Cheyne-Stokes respiration is not related to quality of life or sleepiness in heart failure.

BACKGROUND AND AIMS: The effects of central sleep apnea in Cheyne-Stokes respiration on sleep-related symptoms and quality of life are not very well established. We aimed to investigate whether Cheyne-Stokes respiration is related to health-related quality of life. We also studied the impact on daytime sleepiness and nocturnal dyspnea. METHODS: Included were 203 consecutive patients, stabilized following in-hospital treatment for decompensated congestive heart failure. They underwent overnight cardiorespiratory sleep apnea recordings in hospital and answered a set of questions on symptoms and health-related quality of life questionnaires in the form of the Nottingham Health Profile and the Minnesota Living with Heart Failure Questionnaire. After excluding seven patients with predominantly obstructive apneas and 14 with insufficient recordings, 182 patients were included in the final analysis. RESULTS: One third of the patients had an apnea-hypopnea index (AHI) of >30. Falling asleep in front of the television was the only symptom related to (AHI). Nocturnal dyspnea, daytime sleepiness, generic quality of life or disease-specific quality of life were not related to AHI. CONCLUSIONS: Cheyne-Stokes respiration was not associated with health-related quality of life, daytime sleepiness or nocturnal dyspnea among patients stabilized following treatment for congestive heart failure.

Cigarette smoking: an undertreated risk factor for cardiovascular disease.

Smoking and other forms of tobacco use are major risk factors for cardiovascular disease. The effect of cigarette smoking on cardiovascular health is evident even at the lowest levels of exposure. Yet, the adverse effects of smoking are reversible, with cardiovascular risk decreasing substantially within the first 2 years of smoking cessation. Significantly, the mortality from coronary heart disease is reduced more through smoking cessation than by other secondary preventive therapies such as cholesterol lowering. Smoking cessation is a highly effective way to improve cardiovascular health in smokers and extremely cost-effective. However, smoking cessation therapies are not implemented maximally if they are implemented at all, perhaps because smoking is seen as a lifestyle choice or because smokers frequently relapse, as indicated by very low long-term quit rates. Too often, healthcare professionals, including lipidologists and cardiologists, do little to address their patients' smoking status, in spite of its impact on cardiovascular health. With the advent of new therapies to treat the nicotine addiction that results from smoking and other tobacco use, it is hoped that physicians will be more proactive in encouraging and implementing smoking cessation programs for their patients, with the goal of increasing long-term quit rates, and reducing the morbidity and mortality associated with cardiovascular disease.

Cardiologists' awareness and perceptions of guidelines for chronic heart failure. The ADDress your Heart survey.

BACKGROUND: Several surveys show that patients with chronic heart failure (CHF) are sub-optimally managed and treatment guidelines are not implemented in clinical practice. AIMS: To investigate awareness and perceptions of the 2005 European Society of Cardiology (ESC) guidelines for CHF. METHODS: 467 cardiologists from seven European countries completed an on-line interview using a validated, semi-structured questionnaire including questions about awareness and relevance of CHF guidelines. To assess agreement with ESC guidelines, three fictitious patient cases were presented and respondents' management choices compared with those of an expert panel based on the guidelines. RESULTS: Awareness of CHF guidelines was high, with 98% aware of any guideline and 65% aware of ESC guidelines. ESC guidelines were considered relevant (51%) or very relevant (38%) for guiding treatment decisions. Up to 92% of respondents perceived that they adhered to the ESC guidelines. For the patient cases,

The From The Heart study: a global survey of patient understanding of cholesterol management and cardiovascular risk, and physician-patient communication.

OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. A high level of low-density lipoprotein cholesterol (LDL-C) is a major CVD risk factor. Guidelines recommend effective cholesterol management and set LDL-C goals, yet deficiencies exist in physician implementation of these recommendations and in patient uptake of the advice. However, little is known of patient perceptions about CVD risk. METHODS: Patients and physicians were randomly selected from ten countries to complete a confidential, semi-structured questionnaire. RESULTS: Response rates were 27% (n = 750) for physicians and 83% (n = 1547) for patients. Patients believed cancer (43%) to be a greater cause of mortality than heart attack or stroke (34%). Despite 77% of patients claiming to be satisfied with information on high cholesterol, only 26% were aware that heart attack was a possible consequence, and only 35% of patients thought they had achieved their cholesterol goals. Virtually all physicians (99%) claimed to inform patients of their cholesterol level, while 18% of patients reported that they were not informed. Although patients and physicians were selected at random, limitations of this survey relate typically to the reliability of physician and patient responses and the possibility that the survey population may not represent the overall population. A broad range of patients' backgrounds and a high response rate (83%) suggest these effects would be minimal in the patient population. CONCLUSIONS: The From The Heart study has shown surprisingly poor knowledge of CVD risk amongst patients with elevated cholesterol. This may contribute to poor concordance with recommendations and treatment.

Lipid management in cardiovascular disease prevention guidelines: strategies and tactics for implementation.

Despite the widespread dissemination of clinical practice guidelines on the prevention and treatment of cardiovascular disease (CVD), CVD causes one third of deaths worldwide and almost half of all deaths in the developed world. It is therefore likely that, although some aspects of CVD management have improved, there is still a significant shortfall between what is known about CVD prevention and what is put into action. Twenty-one experts in the field of CVD from around the world attended a focus panel meeting in Marlow-on-Thames, UK (see acknowledgements for a list of meeting participants). These experts were invited to discuss practical strategies and tactics for overcoming barriers to the implementation of guidelines on CVD prevention, and lipid management in particular. This article reviews and updates the key topics presented during the course of the meeting, captures the essence of the group discussions, and summarizes the meeting outcomes. The participants concluded that initial efforts to implement CVD prevention guidelines more effectively are best directed at high-risk patients who have already been identified. Once current patients achieve their targets, more attention can be paid to finding untreated patients at risk. Recommendations from the expert panel included: Harmonize guidelines; focus on common areas of consensus rather than state-of-the-art science. Remove the boundary between primary and secondary prevention and focus on level of overall risk. Help policy makers understand the different components of CVD. Include professional societies from different specialties in guideline development and implementation, to increase ownership and decrease fragmentation of guideline committees.

Comprehensive cardiovascular risk management--what does it mean in practice?

The continued movement away from the treatment of individual cardiovascular (CV) risk factors to managing overall and lifetime CV risk is likely to have a significant impact on slowing the rate of increase in cardiovascular disease (CVD). However, the management of CVD is currently far from optimal even in parts of the world with well-developed and well-funded healthcare systems. Effective implementation of the knowledge, treatment guidelines, diagnostic tools, therapeutic interventions, and management programs that exist for CVD continues to evade us. A thorough understanding of the multifactorial nature of CVD is essential to its effective management. Improvements continue to be made to management guidelines, risk assessment tools, treatments, and care programs pertaining to CVD. Ultimately, however, preventing the epidemic of CVD will require a combination of both medical and public health approaches. In addition to improvements in the "high-risk" strategy, which forms the basis of current CVD management, an increase in the utilization of population-based management strategies needs to be made to attempt to reduce the number of patients falling within the "at-risk" stratum for CVD. This review outlines how a comprehensive approach to CVD management might be achieved.

Effect of carvedilol and metoprolol on the mode of death in patients with heart failure.

BACKGROUND: In the COMET study, carvedilol improved survival compared to metoprolol tartrate in 3029 patients with NYHA II-IV heart failure and EF <35%, followed for an average of 58 months. AIMS: To evaluate whether the effect on overall mortality was specific for a particular mode of death. This may help to identify the mechanism of the observed difference. METHODS: Of the 1112 total deaths, 972 were adjudicated as cardiovascular, including 480 sudden, 365 circulatory failure (CF) and 51 stroke deaths. For each mode of death, the effect of pre-specified baseline variables was assessed, including sex, age, NYHA class, aetiology, heart rate, systolic blood pressure, EF, atrial fibrillation, previous myocardial infarction or hypertension, renal function, concomitant medication, and study treatment allocation. RESULTS: In multivariate Cox regression analyses, compared to metoprolol, carvedilol reduced cardiovascular (RR 0.80, CI 0.7-0.91, p=0.0009), sudden (RR 0.77, CI 0.64-0.93, p=0.0073) and stroke deaths (RR 0.37, CI 0.19-0.71, p=0.0027) with a non-significant trend for CF death (RR 0.83, CI 0.66-1.04, p=0.07). Treatment benefit with carvedilol did not differ between modes of death, except for a greater reduction in stroke death with carvedilol (competing risk analysis, p=0.0071 vs CF death). There were no interactions between treatment allocation and baseline characteristics. CONCLUSION: Mortality reduction with carvedilol compared to metoprolol appears relatively non-specific and could be consistent with a superior effect of carvedilol on cardiac function, arrhythmias or, in view of the greater reduction in stroke deaths, on vascular events.

Rationale, design, and methods for the risk evaluation and communication health outcomes and utilization trial (REACH OUT).

OBJECTIVE: To test the primary study hypothesis that a physician-delivered coronary heart disease risk evaluation and communication program can lower patients' predicted 10-year risk of myocardial infarction or death due to coronary heart disease by 10% within 6 months compared to usual care. DESIGN: Prospective, parallel group, open-label, controlled, cluster-randomized multinational trial; the study site is the unit of randomization. SETTING: Patients were recruited from 106 general practices located in nine European countries. PATIENTS: Men and women aged 45 to 64 (N=1500) with a documented history of hypertension (treated or untreated), systolic blood pressure > or =140 mmHg (or > or =130 mmHg in the presence of renal or kidney disease), no history of cardiovascular disease, and a predicted 10-year risk of myocardial infarction or death due to coronary heart disease > or =10%. INTERVENTION: Sites were randomized to deliver a physician-directed coronary heart disease risk communication and education program or usual care. The intervention program included informing patients of their 10-year risk of myocardial infarction or death due to coronary heart disease, educating patients about modifiable risk factors and their control, and three follow-up phone calls by a physician or study nurse. MAIN OUTCOME MEASURE: Predicted 10-year risk of myocardial infarction or death due to coronary heart disease at 6 months. CONCLUSIONS: REACH OUT will evaluate a novel, patient-focused, physician-implemented application of coronary heart disease risk equations. Results of the study will be of practical relevance to physicians, health care organizations, and those who issue clinical guidelines for the reduction of cardiovascular risk.

Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition.

BACKGROUND: The beneficial effects of angiotensin converting enzyme (ACE)-inhibitors are in part mediated through the inhibition of the degradation of the vasodilator bradykinin. The bradykinin effect is counteracted by cyclooxygenase-inhibitors. Angiotensin receptor blockers (ARBs) do not affect bradykinin. AIMS: To test the hypothesis that renal counteraction from a cyclooxygenase-inhibitor, diclofenac, is different in subjects treated with an ACE-inhibitor, enalapril compared with an ARB, losartan. METHODS: Twelve elderly, healthy, slightly over-hydrated subjects received diclofenac orally after pre-treatment with a diuretic, bendroflumethiazide, and enalapril or bendroflumethiazide and losartan, in a double-blind cross-over fashion, with a wash-out period of at least 1 week. RESULTS: Diclofenac reduced GFR significantly from 81(64-98) ml/min at first observations after dose for enalapril to 29(16-42) and from 76(64-88) after losartan to 35(24-46). There was no significant difference between enalapril and losartan in GFR. Diclofenac induced decreases in urine flow, excretion rates and clearances of sodium, osmolality clearance and free water clearance, irrespective of treatment with enalapril or losartan. However, serum potassium and handling of potassium were significantly lower after losartan-treatment. CONCLUSION: The negative renal effects of diclofenac administration in subjects with activation of the renin-angiotensin system and enalapril treatment are the same in subjects with activation of the renin-angiotensin system and losartan treatment.

Rationale for multiple risk intervention: the need to move from theory to practice.

Incidence of cardiovascular (CV) and metabolic disease is increasing, in parallel with associated risk factors. These factors, such as low-density lipoprotein (LDL)-cholesterol, elevated blood pressure, obesity, and insulin resistance have a continuous, progressive impact on total CV risk, with higher levels and numbers of factors translating into greater risk. Evaluation of all known modifiable risk factors, to provide a detailed total CV disease (CVD) and metabolic risk-status profile is therefore necessary to ensure appropriate treatment of each factor within the context of a multifactorial, global approach to prevention of CVD and metabolic disease. Effective and well-tolerated pharmacotherapies are available for the treatment of risk-factors. Realization of the potential health and economic benefits of effective risk factor management requires improved risk factor screening, early and aggressive treatment, improved public health support (ie, education and guidelines), and appropriate therapeutic interventions based on current guidelines and accurate risk assessment. Patient compliance and persistence to available therapies is also necessary for successful modulation of CVD risk.

Knowing your risk factors for coronary heart disease improves adherence to advice on lifestyle changes and medication.

Implementation of guidelines for coronary heart disease prevention is less optimal in clinical practice. The aim of this study was to investigate if specific knowledge (patients' knowledge about their own coronary heart disease risk factors) would correlate to their adherence as measured by self-reported lifestyle changes, reaching defined treatment goals and adhering to treatment with prescribed drugs. The consecutive medical records of 509 men and women younger than 71 years, hospitalized for a cardiac event, were screened. Of these, 392 patients came for an interview and were subjected to a clinical examination. All patients received a questionnaire regarding their specific knowledge of risk factors and their adherence to lifestyle changes, which was completed by 347 patients. In addition, data were collected and analyzed on how their treatment goals were attained in 8 domains and their adherence to drug treatment. There were significant correlations between specific knowledge and self-reported lifestyle changes, the ability to reach treatment goals in all 8 domains, and adherence to prescribed drugs. Patients with coronary heart disease will benefit from increased specific knowledge of risk factors to adhere with lifestyle changes and prescribed medication after a cardiac event.

A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the "patient journey") in patients with heart failure: a report from the Carvedilol Or Metoprolol European Trial (COMET).

OBJECTIVES: This study was designed to investigate the loss of well-being, in terms of life-years, overall and in patients randomized to metoprolol versus carvedilol in the Carvedilol Or Metoprolol European Trial (COMET). BACKGROUND: The ultimate objectives of treating patients with heart failure are to relieve suffering and prolong life. Although the effect of treatment on mortality is usually described in trials, the effects on patient well-being throughout the trials' courses are rarely reported. METHODS: A total of 3,029 patients randomized in the COMET study were included in the analysis. "Patient journey" was calculated by adjusting days alive and out of hospital over four years using a five-point score completed by the patient every four months, adjusted according to the need for intensification of diuretic therapy. Scores ranged from 0% (dead or hospitalized) to 100% (feeling very well). RESULTS: Over 48 months, 17% of all days were lost through death, 1% through hospitalization, 23% through impaired well-being, and 2% through the need for intensified therapy. Compared with metoprolol, carvedilol was associated with fewer days lost to death, with no increase in days lost due to impaired well-being or days in hospital. The "patient journey" score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD 26.3%) (p < 0.0068). CONCLUSIONS: Despite treatment with beta-blockers, heart failure remains associated with a marked reduction in well-being and survival. Loss of quality-adjusted life-years through death and poor well-being seemed of similar magnitude over four years, and both were much larger than the loss that could be attributed to hospitalization.

The evolution of European guidelines: changing the management of cholesterol levels.

Cardiovascular disease (CVD) is the leading cause of death in Europe and the US. This paper reviews the evolution of the Joint European Societies' guidelines with respect to their lipid recommendations. We stress the importance of lowering lipid levels to, or below, the currently recommended goals and argue that patients' global risk for CVD, rather than baseline lipid levels, should direct the intensity of lipid-lowering treatment. However, the emphasis on near-term (i.e., in the next 10 years) global risk estimation may under-emphasize the importance of considering lifetime cardiovascular risk in treatment decisions. Although various guidelines' thresholds for treatment initiation and recommended goals differ, they are similar in the theme of treating global risk. Most clinical trials have not identified a threshold of cholesterol level beyond which lowering cholesterol levels no longer provides cardiovascular benefit. An urgent call for action is needed to improve goal attainment in patients with or at risk for CVD. Improving access to risk-reducing treatments should be a priority.

Barriers to effective implementation of guideline recommendations.

Cardiovascular disease (CVD) is the leading cause of death worldwide, and its prevention and treatment are important healthcare aims. Hypercholesterolemia is among the most important modifiable risk factors for CVD, and numerous guidelines exist for the treatment of this condition. Nevertheless, despite the existence of well-established and safe pharmacologic therapy for lowering cholesterol and preventing CVD, surveys in the United States and Europe have revealed that many patients have elevated cholesterol levels. There is a clear gap between what is known about treating CVD and the implementation of that knowledge. A survey assessing patients' knowledge about CVD observed that many patients are unaware of the disease prevalence and have little knowledge about the main risk factors, including the importance of cholesterol. Another survey demonstrated that many physicians overestimate patients' awareness of CVD and that physicians also overestimate the extent to which guidelines are implemented in clinical practice. Guideline implementation may be improved by narrowing the discrepancies between what patients and physicians believe and the reality. Many physicians claim that lack of time hinders guideline implementation and improvement of patient education. Physicians also appear to lack the motivation to implement lipid-lowering interventions. A multifactorial approach to improving use of guidelines in clinical practice may improve the treatment and prevention of CVD.

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice.

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.

Hypertensive smokers have a worse cardiovascular risk profile than non-smokers in spite of treatment--a national study in Sweden.

Smoking is a well-established risk factor for cardiovascular disease. Studies have indicated that smoking may outweigh the benefit of blood pressure (BP) control. Our aim was to compare cardiovascular risk factors in smokers vs non-smokers from a national sample of treated hypertensives. Data were collected on smoking habits, BP control, total and low-density lipoprotein (LDL) cholesterol, diabetes, left ventricular hypertrophy (LVH), and microalbuminuria (MA), from records of 4424 consecutive patients by 189 physicians. All technical methods were local. Treated hypertensives who smoked had microalbuminuria significantly more often than non-smokers, 26.2% vs 20.5% (p<0.05), and a higher proportion of smokers were suboptimally controlled (DBP > or = 90 mmHg), 32.7% vs 25.0% (p<0.01). Smoking males had a higher prevalence of LVH (25.7% vs 20.1; p<0.05), microalbuminuria (29.7% vs 24.7%; p<0.01), and a higher proportion of subjects with uncontrolled systolic BP (> or = 140 mmHg) (72.8% vs 68.9%; p<0.01). Both DBP and total cholesterol were higher in smoking vs non-smoking females. An increased prevalence of LVH and microalbuminuria was independently associated with smoking. In summary, smokers with treated hypertension show a higher proportion of LVH (men), microalbuminuria and worse diastolic BP control than non-smokers. This may hypothetically reflect either less compliance with drug treatment in smokers or that smoking impairs the pharmacological effects of antihypertensive drugs.

An emerging role for calcium sensitisation in the treatment of heart failure.

Heart failure occurs in 2 - 3% of the adult population in the developed world. With decompensation of cardiac function, haemodynamic stability can be achieved by using intravenous vasodilators, diuretics and inotropes. Unlike traditional inotropes, Ca2+ sensitisers enhance cardiac function without significantly increasing cardiac oxygen consumption, promoting arrhythmia or impairing lusitropy. The most promising drug in this new class is levosimendan, which has a unique dual mechanism; it enhances cardiac output through a Ca(2+)-dependent stabilisation of cardiac myofilaments and exhibits vasodilatory effects by opening ATP-dependent K(+) channels. Clinical trials have demonstrated the beneficial haemodynamic effects of levosimendan, and prospective trials are currently underway to confirm its potential benefits on long-term prognosis. Updated guidelines from the European Society of Cardiology advise on how to incorporate levosimendan into care for patients who have acute heart failure.

Better knowledge improves adherence to lifestyle changes and medication in patients with coronary heart disease.

BACKGROUND: Many patients with coronary heart disease (CHD) are not managed adequately, and we often fail to reach treatment targets. AIM: To investigate if knowledge of risk factors for CHD, measured by a questionnaire, would show any relation to advice to compliance to lifestyle changes to attain treatment goals and adherence to drug therapy. METHOD: Men and women <71 years who had had a cardiac event were screened consecutively (509) from the medical records. Responders (392) were interviewed, examined and received a questionnaire. Three hundred and forty-seven patients answered the questionnaire regarding their general knowledge of risk factors for CHD, compliance to lifestyle changes to attain treatment goals and adherence to drug therapy. RESULTS: There were statistically significant correlations between general knowledge about risk factors for CHD and compliance to certain lifestyle changes: weight, physical activity, stress management, diet, attainment of lipid level goals and the likelihood of taking prescribed blood pressure-lowering drugs. General knowledge of risk factors had no correlation to blood glucose or blood pressure levels nor on smoking habits or treatment patterns for prescribed lipid- and blood glucose-lowering drugs. CONCLUSION: Knowledge correlates to patient behaviour with respect to some risk factors, which should be recognised in preventive programs.

Cheyne-Stokes respiration in patients hospitalised for heart failure.

BACKGROUND: Previous studies showing a strong relationship between Cheyne-Stokes respiration and the severity of left ventricular systolic dysfunction have usually been done in selected patient populations with lower age and a higher proportion of males than the "typical" in-hospital patient with heart failure. The purpose of the present study was test the strength of this relationship in unselected patients admitted to hospital due to decompensated chronic heart failure. METHODS: We evaluated 191 patients (32% women), mean age 73 years, ready for discharge from the heart failure unit in the University Hospital of Malmo, Sweden. The patients underwent echocardiography for determination of left ventricular ejection fraction and left ventricular inner diastolic diameter. A respiratory investigation during sleep was performed the last night before discharge. RESULTS: We found that 66% of the patients had Cheyne-Stokes respiration more than 10% of the total recording time. Only 7 (3.6%) of the patients had predominantly obstructive apnoeas. There was a significant but very weak relationship between left ventricular ejection fraction and left ventricular inner diastolic diameter on one hand and Cheyne-Stokes respiration on the other. Age was a stronger determinant of Cheyne-Stokes respiration than any of the cardiac or other clinical variables. CONCLUSION: Although presence of Cheyne-Stokes respiration indicates left ventricular dysfunction, its severity seems only weakly related to the severity of heart failure. Age was found to be a stronger determinant, which may reflect the underlying age-dependency found also in healthy subjects. Due to age restrictions or other selection criteria, the importance of age may have been underestimated in many previous studies on factors associated with Cheyne-Stokes respiration.

A description of the clinical characteristics at baseline of patients recruited into the Carvedilol or Metoprolol European Trial (COMET).

BACKGROUND & AIMS: The COMET trial was a prospective, double-blind, randomised trial comparing carvedilol, a comprehensive adrenergic receptor antagonist, with metoprolol, a beta-1-selective agent in patients with heart failure and left ventricular systolic dysfunction. The trial showed a reduction in mortality with carvedilol that was consistent across subgroups. The purpose of this report is to describe in greater detail the heterogeneity of this population at baseline with particular reference to the impact of symptomatic severity, age and gender on patient characteristics. METHODS: A descriptive report using data entered in the COMET study data-base. RESULTS: The characteristics of the population studied were similar to those reported in previous trials of beta-blockers. Almost all patients were receiving diuretics and ACE inhibitors with few patients taking angiotensin receptor blockers. As expected, older patients had more co-morbidity. Older patients and women reported worse symptoms and poorer well-being despite similar ventricular dimensions and systolic dysfunction. NT-proBNP was higher in patients with more severe symptoms and older patients but not in women, although differences in NT-proBNP may have been confounded by differences in renal function. CONCLUSION: Age and gender, as well as the severity of cardiac dysfunction, appear to have an important effect on the severity of heart failure symptoms and patient 'well-being'. This could have important implications for the relationship between symptoms and prognosis and therefore the way in which patients are selected for clinical trials and the goals of treatment. This will be the subject of further analyses.