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Heart Failure

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Definition
Heart failure occurs when abnormal cardiac function causes failure of the heart to pump blood at a rate sufficient for metabolic requirements under normal filling pressure. It is characterised clinically by breathlessness, effort intolerance, fluid retention, and poor survival. Fluid retention and the congestion related to this can often be relieved with diuretic therapy. However, diuretic therapy should generally not be used alone and, if required, should be combined with the pharmacological therapies outlined in this review. Heart failure can be caused by systolic or diastolic dysfunction, and is associated with neurohormonal changes. [1] Left ventricular systolic dysfunction (LVSD) is defined as a left ventricular ejection fraction (LVEF) below 0.40. It may be symptomatic or asymptomatic. Defining and diagnosing diastolic heart failure can be difficult. Recently proposed criteria include: (1) clinical evidence of heart failure; (2) normal or mildly abnormal left ventricular systolic function; (3) evidence of abnormal left ventricular relaxation, filling, diastolic distensibility, or diastolic stiffness; and (4) evidence of elevated N-terminal-probrain natriuretic peptide. [2] However, assessment of some of these criteria is not standardised
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Cardiovascular disorders

Heart failure

Robert McKelvie
• Interventions
• Key points
• About this condition
• Updates (62)
• Guidelines (28)
• References
• Your responses

In this section:

Definition | Incidence / Prevalence | Aetiology / Risk factors | Prognosis | Aims of intervention | Outcomes | Methods
Top

Definition

Heart failure occurs when abnormal cardiac function causes failure of the heart to pump blood at a rate sufficient for metabolic requirements under normal filling pressure. It is characterised clinically by breathlessness, effort intolerance, fluid retention, and poor survival. Fluid retention and the congestion related to this can often be relieved with diuretic therapy. However, diuretic therapy should generally not be used alone and, if required, should be combined with the pharmacological therapies outlined in this review. Heart failure can be caused by systolic or diastolic dysfunction, and is associated with neurohormonal changes. [1] Left ventricular systolic dysfunction (LVSD) is defined as a left ventricular ejection fraction (LVEF) below 0.40. It may be symptomatic or asymptomatic. Defining and diagnosing diastolic heart failure can be difficult. Recently proposed criteria include: (1) clinical evidence of heart failure; (2) normal or mildly abnormal left ventricular systolic function; (3) evidence of abnormal left ventricular relaxation, filling, diastolic distensibility, or diastolic stiffness; and (4) evidence of elevated N-terminal-probrain natriuretic peptide. [2] However, assessment of some of these criteria is not standardised.
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Incidence / Prevalence

Both incidence and prevalence of heart failure increase with age. Studies of heart failure in the US and UK found annual incidence in people 45 years or over to be between 29 and 32 cases/1000 persons/year, and, in those over 85 years of age, incidence was considerably higher, at 45 to 90 cases/1000 persons/year. [3] [4] The study carried out in the US reported a decline in incidence of heart failure (all age groups) over a 10-year period, with incidence falling from 32.2 cases/1000 persons/year in 1994 to 29.1 cases/1000 persons/year in 2003. [4] However, analysis of those aged 65 years or over indicated an increase in prevalence of heart failure (from 89.9 cases/1000 people in 1994 to 121 cases/1000 people in 2003). Prevalence of heart failure was higher in men (130 cases/1000 men) compared with women (115 cases/1000 women). [4] In older people (65 years or over), incidence of heart failure after a myocardial infarction (MI) is on the rise, with one study finding an increase of 25.1% in in-hospital heart failure (from 31.4% to 39.3%, P = 0.001). [5]Furthermore, the study noted that 76% of people who survived MI had developed heart failure at 5 years' follow-up. Prevalence of asymptomatic LVSD is 3% in the general population, and the mean age of people with asymptomatic LVSD is lower than that of symptomatic individuals. [6] Both heart failure and asymptomatic LVSD are more common in men. [6] Prevalence of diastolic heart failure in the community is unknown. Prevalence of heart failure with preserved systolic function in people in hospital with clinical heart failure varies from 13% to 74%. [7] [8] Less than 15% of people with heart failure under 65 years of age have normal systolic function, whereas prevalence is about 40% in people over 65 years of age. [7]
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Aetiology / Risk factors

Coronary artery disease is the most common cause of heart failure. [9] Other common causes include hypertension and idiopathic dilated congestive cardiomyopathy. After adjustment for hypertension, the presence of left ventricular hypertrophy remains a risk factor for the development of heart failure. Other risk factors include cigarette smoking, hyperlipidaemia, and diabetes mellitus. [6] The common causes of left ventricular diastolic dysfunction are coronary artery disease and systemic hypertension. Other causes are hypertrophic cardiomyopathy, restrictive or infiltrative cardiomyopathies, and valvular heart disease. [8]
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Prognosis

The prognosis of heart failure is poor, with 5-year mortality ranging from 26% to 75%. [9] Up to 16% of people are re-admitted with heart failure within 6 months of first admission. In the US, heart failure is the leading cause of hospital admission among people over 65 years of age. [9] In people with heart failure, a new MI increases the risk of death (RR 7.8, 95% CI 6.9 to 8.8). About one third of all deaths in people with heart failure are preceded by a major ischaemic event. [10] Sudden death, mainly caused by ventricular arrhythmia, is responsible for 25% to 50% of all deaths, and is the most common cause of death in people with heart failure. Women with heart failure have a 15% to 20% lower risk of total and cardiovascular mortality compared with men with heart failure: risk after adjustment for demographic and social economic characteristics, comorbidities, cardiovascular treatments, and LVEF. [11] The presence of asymptomatic LVSD increases an individual's risk of having a cardiovascular event. One large prevention trial found that the risk of heart failure, admission for heart failure, and death increased linearly as ejection fraction fell (for each 5% reduction in ejection fraction: RR for mortality 1.20, 95% CI 1.13 to 1.29; RR for hospital admission 1.28, 95% CI 1.18 to 1.38; RR for heart failure 1.20, 95% CI 1.13 to 1.26). [12] The annual mortality for people with diastolic heart failure varies in observational studies (1–18%). [7] Reasons for this variation include age, presence of coronary artery disease, and variation in the partition value used to define abnormal ventricular systolic function. The annual mortality for left ventricular diastolic dysfunction is lower than that found in people with systolic dysfunction. [12]
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Aims of intervention

To relieve symptoms; to improve quality of life; and to reduce morbidity and mortality with minimum adverse effects.
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Outcomes

Effects of treatments in people with heart failure: mortality; functional capacity(assessed by the New York Heart Association functional classification or more objectively by using standardised exercise testing or the 6-minute walk test); [13]hospital admission rates; quality of life (assessed with questionnaires); [14]adverse effects of treatment. Effects of ACE inhibitors in people at high risk of heart failure: mortality; cardiovascular events (including non-fatal MI); hospital admission rates; adverse effects of treatment. Proxy measures of clinical outcome (e.g., LVEF) are used only when clinical outcomes are unavailable. Where a study reported only the composite outcome of death or hospital admission, we have reported this under hospital admission.
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Methods

Clinical Evidence search and appraisal May 2009. The following databases were used to identify studies for this systematic review (SR): Medline 1966 to May 2009, Embase 1980 to May 2009, and The Cochrane Database of Systematic Reviews 2009, Issue 2 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published SRs of RCTs and RCTs in any language, at least single blinded (unless blinding was impossible), and containing more than 100 individuals of whom more than 80% were followed up. Generally, RCTs with less than 500 people have been excluded because of the number of large RCTs available. If, for any comparison, large RCTs or systematic reviews were found, then smaller RCTs have been excluded, even if they include more than 500 people. Size of follow-up was 80% or more. There was no minimum length of follow-up required to include studies. We included SRs of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review ( see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

References

1. Poole-Wilson PA. History, definition, and classification of heart failure. In: Poole-Wilson PA, Colucci WS, Massie BM, et al, eds. Heart failure. Scientific principles and clinical practice. Churchill Livingston, 1997:269–277. 1. Paulus WJ, Tschope C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007;28:2539−2550. [PubMed] 1. de Giuli F, Khaw KT, Cowie MR, et al. Incidence and outcome of persons with a clinical diagnosis of heart failure in a general practice population of 696,884 in the United Kingdom. Eur J Heart Failure 2005;7:295−302. [PubMed] 1. Curtis LH, Whellan DJ, Hammill BG, et al. Incidence and prevalence of heart failure in elderly persons, 1994-2003. Arch Intern Med 2008;168:418−424. [PubMed] 1. Ezekowitz JA, Kaul P, Bakal JA, et al. Declining in-hospital mortality and increasing heart failure incidence in elderly patients with first myocardial infarction. J Am Coll Cardiol 2009;53:13−20. [PubMed] 1. McKelvie RS, Benedict CR, Yusuf S. Prevention of congestive heart failure and management of asymptomatic left ventricular dysfunction. BMJ1999;318:1400–1402. [PubMed] 1. Vasan RS, Benjamin EJ, Levy D. Congestive heart failure with normal left ventricular systolic function. Arch Intern Med 1996;156:146–157. [PubMed] 1. Davie AP, Francis CM, Caruana L, et al. The prevalence of left ventricular diastolic filling abnormalities in patients with suspected heart failure. Eur Heart J 1997;18:981–984. [PubMed] 1. Cowie MR, Mosterd A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J 1997;18:208–225. [PubMed] 1. Yusuf S, Pepine CJ, Garces C, et al. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet1992;340:1173–1178. [PubMed] 1. Parashar S, Katz R, Smith NL, et al. Race, gender, and mortality in adults > or =65 years of age with incident heart failure (from the Cardiovascular Health Study). Am J Cardiol 2009;103:1120−1127. [PubMed] 1. McKelvie RS, Benedict CR, Yusuf S. Prevention of congestive heart failure and treatment of asymptomatic left ventricular dysfunction. In: Yusuf S, Cairns JA, CammAJ, et al, eds. Evidenced based cardiology. BMJ, 2003:643–658. 1. Bittner V, Weiner DH, Yusuf S, et al, for the SOLVD Investigators. Prediction of mortality and morbidity with a 6-minute walk test in patients with left ventricular dysfunction. JAMA 1993;270:1702–1707. [PubMed] 1. Rogers WJ, Johnstone DE, Yusuf S, et al, for the SOLVD Investigators. Quality of life among 5025 patients with left ventricular dysfunction randomized between placebo and enalapril. The studies of left ventricular dysfunction. J Am Coll Cardiol 1994;23:393–400. [PubMed]

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