency v. bioimpedance spectroscopy in bodybuilders.

In bioelectrical impedance spectroscopy (BIS), it is assumed that the current path is only extracellular at the lowest frequencies and that it is both extra- and intracellular at the highest frequencies. We tested validity of BIS assumptions in bodybuilders who have an increased intracellular volume due to hypertrophy of muscle fibres. The study was observational cross-sectional in a study group of thirty professional bodybuilders compared with thirty control subjects. Resistance (R) and reactance (Xc) vector components fitting the Cole's arc with BIS (SFB3 analyser) were compared with components at 50 kHz frequency. The average Cole's arc in bodybuilders was significantly smaller and shifted to the left in the R-Xc plane (both R and Xc values were smaller at any individual frequency). The ratio of Xc at 5 kHz and Xc at the characteristic frequency was 70% in bodybuilders and 64% in control subjects, indicating a huge intracellular flow of the electric current at low frequencies in both groups (expected ratio close to 0 if the current path was extracellular). As a consequence of a common path, the correlation coefficient between R values at 50 kHz and at other frequencies (from 0 to infinity) was 0.94 to 1.00. The correlation between total body water estimated with BIS or with R at 50 kHz was 0.98. Hence, there was equivalence between information provided by the vector components R and Xc at 50 kHz and that provided by 496 correlated vectors that were measured with BIS.

Body mass index and agreement between bioimpedance and anthropometry estimates of body compartments in anorexia nervosa.

BACKGROUND: In 74 women with anorexia nervosa (body mass index [BMI] 10-17.5 kg/m(2)), a progressive disagreement between anthropometry and bioelectrical impedance analysis (BIA) estimates of fat (FM) and fat-free mass (FFM) was documented with a BMI <15 kg/m(2). Below this threshold, an abnormal body composition was detected with vector BIA independent on body weight (useful tool at the bedside). Both anthropometry and BIA are used for body composition assessment. We evaluated the agreement between their estimates of FFM and FM in extremely lean subjects with anorexia nervosa. METHODS: Observational study in 74 women (age 15-45 years; BMI 10.0-17.5 kg/m(2)) with anorexia nervosa. Anthropometry FM and FFM were estimated by skinfold thicknesses. Whole-body impedance vector components, resistance (R) and reactance (X(c)), were measured at the same time (BIA-101 analyzer, 50-kHz frequency; Akern/RJL Systems, Clinton Twp., MI). BIA estimates of FFM and FM were obtained with Sun's equations (BMI 14-39 kg/m(2)). Vector BIA was performed with the RXc graph method. The frequency of disagreement between anthropometry and BIA was evaluated as a function of increasing BMI (receiver operating characteristic curve). RESULTS: The correlation coefficient between methods was 0.80-0.90. The BMI cutoff value of 15 kg/m(2) predicted disagreement of FM and FFM in patients with a BMI <15 kg/m(2). In the RXc graph, the distribution of vectors from patients with disagreement was significantly shifted out of the right border of the reference tolerance ellipses. CONCLUSIONS: Anthropometry and BIA equations should not be used in anorexic patients with a BMI <15 kg/m(2). The distribution of vectors from patients with disagreement of methods was shifted out of the right border of the reference tolerance ellipses and was superposed to vectors from patients with a BMI <15 kg/m(2). The identified impedance pattern for anorexia could be useful for feedback in individual patient refeeding (vector back into the 75% reference ellipse).