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Heart failure: classification and pathophysiology
HEART MUSCLE DISEASE
Heart failure: classification and pathophysiology
What’s new? C
Paul M Haydock Martin R Cowie C
Abstract Heart failure (HF) is a clinical syndrome and not a stand-alone diagnosis e identification of the aetiology of the underlying cardiac abnormality and the whole body’s response to it is key to providing optimal management of the individual patient. The classic triad of clinical features e breathlessness, fatigue and fluid retention e can be the result of any disorder (genetic or acquired) affecting the structure or function of the heart in a manner that impairs its ability to act as an efficient pump. Despite improved understanding of the pathophysiology, and a wider range of therapeutic options, HF remains a serious condition with considerable morbidity and mortality. It is a global problem, though the relative importance of different aetiologies differs between the developed world e where the syndrome is most commonly a consequence of ischaemic heart disease e and the developing world, where rheumatic fever remains an important cause. HF can present either de novo, as a consequence of acute myocardial insult, or in its chronic form, where decompensation secondary to coincident medical problems often requires acute management. The HF syndrome is characterized by cardiac dysfunction with haemodynamic, renal and neurohormonal changes attempting to maintain circulatory homeostasis. Ultimately, such changes are maladaptive and result in excessive sodium and fluid retention, changes in muscle blood flow, altered breathing pattern, arrhythmia, and an inflammatory state with immune activation. Current evidence-based therapies ameliorate these responses and improve survival and quality of life.
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dysfunction. Echocardiography should be performed in all suspected cases, as it is a readily available, reliable method of identifying structural and functional heart disease. Historically, quantification of the extent of any cardiac dysfunction has been made with reference to left ventricular ejection fraction (LVEF), with values of more than 50e60% accepted as normal. However, it is now well recognized that the HF syndrome can present where LVEF is in the normal range (heart failure with preserved ejection fraction [HFPEF]). Diagnosis of HFPEF can be difficult but population studies suggest that up to 50% of cases of incident HF occur with a ‘normal’ LVEF.1 An international consensus on making this clinical diagnosis has recently been reached.2 As with HF where the LVEF is reduced, multiple and distinct underlying aetiologies are responsible for the development of the HF syndrome in HFPEF e hypertension and diabetes are likely to be particularly important.
Keywords demography; epidemiology; heart failure; pathophysiology
Prevalence The overall prevalence of HF is approximately 2% but markedly higher in the elderly, with as many as 15% of those aged over 85 years affected.3 On the basis of population studies performed in the USA and Europe, a conservative estimate is that 4 million Americans and 6 million Europeans currently have HF. Cross-sectional echocardiographic population studies in Europe suggest that approximately 3e4% of the adult population have underlying left ventricular systolic dysfunction (LVSD), rising to 5e6% in the elderly.4 Just under half of these individuals are asymptomatic, with no clinical evidence of the HF syndrome (Figure 1). However, treatment with disease-modifying drug therapy is recommended in these cases to prevent progression to frank HF.
Epidemiology HF is a clinical diagnosis e no ‘gold standard’ diagnostic investigation has been reliably identified, though both resting electrocardiogram (ECG) and measurement of serum natriuretic peptide can be useful as they have high negative predictive value. UK, European and American guidelines exist, and there is broad international agreement that diagnosis of the syndrome should be made on the basis of the symptoms and signs of HF (at rest or during exercise), combined with objective evidence of cardiac
Paul M Haydock MRCP is a Clinical Research Fellow in Cardiology at Imperial College London, UK. Competing interests: none declared.
Incidence The incidence of HF may be determined either by interval reexamination of initially healthy individuals within a cohort, or by undertaking a population-based study in which new cases are prospectively identified by surveillance. The Framingham Heart Study, a large cohort study from the USA, reported an annual incidence of 0.2e0.3% in those aged
Martin R Cowie MD MSc FRCP FESC is Professor of Cardiology at Imperial College London and Honorary Consultant Cardiologist at the Royal Brompton Hospital, London, UK. Competing interests: Dr Cowie provided consultancy advice to companies marketing drugs and devices shown to improve prognosis in randomized trials.
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The prognosis of chronic heart failure (CHF) has improved in the past decade, probably as a result of wider use of drug therapy which modifies the neurohormonal response to cardiac dysfunction (ACE inhibitors, b-blockers, aldosterone antagonists) Electrical device therapy can further improve prognosis and quality of life for selected patients with high risk of sudden death and/or evidence of electrical dyssynchrony The likelihood of hospital admission can be reduced by careful chronic disease monitoring and management by a multidisciplinary team The syndrome of heart failure (HF) with preserved left ventricular (LV) systolic function is increasingly recognized, although effective therapy for this group of patients is still lacking
467
Ó 2010 Elsevier Ltd. All rights reserved.
HEART MUSCLE DISEASE
(Table 1). Coronary artery disease is the single most common cause of HF in the developed world, particularly amongst males and in the elderly population, accounting for approximately twothirds of patients. In the USA, the prevalence of coronary disease and diabetes amongst new cases has risen in recent decades. In contrast, hypertension and valvular heart diseases have decreased in importance, with improved management of blood pressure and the virtual eradication of rheumatic fever in the West. There are few data for developing countries but rheumatic heart disease continues to be a major health problem, particularly in Africa and Asia. Chagas’ disease remains an important cause of HF in South America. In African and African-American populations, hypertension remains the main aetiology of HF in almost half of all cases.
Prevalence of left ventricular systolic dysfunction (EF 30% on transthoracic echocardiography) in the Glasgow MONICA study population 12
Asymptomatic Symptomatic
Prevalence (%)
10
8
6
4
2
Pathophysiology 0
35–44
45–54
55–64
65–74
The most common underlying cardiac abnormality in HF is left ventricular systolic dysfunction, to which the body responds by retaining fluid either in the lungs (pulmonary oedema; previously termed ‘left heart failure’) or in the periphery (previously termed ‘right heart failure’, although only rarely is fluid retention in the periphery due to isolated abnormality of the right side of the heart, e.g. in cor pulmonale). HF may also be classified as ‘acute’ or ‘chronic’, based on the time course of the development of symptoms. The underlying dysfunction of the ventricle may be observed chiefly in systole (‘systolic heart failure’) or in diastole (‘diastolic heart failure’; ‘HFPEF’), although for most patients neither phase of the cardiac cycle is completely normal. The largest evidence base is for systolic HF; recent randomized trials in patients with HFPEF have failed to confirm the benefits of renineangiotensin antagonism which are so clearly evident in systolic HF.
Age group (years) MONICA: Monitoring of Trends and Determinants in Cardiovascular Disease Source: McDonagh T A et al. Lancet 1997; 350: 829–33.4
Figure 1
50e59 years, rising 10-fold in those aged 80e89.5 UK population data are similar, with an annual incidence of 0.12% in those aged 55e64, rising to 1.2% in those aged over 85 (Figure 2). This translates into an estimated 63,000 new cases of HF in the UK each year. The mean age at the time of diagnosis in such studies is 76 years. Incidence is higher in men than in women at all ages (male:female ratio around 1.8:1).6 Aetiology HF is a syndrome, and not a complete diagnosis in itself: it is important to determine the underlying cardiac abnormalities
The clinical syndrome of acute heart failure (AHF) AHF is defined as the rapid onset of symptoms and signs secondary to cardiac dysfunction. It may present as acute de novo HF or as acute decompensation of chronic HF. The underlying cardiac dysfunction can be related to the following factors, either alone or in isolation: systolic or diastolic abnormalities of the left or right ventricle cardiac rhythm disturbance pericardial disease a mismatch in pre-load and after-load The syndrome is characterized by a reduced cardiac output, tissue hypoperfusion, increased pulmonary capillary wedge pressure, and tissue congestion. In its most extreme form it is termed ‘cardiogenic shock’. In rare cases, HF can be transient and reversible but, more often, the cardiac dysfunction is permanent and results in chronic HF. Pulmonary oedema is established when the intravascular pressure (hydrostatic force) exceeds the colloid osmotic pressure (essentially provided by plasma proteins), forcing fluid from the intravascular space into the alveoli. A background of chronically raised intravascular pressure can lead to increased lymphatic drainage, preventing alveolar oedema despite raised intravascular pressure. The onset of pulmonary oedema increases airway resistance, reduces lung compliance and interferes with gas
Incidence (cases per 1000 population per year)
Incidence of heart failure in the Hillingdon Heart Failure study, West London 18 16
Men Women
14 12 10 8 6 4 2 0
25–34
35–44
45–54
55–64
65–74
75–84
85+
Age group (years) Source: Cowie M R. Eur J Heart Fail 1999; 1: 101–7.6
Figure 2
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Ó 2010 Elsevier Ltd. All rights reserved.
HEART MUSCLE DISEASE
Table 1
exchange, leading to breathlessness and hypoxia. The work of breathing is greatly increased and may consume a high proportion of cardiac output. The aim of treatment in acute HF is to re-stabilize the physiology and thereby relieve the symptoms and improve prognosis. If the underlying ventricular dysfunction is at least partially reversible, this task is easier. In the presence of coronary artery disease, there may be a variable amount of ventricular muscle that is non- or poorly contractile, but this may recover in time with the restitution of normal myocardial blood supply. In the context of acute ischaemia, this is termed ‘stunning’, whereas in the more chronic situation it is known as ‘hibernation’. Other reversible causes of AHF include arrhythmia or valve dysfunction, the latter being potentially curable by valve repair or replacement. Where it is not possible to improve the underlying ventricular dysfunction that has precipitated the AHF syndrome, manipulation of ventricular pre-load and after-load, and the neurohormonal response to cardiac dysfunction, may allow resolution of pulmonary oedema and improvement in vital organ perfusion. This ‘acute’ phase may thus merge into the ‘chronic’ HF syndrome.
fatigue and breathlessness, fluid retention and, eventually, cardiac cachexia. The vicious cycles of heart failure Reduced cardiac output decreases renal perfusion, leading to reduced natriuresis and diuresis and increased activation of the renineangiotensinealdosterone system (RAAS). This response helps to maintain cardiac output in the short term, but is harmful in the long term, not only giving rise to symptoms of fluid retention (such as breathlessness and dependent oedema), but causing further damage to the myocardium through fibrosis, apoptosis, and an increased propensity to arrhythmia, mediated chiefly through angiotensin II and aldosterone (Figure 3). Blockade of the action of these two hormones (using ACE inhibitors or angiotensin receptor blockers, and aldosterone antagonists) is of proven prognostic value in heart failure.7e11 The same reduction in cardiac output is detected by reduced wall stress in the arterial baroreceptors, which respond by triggering an increased sympathetic drive, thereby increasing heart rate and myocardial contractility. Activation of the RAAS up-regulates the response of the sympathetic nervous system, enhancing this effect. In the longer term this sympathetic activation, which involves higher circulating concentrations of noradrenaline (norepinephrine), increases strain on the heart and may accelerate the process of left ventricular ‘remodelling’, with progressive dilatation and wall stress (Figure 4). Blocking this ‘compensatory’ mechanism by the gradual introduction and up-titration of b-blockers improves survival.12 In contrast, positive inotropic agents, which improve haemodynamics in the short term, increase mortality in follow-up studies.
The clinical syndrome of chronic heart failure (CHF) Long-term cardiac dysfunction triggers a range of compensatory physiological responses that in the short term help to maintain organ perfusion, but are ultimately maladaptive and result in morbidity. Understanding of the complexity of the syndrome has increased greatly in the past 25 years and it is now clear that marked autonomic, haemodynamic, neurohormonal, and immunological changes occur, and lead to the symptoms of
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Ó 2010 Elsevier Ltd. All rights reserved.
HEART MUSCLE DISEASE
Renin–angiotensin–aldosterone system Angiotensinogen Renin Vasoconstriction Eccentric ventricular hypertrophy Sodium retention Myocardial fibrosis
Angiotensin I Kinin breakdown
ACE ACE-I
Eccentric ventricular hypertrophy Sodium retention Myocardial fibrosis Coronary vasculopathy Cytokine activation
Angiotensin II ARB AA Aldosterone
Angiotensinogen is converted to angiotensin I (catalysed by the release of renin). Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE) leading to the release of aldosterone. ACE also catalyses the breakdown of vasodilatory kinins. Hormonal effects and drug targets are shown. ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blockade; AA, aldosterone antagonist.
Figure 3
Not all of the neurohormonal responses to cardiac dysfunction are harmful. In response to increased myocardial strain, more Btype natriuretic peptide (BNP) is secreted, chiefly by the ventricular myocytes. This peptide acts to increase natriuresis, diuresis and vasodilatation and thus helps to counteract the intense vasoconstriction and fluid retention triggered by other haemodynamic, autonomic and neurohormonal changes.
prognostic and symptomatic value of cardiac resynchronization with atrio-biventricular pacemakers in patients with HF who have reduced LVEF and electrical evidence of dyssynchrony.13 Atrial fibrillation and other arrhythmias Atrial fibrillation (AF), either persistent or paroxysmal, is common in patients with HF.14 Raised atrial pressure is common and results in a propensity to AF, the onset of which may result in the development of the AHF syndrome. Less commonly, chronic rapid and irregular cardiac contraction may lead to structural changes in myocytes and the ultimate development of a ‘tachycardia-associated’ cardiomyopathy. Ventricular arrhythmias are also frequent in patients with HF. The underlying cause is likely to be micro re-entry circuits set up by a combination of factors, including raised sympathetic nervous system and RAAS activity, myocardial necrosis and fibrosis, inhomogeniety of repolarization, frequent ectopy, and
Ventricular dyssynchrony Normal cardiac contraction consists of synchronized contraction of the atria and then both ventricles, with rapid spread of electrical conduction and efficient excitationecontraction coupling throughout the ventricular myocardium. Myocardial dysfunction and consequent remodelling disturbs normal electro-mechanical function and results in atrioventricular, interventricular and/or intraventricular dyssynchrony, with further reduction in pump efficiency. Several clinical trials have demonstrated the
The basic pathophysiology of heart failure due to left ventricular damage Left ventricular failure
Blood pressure
Renal perfusion
Sympathetic activation/norepinephrine release Direct myocardial toxicity
Increased heart rate
Vasoconstriction
O demand
Wall stress
RAAS activation Na/H O reabsorption
Interstitial fibrosis
Other mechanisms at work: • Neurohormonal activation • Cytokine activation • Oxidative stress • Apoptosis • Altered gene expression
Ventricular remodelling RAAS, renin–angiotensin–aldosterone system
Figure 4
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Ó 2010 Elsevier Ltd. All rights reserved.
HEART MUSCLE DISEASE
electrolyte abnormalities. Sudden, presumed arrhythmic, death is a common mode of death in patients with heart failure, particularly those with milder symptoms.15 This risk can be reduced by neurohormonal antagonists, such as b-blockers and aldosterone antagonists, or by device therapy with cardiac resynchronization and/or implantable defibrillators.
absorption are also likely to have a role, along with insulin resistance (loss of anabolic function) and raised levels of TNF-a and noradrenaline (norepinephrine). Exercise training in carefully selected patients with stable mild-to-moderate CHF can improve symptoms and exercise tolerance.20
Prognosis Renal dysfunction Many patients with HF have at least moderate renal impairment, with a glomerular filtration rate less than 60 ml/min/1.72 m2 body surface area. This is usually the result of an ageing kidney with low perfusion and high venous pressure, but pre-existing damage as a result of diabetes or hypertension may exacerbate this problem in some patients.16 Renal perfusion may worsen with intense diuretic therapy, hypotension, and RAAS antagonism. The situation may also be compounded by co-existing renal artery stenosis in individuals with extensive atherosclerosis. A vicious cycle of progressive cardiac and renal dysfunction (‘the cardiorenal syndrome’) has been recognized and is associated with a poor prognosis.
The prognosis of HF is poor, with a particularly high early mortality. UK data demonstrate a 6-month mortality rate of 30%, and over 40% of patients do not survive 18 months from the time of diagnosis.21 This prognosis is worse than many common malignancies, such as breast or colorectal cancer. Recent data from North America and Europe suggest that survival may be improving.22 presumably related to the wider use of angiotensin-converting enzyme (ACE) inhibitors and b-blockers; however, overall prognosis remains poor, with 5-year mortality rates of around 50%.23
Hospitalization Each year, 0.2% of the UK population are hospitalized for HF, accounting for 4e5% of all adult medical admissions. The average length of hospital stay is 9.5 days, second only to stroke admissions. HF is also associated with high rates of repeat admission e approximately one-third of patients are re-admitted within 12 months of initial hospital discharge. Chronic disease monitoring, both by the patient and the heart failure medical/nursing team, can reduce the risk of hospitalization and improve prognosis.24
Anaemia Many patients with moderate-to-severe HF will develop anaemia of chronic disease. The mechanism appears to relate to changes in iron handling and sensitivity of the red blood cell precursors to erythropoietin, the hormone produced by the renal cortex in response to hypoxia. Chronic renal dysfunction can lead to reduced erythropoietin production and further worsening of anaemia. Trials of intravenous iron replacement in those with iron deficiency suggest improvement in symptoms and reduced need for hospitalization,17 although the additional use of synthetic erythropoietin may be harmful. Other causes of anaemia in patients with heart failure, such as poor diet or gastrointestinal blood loss, should not be overlooked.
Cost HF accounts for around 2% of healthcare expenditure in Europe and North America; up to 75% of this relates to the cost of hospitalization.
Cardiac cachexia and metabolic abnormalities Severe HF can cause cachexia, with a general loss of fat, and lean and bony tissue. Such patients have a particularly poor prognosis.18 Cachexia is usually associated with neurohormonal and immunological changes, including raised plasma concentrations of adrenaline (epinephrine), noradrenaline (norepinephrine), cortisol, renin, aldosterone and inflammatory cytokines, such as tumour necrosis factor (TNF)-a, interleukins 1 and 6, interferong and transforming growth factor (TGF)-b. The mechanism of such immune activation is not clear but may be related to endotoxin absorption from the oedematous gut.19 Elevated plasma urate concentrations (which may trigger gout) in patients with severe HF reflect a poor prognosis. This elevation is usually explained by diuretic use, renal dysfunction, and subtle changes in urate metabolism.
Future trends Several studies in the developed world predict a 50e70% increase in the prevalence of HF over the next two decades. The prognosis of HF appears to be improving, presumably related to wider (although still inadequate) use of life-prolonging therapies, such as ACE inhibitors and b-blockers. Improved uptake of such therapies, combined with treatment using electrical devices shown to improve prognosis for selected patients, should lead to further benefit. Better chronic disease monitoring, allowing early detection of deterioration and access to a multidisciplinary healthcare team, is also likely to improve prognosis and reduce the need for hospitalization in the increasing number of people living with this condition.25 A
Skeletal muscle abnormalities Skeletal muscle is abnormal in CHF with a loss of bulk (wasting), impaired intrinsic perfusion, increased (and earlier) fatigue and underlying abnormal histology and metabolism. The underlying abnormalities and degree of wasting correlate with symptoms of fatigue, exercise intolerance and poor prognosis. Patients with HF and substantial skeletal muscle wasting demonstrate exaggerated release of catabolic cytokines and resistance to growth hormone. Physical inactivity, anorexia and poor intestinal
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REFERENCES 1 Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355: 251e9. 2 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: 2539e50.
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Ó 2010 Elsevier Ltd. All rights reserved.
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3 Davies M, Hobbs F, Davis R, et al. Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study. Lancet 2001; 358: 439. 4 McDonagh TA, Morrison CE, Lawrence A, et al. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population. Lancet 1997; 350: 829e33. 5 Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993; 22: 6e13. 6 Cowie MR. Annotated references in epidemiology. Eur J Heart Fail 1999; 1: 101e7. 7 Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med 1987; 316: 1429e35. 8 Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991; 325: 293e302. 9 Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003; 362: 759e66. 10 Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709e17. 11 Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309e21. 12 The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353: 9e13. 13 Cleland JGF, Daubert J-C, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005; 352: 1539e49. 14 Cleland JGF, Swedberg K, Follath F, et al. The EuroHeart failure survey programme e a survey on the quality of care among patients with heart failure in Europe: Part 1: patient characteristics and diagnosis. Eur Heart J 2003; 24: 442e63. 15 Mehta PA, Dubrey SW, McIntyre HF, et al. Mode of death in patients with newly diagnosed heart failure in the general population. Eur J Heart Fail 2008; 10: 1108e16. 16 Damman K, Navis G, Smilde TDJ, et al. Decreased cardiac output, venous congestion and the association with renal impairment in patients with cardiac dysfunction. Eur J Heart Fail 2007; 9: 872e8. 17 Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency. FERRIC-HF: a Randomized, Controlled, Observer-Blinded Trial. J Am Coll Cardiol 2008; 51: 103e12. 18 von Haehling S, Lainscak M, Springer J, Anker SD. Cardiac cachexia: a systematic overview. Pharmacol Ther 2009; 121: 227e52. 19 Heymans S, Hirsch E, Anker SD, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2009; 11: 119e29. 20 O’Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION Randomized Controlled Trial. JAMA 2009; 301: 1439e50. 21 Cowie MR, Wood DA, Coats AJS, et al. Survival of patients with a new diagnosis of heart failure: a population based study. Heart 2000; 83: 505e10.
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22 Mehta PA, Dubrey SW, McIntyre HF, et al. Improving survival in the 6 months after diagnosis of heart failure in the past decade: population-based data from the UK. Heart 2009; 95: 1851. 23 Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002; 347: 1397e402. 24 Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995; 333: 1190e5. 25 McAlister FA, Stewart S, Ferrua S, McMurray JJJV. Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials. J Am Coll Cardiol 2004; 44: 810e19. FURTHER READING Authors/Task Force Members, Dickstein K, Cohen-Solal A, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29: 2388e442. British Heart Foundation statistics website. www.heartstats.org Francis GS. Pathophysiology of chronic heart failure. Am J Med 2001; 110 (suppl): 37Se46. Gheorghiade M, Pang PS. Acute heart failure syndromes. J Am Coll Cardiol 2009; 53: 557e73. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart 2007; 93: 1137e46.
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The prevalence of HF is rising, mainly as a result of the ageing population and improved treatment of acute manifestations of coronary artery disease Coronary artery disease (often associated with hypertension) is the single most common cause of HF in the developed world HF can result from systolic or diastolic dysfunction of the left (and/or right) ventricle, valve disease, arrhythmia, pericardial disease, or a combination of these problems HF is associated with a poor prognosis, with an 18-month mortality of at least 40%, although this has improved in the past decade HF is associated with haemodynamic, autonomic, and neurohormonal changes which accelerate decline in cardiac and total body function Better understanding of the pathophysiology of HF caused by LV systolic dysfunction has led to effective therapies, such as angiotensin-converting enzyme inhibitors, b-blockers and aldosterone antagonists HF can be associated with ventricular dyssynchrony and cardiac arrhythmias, which can be treated with electrical devices in addition to appropriate use of ACE inhibitors, bblockers and aldosterone antagonists HF is often associated with renal dysfunction, anaemia, skeletal muscle abnormalities and (in advanced cases) cachexia
Ó 2010 Elsevier Ltd. All rights reserved.
Heart failure: classification and pathophysiology
What’s new? C
Paul M Haydock Martin R Cowie C
Abstract Heart failure (HF) is a clinical syndrome and not a stand-alone diagnosis e identification of the aetiology of the underlying cardiac abnormality and the whole body’s response to it is key to providing optimal management of the individual patient. The classic triad of clinical features e breathlessness, fatigue and fluid retention e can be the result of any disorder (genetic or acquired) affecting the structure or function of the heart in a manner that impairs its ability to act as an efficient pump. Despite improved understanding of the pathophysiology, and a wider range of therapeutic options, HF remains a serious condition with considerable morbidity and mortality. It is a global problem, though the relative importance of different aetiologies differs between the developed world e where the syndrome is most commonly a consequence of ischaemic heart disease e and the developing world, where rheumatic fever remains an important cause. HF can present either de novo, as a consequence of acute myocardial insult, or in its chronic form, where decompensation secondary to coincident medical problems often requires acute management. The HF syndrome is characterized by cardiac dysfunction with haemodynamic, renal and neurohormonal changes attempting to maintain circulatory homeostasis. Ultimately, such changes are maladaptive and result in excessive sodium and fluid retention, changes in muscle blood flow, altered breathing pattern, arrhythmia, and an inflammatory state with immune activation. Current evidence-based therapies ameliorate these responses and improve survival and quality of life.
C
C
dysfunction. Echocardiography should be performed in all suspected cases, as it is a readily available, reliable method of identifying structural and functional heart disease. Historically, quantification of the extent of any cardiac dysfunction has been made with reference to left ventricular ejection fraction (LVEF), with values of more than 50e60% accepted as normal. However, it is now well recognized that the HF syndrome can present where LVEF is in the normal range (heart failure with preserved ejection fraction [HFPEF]). Diagnosis of HFPEF can be difficult but population studies suggest that up to 50% of cases of incident HF occur with a ‘normal’ LVEF.1 An international consensus on making this clinical diagnosis has recently been reached.2 As with HF where the LVEF is reduced, multiple and distinct underlying aetiologies are responsible for the development of the HF syndrome in HFPEF e hypertension and diabetes are likely to be particularly important.
Keywords demography; epidemiology; heart failure; pathophysiology
Prevalence The overall prevalence of HF is approximately 2% but markedly higher in the elderly, with as many as 15% of those aged over 85 years affected.3 On the basis of population studies performed in the USA and Europe, a conservative estimate is that 4 million Americans and 6 million Europeans currently have HF. Cross-sectional echocardiographic population studies in Europe suggest that approximately 3e4% of the adult population have underlying left ventricular systolic dysfunction (LVSD), rising to 5e6% in the elderly.4 Just under half of these individuals are asymptomatic, with no clinical evidence of the HF syndrome (Figure 1). However, treatment with disease-modifying drug therapy is recommended in these cases to prevent progression to frank HF.
Epidemiology HF is a clinical diagnosis e no ‘gold standard’ diagnostic investigation has been reliably identified, though both resting electrocardiogram (ECG) and measurement of serum natriuretic peptide can be useful as they have high negative predictive value. UK, European and American guidelines exist, and there is broad international agreement that diagnosis of the syndrome should be made on the basis of the symptoms and signs of HF (at rest or during exercise), combined with objective evidence of cardiac
Paul M Haydock MRCP is a Clinical Research Fellow in Cardiology at Imperial College London, UK. Competing interests: none declared.
Incidence The incidence of HF may be determined either by interval reexamination of initially healthy individuals within a cohort, or by undertaking a population-based study in which new cases are prospectively identified by surveillance. The Framingham Heart Study, a large cohort study from the USA, reported an annual incidence of 0.2e0.3% in those aged
Martin R Cowie MD MSc FRCP FESC is Professor of Cardiology at Imperial College London and Honorary Consultant Cardiologist at the Royal Brompton Hospital, London, UK. Competing interests: Dr Cowie provided consultancy advice to companies marketing drugs and devices shown to improve prognosis in randomized trials.
MEDICINE 38:9
The prognosis of chronic heart failure (CHF) has improved in the past decade, probably as a result of wider use of drug therapy which modifies the neurohormonal response to cardiac dysfunction (ACE inhibitors, b-blockers, aldosterone antagonists) Electrical device therapy can further improve prognosis and quality of life for selected patients with high risk of sudden death and/or evidence of electrical dyssynchrony The likelihood of hospital admission can be reduced by careful chronic disease monitoring and management by a multidisciplinary team The syndrome of heart failure (HF) with preserved left ventricular (LV) systolic function is increasingly recognized, although effective therapy for this group of patients is still lacking
467
Ó 2010 Elsevier Ltd. All rights reserved.
HEART MUSCLE DISEASE
(Table 1). Coronary artery disease is the single most common cause of HF in the developed world, particularly amongst males and in the elderly population, accounting for approximately twothirds of patients. In the USA, the prevalence of coronary disease and diabetes amongst new cases has risen in recent decades. In contrast, hypertension and valvular heart diseases have decreased in importance, with improved management of blood pressure and the virtual eradication of rheumatic fever in the West. There are few data for developing countries but rheumatic heart disease continues to be a major health problem, particularly in Africa and Asia. Chagas’ disease remains an important cause of HF in South America. In African and African-American populations, hypertension remains the main aetiology of HF in almost half of all cases.
Prevalence of left ventricular systolic dysfunction (EF 30% on transthoracic echocardiography) in the Glasgow MONICA study population 12
Asymptomatic Symptomatic
Prevalence (%)
10
8
6
4
2
Pathophysiology 0
35–44
45–54
55–64
65–74
The most common underlying cardiac abnormality in HF is left ventricular systolic dysfunction, to which the body responds by retaining fluid either in the lungs (pulmonary oedema; previously termed ‘left heart failure’) or in the periphery (previously termed ‘right heart failure’, although only rarely is fluid retention in the periphery due to isolated abnormality of the right side of the heart, e.g. in cor pulmonale). HF may also be classified as ‘acute’ or ‘chronic’, based on the time course of the development of symptoms. The underlying dysfunction of the ventricle may be observed chiefly in systole (‘systolic heart failure’) or in diastole (‘diastolic heart failure’; ‘HFPEF’), although for most patients neither phase of the cardiac cycle is completely normal. The largest evidence base is for systolic HF; recent randomized trials in patients with HFPEF have failed to confirm the benefits of renineangiotensin antagonism which are so clearly evident in systolic HF.
Age group (years) MONICA: Monitoring of Trends and Determinants in Cardiovascular Disease Source: McDonagh T A et al. Lancet 1997; 350: 829–33.4
Figure 1
50e59 years, rising 10-fold in those aged 80e89.5 UK population data are similar, with an annual incidence of 0.12% in those aged 55e64, rising to 1.2% in those aged over 85 (Figure 2). This translates into an estimated 63,000 new cases of HF in the UK each year. The mean age at the time of diagnosis in such studies is 76 years. Incidence is higher in men than in women at all ages (male:female ratio around 1.8:1).6 Aetiology HF is a syndrome, and not a complete diagnosis in itself: it is important to determine the underlying cardiac abnormalities
The clinical syndrome of acute heart failure (AHF) AHF is defined as the rapid onset of symptoms and signs secondary to cardiac dysfunction. It may present as acute de novo HF or as acute decompensation of chronic HF. The underlying cardiac dysfunction can be related to the following factors, either alone or in isolation: systolic or diastolic abnormalities of the left or right ventricle cardiac rhythm disturbance pericardial disease a mismatch in pre-load and after-load The syndrome is characterized by a reduced cardiac output, tissue hypoperfusion, increased pulmonary capillary wedge pressure, and tissue congestion. In its most extreme form it is termed ‘cardiogenic shock’. In rare cases, HF can be transient and reversible but, more often, the cardiac dysfunction is permanent and results in chronic HF. Pulmonary oedema is established when the intravascular pressure (hydrostatic force) exceeds the colloid osmotic pressure (essentially provided by plasma proteins), forcing fluid from the intravascular space into the alveoli. A background of chronically raised intravascular pressure can lead to increased lymphatic drainage, preventing alveolar oedema despite raised intravascular pressure. The onset of pulmonary oedema increases airway resistance, reduces lung compliance and interferes with gas
Incidence (cases per 1000 population per year)
Incidence of heart failure in the Hillingdon Heart Failure study, West London 18 16
Men Women
14 12 10 8 6 4 2 0
25–34
35–44
45–54
55–64
65–74
75–84
85+
Age group (years) Source: Cowie M R. Eur J Heart Fail 1999; 1: 101–7.6
Figure 2
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Table 1
exchange, leading to breathlessness and hypoxia. The work of breathing is greatly increased and may consume a high proportion of cardiac output. The aim of treatment in acute HF is to re-stabilize the physiology and thereby relieve the symptoms and improve prognosis. If the underlying ventricular dysfunction is at least partially reversible, this task is easier. In the presence of coronary artery disease, there may be a variable amount of ventricular muscle that is non- or poorly contractile, but this may recover in time with the restitution of normal myocardial blood supply. In the context of acute ischaemia, this is termed ‘stunning’, whereas in the more chronic situation it is known as ‘hibernation’. Other reversible causes of AHF include arrhythmia or valve dysfunction, the latter being potentially curable by valve repair or replacement. Where it is not possible to improve the underlying ventricular dysfunction that has precipitated the AHF syndrome, manipulation of ventricular pre-load and after-load, and the neurohormonal response to cardiac dysfunction, may allow resolution of pulmonary oedema and improvement in vital organ perfusion. This ‘acute’ phase may thus merge into the ‘chronic’ HF syndrome.
fatigue and breathlessness, fluid retention and, eventually, cardiac cachexia. The vicious cycles of heart failure Reduced cardiac output decreases renal perfusion, leading to reduced natriuresis and diuresis and increased activation of the renineangiotensinealdosterone system (RAAS). This response helps to maintain cardiac output in the short term, but is harmful in the long term, not only giving rise to symptoms of fluid retention (such as breathlessness and dependent oedema), but causing further damage to the myocardium through fibrosis, apoptosis, and an increased propensity to arrhythmia, mediated chiefly through angiotensin II and aldosterone (Figure 3). Blockade of the action of these two hormones (using ACE inhibitors or angiotensin receptor blockers, and aldosterone antagonists) is of proven prognostic value in heart failure.7e11 The same reduction in cardiac output is detected by reduced wall stress in the arterial baroreceptors, which respond by triggering an increased sympathetic drive, thereby increasing heart rate and myocardial contractility. Activation of the RAAS up-regulates the response of the sympathetic nervous system, enhancing this effect. In the longer term this sympathetic activation, which involves higher circulating concentrations of noradrenaline (norepinephrine), increases strain on the heart and may accelerate the process of left ventricular ‘remodelling’, with progressive dilatation and wall stress (Figure 4). Blocking this ‘compensatory’ mechanism by the gradual introduction and up-titration of b-blockers improves survival.12 In contrast, positive inotropic agents, which improve haemodynamics in the short term, increase mortality in follow-up studies.
The clinical syndrome of chronic heart failure (CHF) Long-term cardiac dysfunction triggers a range of compensatory physiological responses that in the short term help to maintain organ perfusion, but are ultimately maladaptive and result in morbidity. Understanding of the complexity of the syndrome has increased greatly in the past 25 years and it is now clear that marked autonomic, haemodynamic, neurohormonal, and immunological changes occur, and lead to the symptoms of
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Renin–angiotensin–aldosterone system Angiotensinogen Renin Vasoconstriction Eccentric ventricular hypertrophy Sodium retention Myocardial fibrosis
Angiotensin I Kinin breakdown
ACE ACE-I
Eccentric ventricular hypertrophy Sodium retention Myocardial fibrosis Coronary vasculopathy Cytokine activation
Angiotensin II ARB AA Aldosterone
Angiotensinogen is converted to angiotensin I (catalysed by the release of renin). Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE) leading to the release of aldosterone. ACE also catalyses the breakdown of vasodilatory kinins. Hormonal effects and drug targets are shown. ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blockade; AA, aldosterone antagonist.
Figure 3
Not all of the neurohormonal responses to cardiac dysfunction are harmful. In response to increased myocardial strain, more Btype natriuretic peptide (BNP) is secreted, chiefly by the ventricular myocytes. This peptide acts to increase natriuresis, diuresis and vasodilatation and thus helps to counteract the intense vasoconstriction and fluid retention triggered by other haemodynamic, autonomic and neurohormonal changes.
prognostic and symptomatic value of cardiac resynchronization with atrio-biventricular pacemakers in patients with HF who have reduced LVEF and electrical evidence of dyssynchrony.13 Atrial fibrillation and other arrhythmias Atrial fibrillation (AF), either persistent or paroxysmal, is common in patients with HF.14 Raised atrial pressure is common and results in a propensity to AF, the onset of which may result in the development of the AHF syndrome. Less commonly, chronic rapid and irregular cardiac contraction may lead to structural changes in myocytes and the ultimate development of a ‘tachycardia-associated’ cardiomyopathy. Ventricular arrhythmias are also frequent in patients with HF. The underlying cause is likely to be micro re-entry circuits set up by a combination of factors, including raised sympathetic nervous system and RAAS activity, myocardial necrosis and fibrosis, inhomogeniety of repolarization, frequent ectopy, and
Ventricular dyssynchrony Normal cardiac contraction consists of synchronized contraction of the atria and then both ventricles, with rapid spread of electrical conduction and efficient excitationecontraction coupling throughout the ventricular myocardium. Myocardial dysfunction and consequent remodelling disturbs normal electro-mechanical function and results in atrioventricular, interventricular and/or intraventricular dyssynchrony, with further reduction in pump efficiency. Several clinical trials have demonstrated the
The basic pathophysiology of heart failure due to left ventricular damage Left ventricular failure
Blood pressure
Renal perfusion
Sympathetic activation/norepinephrine release Direct myocardial toxicity
Increased heart rate
Vasoconstriction
O demand
Wall stress
RAAS activation Na/H O reabsorption
Interstitial fibrosis
Other mechanisms at work: • Neurohormonal activation • Cytokine activation • Oxidative stress • Apoptosis • Altered gene expression
Ventricular remodelling RAAS, renin–angiotensin–aldosterone system
Figure 4
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electrolyte abnormalities. Sudden, presumed arrhythmic, death is a common mode of death in patients with heart failure, particularly those with milder symptoms.15 This risk can be reduced by neurohormonal antagonists, such as b-blockers and aldosterone antagonists, or by device therapy with cardiac resynchronization and/or implantable defibrillators.
absorption are also likely to have a role, along with insulin resistance (loss of anabolic function) and raised levels of TNF-a and noradrenaline (norepinephrine). Exercise training in carefully selected patients with stable mild-to-moderate CHF can improve symptoms and exercise tolerance.20
Prognosis Renal dysfunction Many patients with HF have at least moderate renal impairment, with a glomerular filtration rate less than 60 ml/min/1.72 m2 body surface area. This is usually the result of an ageing kidney with low perfusion and high venous pressure, but pre-existing damage as a result of diabetes or hypertension may exacerbate this problem in some patients.16 Renal perfusion may worsen with intense diuretic therapy, hypotension, and RAAS antagonism. The situation may also be compounded by co-existing renal artery stenosis in individuals with extensive atherosclerosis. A vicious cycle of progressive cardiac and renal dysfunction (‘the cardiorenal syndrome’) has been recognized and is associated with a poor prognosis.
The prognosis of HF is poor, with a particularly high early mortality. UK data demonstrate a 6-month mortality rate of 30%, and over 40% of patients do not survive 18 months from the time of diagnosis.21 This prognosis is worse than many common malignancies, such as breast or colorectal cancer. Recent data from North America and Europe suggest that survival may be improving.22 presumably related to the wider use of angiotensin-converting enzyme (ACE) inhibitors and b-blockers; however, overall prognosis remains poor, with 5-year mortality rates of around 50%.23
Hospitalization Each year, 0.2% of the UK population are hospitalized for HF, accounting for 4e5% of all adult medical admissions. The average length of hospital stay is 9.5 days, second only to stroke admissions. HF is also associated with high rates of repeat admission e approximately one-third of patients are re-admitted within 12 months of initial hospital discharge. Chronic disease monitoring, both by the patient and the heart failure medical/nursing team, can reduce the risk of hospitalization and improve prognosis.24
Anaemia Many patients with moderate-to-severe HF will develop anaemia of chronic disease. The mechanism appears to relate to changes in iron handling and sensitivity of the red blood cell precursors to erythropoietin, the hormone produced by the renal cortex in response to hypoxia. Chronic renal dysfunction can lead to reduced erythropoietin production and further worsening of anaemia. Trials of intravenous iron replacement in those with iron deficiency suggest improvement in symptoms and reduced need for hospitalization,17 although the additional use of synthetic erythropoietin may be harmful. Other causes of anaemia in patients with heart failure, such as poor diet or gastrointestinal blood loss, should not be overlooked.
Cost HF accounts for around 2% of healthcare expenditure in Europe and North America; up to 75% of this relates to the cost of hospitalization.
Cardiac cachexia and metabolic abnormalities Severe HF can cause cachexia, with a general loss of fat, and lean and bony tissue. Such patients have a particularly poor prognosis.18 Cachexia is usually associated with neurohormonal and immunological changes, including raised plasma concentrations of adrenaline (epinephrine), noradrenaline (norepinephrine), cortisol, renin, aldosterone and inflammatory cytokines, such as tumour necrosis factor (TNF)-a, interleukins 1 and 6, interferong and transforming growth factor (TGF)-b. The mechanism of such immune activation is not clear but may be related to endotoxin absorption from the oedematous gut.19 Elevated plasma urate concentrations (which may trigger gout) in patients with severe HF reflect a poor prognosis. This elevation is usually explained by diuretic use, renal dysfunction, and subtle changes in urate metabolism.
Future trends Several studies in the developed world predict a 50e70% increase in the prevalence of HF over the next two decades. The prognosis of HF appears to be improving, presumably related to wider (although still inadequate) use of life-prolonging therapies, such as ACE inhibitors and b-blockers. Improved uptake of such therapies, combined with treatment using electrical devices shown to improve prognosis for selected patients, should lead to further benefit. Better chronic disease monitoring, allowing early detection of deterioration and access to a multidisciplinary healthcare team, is also likely to improve prognosis and reduce the need for hospitalization in the increasing number of people living with this condition.25 A
Skeletal muscle abnormalities Skeletal muscle is abnormal in CHF with a loss of bulk (wasting), impaired intrinsic perfusion, increased (and earlier) fatigue and underlying abnormal histology and metabolism. The underlying abnormalities and degree of wasting correlate with symptoms of fatigue, exercise intolerance and poor prognosis. Patients with HF and substantial skeletal muscle wasting demonstrate exaggerated release of catabolic cytokines and resistance to growth hormone. Physical inactivity, anorexia and poor intestinal
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REFERENCES 1 Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355: 251e9. 2 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: 2539e50.
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3 Davies M, Hobbs F, Davis R, et al. Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study. Lancet 2001; 358: 439. 4 McDonagh TA, Morrison CE, Lawrence A, et al. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population. Lancet 1997; 350: 829e33. 5 Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993; 22: 6e13. 6 Cowie MR. Annotated references in epidemiology. Eur J Heart Fail 1999; 1: 101e7. 7 Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med 1987; 316: 1429e35. 8 Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991; 325: 293e302. 9 Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003; 362: 759e66. 10 Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709e17. 11 Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309e21. 12 The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353: 9e13. 13 Cleland JGF, Daubert J-C, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005; 352: 1539e49. 14 Cleland JGF, Swedberg K, Follath F, et al. The EuroHeart failure survey programme e a survey on the quality of care among patients with heart failure in Europe: Part 1: patient characteristics and diagnosis. Eur Heart J 2003; 24: 442e63. 15 Mehta PA, Dubrey SW, McIntyre HF, et al. Mode of death in patients with newly diagnosed heart failure in the general population. Eur J Heart Fail 2008; 10: 1108e16. 16 Damman K, Navis G, Smilde TDJ, et al. Decreased cardiac output, venous congestion and the association with renal impairment in patients with cardiac dysfunction. Eur J Heart Fail 2007; 9: 872e8. 17 Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency. FERRIC-HF: a Randomized, Controlled, Observer-Blinded Trial. J Am Coll Cardiol 2008; 51: 103e12. 18 von Haehling S, Lainscak M, Springer J, Anker SD. Cardiac cachexia: a systematic overview. Pharmacol Ther 2009; 121: 227e52. 19 Heymans S, Hirsch E, Anker SD, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2009; 11: 119e29. 20 O’Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION Randomized Controlled Trial. JAMA 2009; 301: 1439e50. 21 Cowie MR, Wood DA, Coats AJS, et al. Survival of patients with a new diagnosis of heart failure: a population based study. Heart 2000; 83: 505e10.
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22 Mehta PA, Dubrey SW, McIntyre HF, et al. Improving survival in the 6 months after diagnosis of heart failure in the past decade: population-based data from the UK. Heart 2009; 95: 1851. 23 Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002; 347: 1397e402. 24 Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995; 333: 1190e5. 25 McAlister FA, Stewart S, Ferrua S, McMurray JJJV. Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials. J Am Coll Cardiol 2004; 44: 810e19. FURTHER READING Authors/Task Force Members, Dickstein K, Cohen-Solal A, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29: 2388e442. British Heart Foundation statistics website. www.heartstats.org Francis GS. Pathophysiology of chronic heart failure. Am J Med 2001; 110 (suppl): 37Se46. Gheorghiade M, Pang PS. Acute heart failure syndromes. J Am Coll Cardiol 2009; 53: 557e73. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart 2007; 93: 1137e46.
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The prevalence of HF is rising, mainly as a result of the ageing population and improved treatment of acute manifestations of coronary artery disease Coronary artery disease (often associated with hypertension) is the single most common cause of HF in the developed world HF can result from systolic or diastolic dysfunction of the left (and/or right) ventricle, valve disease, arrhythmia, pericardial disease, or a combination of these problems HF is associated with a poor prognosis, with an 18-month mortality of at least 40%, although this has improved in the past decade HF is associated with haemodynamic, autonomic, and neurohormonal changes which accelerate decline in cardiac and total body function Better understanding of the pathophysiology of HF caused by LV systolic dysfunction has led to effective therapies, such as angiotensin-converting enzyme inhibitors, b-blockers and aldosterone antagonists HF can be associated with ventricular dyssynchrony and cardiac arrhythmias, which can be treated with electrical devices in addition to appropriate use of ACE inhibitors, bblockers and aldosterone antagonists HF is often associated with renal dysfunction, anaemia, skeletal muscle abnormalities and (in advanced cases) cachexia
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