Rationale and study design of intravenous loop diuretic administration in acute heart failure. DIUR-AHF

Aims: Although loop diuretics are the most commonly used drugs in acute heart failure (AHF) treatment, their short-term and long-term effects are relatively unknown. The significance of worsening renal function occurrence during intravenous treatment is not clear enough. This trial aims to clarify all these features and contemplate whether continuous infusion is better than an intermittent strategy in terms of decongestion efficacy, diuretic efficiency, renal function, and long-term prognosis. Methods and results: This is a prospective, multicentre, randomized study that compares continuous infusion to intermittent infusion and a low vs. high diuretic dose of furosemide in patients with a diagnosis of acute heart failure, BNP ≥ 100 pg/mL, and specific chest X-ray signs. Randomization criteria have been established at a 1:1 ratio using a computer-generated scheme of either twice-daily bolus injection or continuous infusion for a time period ranging from 72 to 120 h. The initial dose will be 80 mg/day of intravenous furosemide and, in the case of poor response, will be doubled using an escalation algorithm. A high diuretic dose is defined as a furosemide daily amount >120 mg/day respectively. Conclusions: Continuous and high dose groups could reveal a more intensive diuresis and a greater decongestion with respect to intermittent and low dose groups; high dose and poor loop diuretic efficiency should be related to increased diuretic resistance, renal dysfunction occurrence, and greater congestion status. Poor diuretic response will be associated with less decongestion and an adverse prognosis

Combined use of lung ultrasound, B-type natriuretic peptide, and echocardiography for outcome prediction in patients with acute HFrEF and HFpEF

Background: Lung ultrasound (LUS) can be used to assess pulmonary congestion by imaging B-lines (‘comets’) for patients with acute heart failure (AHF). Objectives: Investigate relationship of B-lines, plasma concentrations of B-type natriuretic peptide (BNP), and echocardiographic left ventricular (LV) function measured at admission and discharge and their relationship to prognosis for AHF with preserved (HFpEF) or reduced (HFrEF) LV ejection fraction. Methods: Patients with AHF had the above tests done at admission and discharge. The primary outcome was re-hospitalization for heart failure or death at 6 months. Results: Of 162 patients enrolled, 95 had HFrEF and 67 had HFpEF, median age was 80 [77–85] years, and 85 (52%) were women. The number of B-lines at admission (median 31 [27–36]) correlated with respiratory rate (r = 0.75; p < 0.001), BNP (r = 0.43; p < 0.001), clinical congestion score (r = 0.25; p = 0.001), and systolic pulmonary artery pressure (r = 0.42; p < 0.001). At discharge, B-lines were also correlated with BNP (r = 0.69; p < 0.001) and congestion score (r = 0.57; p < 0.001). B-line count at discharge predicted outcome (AUC 0.83 [0.77–0.90]; univariate HR 1.12 [1.09–1.16]; p < 0.001; multivariable HR 1.16 [1.11–1.21]; p < 0.001). Results were similar for HFpEF and HFrEF. Conclusions: LUS appears a useful method to assess severity and monitor the resolution of lung congestion. At hospital admission, B-lines are strongly related to respiratory rate, which may be a key component of the sensation of dyspnea. Measurement of lung congestion at discharge provides prognostic information for patients with either HFpEF or HFrEF

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial.

Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.Methods: Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge.Results: A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04).Conclusions: In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months

Natriuretic peptides and NGAL in heart failure: does a link exist?

In recent years there has been growing interest in the development of new diagnostic tools and particularly in laboratory tests for the identification of heart failure (HF) patients. Because of the rise in HF occurrence, it is necessary to use simple and reliable method to recognize those patients at risk before the onset of the clinical symptoms. To date HF diagnosis remains difficult: its symptoms and signs are often non specific as well as being poor sensitive indicators for HF severity. Throughout the last 10 years published literature has highlighted a boom in the use of biomarkers for HF. Both B-type and N-terminal pro-B-type natriuretic peptides have demonstrated specific role in heart failure diagnosis, as well as risk assessment. A single determination of BNP at any time during the development of chronic heart failure (CHF) provides a clinically useful tool to establish the outcome. Renal dysfunction is often associated with heart failure and predicts adverse clinical outcomes. Many studies have recently suggested the clinical use of serum neutrophil gelatinase-associated lipocalin (NGAL) levels in patients admitted to the hospital for acute HF can be used to estimate the risk of early worsening renal function. This could be potentially applied in clinical practice for early identification of renal dysfunction development in patients with HF. NGAL levels appear also to predict renal dysfunction in patients with chronic HF and preserved renal function. For all these reasons, BNP and NGAL are two emerging tools useful for diagnosis and prognosis in HF. The combination of two laboratory biomarkers could potentially identify patients with more elevated risks of both cardiac hemodynamic impairment and kidney dysfunction

Natriuretic peptides (BNP and NT-proBNP): measurement and relevance in heart failure

For patients presenting with acute dyspnea, an incorrect diagnosis could increase the mortality risk. When used in the evaluation of patients with acute symptoms, brain natriuretic peptide and N-terminal pro-brain natriuretic peptide (BNP and NT-proBNP, respectively) testing is highly sensitive for the diagnosis or exclusion of acute or chronic decompensated heart failure (HF). It has been demonstrated that BNP and proBNP levels can facilitate diagnosis and guide HF therapy. Natriuretic peptide (NP) levels are strictly related with HF severity; they are particularly increased in more advanced New York Heart Association (NYHA) classes and in patients with poor outcome. Therefore elevated NP levels were found to correlate with the severity of left ventricular systolic dysfunction, right ventricular dysfunction and pressures, and left ventricular filling alterations. However, the optimal use of NP determination agrees with patient history, physical examination, and all other diagnostic tools. There are some clinical conditions (ie, obesity, renal insufficiency anemia) for which the NP measurement is not diagnostic. Algorithm building taking into consideration all clinical and echocardiographic parameters, as well as NP measurements, may lead to the earlier identification and better risk stratification of patients with chronic HF, independently from etiology

B-type natriuretic peptide levels predict extent and severity of coronary disease in non-ST elevation coronary syndromes and normal left ventricular systolic function.

BACKGROUND: B-type natriuretic peptide (BNP) has been used recently as a biological marker in patients with coronary artery disease (CAD) with ST-elevation, as well as without ST-elevation. BNP is able to predict systolic dysfunction, adding new prognostic information to existing traditional markers. However is not known if there is a relation between the quantity of BNP levels and the severity of coronary artery disease. METHODS: This study compared B-type natriuretic peptide (BNP) levels in patients with stable angina (SA) and acute coronary syndromes (ACS) without ST-elevation in relation to angiographic lesions using TIMI and Gensini Scores. We studied 282 patients with CAD without ST elevation and preserved systolic function. BNP samples were measured in all recruited patients within 24 hours of hospitalization. RESULTS: BNP values were progressively increased in relation to the severity of diagnosis: SA (52.6±49.4 pg/mL ) UA (243.3±212 pg/mL) NSTE-ACS (421.7±334 pg/mL) (p<0.0001 and p<0.007 respectively). No statistically significant difference was observed between patients with SA and controls (21.2±6.8 pg/mL). The analysis of BNP levels in relation to the number of involved vessels demonstrated significantly increased levels in patients with multivessel disease compared to patients with 1 or 2 vessel disease (1-86.2±46.3 pg/mL; 2-127±297 pg/mL; 3-295±318 pg/mL; 4-297±347 pg/mL p<0.001 and p<0.003). Evaluation of BNP using Gensini Score showed a strong relation between BNP and coronary disease extension (r=0.38 p<0.0001).This trend was maintained in all CAD groups (SA=r 0.54; UA r=0.36 NSTE-ACS r=0.28). CONCLUSIONS: Circulating BNP levels appear elevated in ACS with diffuse coronary involvement, even in the absence of systolic dysfunction. BNP is also associated with multi-vessel disease and the extension of coronary disease

The role of erythropoietin stimulating agents in anemic patients with heart failure: solved and unresolved questions.

Anemia is a common finding in congestive heart failure (CHF) and is associated with an increased mortality and morbidity. Several conditions can cause depression of erythroid progenitor cells: reduction of iron absorption and reuptake, decreased bone marrow activity, reduced endogenous erythropoietin production, and chronic inflammatory state. Anemia's etiology in CHF is complex and partially understood; it involves several systems including impaired hemodynamic condition, reduced kidney and bone perfusion, increased inflammatory activity, and neurohormonal overdrive. The use of erythropoiesis stimulating agents (ESAs) such as erythropoietin and its derivatives is recently debated; the last interventional trial seems to demonstrate a neutral or negative effect in the active arm with darbepoetin treatment. The current data is opposite to many single blind studies and previous meta-analysis showing an improvement in quality of life, New York Heart Association class, and exercise tolerance using ESA therapy. These contrasting data raise several concerns regarding the target of hemoglobin levels needing intervention, the exact anemia classification and categorization, and the standardization of hematocrit cutoffs. Some cardiac and systemic conditions (ie, hypertension, atrial fibrillation, prothrombotic status) may predispose to adverse events, and ESA administration should be avoided. To prevent the negative effects, high-dosage and chronic administration should be avoided. Clarification of these items could probably identify patients that may benefit from additional iron or ESA treatment. In this review, we discuss the interventional trials made in anemic heart failure patients, the underlying mechanism of anemia in CHF, and the potential role of ESA in this setting

Thirty years of evidence on the efficacy of drug treatments for chronic heart failure with reduced ejection fraction: A network meta-analysis

Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction