Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction

Intravenous loop diuretics are still the cornerstone of therapy in acute decompensated heart failure, however, the optimal dosage and administration strategies remain poorly defined particularly in patients with an associated renal dysfunction. This is a single-center, pilot, randomized trial involving patients with acute HF and renal dysfunction. Patients were assigned to receive continuous furosemide infusion (cIV) or bolus injections of furosemide (iIV). Primary end points were the evaluation of urine output volumes, renal function, and b-type natriuretic peptide (BNP) levels during treatment time. Secondary end point included: weight loss, length of hospitalization, differences in plasma electrolytes, need for additional treatment, and evaluation of cardiac events during follow-up period. 57 patients were included in the study. The cIV group showed an increase in urine output (2,505 ± 796 vs 2140 ± 468 ml/day, p < 0.04) and a more significant decrease of BNP levels in respect to the iIV group (679.6 ± 397 vs 949 ± 548 pg/ml, p < 0.04). We observed a significant increase in creatinine levels (1.78 ± 0.5 vs 1.41 ± 0.3 mg/dl, p < 0.01), and a reduction of the estimated glomerular filtration rate in cIV (44.8 ± 6.1 vs 46.7 ± 6.1 ml/min, p < 0.05). We observed a significant difference in eGFR (p = 0.01), creatinine (p = 0.02) and BNP levels (p = 0.03) from baseline to the end of treatment in both groups. A significant increase of in-hospital additional treatment as well as length of hospitalization was observed in cIV. Finally, cIV revealed a higher rate of adverse events during the follow-up period (p < 0.03). cIV appears to provide a more efficient diuresis and BNP level reduction during hospitalization, however, it was associated with increased rate of worsening renal function during hospitalization. cIV also appears related to a longer hospitalization and an increased number of adverse events during follow-up. For all of these reasons, a larger multi-center study is required to determine whether high-dose diuretics are responsible for worsening renal function and to define the best modality of administratio

Diagnostic utility of contemporary echo and BNP assessment in patients with acute heart failure during early hospitalization

Background The use of B-type natriuretic peptide (BNP) and echocardiography in acute heart failure (AHF) diagnosis is poorly employed in the Emergency Department. The aim of the present study is to evaluate relation among BNP levels systolic and diastolic dysfunction during early phases of AHF hospitalization. Methods We performed contemporary echocardiographic and BNP assessment in 310 patients with AHF within 12 h since hospital admission. We studied the correlation among BNP and degree of diastolic dysfunction evaluated by pulsed Doppler transmitral flow and Tissue Doppler flow. Finally we investigated the relation among BNP and the right systolic longitudinal ventricular function (TAPSE) and the systolic pulmonary arterial pressure (PAPs). Results BNP levels were 1417 ± 1126, 1081 ± 955, 894 ± 901 pg/mL, for patients with EF ≤ 25%, EF 25-40% and EF 40-50% (p = 0.005), respectively. BNP levels linearly correlate with the degree of diastolic dysfunction: 582 ± 406 pg/mL in altered relaxation pattern, 712 ± 557 pg/mL in pseudonormal pattern and 1694 ± 805 in restrictive filling pattern (p < 0.001 for all patterns). BNP levels were significantly increased in patients with right systolic ventricular dysfunction (TAPSE < 18 mm; p = 0.006) and in patients with PAPs ≥ 40 mmHg (p = 0.001). ROC curve and logistic regression analysis highlighted the power of BNP to detect severe systolic dysfunction, right ventricular (RV) overload and dysfunction and diastolic dysfunction patterns. Conclusions BNP levels correlate linearly with LV systolic dysfunction as well as with impaired degree of diastolic dysfunction. Significant PAP increase is a further factor influencing BNP elevation in patients with AHF during early hospitalization phase

The prognostic combined role of B-type natriuretic peptide, blood urea nitrogen and congestion signs persistence in patients with acute heart failure

AIMS: B-type natriuretic peptide (BNP) decrease during hospitalization has been related to reduced risk of readmission and death in patients with acute heart failure (AHF). Conversely, the exact role of blood urea nitrogen (BUN) is still debated. Currently, no data have been published regarding the relation between these two biomarkers and the relation between them and clinical signs of congestion. METHODS: We consecutively studied 107 patients with diagnosis of AHF and systolic dysfunction. All patients were observed during a 6-month follow-up period. BUN and BNP were measured according to the decrease of BNP levels at discharge of greater than 30% with respect to basal values; the persistence of congestion signs at discharge and BUN increase at discharge to more than 20% with respect to baseline. RESULTS: In all patients mean BNP was 1014?±?767?pg/ml; in patients with severe systolic dysfunction BNP was higher (1382?±?1025 vs. 848?±?549; P?=?0.002). Mean BUN in all patients was 93?±?42?mg/dl; BUN was higher in patients affected by chronic kidney disease compared with patients with preserved renal function (114?±?45 vs. 68?±?21?mg/dl; P?<?0.001). Cox regression analysis demonstrated that BNP decrease of at least 30% together with congestion signs resolution was related to outcome improvement (univariate hazard ratio: 0.45 [0.19–0.97], P?=?0.05; multivariate hazard ratio: 0.44 [0.20–0.98], P?=?0.05). BUN increase of greater than 20% at discharge was associated with poor outcome independent of persistence of congestion signs (univariate hazard ratio: 2.72 [1.03–7.28], P?=?0.04; multivariate hazard ratio: 3.00 [1.12–8.06], P?=?0.03). Changes (Δ) of both BNP (univariate hazard ratio: 1.30 [1.04–1.61], P?=?0.01) and BUN (univariate hazard ratio: 5.24 [1.72–15.95], P?=?0.003) were associated with mortality, independently of congestion. CONCLUSIONS: In patients with AHF, BNP reduction of greater than 30% during hospitalization is associated with outcome improvement only if it occurs together with congestion resolution. Conversely, BUN increase of more than 20% was associated with poor outcome, independently of the persistence of congestion signs

Different trajectories and significance of B-type natriuretic peptide, congestion and acute kidney injury in patients with heart failure

The exact relationship existing among congestion status, brain natriuretic peptide (BNP) changes and acute kidney injury (AKI) has not been elucidated in patients with acute heart failure (AHF). The aims of this study are: to investigate the relation and prognostic role of BNP, AKI and clinical congestion after discharge; to define the exact BNP cut off value or a BNP in-hospital reduction to identify patients with higher risk during vulnerable post-discharge phase. We consecutively enrolled 157 patients with a diagnosis of AHF. BNP and creatinine were measured in all patients, and degree of failure was assessed. AKI was defined as a creatinine increase ≥0.3 mg/dL or eGFR reduction ≥20% during hospitalization. All patients were followed for 1 and 3 months. Of 146 included patients, 110 patients (75%) displayed effective decongestion, 116 (79%) showed a BNP decrease ≥30%, and 28 (19%) developed in-hospital AKI. BNP in-hospital decrease ≥30% was found more often in patients who showed good decongestion in comparison to patients in persistent failure (63 vs 22%; p < 0.001). The ROC curve analyses at 3 months show that both BNP reduction of 30% between admission and discharge and decongestion at discharge identifies patients with a reduced incidence of cardiovascular events (AUC = 0.79, confidence interval 0.68–0.90, sensibility 90%, sensitivity 50% p < 0.001). Kaplan–Meier survival plots show a better outcome in patients with a BNP decrease ≥30% and good decongestion at discharge (p = 0.03). BNP reduction in AHF is associated with decongestion. BNP reduction associated with decongestion at discharge is a favorable prognostic indicator at 90-day survival irrespective of the AKI occurrence

Additional value of Galectin-3 to BNP in acute heart failure patients with preserved ejection fraction

Background: Almost half of patients with acute heart failure have preserved ejection fraction (HFpEF). HFpEF is a diagnostic challenge using traditional investigation tools; Galectin-3 (Gal-3) is an emerging biomarker useful in individuals at risk for HF. The aim of our study is to analyse the relation and prognostic value of Gal-3, BNP and renal dysfunction in patients with HFpEF compared to patients with reduced ejection fraction (HFrEF). Methods: We enrolled 98 patients with acute heart failure (AHF) and measured Gal-3, BNP, and estimated glomerular filtration rate (eGFR) within 12 h of hospital admission. On the basis of echocardiographic findings we divided our sample into two groups: patients with HFrHF (ejection fraction 50%). Patients were followed up at 6 months. Results: No differences in Gal-3 levels were found in the two subgroups (HFrEF: 19.5 ± 5.1 ng/mL; HFpEF: 20.5 ± 8.7, p = 0.56). Gal-3 was inversely related to renal dysfunction (LogGal-3 vs eGFR: r = -. 0.30, p = 0.01) but did not correlate with LogBNP levels (r = 0.07, p = 0.55). Gal-3 was associated with more advanced diastolic dysfunction in HFpEF (p = 0.009). In addition LogGal-3 was related to diastolic LV stiffness (all patients: r = 0.45, p 1.30 was related to poor outcome independently from renal dysfunction and other risk factors only in HFpEF (univariate HR 23.98 [3.03-89.45]; p < 0.001). Adjusted for renal dysfunction (HR 16.32 [1.98-34.09]; p = 0.009). Conclusions: Gal-3 is not able to distinguish between HFrEF and HFpEF patients. However it is related to diastolic dysfunction severity and LV stiffness in HFpEF. Gal-3 demonstrates a prognostic role independently from renal dysfunction in subjects with HFpEF

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of b-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous β-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with β-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate

The association of body composition and sexhormones with quantitative ultrasound parameters at the calcaneus and phalanxes in elderly women.

We investigated the associations of body composition and sex hormones with quantitative ultrasound (QUS) parameters carried out at different skeletal sites. In 897 postmenopausal women (64.1 ± 6.6 years) we measured QUS at the calcaneus (stiffness) by Achilles-GE and at phalanxes (amplitude-dependent speed of sound [AD-SOS], bone transmission time [BTT], and ultrasound bone profile index [UBPI]) by Bone Profiler-IGEA. In all subjects we measured fat mass (FM), lean mass (LM), android fat, and gynoid fat by DXA. In all subjects we also assessed serum testosterone (T), estradiol (E 2), sex-hormone binding globulin, free estrogen index (FEI), free androgen index, 25-hydroxyvitamin D (25OHD), bone alkaline phosphatase (B-ALP), and type I collagen β carboxy telopeptide. Both E 2 and FEI showed weak but significant correlations with stiffness and QUS parameters at phalanxes. No significant relationships were found between T and QUS. BMI and LM were positively correlated with stiffness (r = 0.14 and r = 0.17, respectively), whereas BMI and FM showed negative correlations with AD-SOS, BTT, and UBPI. 25OHD showed positive relationships with stiffness and QUS at phalanxes. In multivariate models LM and age were associated with stiffness whereas E 2 and age were significant predictors of BTT. AD-SOS was negatively associated with FM, B-ALP, and age but positively with E 2 and 25OHD. In postmenopausal women QUS parameters at the calcaneus and at phalanxes are significantly, but diversely, associated with body composition, sex hormones, 25OHD, and bone turnover markers

Comparison of neutrophil gelatinase-associated lipocalin versus B-type natriuretic peptide and cystatin C to predict early acute kidney injury and outcome in patients with acute heart failure

Neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic heart failure (HF) as marker of tubular damage and renal dysfunction; however, less data are available in patients with acute HF. Because of high rate of acute kidney injury (AKI) development, we aimed to investigate the role of NGAL in predicting early AKI development; second, we compared NGAL with respect to cystatin C, B-type natriuretic peptide (BNP), renal function, and blood urea nitrogen (BUN) for outcome prediction. We measured admission serum NGAL, cystatin C, and BNP in 231 patients affected to acute HF; all patients were submitted to daily creatinine, estimated glomerular filtration rate, and measurement to identify inhospital AKI defined by Risk, Injury, Failure, Loss, End-Stage Kidney Disease and Acute Kidney Injury Network criteria. We also measured admission and discharge estimated glomerular filtration rate, creatinine, and BUN to evaluate their prognostic role during a 6-month follow-up period; 78 patients developed AKI during hospitalization. In these subjects, NGAL levels were significantly increased respect to patients without AKI (295 ± 228 vs 129 ± 108 ng/ml, p <0.001). A cutoff of 134 ng/ml has been related to AKI with good sensibility and specificity (85% and 80%, respectively; area under the curve 0.81, p <0.001). BNP was also mildly increased (1,000 ± 906 vs 746 ± 580 pg/ml, p = 0.03) but not cystatin C. Patients with chronic kidney disease demonstrated higher NGAL levels compared with subjects with preserved renal function (258 ± 249 and 120 ± 77 ng/ml, p <0.001). The receiver-operating characteristic curve analysis demonstrated that increased NGAL values were associated with increased mortality (cutoff 170 ng/ml, sensibility 60%, specificity 82%, accuracy 71%, area under the curve 0.77, p <0.001). The same significant correlation was also found for BUN at discharge (cutoff 100 mg/dl, sensibility 65%, specificity 85%, accuracy 71%, area under the curve 0.77, p <0.001). Multivariable Cox regression analysis showed that cutoff 170 ng/ml was related with adverse outcome (hazard ratio 1.77, confidence interval 1.24 to 2.83, p = 0.01). In conclusion, NGAL measurement is a sensible tool to predict AKI during hospitalization. Elevated NGAL levels appear to be related to BUN increase and post-discharge outcome. This suggests a prognostic role of tubular damage beyond renal dysfunction

Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes.

CONTEXT: Previous observations showed a condition of low bone turnover and decreased osteoblast activity in both type 1 and 2 diabetes mellitus (DM1 and DM2). Sclerostin is a secreted Wnt antagonist produced by osteocytes that regulates osteoblast activity and thus bone turnover. Its levels increase with age and are regulated by PTH. OBJECTIVES: The aim of the present study was to evaluate circulating sclerostin levels in patients with DM1 or DM2 with normal renal function and to analyze its relationship with PTH, 25-hydroxyvitamin D, and bone turnover markers. DESIGN, AND SETTING: This was a cross-sectional study conducted at a clinical research center. PARTICIPANTS: Forty DM2 and 43 DM1 patients were studied and compared with a reference control group (n = 83). RESULTS: In the overall cohort, sclerostin levels were higher in males than in females and significantly increased with age in both genders. The positive correlation between sclerostin and age was maintained in DM1 but not in DM2 patients. Moreover, sclerostin levels were higher in DM2 than in controls or DM1 patients, and this difference persisted when adjustments were made for age and body mass index. Consistent with previous clinical and experimental observations, sclerostin was negatively associated with PTH in nondiabetic patients (r = -0.30; P < 0.01), independently of age and gender. Conversely, an opposite but nonsignificant trend between PTH and sclerostin was observed in both DM1 (r = 0.26; P = 0.09) and DM2 (r = 0.32; P = 0.07) cohorts. CONCLUSIONS: These findings suggest that sclerostin is increased in DM2. Moreover, the transcriptional suppression of sclerostin production by PTH might be impaired in both DM1 and DM2