Ultrafiltration versus usual care for hospitalized patients with heart failure: the Relief for Acutely Fluid-Overloaded Patients With Decompensated Congestive Heart Failure (RAPID-CHF) trial.

OBJECTIVES: The purpose of this research was to assess the safety and efficacy of ultrafiltration (UF) in patients admitted with decompensated congestive heart failure (CHF). BACKGROUND: Ultrafiltration for CHF is usually reserved for patients with renal failure or those unresponsive to pharmacologic management. We performed a randomized trial of UF versus usual medical care using a simple UF device that does not require special monitoring or central intravenous access. METHODS: Patients admitted for CHF with evidence of volume overload were randomized to a single, 8 h UF session in addition to usual care or usual care alone. The primary end point was weight loss 24 h after the time of enrollment. RESULTS: Forty patients were enrolled (20 UF, 20 usual care). Ultrafiltration was successful in 18 of the 20 patients in the UF group. Fluid removal after 24 h was 4,650 ml and 2,838 ml in the UF and usual care groups, respectively (p = 0.001). Weight loss after 24 h, the primary end point, was 2.5 kg and 1.86 kg in the UF and usual care groups, respectively (p = 0.240). Patients tolerated UF well. CONCLUSIONS: The early application of UF for patients with CHF was feasible, well-tolerated, and resulted in significant weight loss and fluid removal. A larger trial is underway to determine the relative efficacy of UF versus standard care in acute decompensated heart failure.     

Overview of Acutely Decompensated Congestive Heart Failure (ADHF): A Report from the ADHERE Registry

Acute decompensated heart failure (ADHF) has emerged as a major public health problem, and HF has become the leading cause of hospitalization in persons over 65 years of age. It is estimated that there are 6.5 million hospital days attributed to ADHF each year. Patients hospitalized with ADHF face a substantial risk of readmission, as high as 50% by 6 months after discharge. Despite the large number of patients hospitalized and this substantial risk, data on these patients have been limited and there has been little effort to improve the quality of care for patients hospitalized with ADHF. The Acute Decompensated Heart Failure National Registry (ADHERE®) was designed to bridge this gap in knowledge and care by prospectively studying the characteristics, management, and outcomes of a broad spectrum of patients hospitalized with ADHF. Participating community and university hospitals identified patients with a primary or secondary discharge diagnosis of HF and collected medical history, management, treatments, and health outcomes via secure Web browser technology. As of October 2004, more than 160,000 patients from 281 hospitals have been enrolled. These patients differ substantially from those typically enrolled in randomized clinical trials. Initial data from the ADHERE registry have provided important insights into the clinical characteristics, patterns of care, and outcomes of patients with ADHF. ADHERE has documented significant delays in diagnosis and initiation of ADHF therapies as well as a substantial under-use of evidenced-based, guideline-recommended chronic HF therapies at hospital discharge. As such, there are substantial opportunities to improve the quality of care for ADHF patients in the nations hospitals.Dr. Fonarow has received research grants, is a consultant for, and is a member of the Speakers Bureau of, Scios Inc. ADHERE is sponsored by Scios Inc., Fremont, CA.     

Worsening Renal Function in Patients With Acute Decompensated Heart Failure Treated With Ultrafiltration: Predictors and Outcomes

BackgroundUltrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure (WRF) on mortality in patients treated with UF.Methods and ResultsBased on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 9.7 to 2.2 ± 2.0 mg/dL (P < .001), and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 45 vs 144 ± 42 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17–13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48–48.42; P = .03), and E/E′ ≥15 (OR 3.78, 95% CI 1.26–17.55; P = .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60 mg/dL who developed WRF during UF had a 75% 1-year mortality rate.ConclusionsWRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.     

Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure.

OBJECTIVES: This study was designed to compare the safety and efficacy of veno-venous ultrafiltration and standard intravenous diuretic therapy for hypervolemic heart failure (HF) patients. BACKGROUND: Early ultrafiltration may be an alternative to intravenous diuretics in patients with decompensated HF and volume overload. METHODS: Patients hospitalized for HF with > or =2 signs of hypervolemia were randomized to ultrafiltration or intravenous diuretics. Primary end points were weight loss and dyspnea assessment at 48 h after randomization. Secondary end points included net fluid loss at 48 h, functional capacity, HF rehospitalizations, and unscheduled visits in 90 days. Safety end points included changes in renal function, electrolytes, and blood pressure. RESULTS: Two hundred patients (63 +/- 15 years, 69% men, 71% ejection fraction < or =40%) were randomized to ultrafiltration or intravenous diuretics. At 48 h, weight (5.0 +/- 3.1 kg vs. 3.1 +/- 3.5 kg; p = 0.001) and net fluid loss (4.6 vs. 3.3 l; p = 0.001) were greater in the ultrafiltration group. Dyspnea scores were similar. At 90 days, the ultrafiltration group had fewer patients rehospitalized for HF (16 of 89 [18%] vs. 28 of 87 [32%]; p = 0.037), HF rehospitalizations (0.22 +/- 0.54 vs. 0.46 +/- 0.76; p = 0.022), rehospitalization days (1.4 +/- 4.2 vs. 3.8 +/- 8.5; p = 0.022) per patient, and unscheduled visits (14 of 65 [21%] vs. 29 of 66 [44%]; p = 0.009). No serum creatinine differences occurred between groups. Nine deaths occurred in the ultrafiltration group and 11 in the diuretics group. CONCLUSIONS: In decompensated HF, ultrafiltration safely produces greater weight and fluid loss than intravenous diuretics, reduces 90-day resource utilization for HF, and is an effective alternative therapy. (The UNLOAD trial; http://clinicaltrials.gov/ct/show/NCT00124137?order=1; NCT00124137).     

The Interleukin-1 Axis and Risk of Death in Patients With Acutely Decompensated Heart Failure

Background

Soluble ST2 (sST2), which is the soluble form of interleukin (IL)-1 receptor-like 1, identifies risk in acutely decompensated heart failure (ADHF). IL-1β is an inflammatory cytokine that has deleterious effects in myocardial remodeling and function. IL-1β inhibition has beneficial effects after acute myocardial infarction. However, the role of IL-1β in ADHF and its relationship to ST2 remain unclear.

Continuous Ultrafiltration for Congestive Heart Failure: The CUORE Trial

BackgroundThere are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload.Methods and ResultsFifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; n = 27). The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 5.5 and 7.9 ± 9.0 kg, respectively; P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04–0.48; P = .002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33).ConclusionsIn HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.     

Ultrafiltration is Associated With Fewer Rehospitalizations than Continuous Diuretic Infusion in Patients With Decompensated Heart Failure: Results From UNLOAD

BackgroundCompare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics.Methods and ResultsOutcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 ± 3.1 UF, 3.6 ± 3.5 continuous infusion, and 2.9 ± 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 ± 2.6 UF, 3.9 ± 2.7 continuous infusion, and 3.1 ± 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 ± 1.36) than in continuous infusion (2.29 ± 3.23; P = .016 versus UF) and bolus diuretics (1.31 ± 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days.ConclusionsDespite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.     

Impact of dopamine infusion on renal function in hospitalized heart failure patients: results of the Dopamine in Acute Decompensated Heart Failure (DAD-HF) Trial

BackgroundWorsening renal function (WRF) and hypokalemia related to diuretic use for acute decompensated heart failure (ADHF) are common and associated with poor prognosis. Low-dose dopamine infusion improves renal perfusion; its effect on diuresis or renal function specifically in ADHF is not known.Methods and ResultsSixty consecutive ADHF patients (age 75.7 ± 11.2 years; 51.7% female; left ventricular ejection fraction 35.3 ± 12.1%) were randomized, after receiving a 40 mg intravenous furosemide bolus, to either high-dose furosemide (HDF, 20 mg/h continuous infusion for 8 hours) or low-dose furosemide combined with low-dose dopamine (LDFD, furosemide 5 mg/h plus dopamine 5 μg kg^?1 min^?1 continuous infusion for 8 hours). Both strategies were compared for total diuresis, WRF (defined as a rise in serum creatinine of >0.3 mg/dL from baseline to 24 hours), electrolyte balance, and 60-day postdischarge outcomes. Mean hourly excreted urine volume (272 ± 149 mL in HDF vs 278 ± 186 mL in LDFD group; P = .965) and changes in dyspnea score (Borg index: ?4.4 ± 2.1 in HDF group vs ?4.7 ± 2.0 in LDFD group; P = .575) during the 8 hours of protocol treatment were similar in the two groups. WRF was more frequent in the HDF (n = 9; 30%) than in the LDFD group (n = 2; 6.7%; P = .042). Serum potassium changed from 4.3 ± 0.5 to 3.9 ± 0.4 mEq/L at 24 hours (P = .003) in the HDF group and from 4.4 ± 0.5 to 4.2 ± 0.5 mEq/L at 24 hours (P = .07) in the LDFD group. Length of stay and 60-day mortality or rehospitalization rates (all-cause, cardiovascular, and worsening HF) were similar in the two groups.ConclusionsIn ADHF patients, the combination of low-dose furosemide and low-dose dopamine is equally effective as high-dose furosemide but associated with improved renal function profile and potassium homeostasis.Clinical Trial Registration InformationClinicalTrials.gov Identifier: NCT00937092 (http://clinicaltrials.gov/ct2/show/NCT00937092)     

Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial.

PRIMARY OBJECTIVE: To determine the effects of pimobendan 2.5 and 5 mg daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, placebo controlled trial of the addition of pimobendan to conventional treatment with a minimum follow up of 24 weeks. SETTING: Outpatient cardiology clinics in six European countries. PATIENTS: 317 patients with stable symptomatic heart failure, objectively impaired exercise capacity, and an ejection fraction of 45% or lower who were treated with at least an angiotensin converting enzyme inhibitor and a diuretic and who tolerated a test dose of pimobendan. RESULTS: Compared with placebo, both pimobendan 2.5 and 5 mg daily improved exercise duration (bicycle ergometry) by 6% (P = 0.03 and 0.05) after 24 weeks of treatment. At that time 63% of patients allocated to pimobendan and 59% of those allocated to placebo were alive and able to exercise to at least the same level as at entry (P = 0.5). No significant effects on oxygen consumption (assessed in a subgroup of patients) and on quality of life (assessed by questionnaire) were observed. Pimobendan was well tolerated. Proarrhythmic effects (24-hour electrocardiography) were not observed. In both pimobendan groups combined the hazard of death was 1.8 (95% confidence interval 0.9 to 3.5) times higher than in the placebo group. CONCLUSIONS: Pimobendan improves exercise capacity in patients with chronic heart failure who are also on conventional treatment. The balance between benefit and risk of treatment with this compound remains to be established however.     

Serial Monitoring of Soluble Interleukin Family Member ST2 in Patients with Acutely Decompensated Heart Failure

Objectives: To determine whether serial measures of the interleukin receptor family member soluble ST2 (sST2) provide additional prognostic information to baseline measures for long-term risk stratification of acutely decompensated heart failure (ADHF) patients. Methods: We prospectively enrolled 72 ADHF patients. Blood samples were collected to measure sST2 concentrations at presentation and on day 4 of hospitalization. All patients were clinically followed, and vital status was registered. Results: Between presentation and day 4, sST2 concentrations decreased from 62 ng/ml (interquartile range 38-105) to 44 ng/ml (interquartile range 26-72; p < 0.001). Both sST2 concentrations at presentation [hazard ratio (HR) 1.011, 95% confidence interval (CI) 1.005-1.016; p < 0.001] and on day 4 (HR 1.015, 95% CI 1.005-1.024; p = 0.003) were independent predictors of mortality. Patients with sST2 ≤76 ng/ml at presentation and ≤46 ng/ml on day 4 had the lowest mortality rates (3%), whereas those with both sST2 values above these cutoff points had the highest mortality (50%). C index and reclassification analyses demonstrated that the use of serial sST2 measures resulted in an improvement in the accuracy of mortality prediction. Conclusions: Among ADHF patients, sST2 concentrations tend to decrease following initiation of treatment and are prognostic both at presentation and during hospitalization. Serial sampling of sST2 adds prognostic information and may provide a basis for enhanced clinical decision making.     

Acutely decompensated heart failure: characteristics of hospitalized patients and opportunities to improve their care.

Heart failure (HF) remains a major public health problem in western countries, despite the enormous progress in its diagnosis and treatment. Acute and chronic decompensated HF are leading medical causes of hospitalization among people aged over 65 years in European countries, the USA, Australia and New Zealand. However, there have been few studies on acute and chronic decompensated HF and the European Society of Cardiology (ESC) guidelines on this subject have only just been published. AIM: To evaluate the overall prevalence of hospitalization due to HF according to its subtypes, comorbidities, and decompensating factors, in the Medical Department of a central teaching hospital in an urban area. METHODS: We performed a retrospective observational study of patients admitted consecutively to the Medical Department via the emergency room between January and June 2001. Discharge casenotes on 1038 admissions were reviewed. Those with a diagnosis of HF or cardiovascular conditions associated with or precursors of HF were analyzed. Cases with a final diagnosis of HF according to the criteria of the ESC guidelines were included in the study. We evaluated the overall prevalence of HF and subtypes of cardiac dysfunction, etiological risk factors, patients' demographic characteristics, decompensating factors, comorbidity, mean length of hospital stay, and in-hospital mortality rate. RESULTS: We identified 180 patients with HF (17.4%), mean age 74.6 +/- 14; 87 were male (48%), aged 73.7 +/- 14.2, and 93 female (52%), aged 75.6 +/- 14. Left ventricular systolic dysfunction (LVSD) was present in 42.2% of cases, preserved left ventricular systolic function in 32.6%, and valvular heart disease in 10.6%. Hypertension and coronary artery disease were the main etiological risk factors (62.2% and 42.8% respectively). Atrial fibrillation was recorded in 43.4% of the patients, diabetes was diagnosed in 21.6%, and anemia and chronic obstructive pulmonary disease in about one third. Infection, predominantly respiratory, was the main factor triggering decompensation, followed by uncontrolled hypertension and supraventricular tachyarrhythmia. At admission, 42.2% of the patients were in NYHA class III and 44.8% in NYHA class IV. HF patients had a mean hospital stay of 13.8 days, slightly shorter than the mean overall stay of patients admitted to the Medical Department in the same period (14.5 days). In-hospital mortality for HF patients was 7.7%, with HF being the first cause of admission to the Medical Department, followed by stroke (10.6%). CONCLUSIONS: This study confirms the high prevalence of acute or chronic decompensated HF in patients hospitalized in the Medical Department of a central teaching hospital in an urban area. The patients were mainly elderly, of both genders, with a slightly higher proportion of HF due to LVSD. Most patients were in NYHA classes III and IV. Mean hospital stay was no longer than that of all patients admitted in the same period. The in-hospital mortality rate was low. The age-group affected and the high prevalence of multiple comorbidities emphasize the need to establish HF clinics with multidisciplinary teams to manage these patients, and health authorities must be made aware of the burden of this syndrome.