Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

BACKGROUND: Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. AIM: We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). DESIGN: Individual person data meta-analysis. METHODS: Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. RESULTS: Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. CONCLUSIONS: Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF.

The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data.

BACKGROUND: In heart failure (HF), obesity, defined as body mass index (BMI) ≥30 kg m(-2), is paradoxically associated with higher survival rates compared with normal-weight patients (the 'obesity paradox'). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)). PATIENTS AND METHODS: A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5-24.9 (referent), 25-29.9, 30-34.9 and ≥35 kg m(-2). Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups. RESULTS: BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m(-2), the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15-1.50) for BMI <22.5, 0.85 (0.76-0.96) for BMI 25.0-29.9, 0.64 (0.55-0.74) for BMI 30.0-34.9 and 0.95 (0.78-1.15) for BMI ≥35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80-1.57) for BMI <22.5, 0.74 (0.56-0.97) for BMI 25.0-29.9, 0.64 (0.46-0.88) for BMI 30.0-34.9 and 0.71 (0.49-1.05) for BMI ≥35. CONCLUSIONS: In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0-34.9 kg m(-2).

Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study.

BACKGROUND: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist, with undefined prognostic and therapeutic implications. We investigated clinical profile and outcomes of patients with chronic HF and COPD, notably the efficacy and safety of ivabradine, a heart rate-reducing agent. METHODS: 6505 ambulatory patients, in sinus rhythm, heart rate ≥ 70 bpm and stable systolic HF were randomised to placebo or ivabradine (2.5 to 7.5mg bid). Multivariate Cox model analyses were performed to compare the COPD (n=730) and non-COPD subgroups, and the ivabradine and placebo treatment effects. RESULTS: COPD patients were older and had a poorer risk profile. Beta-blockers were prescribed to 69% of COPD patients and 92% of non-COPD patients. The primary endpoint (PEP) and its component, hospitalisation for worsening HF, were more frequent in COPD patients (HRs f, 1.22 [p=0.006]; and 1.34 [p<0.001]) respectively, but relative risk was reduced similarly by ivabradine in both COPD (14%, and 17%) and non-COPD (18% and 27%) patients (p interaction=0.82, and 0.53, respectively). Similar effect was noted also for cardiovascular death. Adverse events were more common in COPD patients, but similar in treatment subgroups. Bradycardia occurred more frequently in ivabradine subgroups, with similar incidence in patients with or without COPD. CONCLUSIONS: The association of COPD and HF results in a worse prognosis, and COPD represents a barrier to optimisation of beta-blocker therapy. Ivabradine is similarly effective and safe in chronic HF patients with or without COPD, and can be safely combined with beta-blockers in COPD.

Trends in mortality after first hospitalization with atrial fibrillation diagnosis in Sweden 1987 to 2006.

BACKGROUND: To examine trends in 3-year mortality after a first hospitalization with diagnosed atrial fibrillation in a large cohort with and without important comorbidities. METHODS: The Swedish Hospital Discharge and Cause of Death Registries were linked to investigate trends in mortality for all patients 35 to 84 years hospitalized for the first time with a discharge diagnosis (principal or contributory) of atrial fibrillation in Sweden during 1987 to 2006.We performed an analysis of temporal trends in mortality stratified for presence or absence of co-morbidities affecting survival. RESULTS: Exactly 376,000 patients (56% male, mean age 72 years) with a first diagnosis of atrial fibrillation during 1987­2006 were identified and followed for 3 years. Patients with one or more of the prespecified comorbidities had the highest mortality and the largest absolute decline in mortality, but patients without these comorbidities had a slightly larger relative decline (absolute risk reduction in 3-year mortality (AAR) from 42.5 to 34.7%, Hazard Ratio (HR) 0.76; 95% confidence interval (95% CI) 0.74 to 0.77 versus ARR 16.2% to 11.7%, HR 0.71; 0.68 to 0.74. In patients aged below 65 years,with no comorbidities, there was minimal change inmortality, and they still had a 2 times increased mortality compared to the general population (SMR 1.95; 1.84-2.06). CONCLUSIONS: Survival after a first hospitalization with a diagnosis of atrial fibrillation improved regardless comorbidities. Patients aged < 65 years old without diagnosed comorbidities still had a poor prognosis compared to the general population.

Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Prevalence and prognostic implications of electrocardiographic left ventricular hypertrophy in heart failure: evidence from the CHARM programme.

BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG LVH) is a powerful independent predictor of cardiovascular morbidity and mortality in hypertension. OBJECTIVE: To determine the contemporary prevalence and prognostic implications of ECG LVH in a broad spectrum of patients with heart failure with and without reduced left ventricular ejection fraction (LVEF). METHODS AND OUTCOME: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic heart failure to receive candesartan or placebo. The primary outcome comprised cardiovascular death or hospital admission for worsening heart failure. The relative risk (RR) conveyed by ECG LVH compared with a normal ECG was examined in a Cox model, adjusting for as many as 31 covariates of prognostic importance. RESULTS: The prevalence of ECG LVH was similar in all three CHARM trials (Alternative, 15.4%; Added, 17.1%; Preserved, 14.7%; Overall, 15.7%) despite a more frequent history of hypertension in CHARM-Preserved. ECG LVH was an independent predictor of worse prognosis in CHARM-Overall. RR for the primary outcome was 1.27 (95% confidence interval (CI) 1.04 to 1.55, p = 0.018). The risk of secondary end points was also increased: cardiovascular death, 1.50 (95% CI 1.13 to 1.99, p = 0.005); hospitalisation due to heart failure, 1.19 (95% CI 0.94 to 1.50, p = 0.148); and composite major cardiovascular events, 1.35 (95% CI 1.12 to 1.62, p = 0.002). CONCLUSION: ECG LVH is similarly prevalent in patients with symptomatic heart failure regardless of LVEF. The simple clinical finding of ECG LVH was an independent predictor of a worse clinical outcome in a broad spectrum of patients with heart failure receiving extensive contemporary treatment. Candesartan had similar benefits in patients with and without ECG LVH.

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

What can we learn from Europe?

The European Society of Cardiology has produced guidelines for the treatment of acute myocardial infarction as well as for chronic heart failure and for the use of beta blockers and angiotensin converting enzyme inhibitors. These documents provide clear evidence and strength of recommendations for the secondary prevention of complications after a myocardial infarction. The identification of heart failure and left ventricular systolic dysfunction are important risk factors in this context. The use of secondary prevention treatments in Europe has been evaluated in several surveys. The use of treatments varies across the participating countries and evidence based therapies in general are under-utilised. Various approaches have been taken to disseminate evidence based secondary prevention. Experience from the Italian BRING-UP collaboration illustrates how the use of beta blockers can be increased. Similarly, the Swedish RIKS-HIA registry of acute myocardial infarction has increased the use of secondary preventive treatments.

Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey.

AIMS: Due to a lack of clinical trials, scientific evidence regarding the management of patients with chronic heart failure and preserved left ventricular function (PLVF) is scarce. The EuroHeart Failure Survey provided information on the characteristics, treatment and outcomes of patients with PLVF as compared to patients with a left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: We performed a secondary analysis using data from the EuroHeart Failure Survey, only including patients with a measurement of LV function (n = 6806). We selected two groups: patients with LVSD (54%) and patients with a PLVF (46%). Patients with a PLVF were, on average, 4 years older and more often women (55% vs. 29%, respectively, p < 0.001) as compared to LVSD patients, and were more likely to have hypertension (59% vs. 50%, p < 0.001) and atrial fibrillation (25% vs. 23%, p = 0.01). PLVF patients received less cardiovascular medication compared to PLVF patients, with the exception of calcium antagonists. Multivariate analysis revealed that LVSD was an independent predictor for mortality, while no differences in treatment effect on mortality between the two groups was observed. A sensitivity analysis, using different thresholds to separate patients with and without LVSD revealed comparable findings. CONCLUSIONS: In the EuroHeart Failure Survey, a high percentage of heart failure patients had PLVF. Although major clinical differences were seen between the groups, morbidity and mortality was high in both groups.

Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: To describe the clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure (CHF) randomised in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartan. METHODS AND RESULTS: CHARM Alternative, CHARM Added and CHARM Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and 3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more often female. The proportion of women in CHARM Preserved was 40% compared to 32% in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were also more often hypertensive than in the other two trials (64% vs. 50% and 48%, respectively). Symptoms and signs (with the exception of a third heart sound) were similar in all three patient groups. Beta-blockers were used in over half of patients in all three groups. Digoxin and spironolactone were used less frequently and calcium antagonists more frequently in CHARM Preserved. Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE inhibitor intolerant patients. CONCLUSIONS: The CHARM Programme provides the largest and most detailed comparison to date of patients low- and preserved-LVEF CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort of patients and the other treatment which these patients receive.

Prognostic importance of the oxidized product of catecholamines, adrenolutin, in patients with severe heart failure.

OBJECTIVES: The purpose of this study was to assess whether adrenolutin, the inert product of the highly reactive molecules aminochromes, is increased in severe chronic heart failure and whether it is associated with a poor prognosis. BACKGROUND: Experimental evidence suggests that oxidative products of catecholamines, aminochromes, are more cardiotoxic than unoxidized catecholamines and may be increased in heart failure. METHODS: Adrenolutin was measured at baseline and at 1 and 3 months in 263 patients with chronic New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 22% +/- 7%. Adrenolutin levels were compared with normal levels, and their relation to prognosis was evaluated. RESULTS: Baseline adrenolutin was increased (55 +/- 90 pg/mL vs 8.4 +/- 9.1 pg/mL for control, P <.02) and remained increased at 1 month (49 +/- 65 pg/mL). During a mean follow-up of 309 +/- 148 days (22-609 days), 57 patients died. Baseline adrenolutin levels correlated with mortality rates by univariate and multivariate analyses (relative risk 1.06, 95% CI 1.01-1.10 for each 17.9-pg/mL rise, P =.032). Left ventricular ejection fraction (P =.013) and New York Heart Association class (P =.009) were the only other variables associated with survival. Age, sex, plasma creatinine, plasma N-terminal atrial natriuretic peptide, and plasma norepinephrine levels were not retained in our model. Adrenolutin levels 1 month after random assignment were not significantly correlated with total mortality rate (P =.061) but were correlated with mortality rate from low output (relative risk 1.14, 95% CI 1.06-1.22, P =.002). CONCLUSIONS: Plasma adrenolutin is increased in patients with heart failure and correlates with a poor prognosis independent of other important predictors of survival. This finding has potentially important pathophysiologic, prognostic, and therapeutic implications.

Heart failure in an elite soccer player.

The following case illustrates several important features: firstly, the occurrence of tachycardia-induced cardiomyopathy during sustained atrial tachycardia at a relatively modest heart rate of 130 beats per minute, in an elite athlete. Secondly, tachycardia may induce severe and occasionally life-threatening impairment of the systolic ventricular function without a history of palpitations. Finally, our patient is an excellent example of the complete recovery that may follow successful radiofrequency catheter ablation, performed promptly once the correct diagnosis has been confirmed.

The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis.

BACKGROUND: The European Society of Cardiology (ESC) has published guidelines for the investigation of patients with suspected heart failure and, if the diagnosis is proven, their subsequent management. Hospitalisation provides a key point of care at which time diagnosis and treatment may be refined to improve outcome for a group of patients with a high morbidity and mortality. However, little international data exists to describe the features and management of such patients. Accordingly, the EuroHeart Failure survey was conducted to ascertain if appropriate tests were being performed with which to confirm or refute a diagnosis of heart failure and how this influenced subsequent management. METHODS: The survey screened consecutive deaths and discharges during 2000-2001 predominantly from medical wards over a 6-week period in 115 hospitals from 24 countries belonging to the ESC, to identify patients with known or suspected heart failure. RESULTS: A total of 46788 deaths and discharges were screened from which 11327 (24%) patients were enrolled with suspected or confirmed heart failure. Forty-seven percent of those enrolled were women. Fifty-one percent of women and 30% of men were aged >75 years. Eighty-three percent of patients had a diagnosis of heart failure made on or prior to the index admission. Heart failure was the principal reason for admission in 40%. The great majority of patients (>90%) had had an ECG, chest X-ray, haemoglobin and electrolytes measured as recommended in ESC guidelines, but only 66% had ever had an echocardiogram. Left ventricular ejection fraction had been measured in 57% of men and 41% of women, usually by echocardiography (84%) and was <40% in 51% of men but only in 28% of women. Forty-five percent of women and 22% of men were reported to have normal left ventricular systolic function by qualitative echocardiographic assessment. A substantial proportion of patients had alternative explanations for heart failure other than left ventricular systolic or diastolic dysfunction, including valve disease. Within 12 weeks of discharge, 24% of patients had been readmitted. A total of 1408 of 10434 (13.5%) patients died between admission and 12 weeks follow-up. CONCLUSIONS: Known or suspected heart failure comprises a large proportion of admissions to medical wards and such patients are at high risk of early readmission and death. Many of the basic investigations recommended by the ESC were usually carried out, although it is not clear whether this was by design or part of a general routine for all patients being admitted regardless of diagnosis. The investigation most specific for patients with suspected heart failure (echocardiography) was performed less frequently, suggesting that the diagnosis of heart failure is still relatively neglected. Most men but a minority of women who underwent investigation of cardiac function had evidence of moderate or severe left ventricular dysfunction, the main target of current advances in the treatment of heart failure. Considerable diagnostic uncertainty remains for many patients with suspected heart failure, even after echocardiography, which must be resolved in order to target existing and new therapies and services effectively.

The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment.

BACKGROUND: National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. METHODS: The survey screened discharge summaries of 11304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. RESULTS: Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age <70 years, male gender and ischaemic aetiology were associated with an increased odds ratio for receiving an ACE inhibitor. Prescription of ACE inhibitors was also greater in diabetic patients and in patients with low ejection fraction (<40%) and lower in patients with renal dysfunction. The odds ratio for receiving a beta-blocker was reduced in patients >70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. CONCLUSION: Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.

Factors influencing the length of hospital stay of patients with heart failure.

INTRODUCTION: Heart failure (HF) is characterised by frequent hospital admissions and prolonged length of hospital stay. Admissions for HF have increased over the last decade while length of stay has decreased; the reasons for this change in length of stay are uncertain. This study investigates the effect of patient-related variables, in-hospital progress and complications on length of stay. METHODS: Patients admitted to Auckland Hospital general medical service and randomised into the Auckland Heart Failure Management Programme were included in this study. RESULTS: One hundred and ninety-seven patients were included in this study. Mean age 73 years, mean left ventricular ejection fraction 32%; 52% had one or more previous HF admissions and 75% were New York Heart Association class IV at admission. Median length of hospital stay was 6 days (IQR 4, 9) which is comparable to the national average from New Zealand admission databases. Longer than average length of stay, defined as >6 days, was associated with the presence of peripheral congestion, duration of treatment with intravenous diuretic, the development of renal impairment, other acute medical problems at admission, iatrogenic complications during hospital stay, and social problems requiring intervention. Factors independently associated with length of stay in the top quartile (>10 days) on logistic regression included the presence of oedema at admission (OR 10.5), change in weight during stay (OR 1.3), duration of treatment with iv diuretic (OR 7.5), the development of renal impairment (OR 9.8), concurrent respiratory problems requiring specific treatment (OR 3.8), and social problems requiring intervention (OR 6.8). CONCLUSIONS: Peripheral congestion, concomitant acute medical problems requiring specific treatment, the development of renal impairment and the presence of social problems were related to a longer than average length of hospital stay. Multivariate models only partly explained variance in hospital stay, suggesting the importance of pre-admission and post-discharge factors, including the healthcare environment, the availability of primary and secondary care resources, and the threshold for hospital admission.

Management of heart failure in primary care (the IMPROVEMENT of Heart Failure Programme): an international survey.

BACKGROUND: Heart failure is a prevalent condition that is generally treated in primary care. The aim of this study was to assess how primary-care physicians think that heart failure should be managed, how they implement their knowledge, and whether differences exist in practice between countries. METHODS: The survey was undertaken in 15 countries that had membership of the European Society of Cardiology (ESC) between Sept 1, 1999, and May 31, 2000. Primary-care physicians' knowledge and perceptions about the management of heart failure were assessed with a perception survey and how a representative sample of patients was managed with an actual practice survey. FINDINGS: 1363 physicians provided data for 11062 patients, of whom 54% were older than 70 years and 45% were women. 82% of patients had had an echocardiogram but only 51% of these showed left ventricular systolic dysfunction. Ischaemic heart disease, hypertension, diabetes mellitus, atrial fibrillation, and major valve disease were all common. Physicians gave roughly equal priority to improvement of symptoms and prognosis. Most were aware of the benefits of ACE inhibitors and beta blockers. 60% of patients were prescribed ACE inhibitors, 34% beta blockers but only 20% received these drugs in combination. Doses given were about 50% of targets suggested in the ESC guidelines. If systolic dysfunction was documented, ACE inhibitors were more likely and beta blockers less likely to be prescribed than when there was no evidence of systolic dysfunction. INTERPRETATION: Results from this survey suggest that most patients with heart failure are appropriately investigated, although this finding might be as a result of high rates of hospital admissions. However, treatment seems to be less than optimum, and there are substantial variations in practice between countries. The inconsistencies between physicians' knowledge and the treatment that they deliver suggests that improved organisation of care for heart failure is required.

Current perspectives for AT(1)-receptor blockers in the management of heart failure.

Despite improvements in therapy, long-term mortality remains high in patients with heart failure and thus there remains a need for new treatment strategies to reduce the burden of mortality and morbidity associated with this condition. AT(1)-receptor blockers represent a rational approach to the management of heart failure, and have been shown to have beneficial effects on heart failure symptoms and exercise tolerance. However, the two outcome trials reported to date have not shown conclusive evidence of improvements in mortality. The potential benefits of AT(1)-receptor blockers in heart failure are currently being investigated in several trials. The CHARM programme (Candesartan in Heart failure - Assessment of Reduction in Mortality and morbidity) is the largest heart failure trial so far. This comprises three trials: CHARM Alternative, in patients with left ventricular dysfunction who are intolerant to ACE inhibitors; CHARM Added, in patients with left ventricular dysfunction who are also receiving ACE inhibitors; CHARM Preserved, in patients with preserved left ventricular systolic function (ejection fraction >40%). The primary end point will be a composite of cardiovascular mortality and hospitalisation for the treatment of heart failure. Other trials are currently investigating the effects of AT(1)-receptor blockers when used as an alternative or in addition to ACE inhibitors. The CHARM programme, together with other studies, should clarify the role of these agents in the management of heart failure.

Prognostic usefulness of the six-minute walk in patients with advanced congestive heart failure secondary to ischemic or nonischemic cardiomyopathy.

Clinicians have relied on history and results from physical examinations to guide treatment of patients with advanced congestive heart failure, but these results may not reflect disease severity or hemodynamic status. We assessed how the distance walked in 6 minutes relates to clinical outcomes and symptoms of such patients. We compared the rates of death, hospitalization, and their composite at 1 year by the distance walked in 6 minutes at baseline and at 1 month, and by the change in distance between baseline and 1 month in 440 patients enrolled in a randomized trial. We also assessed the relations of baseline distance walked to symptom score and New York Heart Association class. The median distance increased from 218 m at baseline to 280 m at 1 month. Of 365 patients able to perform the baseline walk, 121 (33%) died and 217 (60%) were hospitalized compared with 46 (61%) and 34 (45%) of 75 patients unable to walk at baseline. Baseline distance significantly predicted mortality (hazard ratio 0.58/100-m increase, 95% confidence interval 0.50 to 0.68, p <0.001), even after adjustment. Baseline distance also significantly predicted hospitalization and the composite end point, as did the 1-month distance walked. The change in distance walked from baseline to 1 month did not predict any end point. Baseline distance correlated only moderately with symptom score (r = -0.385, p <0.001) and New York Heart Association class (r = -0.468, p <0.001). Distance walked during 6 minutes independently and strongly predicts mortality and hospitalization in patients with advanced congestive heart failure. This may be a simple, noninvasive, objective way to risk-stratify these patients and standardize their treatment.