Prognostic implications of renal dysfunction in patients hospitalized with heart failure: data from the last decade of clinical investigations.

Numerous studies over the last decade have demonstrated that renal dysfunction and worsening renal function (WRF) are common in patients hospitalized for heart failure (HHF) and appear to be associated with poor in-hospital and post-discharge outcomes. Unfortunately, its etiology has not been completely understood, and its prediction during hospitalization remains challenging. The evaluation of renal impairment during hospitalization should take into consideration the underlying renal substrate (e.g., predisposing clinical comorbidities such as diabetes and hypertension), initiating mechanisms (e.g., in-hospital therapies such as diuretics), and amplifying factors (neurohormonal and hemodynamic profile changes). Various patterns of WRF may have different prognostic implications and may require different therapeutic approaches. WRF may be initially classified by duration (transient vs. persistent) and by etiology (elevated venous pressures vs. arterial underfilling). Other critical contributing factors during hospitalization include progressive left ventricular dysfunction, neurohormonal activation, and medications. Transient WRF as a result of aggressive therapy targeting congestion may not be associated with poor outcomes. Persistent WRF seen in patients with severe hemodynamic derangements may be associated with poor post-discharge prognosis. Future investigations must clarify the pathophysiological correlates of various patterns of WRF. To date, there is an unmet clinical need to achieve adequate control over congestion while preserving renal function in HHF patients. Thus, the aim of this review is to provide an in-depth and critical interpretation of the available data on the prognostic importance of RD and WRF during hospitalization in an effort to improve HF management.

[Management strategies and choice of antithrombotic treatment in patients admitted with acute coronary syndrome--executive summary for clinical practice. Consensus Document of the Regional Chapters of the Italian National Association of Hospital Cardiologists (ANMCO) and of the Italian Society of Emergency Medicine (SIMEU)]. / Strategie Assistenziali e Scelta della Terapia Antitrombotica nei Pazienti Ricoverati con Diagnosi di Sindrome Coronarica Acuta--Sintesi Operativa per la Pratica Clinica. Documento congiunto delle Sezioni Regionali del Lazio dell'Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) e della Società Italiana di Medicina di Emergenza-Urgenza (SIMEU).

This document has been developed by the Lazio regional chapters of two scientific associations, the Italian National Association of Hospital Cardiologists (ANMCO) and the Italian Society of Emergency Medicine (SIMEU), whose members are actively involved in the everyday management of Acute Coronary Syndromes (ACS). The document is aimed at providing a specific, practical, evidence-based guideline for the effective management of antithrombotic treatment (antiplatelet and anticoagulant) in the complex and ever changing scenario of ACS. The document employs a synthetic approach which considers two main issues: the actual operative context of treatment delivery and the general management strategy.

Effects of Candesartan on Left Ventricular Function, Aldosterone and BNP in Chronic Heart Failure.

PURPOSE: Heart failure (HF) is characterized by activation of neurohormonal systems such as aldosterone and natriuretic peptides. In the absence of published data, CandHeart trial was designed to assess the effects on left ventricular (LV) function, aldosterone and brain natriuretic peptide (BNP) of candesartan in patients with HF and preserved (LVEF ≥ 40%) or depressed (LVEF <40%) LV systolic function. METHODS: A total of 514 patients with stable symptomatic NYHA II-IV HF and any left ventricular ejection fraction (LVEF)were randomized to candesartan (target dose 32 mg once daily) as add-on therapy or standard medical therapy alone. Standardized echocardiographic exams were performed locally under central quality control, whereas biomarkers were assayed in a core laboratory. RESULTS: The majority of patients (73.3%) were NYHA II and on ACE inhibitors (91.8%) and beta-blockers (85.4%). Mean age was 66 ± 11 years. Mean LVEF was 36.2 ± 9.7% and 24.9% of patients had LVEF ≥ 40%. LVEF increased significantly more in the candesartan group (p = 0.09 at 12 weeks and p = 0.01 at 48 weeks) and left ventricular end-diastolic diameter decreased in candesartan group (p = 0.05 at 12 weeks). Candesartan significantly reduced aldosterone at 48 weeks (p = 0.009). BNP was reduced similarly over time in both study groups (p = 0.35 and p = 0.98 at 12 and 48 weeks, respectively). There were 6.6% of discontinuations of candesartan for adverse events. CONCLUSIONS: In CandHeart, the addition of candesartan to standard medical treatment did not reduce circulating BNP more than standard therapy (primary endpoint), but it significantly improved LV function and produced a marked decrease in aldosterone levels at study end.

[Selection criteria for referral to cardiac rehabilitation centers]. / Criteri per la selezione dei pazienti da inviare ai centri di cardiologia riabilitativa.

Current guidelines state that cardiac rehabilitation is indicated after the acute phase of major cardiovascular diseases and interventions; on the other hand implementation of these indications is difficult because of several barriers, i.e. the number of patients per year with an indication exceeds by far the accommodation offer of cardiac rehabilitation centers; the demand for access to cardiac rehabilitation from acute cardiac care hospitals is low because the attention is focused on the acute phase of cardiac diseases. The present Consensus Document describes the changes in clinical epidemiology of the main cardiovascular diseases, showing that complications are increasingly more frequent in the postacute phase, especially in the setting of myocardial infarction. The Joint ANMCO/IACPR-GICR Committee defines priority criteria based on clinical risk for admission to cardiac rehabilitation centers as inpatients. This Consensus Document represents, therefore, an important step forward in the search for continuity of care in high-risk patients during the post-acute phase.

Comparison between male and female breast cancer survival using propensity score matching analysis.

Male breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management.

Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results.

AIMS: To test whether canrenone, an aldosterone receptor antagonist, improves left ventricular (LV) remodelling in NYHA class II heart failure (HF). Aldosterone receptor antagonists improve outcome in severe HF, but no information is available in NYHA class II. METHODS AND RESULTS: AREA IN-CHF is a randomized, double-blind, placebo-controlled study testing canrenone on top of optimal treatment in NYHA class II HF with low ejection fraction (EF) to assess 12-month changes in LV end-diastolic volume (LVEDV). Brain natriuretic peptide (BNP) was also measured. Information was available for 188 subjects on canrenone and 194 on placebo. Left ventricular end-diastolic volume was similarly reduced (-18%) in both arms, but EF increased more (P = 0.04) in the canrenone (from 40% to 45%) than in the placebo arm (from 40-43%). Brain natriuretic peptide (n = 331) decreased more in the canrenone (-37%) than in the placebo arm (-8%; P < 0.0001), paralleling a significant reduction in left atrial dimensions (-4% vs. 0.2%; P = 0.02). The composite endpoint of cardiac death and hospitalization was significantly lower in the canrenone arm (8% vs. 15%; P = 0.02). CONCLUSION: Canrenone on top of optimal treatment for HF did not have additional effects on LVEDV, but it increased EF, and reduced left atrial size and circulating BNP, with potential beneficial effects on outcome. A large-scale randomized study should be implemented to confirm benefits on cardiovascular outcomes in patients with HF in NYHA class II.

Elimination kinetic of 17beta-estradiol 3-benzoate and 17beta-nandrolone laureate ester metabolites in calves' urine.

Efficient control of the illegal use of anabolic steroids must both take into account metabolic patterns and associated kinetics of elimination; in this context, an extensive animal experiment involving 24 calves and consisting of three administrations of 17beta-estradiol 3-benzoate and 17beta-nandrolone laureate esters was carried out over 50 days. Urine samples were regularly collected during the experiment from all treated and non-treated calves. For sample preparation, a single step high throughput protocol based on 96-well C(18) SPE was developed and validated according to the European Decision 2002/657/EC requirements. Decision limits (CCalpha) for steroids were below 0.1 microg L(-1), except for 19-norandrosterone (CCalpha=0.7 microg L(-1)) and estrone (CCalpha=0.3 microg L(-1)). Kinetics of elimination of the administered 17beta-estradiol 3-benzoate and 17beta-nandrolone laureate were established by monitoring 17beta-estradiol, 17alpha-estradiol, estrone and 17beta-nandrolone, 17alpha-nandrolone, 19-noretiocholanolone, 19-norandrostenedione, respectively. All animals demonstrated homogeneous patterns of elimination both from a qualitative (metabolite profile) and quantitative point of view (elimination kinetics in urine). Most abundant metabolites were 17alpha-estradiol and 17alpha-nandrolone (>20 and 2 mg L(-1), respectively after 17beta-estradiol 3-benzoate and 17beta-nandrolone laureate administration) whereas 17beta-estradiol, estrone, 17beta-nandrolone, 19-noretiocholanolone and 19-norandrostenedione were found as secondary metabolites at concentration values up to the microg L(-1) level. No significant difference was observed between male and female animals. The effect of several consecutive injections on elimination profiles was studied and revealed a tendency toward a decrease in the biotransformation of administered steroid 17beta form.

Multiparametric risk stratification in patients with mild to moderate chronic heart failure.

BACKGROUND: Whether brain natriuretic peptide (BNP) combined with cardiopulmonary exercise test (CPx) and echocardiographic findings improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is unclear. METHODS AND RESULTS: A total of 244 consecutive stable outpatients, median age of 71 (62-76) years, with New York Heart Association (NYHA) Class I-III HF and left ventricular ejection fraction (LVEF) < 45% underwent BNP measurement, Doppler echocardiography, and a maximal CPx. Median BNP was 166 (70-403) pg/mL, median LVEF 35% (28%-40%). A restrictive filling pattern (RFP) was present in 44 patients (18%). At CPx, peak oxygen uptake was 12 (9.7, 14.4) mL/kg/min and an enhanced ventilatory response to exercise (EVR, slope of the ventilation to CO2 production ratio, > or = 35) was found in 90 patients (37%) During 18 (9-37) follow-up months, 80 patients died or were admitted for worsening HF (33%). In addition to simple bedside clinical variables (NYHA Class III, creatinine clearance, hemoglobin), BNP levels were predictive of outcome (HR 1.35 [1.12-1.63]). However, both RFP (HR 3.36 [2.09-5.41]) and a steeper minute ventilation-carbon dioxide output slope (HR 1.50 [1.19-1.88]) outperformed BNP as prognostic markers. Patients with both RFP and EVR had a 7.30 (95% CI 4.02-13.25) HR for death or HF-admission versus subjects with neither predictor. CONCLUSIONS: This study highlights the importance of a multiparametric approach for optimal risk stratification in the elderly with mild-to-moderate HF. Patients at high risk should undergo closer follow-up and be carefully evaluated for different therapeutic options, including nonpharmacologic treatment.

[The AREA IN-CHF trial (antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure): rationale and design]. / Lo studio AREA IN-CHF (antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure): razionale e disegno.

The RALES study has shown that spironolactone reduces the risk of morbidity and mortality both from progressive heart failure and sudden death in patients with NYHA class III or IV heart failure. This favorable effect was clearly independent of a diuretic effect. EPHESUS extended these results to eplerenone in patients with acute myocardial infarction complicated by left ventricular dysfunction and signs of heart failure. Antialdosterone drugs may be effective because they oppose the effects of aldosterone to sodium retention, loss of magnesium and potassium, sympathetic activation, baroreceptor function and vascular compliance. Antialdosterone treatment may also antagonize the effect of aldosterone in promoting cardiac fibrosis. In a RALES substudy baseline serum PIIINP, a marker of extracellular matrix turnover, showed an independent negative correlation with survival and chronic heart failure hospitalizations in the placebo group. Therefore it seems interesting to evaluate the effect of canrenone, an aldosterone receptor blocker, on the progression of left ventricular dysfunction in patients with mild heart failure assuming standard therapy.

[Economic impact of cardiac resynchronization therapy in patients with heart failure. Available evidence and evaluation of the CRT-Eucomed model for analysis of cost-effectiveness]. / L'impatto economico della terapia di resincronizzazione in pazienti con scompenso cardiaco. Evidenze disponibili e valutazione del modello CRT-Eucomed per l'analisi del rapporto costo-efficacia.

Several clinical trials show that cardiac resynchronization therapy (CRT) in patients with moderate-severe heart failure increases survival, improves quality of life and reduces hospital admissions. The high cost of this new technology, incurred by health organizations at the moment of the implant, requires to assess whether its use is economically rational for the Italian Health Service. The paper summarizes evidences of the impact of CRT on the use of hospital resources and on quality of life, and presents a model to calculate incremental costs per quality adjusted life years (QALYs) gained in patients with moderate-severe heart failure treated with optimal medical therapy. The model is based on efficacy data drawn from clinical trials and on other information concerning the Italian context collected and validated by a team of experts from Assobiomedica and the Italian Federation of Cardiology. The model estimates that the incremental cost per QALY gained attributable to CRT is Euro 63,225 if all effects (years of life gained, increased quality of life and reduction of hospital costs) are censored at the end of the first year after the implant and Euro 21,720 if all effects are censored at the end of the third year. Cost-effectiveness of CRT is thus strongly dependent upon the duration of its effects: longer benefits of the therapy compensate initial costs and thus make the technology more cost-effective. In order to get better estimates of the economic profile of CRT it is required to collect more precise data from routine practice on survival, quality of life and hospital resources. The model presented can be easily adapted to take into account new evidence and to calculate cost per QALY gained in regional and local contexts.

[Dilated cardiomyopathy: indication and role of non-invasive instrumental evaluation]. / Cardiomiopatia dilatativa: quando è indicato e cosa chiedere alla valutazione strumentale non invasiva.

Typical morphological and functional abnormalities of dilated cardiomyopathy can be well evaluated non-invasively by the echocardiographic and echo-Doppler study. However it is important to remember that left ventricular dilation and depressed systolic function can be found also in other diseases that may mimic idiopathic dilated cardiomyopathy (coronary heart disease, myocarditis, biventricular dysplasia, advanced hypertrophic cardiomyopathy, hypertensive or valvular heart diseases). Unusual echocardiographic findings for dilated cardiomyopathy, i.e. a mildly dilated and/or hypertrophic left ventricle, segmental rather than diffuse wall motion abnormalities, predominant right ventricular dilation and dysfunction or severe valvular abnormalities should increase the clinical suspicion of a different disease. Transesophageal and dobutamine stress echocardiography can be employed in selected patients. However, for definitive diagnosis invasive hemodynamic study with coronary angiography and sometimes endomyocardial biopsy is often required. The diagnostic role of other non-invasive studies, such as magnetic resonance, computed tomography and nuclear techniques, is not well known, considering the cost and the limited availability of these clinical tools.

[Intervention strategies in refractory heart failure]. / Strategie di intervento nello scompenso cardiaco refrattario.

Although the additional therapies with beta-blockers and spironolactone have recently proved to be significantly beneficial for the treatment of advanced heart failure, in the end stages of this disease the prognosis remains quite poor. Moreover, the quality of life of patients with advanced heart failure is still heavily influenced by symptoms and by a high rate of hospitalizations. In selected patients heart transplantation constitutes the only chance, but the low availability of donors limits a wider diffusion of this procedure. Mechanical left ventricular assistance is still considered a bridge to heart transplantation and, at present, technical reasons limit the long-term utilization of these devices. Xenotransplantation and regeneration of cardiac myocytes from bone marrow stem cells remain the greatest hopes for the future. Several other possibilities of offering broader opportunities to patients with end-stage heart failure are under investigation. The expectations regarding the antagonism of cytokines and endothelin were not confirmed by the recent results of several studies. The association between beta-blockers and non-adrenergic inotropes could have a rationale, but needs to be investigated with appropriate trials. Other surgical procedures, such as myocardial revascularization in case of severe ischemic left ventricular dysfunction or repair of severe secondary mitral regurgitation, represent surgical options the use of which may be more widespread, but their indications are still based on a rather empirical approach. The preliminary results of the electrical therapy of ventricular resynchronization are encouraging, but the selection of patients and the long-term advantages need to be defined further on. Moreover, advanced heart failure has a major impact on health costs and organization. This makes mandatory the definition of operative hospital- and home-care models, the use of which in clinical practice is to be proposed.

Multicenter prospective observational study on acute and chronic heart failure: one-year follow-up results of IN-HF (Italian Network on Heart Failure) outcome registry.

BACKGROUND: Clinical observational studies on heart failure (HF) deal mostly with hospitalized patients, few with chronic outpatients, all with no or limited longitudinal observation. METHODS AND RESULTS: This is a multicenter, nationwide, prospective observational trial on a population of 5610 patients, 1855 hospitalized for acute HF (AHF) and 3755 outpatients with chronic HF (CHF), followed up for 1 year. The cumulative total mortality rate at 1 year was 24% in AHF (19.2% in 797 patients with de novo HF and 27.7% in 1058 with worsening HF) and 5.9% in CHF. Cardiovascular deaths accounted for 73.1% and 65.3% and HF deaths for 42.4% and 40.5% of total deaths in AHF and CHF patients, respectively. One-year hospitalization rates were 30.7% in AHF and 22.7% in CHF patients. Among the independent predictors of 1-year all-cause death, age, low systolic blood pressure, anemia, and renal dysfunction were identified in both acute and chronic patients. A few additional variables were significant only in AHF (signs of cerebral hypoperfusion, low serum sodium, chronic obstructive pulmonary disease, and acute pulmonary edema), whereas others were observed only in CHF patients (lower body mass index, higher heart rate, New York Heart Association class, large QRS, and severe mitral regurgitation). CONCLUSIONS: In this contemporary data set, patients with CHF had a relatively low mortality rate compared with those with AHF. Rates of adverse outcomes in patients admitted for AHF remain very high either in-hospital or after discharge. Most deaths were cardiovascular in origin and ≈40% of deaths were directly related to HF.

Clinical features, and in-hospital and 1-year mortalities of patients with acute heart failure and severe renal dysfunction. Data from the Italian Registry IN-HF Outcome.

BACKGROUND: Chronic renal dysfunction (RD) frequently coexists with heart failure (HF) and influences outcome. Patients with acute HF (AHF) and severe RD are frequently excluded in the trials. We characterized these subjects and assessed incidence and predictors of in-hospital and one-year mortalities. METHODS: We selected the 455 patients included in the "IN-HF Outcome" Italian registry belonging to the lowest quartile of estimated glomerular filtration rate (eGFR<40 ml/min/1.73 m(2)). RESULTS: Mean eGFR at entry in severe RD patients was 28±9 ml/min/1.73 m(2). Compared to 1368 patients with more preserved eGFR, they were older, with more co-morbidities and more frequently ischemic etiology of HF. In-hospital and one-year all-cause mortality rates were 14% and 44% respectively, twice higher than the entire population. Predictors of in-hospital mortality were an abnormal status of consciousness, older age, hyponatremia, lower systolic blood pressure and eGFR. The same conditions (except eGFR) predicted one-year mortality together with the absence of diabetes and no treatment with beta-blockers or diuretics. CONCLUSIONS: In patients with AHF and severe RD, in-hospital and one-year all-cause mortality rates are very high. Independent predictors such as older age, and signs of hypoperfusion and hyponatremia may be identified but preventing and reversing RD remain the key targets for the clinical management of these patients.

Acute heart failure patient profiles, management and in-hospital outcome: results of the Italian Registry on Heart Failure Outcome.

AIMS: Registries and surveys improve knowledge of the 'real world'. This paper aims to describe baseline clinical profiles, management strategies, and the in-hospital outcome of patients admitted to hospital for an acute heart failure (AHF) episode. METHODS AND RESULTS: IN-HF Outcome is a nationwide, prospective, multicentre, observational study conducted in 61 Cardiology Centres in Italy. Up to December 2009, 5610 patients had been enrolled, 1855 (33%) with AHF and 3755 (67%) with chronic heart failure (CHF). Baseline and in-hospital outcome data of AHF patients are presented. Mean age was 72 ± 12 years, and 39.8% were female. Hospital admission was due to new-onset heart failure (HF) in 43% of cases. Co-morbid conditions were observed more frequently in the worsening HF group, while those with de novo HF showed a higher heart rate, blood pressure, and more preserved left ventricular ejection fraction (LVEF). Electrical devices were previously implanted in 13.3% of the entire group. Inotropes were administered in 19.4% of the patients. The median duration of hospital stay was 10 days (interquartile range 7-15). All-cause in-hospital death was 6.4%, similar in worsening and de novo HF. Older age, hypotension, cardiogenic shock, pulmonary oedema, symptoms of hypoperfusion, hyponatraemia, and elevated creatinine were independent predictors of all-cause death. CONCLUSION: Our registry confirms that in-hospital mortality in AHF is still high, with a long length of stay. Pharmacological treatment seems to be practically unchanged in the last decades, and the adherence to HF guidelines concerning implantable cardioverter defibrillators/cardiac resynchronization therapy is still very low. Some AHF phenotypes are characterized by worst prognosis and need specific research projects.

Prevalence of preclinical and clinical heart failure in the elderly. A population-based study in Central Italy.

AIMS: We conducted a population-based cross-sectional study to assess the prevalence of both preclinical and clinical heart failure (HF) in the elderly. METHODS AND RESULTS: A sample of 2001 subjects, 65- to 84-year-old residents in the Lazio Region (Italy), underwent physical examination, biochemistry/N-terminal pro brain natriuretic peptide (NT-proBNP) assessment, electrocardiography, and echocardiography. Systolic left ventricular dysfunction (LVD) was defined as left ventricular ejection fraction (LVEF) <50%. Diastolic LVD was defined by a Doppler-derived multiparametric algorithm. The overall prevalence of HF was 6.7% [95% confidence interval (CI) 5.6-7.9], mainly due to HF with preserved LVEF (HFpEF) (4.9%; 95% CI 4.0-5.9), and did not differ by gender. A systolic asymptomatic LVD (ALVD) was detected more frequently in men (1.8%; 95% CI 1.0-2.7) than in women (0.5%; 95% CI 0.1-1.0; P = 0.005), whereas the prevalence of diastolic ALVD was comparable between genders (men: 35.8%; 95% CI = 32.7-38.9; women: 35.0%; 95% CI = 31.9-38.2). The NT-proBNP levels and severity of LVD increased with age. Overall, 1623 subjects (81.1% of the entire studied population) had preclinical HF (Stage A: 22.2% and stage B: 59.1% respectively). A large number of subjects in stage B of HF showed risk factor levels not at target. CONCLUSIONS: In a population-based study, the prevalence of preclinical HF in the elderly is high. The prevalence of clinical HF is mainly due to HFpEF and is similar between genders.

[Selection criteria for patient admission to cardiac rehabilitation centers]. / Criteri per la selezione dei pazienti da inviare ai centri di cardiologia riabilitativa.

Current guidelines state that cardiac rehabilitation is indicated after the acute phase of major cardiovascular diseases and interventions; on the other hand implementation of these indications is difficult because of several barriers, i.e. the number of patients per year with an indication exceeds by far the accommodation offer of cardiac rehabilitation centers; the demand for access to cardiac rehabilitation from acute cardiac care hospitals is low because the attention is focused on the acute phase of cardiac diseases. The present Consensus Document describes the changes in clinical epidemiology of the main cardiovascular diseases, showing that complications are increasingly more frequent in the post-acute phase, especially in the setting of myocardial infarction. The Joint ANMCO/IACPR-GICR Committee defines priority criteria based on clinical risk for admission to cardiac rehabilitation centers as inpatients. This Consensus Document represents, therefore, an important step forward in the search for continuity of care in high-risk patients during the post-acute phase.

Diuretic therapy in heart failure: current controversies and new approaches for fluid removal.

Hospitalization for heart failure is a major health problem with high in-hospital and postdischarge mortality and morbidity. Non-potassium-sparing diuretics (NPSDs) still remain the cornerstone of therapy for fluid management in heart failure despite the lack of large randomized trials evaluating their safety and optimal dosing regimens in both the acute and chronic setting. Recent retrospective data suggest increased mortality and re-hospitalization rates in a wide spectrum of heart failure patients receiving NPSDs, particularly at high doses. Electrolyte abnormalities, hypotension, activation of neurohormones, and worsening renal function may all be responsible for the observed poor outcomes. Although NPSD will continue to be important agents to promptly resolve signs and symptoms of heart failure, alternative therapies such as vasopressine antagonists and adenosine blocking agents or techniques like veno-venous ultrafiltration have been developed in an effort to reduce NPSD exposure and minimize their side effects. Until other new agents become available, it is probably prudent to combine NPSD with aldosterone blocking agents that are known to improve outcomes.