Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: This study sought to investigate whether darbepoetin alfa, an erythropoiesis-stimulating protein (ESP), improves exercise capacity in patients with symptomatic chronic heart failure (CHF) and anemia. BACKGROUND: Anemia is common in patients with CHF. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study, CHF patients with anemia (hemoglobin > or =9.0 to < or =12.0 g/dl) received subcutaneous placebo (n = 22) or darbepoetin alfa (n = 19) at a starting dose of 0.75 microg/kg every 2 weeks for 26 weeks. The primary end point was change in exercise tolerance from baseline to week 27 as measured by peak oxygen uptake (ml/min/kg body weight). Other end points included changes in absolute peak VO2 (ml/min), exercise duration, and health-related quality of life. RESULTS: Differences (95% confidence interval) in mean changes from baseline to week 27 between treatment groups were 1.5 g/dl (0.5 to 2.4) for hemoglobin concentration (p = 0.005), 0.5 ml/kg/min (-0.7 to 1.7) for peak VO2 (p = 0.40), 45 ml/min (-35 to 127) for absolute peak VO2 (p = 0.27), and 108 s (-11 to 228) for exercise duration (p = 0.075). Patients receiving darbepoetin alfa compared with placebo had an improvement in self-reported Patient's Global Assessment of Change (79% vs. 41%, p = 0.01) but no significant differences in the Kansas City Cardiomyopathy and Minnesota Living with Heart Failure Questionnaire scores. Darbepoetin alfa was well tolerated. CONCLUSIONS: In patients with symptomatic CHF and anemia, darbepoetin alfa increased and maintained hemoglobin concentrations and improved health-related quality of life. A trend toward increased exercise time but not peak VO2 was observed. (Impact of Darbepoetin Alfa on Exercise Tolerance and Left Ventricular Structure in Subjects With Symptomatic Congestive Heart Failure (CHF) and Anemia; http://clinicaltrials.gov/ct/show/NCT00117234?order = 1; NCT00117234).

Progression of preserved systolic function heart failure to systolic dysfunction -- a natural history study.

OBJECTIVES: To assess the natural history of left ventricular (LV) structure and function in sequential heart failure admissions with preserved systolic function. BACKGROUND: Heart failure (HF) with preserved LV systolic function accounts for between 20% and 30% of typical HF populations. Few data are available concerning the natural history of structural and functional changes in the LV in this patient population. METHODS: We consented sequential admissions from the community with confirmed heart failure to participate in this study. Doppler-echocardiography was used to assess Ejection Fraction (EF), LV structure, regional wall motion and parameters of diastolic function including E:A ratio, E-wave deceleration time (DtE) and isovolumic relaxation time (IVRT). Follow-up echocardiography was carried out at three months (mean 103+/-13 days) from discharge. RESULTS: Of 210 sequential admissions with primary heart failure 56 had preserved systolic function (LVEF> or =45%). Follow-up data at three months were available in 38 patients (mean age 72 years) with preserved LV systolic function. Of the group, 9 had been admitted within three months of discharge, 5 for recurrent HF. Eight patients (21%) exhibited significant decline in LV systolic function at follow-up, all with LVEF<45%. Three exhibited regional wall-motion abnormalities with the remainder showing dilatation and global reduction in function. None of these eight had presented to hospital for any cause other than routine outpatient department (OPD) visits during the 3 months. CONCLUSION: Patients with preserved systolic function HF, a significant number may progress to systolic dysfunction with or without clinical events.

Heart failure care in a hospital unit: a comparison of standard 3-month and extended 6-month programs.

BACKGROUND: We have previously shown that a structured in-hospital and outpatient heart failure (HF) program reduces clinical events over a 3-month period following hospital discharge. AIMS: This prospective randomized controlled study examines the additional benefits of extending the standard 3-month HF program to 6 months on death and readmission over a 2-year follow-up period. METHODS: Of 161 patients admitted with NYHA class IV HF who completed the standard 3-month HF program, 130 consenting patients (mean age 69.9+/-12.2 years, 65% male) were randomized to the extended 6-month HF program (EP; n=62) or standard care (SP; n=68). The primary endpoint was death and/or unplanned rehospitalization for HF at 2 years postrandomization. RESULTS: In the 2-year follow-up period, there were eight people with unplanned hospitalizations for HF and 16 deaths in the EP group (event rate 38.7%) compared to seven people with unplanned HF readmissions and 14 deaths in the SP group (event rate 30.9%, p=0.348 versus EP). Kaplan-Meier survival analysis demonstrated no difference in outcome between standard and extended program (p=0.315). There were no differences between the groups in terms of unscheduled clinic visits or non-HF-related readmissions in the 2-year follow-up period. CONCLUSIONS: There is no measured clinical advantage in terms of death and/or HF readmission in extending a structured hospital-based disease management program for HF beyond 3 months postdischarge. However, it appears that patients continue to need access to the service to help abort clinical deteriorations, and this may have implication for the optimal organisation of such programs.

Specialist care of heart failure improves appropriate pharmacotherapy at the expense of greater polypharmacy and drug-interactions.

BACKGROUND: There is growing concern at the nature and extent of polypharmacy in heart failure (HF), which may be associated with increased drug interactions, adverse drug effects and a poor understanding of and compliance with therapy. AIMS: This study evaluates polypharmacy in a relatively unselected community heart failure population following emergency admission and determines the impact of an in-hospital, specialist heart failure care programme on appropriate pharmacotherapy, polypharmacy and drug interactions. METHODS: We analysed the medication profiles of 91 consecutive patients with an emergency admission for HF to our institution on admission and discharge. The numbers of inappropriate medicines, inappropriate dosages and omitted medicines according to guidelines were recorded. Medication profiles were analysed for potential drug-drug, drug-liver and drug-kidney interactions using standard criteria. RESULTS: In the study population, average age 71.1+/-10.4 years, 65.9% were male, 68.1% had left ventricular systolic dysfunction and the average ejection fraction on transfer to the specialist HF service was 38+/-13%. A total of 66 inappropriate medicines, 107 omitted medicines and 37 inappropriate dosage regimens were identified in the cohort on admission. These figures had dropped to 31, 33 and 19, respectively, on discharge, with per patient averages decreasing significantly (all P<0.0001). However, polypharmacy and potential drug interactions increased by 33% and 62%, respectively, from admission to discharge (P<0.0001) as did drug-kidney interactions and drug-liver interactions. Only ischemic aetiology and hypercholesterolaemia predicted polypharmacy in this cohort on discharge, whereas age, sex, renal function and heart failure type did not. CONCLUSIONS: Specialist care of heart failure following emergency admission results in more appropriate pharmacotherapy of heart failure. However, increased polypharmacy and drug-interactions are an inevitable consequence independent of age, sex and renal function. We advocate a practice of systematic evaluation of polypharmacy in all heart failure patients to identify potential problems and modify therapy where appropriate.

Is multidisciplinary care of heart failure cost-beneficial when combined with optimal medical care?

BACKGROUND: Multidisciplinary care (MDC) of heart failure (HF) can significantly reduce rates of unplanned hospitalisation, the major cost component of HF care. AIMS: This prospective, randomised, controlled study examines the cost-benefits of MDC of HF in the setting of optimal medical care. METHODS: 98 NYHA class IV HF patients (mean age 70.8+/-10.5 years) were randomised to MDC (n=51) or routine care (RC; n=47) of HF. A direct intervention cost was calculated from contact time (scheduled and unscheduled) spent by the MDC team. Unplanned hospitalisation costs for HF were calculated at a daily rate of 242. Outcomes were determined in monetary terms, i.e. the cost of the service per hospitalisation prevented and net costs/savings at 3 months. RESULTS: The direct intervention cost of the MDC team was 5860, with an average cost per patient of 113 (95% Cl: 97-128). At 3 months, there were a total of 12 unplanned HF readmissions in the RC group (25.5% rate, 195 days) compared to 2 in the MDC group (3.9% rate, 17 days). The number needed to treat to prevent one hospitalisation for HF was 6 over 3 months. The cost of the service per hospitalisation prevented was 586. The intervention produced a net cost saving of 37,216 for 51 patients treated over 3 months. Sensitivity analyses using 50% variation in costs and lower relative risk reductions confirmed the cost-benefits of the intervention. CONCLUSION: MDC of HF remains cost-beneficial when combined with optimal, medical care. The significant clinical and cost-benefits suggest that this intensive approach to MDC and medical management should become the standard of care for HF.

Heart failure management: multidisciplinary care has intrinsic benefit above the optimization of medical care.

PURPOSE: This work addresses the unanswered question of whether multidisciplinary care (MDC) of heart failure (HF) can reduce readmissions when optimal medical care is applied in both intervention and control groups. METHODS: In a randomized, controlled study, 98 patients (mean age, 70.8 +/- 10.5 years) admitted to hospital with left ventricular failure (New York Heart Association Class IV) were assigned to routine care (RC, n = 47) or MDC (n = 51). All patients received the same components of inpatient, optimal medical care of HF: specialist-led inpatient care; titration to maximum tolerated dose of angiotensin-converting enzyme inhibitor before discharge; attainment of predetermined discharge criteria (weight stable, off all intravenous therapy, and no change in oral regimen for 2 days). Only those in the MDC group received inpatient and outpatient education and close telephone and clinic follow-up. The primary study endpoint was rehospitalization or death for a HF-related issue at 3 months. MAIN FINDINGS: At 3 months, four people had events in the MDC group (7.8% rate over 3 months) compared with 12 people (25.5% rate over 3 months) in the RC group (P = 0.04). CONCLUSION: These data demonstrate for the first time the intrinsic benefit of MDC in the setting of protocol-driven, optimal medical management of HF. Moreover, the event rate of 7.8% at 3 months, as the lowest reported rate for such a high-risk group, underlines the value of this approach to the management of heart failure.