Clinical burden and health service challenges of chronic heart failure

Heart failure and left ventricular systolic dysfunction (LVSD) are increasingly important chronic disease syndromes that are associated with a poor prognosis, a very poor quality of life, and among the highest healthcare costs for a single condition.22,41 Annual mortality rates in severe heart failure are approximately 60%.14 In the general population, where all grades of heart failure are represented, the 5-year mortality is around 42%.30 Where the diagnosis of heart failure is established during hospital admission, the 5-year mortality is higher, at 50–75%.24,36 The earliest studies of heart failure prevalence adopted clinical diagnostic criteria, which are known to be inaccurate, particularly early in the disease process.9,43 More recent studies of prevalence included objective assessments of LV function, usually with echocardiography. These studies reported a prevalence for LVSD of 2.9% in patients under 75 years and up to 7.5% in those aged 75–84 years.34,39 However, there were limitations also to these studies, including a lack of screening in all adult age groups, with data lacking particularly in the elderly.34,39 In the largest recent prospective evaluation of heart failure in the community (ECHOES), LVSD was present in 1.8% (95% CI 1.4–2.3) of the population aged 45 years or over. Borderline LV dysfunction (i.e. an LV ejection fraction [LVEF] 40–50%) was identified in a further 3.5% (95% CI 3.0–4.1) and definite heart failure in 2.3% (95% CI 1.9–2.8); 41% of the latter had an LVEF <40%.17 Using an LVEF cutoff of <50 rather than <40, 3.1% (95% CI 2.6–3.7) of the population aged 45 years or over had heart failure.17 Annual estimates of heart failure incidence vary from 0.9 to 2.2 cases per 1000 population in women aged 45–74 years and from 1.6 to 4.6 cases per 1000 population in men aged 45–74 years.15,24 The incidence rises rapidly in the elderly, with 1% of men per year developing heart failure after 75 years, increasing to almost 2% per year in those aged over 85 years. Mortality rates in heart failure are high. Annual mortality rates in the placebo arms of recent clinical trials have ranged from 7% in mild heart failure (New York Heart Association [NYHA] grade II), to 11% to 13% in moderate cases (NYHA III), and up to 20%, 23%, or 28% in severe heart failure.17,18,19,36,38,47 By comparison, the Framingham cohort reported an overall one-year mortality rate of 17% for heart failure, which was defined initially based on electrocardiographic [ECG] criteria, but latterly on echocardiography. Two-year and 10-year mortality rates were 30% and 78%, respectively.25 The National Health and Nutrition Examination Survey (NHANES) study, conducted in the United States from 1971–1986, provided 10-year mortality rates of 43% for patients with self-reported heart failure and 38% for patients with heart failure defined by clinical score.50 Mortality data from more recent epidemiological studies provide more reliable case definitions, but report mainly on LVSD heart failure alone, on younger populations, or on patients presenting to hospital, usually with incident symptomatic heart failure.10,35,54. In the latter studies, mortality was particularly high, with a two-year rate of 50%, probably representing late presentations. These rates equate to prognoses for men with newly diagnosed colorectal cancer and for women with ovarian cancer. A more accurate estimate of the prognosis for prevalent heart failure, across all ages and stages, is available from follow-up of the ECHOES cohort.30 The five-year survival rate was 58% for patients with a prevalent diagnosis of LVSD and 58% for those with prevalent definite heart failure, compared to 93% in the general population. The median survival time for patients with definite heart failure was 7 years and 7 months. Patients with a prior diagnostic label of heart failure had the lowest survival compared with the general population, and survival improved significantly with increasing ejection fraction. Importantly, mortality rates were significantly lower among patients with ‘borderline’ ejection fraction levels of 40–50%. Indeed, patients with this degree of ‘minor’ systolic impairment suffered mortality rates over 1.5 times higher than those with ejection fractions above 50%. Patients with multiple causes of heart failure had poorer survival. The ECHOES mortality data provide confirmation of the poor prognosis for patients suffering heart failure across the community, providing a generalizable mortality risk estimate of 8–9% per year.30 Importantly, outcomes in heart failure are improving, presumably due to the better initiation and maintenance of evidence-based therapies.56 Morbidity in heart failure is considerable, whether measured by symptom severity, quality of life, need for consultation, treatment, or hospital admission. Studies with comparative normative data are few, but they suggest that heart failure has a greater impact on the patient's quality of life than other chronic diseases and that women may suffer worse impairment than men.13,53 Other studies have shown that heart failure is associated with depressive illness, and that this association is linked with a worse prognosis.23,40 Patients with heart failure have significant impairment of all measured aspects of physical and mental health, and not physical functioning alone. Significantly worse impairment is found in patients with more severe heart failure measured by NYHA class. Patients with asymptomatic left ventricular dysfunction and those rendered asymptomatic by treatment have scores similar to the random population sample. Angiotensin converting enzyme (ACE) inhibitors and beta-blockers have been shown to improve exercise tolerance and symptoms (as assessed by NYHA functional class) in patients with heart failure due to LVSD, as well as to significantly prolong survival and reduce hospitalization rates.21,33 These drugs have also been shown to improve global quality of life,51,52 as have other interventions that produce symptom gains, such as exercise training and intensive nurse-led discharge and outreach programs.49,60 Chronic heart failure remains one of the most costly conditions to manage in many health systems. This is principally because the syndrome is common, frequently results in hospital admission (which is a disproportionate driver of healthcare expenditure), mean admissions are prolonged (averaging 11 days in Europe), and readmission is frequent (nearly 25% of patients are readmitted within 12 weeks of discharge).11 In one hospital in the UK, 4.9% of admissions were for heart failure, which extrapolated to 120 000 admissions per year nationally.55 Admissions continue to rise.20,37 As a consequence, heart failure accounts for at least 2% of total healthcare expenditure,6 representing €26 m per million population in the UK, €37 m per million in Germany, €39 m per million in France, and €70 m per million in the United States. The average cost per hospital admission in Europe is €10 000.37 The burden of heart failure is expected to rise as the prevalence rises, attributable to the improved survival of patients post-myocardial infarction and to better treatment of heart failure once developed.42 ACE inhibitors improve both morbidity and mortality in all grades of symptomatic heart failure due to LVSD.21 In patients with asymptomatic LVSD, these drugs can delay or prevent progression to symptomatic heart failure.44,51 Beta-blocker therapy in heart failure due to LVSD has also been demonstrated to improve prognosis and to reduce admission rates, although these agents have to be introduced slowly and are associated with a slight initial worsening of symptoms in a proportion of patients.2,7 Aldosterone blockers reduce hospitalization and mortality rates in severely symptomatic (NYHA grade II and IV) patients and in those post-MI LVSD.46,47 However, care is needed with these agents in the elderly community, because, if not, they may be associated with increased mortality.32 Recent data have demonstrated the general utility of angiotensin receptor blockers in patients who are intolerant to ACE inhibitors and as additional therapy to ACE inhibitors and beta-blockers in patients with impaired LV function.45 Despite the availability of these treatments, heart failure remains suboptimally diagnosed and treated in many countries.8,27 The explanation is, at least in part, that many patients with suspected heart failure are not receiving formal assessment of LV function.27 An essential element for treatment success is a reliable and precise diagnosis of heart failure. The major issue in diagnosis relates to the definition criteria adopted. Guidelines for the evaluation and management of heart failure are established in both the USA and Europe (ACC/AHA and Consensus Recommendations,31; European Society of Cardiology [ESC],56). These guidelines state that the diagnosis of heart failure is justified when there are typical signs and symptoms of heart failure and myocardial dysfunction, confirmed by objective evidence of cardiac dysfunction at rest. In cases of diagnostic uncertainty, a clinical response to a treatment that is directed at heart failure is helpful in establishing the diagnosis. Simple and reliable diagnostic procedures are very important for primary care physicians, who are responsible for the early diagnosis of heart failure and the implementation of adequate therapy. Unfortunately, primary care physicians in Europe have variable and often delayed access to the most appropriate objective test, namely echocardiography. As a consequence, many physicians believe that they should rely on alternatives to echocardiography, such as ECG or chest X-ray - both of which were used in most heart failure cases in the IMPROVEMENT study.12 A normal ECG recording will exclude left ventricular dysfunction in most patients.16,57 However, ECG changes in heart failure may be subtle and a lack of interpretation skills may require referral for specialist opinion. Chest X-rays are often cited as useful in diagnosis, but a normal result does not exclude heart failure.1,4 Symptoms and signs may indicate the possibility of heart failure, but they are not reliable for establishing the diagnosis.5 It is therefore not surprising that studies exploring the validity of a clinical diagnosis of heart failure in primary care reported high rates of misdiagnosis when patients were also assessed with objective criteria. The accuracy rates of clinical diagnoses ranged from 25% to 50% in different series.26,48,59 Under-diagnosis of heart failure is not confined to primary care physicians, however, as shown in a study where hospital physicians offered echocardiography to only 31% of patients following referral for possible heart failure.3,8 In this context, a potential role has emerged for natriuretic peptides in the diagnosis of heart failure. Natriuretic peptides can be measured by a simple and inexpensive blood test. Numerous studies have demonstrated the feasibility of natriuretic peptide testing, although there are relatively few data confirming the validity of natriuretic peptide testing in the clinical setting where they would be most used, i.e. in adults presenting with persisting breathlessness in the community. What is clear is that maximizing the cutoff values to ensure a high negative predictive value, which is important in the primary care setting, reduces the specificity of the test. For example, both N-terminal brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) assays set at cutoffs to achieve a sensitivity of 100% demonstrated a specificity of 70%, a positive predictive value of 7%, a negative predictive value of 100%, and an area under the receiver operator characteristic curve of 0.92 (95% CI 0.82–1.0) for diagnosing heart failure in the general population.28 The performance of these assays was similar whatever the cause of heart failure, and similar negative predictive values were obtained for diagnosing LVSD.29 These data should be interpreted as showing that a normal level of natriuretic peptide virtually guarantees that heart failure is not present, but that confirmatory echocardiography is needed to confirm the diagnosis in patients with elevated natriuretic peptides. The cost-effectiveness of natriuretic peptides versus standard diagnostic triage is not established. However, natriuretic peptides may also have an important role in guiding therapy, at least in specialist settings, based on the results of small follow-up studies.58 Heart failure is a common disorder, especially in the elderly, and is assuming major significance for both patients and healthcare systems. We need better identification of patients and more intensive attempts to introduce and maintain therapies for which there is a large evidence base. Given the burden of disease, however, prevention of heart failure is a priority and this requires formalized programs of cardiovascular prevention.