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Guidelines on the Contemporary Management of the Patient with Chronic Heart Failure in Australia

Copyright: 2002 National Heart Foundation of Australia and The Cardiac Society of Australia and New Zealand. All rights reserved throughout the world. No part of this publication may be reproduced by any process in any language without the written consent of the copyright owners.

Guidelines on the Contemporary Management of the Patient with Chronic Heart Failure in Australia

Chronic Heart Failure Clinical Practice Guidelines

1. Scope and objective Page 4

2. Comment on definition of CHF

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3. Epidemiology and public health significance 3.1 Prevention of chronic heart failure

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4. Aetiology 4.1 Causes of systolic heart failure 4.2 Causes of diastolic heart failure

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5. Pathophysiology 5.1 Myocardial pathophysiology 5.2 Neurohormonal activation 5.3 Vascular function in chronic heart failure 5.4 Skeletal muscle in chronic heart failure

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6. Diagnosis 6.1 Symptoms of chronic heart failure 6.2 Symptom classification 6.3 Physical examination 6.4 Functional evaluation 6.5 Diagnostic investigations

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7. Non-pharmacological management 7.1 Exercise and rehabilitation 7.2 Lifestyle modification 7.3 Self management 7.4 Patient support 7.5 Psychosocial aspects 7.6 Other

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8. Specific pharmacological therapy 8.1 Prevention of CHF and treatment of asymptomatic left ventricular dysfunction 8.2 Treatment of symptomatic systolic heart failure 8.3 Treatment of symptomatic diastolic heart failure

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Chronic Heart Failure Clinical Practice Guidelines 8.4 Treatment of advanced systolic heart failure 8.5 Treatment of associated disorders Page 29 Page 29

9. Ancillary therapies 9.1 Pacing 9.2 Surgery (other than revascularisation)

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10. Palliative support in chronic heart failure 10.1 Symptom control 10.2 Community palliative support

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11. Management flowcharts 11.1 Diagnostic algorithm for CHF 11.2 Questions the specialist must answer 11.3 Specialist advanced diagnostics algorithm 11.4 Treatment of asymptomatic LV dysfunction 11.5 Treatment of systolic heart failure (NYHA Class II-III) 11.6 Treatment of systolic heart failure (NYHA Class IV) 11.7 Management of diastolic heart failure

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12. Supporting people with CHF

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13. Appendices

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14. References

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Chronic Heart Failure Clinical Practice Guidelines

1 Scope and objective

These guidelines for the management of chronic heart failure (CHF) summarise the evidence that exists for the most effective diagnosis, treatment and management of CHF. The aim of these guidelines is to: encourage management of CHF that improves health outcomes; reduce unwarranted variation from best practice treatment of CHF throughout Australia.

The target audiences for these guidelines include: general practitioners managing people with CHF; cardiologists and cardiology registrars; those preparing educational material about CHF; people with CHF who are seeking detailed information about management options.

These guidelines provide evidence-based recommendations for CHF management based on the criteria developed by the National Health and Medical Research Council (NHMRC)1 (see Appendix I: NHMRC Designations of levels of evidence). Recommendations based on consensus expert opinion are also included where evidence-based recommendations are not available. These guidelines are not prescriptive, as patient circumstances and clinical judgement will determine the most appropriate course of treatment in each person with CHF. Throughout the document boxed practice points highlight key issues, with summaries of recommendations provided in tables in most sections and in both Section 9 (Management algorithms) and Section 11 (Summary of recommendations). A quick reference guide, diagnosis and treatment algorithms and a guide for people with CHF are available through Heartline (call 1300 36 27 87) and through the Heart Foundation website: and the Cardiac Society of Australia and New Zealand website:

2 Comment on definition of CHF

The definition of CHF is somewhat controversial. Some clinicians base the diagnosis purely on clinical criteria. Others require objective evidence of ventricular dysfunction, for example on echocardiography. The definition usually includes either systolic or diastolic dysfunction of the ventricle(s) or a combination of both. For the purposes of these guidelines it should also be noted that: Controlled trials upon which recommendations are based often require demonstration of ventricular dysfunction in addition to clinical features consistent with the diagnosis. There is much more trial evidence pertaining to systolic ventricular dysfunction. However, the management of diastolic dysfunction, which often coexists, is also included here because of its importance in an increasingly ageing population with high rates of hypertension.

Systolic CHF relates to the inability of the heart to pump normally and remains the most common cause of CHF. This reflects the prevalence of ischaemic heart disease (IHD) in the Western world. Hypertension is still a significant contributor to systolic heart failure, although a less common cause than IHD.

Chronic Heart Failure Clinical Practice Guidelines Diastolic CHF relates to the inability to fill the heart at normal filling pressures, despite normal ventricular contraction. It is difficult to obtain accurate data regarding its prevalence but it is certainly more common in the elderly, where combined ischaemia, hypertrophy and age-related fibrosis may act together to produce increased myocardial stiffness or delayed relaxation.

3 Epidemiology and public health significance

Most current information on the epidemiology of chronic heart failure (CHF) is derived from seven major overseas epidemiological studies published since 1985.2 There have been several consistent findings, including a sharp increase in prevalence with age and a strong male preponderance.3 The prevalence of CHF has been shown to increase from approximately 1% in those aged 50 to 59 years, to over 50% in those 85 years and older.3 Information about the overall incidence and prevalence of CHF in Australia is derived mainly by extrapolation. Based on United States data,4 it is likely that around 300,000 Australians are affected with CHF and about 30,000 new cases diagnosed annually. There are more reliable data for Australia regarding hospitalisation. The Australian Institute of Health and Welfare has reported that, in 1996 and 1997, 41,000 hospitalisations reported CHF as a principal diagnosis.5 In 199697, CHF accounted for 0.8% of all hospitalisations in Australia, with those aged 70 years and over accounting for over three quarters of all hospitalisations for CHF. During 1996 and 1997, CHF contributed 2% of all deaths.5 CHF also constitutes a common reason for general practitioner contact. A recent survey of 341 Australian general practitioners6 estimated that for every 100 patients aged 60 years and over, 11 had known CHF and two could be newly diagnosed based on clinical features and known aetiological factors. The burden associated with CHF is expected to increase markedly7 due to a number of factors, including: Ageing of the population. The projected increase in the number of elderly people with coronary heart disease and hypertension (Figure 17). The decrease in case-fatality rates associated with acute coronary syndromes. Improved diagnosis of CHF because of greater utilisation of sensitive techniques, such as echocardiography.
Projected numbers of older patients with coronary heart disease, high blood pressure and heart failure in Australia

numbers of patients ('000)

1,000,000 800,000 600,000 400,000 200,000 -







65-75 years Coronary heart disease

75+ years High blood pressure Heart failure

Figure 1. Projected prevalence of coronary heart disease, hypertension and chronic heart failure in older Australians.


Chronic Heart Failure Clinical Practice Guidelines There are no precise data for Australia relating to the economic burden associated with CHF. However, direct health costs for cardiovascular disease in 199394 were estimated at $3,719 million (12% of total). CHF has been estimated to account for $411 million of these costs in 1993-94 (11% of cardiovascular disease costs;5 $140 million per annum for hospitalisation and $135 million per annum for nursing home costs).


Prevention of chronic heart failure

The basic aims of prevention are to: limit myocardial damage, and modulate and reduce neuroendocrine and cytokine activation.

The treatment of coronary risk factors (especially smoking, hypertension and dyslipidaemia) reduces the risk of myocardial infarct (MI) and myocardial damage. All smokers should be strongly encouraged to stop. Treatment of hypertension leads to a reduction in coronary heart disease events, including MI, although to a lesser extent than stroke.8 Adequate treatment also limits LV hypertrophy and diastolic dysfunction.9 Both primary10 and secondary prevention studies of statins have shown reduction in coronary heart disease endpoints.11,12,13 Adequate treatment, including secondary prevention, is very important for patients who have MI14. Prompt restoration of coronary patency (where indicated) with thrombolytic agents or angioplasty reduces infarct size. Aspirin, beta-blocking drugs, ACE inhibitors, cholesterol-lowering with statins and gemfibrozil, and rehabilitation also improve prognosis.14 In any person with known IHD, consideration must also be given to the possibility that significant reversible myocardial ischaemia may be present (see Section 6.5: Diagnostic Investigations). Appropriate patients showing significant reversible ischaemia should be considered for revascularisation. Diabetes is a major risk factor for coronary artery disease (CAD). Trials of improved hyperglycaemic control have shown reductions in microvascular complications, but disappointing results in terms of macrovascular disease.15 However, new data confirms the importance of aggressive control of coexistent risk factors, such as hypertension and dyslipidaemia, in those with diabetes.

In addition: Known treatable causes of cardiomyopathy, such as thyrotoxicosis and excessive alcohol intake, must be recognised. Severe mitral and aortic valve disease lead to progressive LV dysfunction and surgery should always be considered for such patients. Tachycardias and bradycardias (especially complete atrio-ventricular block or atrial fibrillation with a rapid ventricular response) will worsen CHF and should be treated appropriately.

Lifestyle interventions to reduce absolute cardiovascular risk Smoking cessation Strongly advise patients to stop smoking and provide appropriate counselling. Nicotine replacement therapy may be of benefit in motivated smokers and has been shown to be safe for use in patients with CHF. Inform smokers about Quitline (Telephone: 131 848).

Chronic Heart Failure Clinical Practice Guidelines

Healthy eating Advise patients to enjoy healthy eating as it improves blood lipid profiles and assists with weight reduction and blood pressure management. Encourage them to choose mainly plant-based foods such as bread, cereals, rice, pasta, vegetables, fruits and legumes (dried peas, beans and lentils); moderate amounts of lean meats, poultry, fish and reduced fat dairy products (e.g. yoghurt, milk, cheese); and replace saturated fats with moderate amounts of polyunsaturated or monounsaturated fats e.g. sunflower, soybean, canola and olive oils and polyunsaturated and monounsaturated margarines. Weight reduction Reducing excess weight is a priority in managing hypertension and dyslipidaemia. Weight reduction by as little as 5 kg reduces blood pressure in most individuals who are more than 10% overweight. Regular physical activity Advise patients of any age to do at least 30 minutes of moderate exercise on most days. Hypertensive patients should be advised against isometric exercise. Alcohol Advise patients to limit their intake of alcohol to no more than 2 standard drinks per day. Salt intake Advise patients to use reduced salt or no-added salt processed foods (< 120 mg sodium/100 g) and not to add salt to food at the table or in cooking.

(from: 1999 Guide to Management of Hypertension for Doctors, pp 910. National Heart Foundation 199916)

4 Aetiology
Although systolic and diastolic heart failure often coexist, the distinction between them is relevant to the therapeutic approach.


Causes of systolic heart failure (impaired ventricular contraction)

Common causes Ischaemic heart disease and prior myocardial infarction (MI), which account for approximately two-thirds of patients with systolic heart failure. Essential hypertension, which may contribute to heart failure via increased afterload and acceleration of coronary artery disease.

Less common causes Non-ischaemic idiopathic dilated cardiomyopathy, most commonly idiopathic. Patients tend to be younger and about 20% have a family history of cardiomyopathy.


Chronic Heart Failure Clinical Practice Guidelines

Uncommon causes Valvular heart disease, especially mitral and aortic incompetence. Alcoholic cardiomyopathy, which accounts for up to one third of the cases of nonischaemic dilated cardiomyopathy in the Western world. Inflammatory cardiomyopathy, or myocarditis, traditionally associated with a history of viral infections e.g. enteroviruses, especially Coxsackie B virus. Chronic arrhythmia. HIV-related cardiomyopathy. Drug-induced cardiomyopathy esp. anthracyclines e.g. daunorubicin and doxorubicin, cyclophosphamide, paclitaxel and mitoxantrone.

Peripartum cardiomyopathy, a rare cause of systolic failure.


Causes of diastolic heart failure (impaired ventricular relaxation)

Common causes Hypertension (especially systolic hypertension). Patients tend to be elderly, female and have a history of hypertension. This cause now represents 4050% of all hospital admissions for CHF. Ischaemic heart disease, which may lead to impaired myocardial relaxation. Practice Point The epidemiology of diastolic heart failure has been incompletely described. The main risk factors are advancing age, hypertension, diabetes, LV hypertrophy and coronary artery disease.

Diabetes. Diabetic men are twice as likely to develop heart failure when compared with non-diabetic male subjects, and diabetic women are at a five-fold greater risk. These differences persist after taking into account age, blood pressure, weight, cholesterol and known coronary artery disease. Myocardial ischaemia is very common in diabetes and augmented by hyperglycaemia, as well as concomitant hypertension and hyperlipidaemia. However, diabetes is additionally associated (independent of ischaemia) with interstitial fibrosis, myocyte hypertrophy and apoptosis, as well as both autonomic and endothelial dysfunction, all of which may contribute to the diabetic cardiomyopathic state.

Less common causes Valvular disease, particularly aortic stenosis. Uncommon causes Hypertrophic cardiomyopathy, an uncommon cause of CHF. About 60% of cases are hereditary (major loci on chromosomes 11 and 14). Restrictive cardiomyopathy, either idiopathic or secondary to infiltrative disease, such as amyloidosis.


Chronic Heart Failure Clinical Practice Guidelines

5 5Pathophysiology
The vicious cycle of CHF pathophysiology ventricular dysfunction leads to, and is worsened by, neurohormonal activation, myocardial damage and both peripheral and renal vasoconstriction.


Myocardial pathophysiology

The syndrome of CHF is initiated in the setting of a diverse group of disorders that reduce myocardial performance. In general terms, ventricular impairment may result from: conditions that directly impair cardiac muscle function (e.g. MI); conditions that cause pressure overload (e.g. aortic stenosis, chronic hypertension) or volume overload (e.g. mitral regurgitation); uncontrolled arrhythmias, both acute and chronic; diseases involving the pericardium (occasionally).

While CHF is most often considered in the context of reduced systolic function, isolated abnormalities of diastolic performance (active relaxation and passive compliance) may also occur. In response to compromised ventricular function a number of adaptive responses develop, including changes in myocardial structure and geometry and neurohormonal activation (see below). The failing ventricle is characterised by ventricular dilatation and hypertrophy with an associated increase in wall stress. This process is initially associated with maintained resting cardiac output, although the cardiac output response to exercise is diminished. Ventricular dilatation is accompanied by a decrease in chamber compliance so that any increase in chamber filling, such as exercise, is associated with a marked rise in the diastolic filling pressure. This abnormality of diastolic function can also occur in isolation, again being associated with marked elevations in diastolic filling pressure during certain circumstances, including tachycardia and fluid overload.17 As the ventricular chamber enlarges, a number of added secondary consequences may also result. These include the development of both mitral regurgitation, due to enlargement of the mitral valve annulus, and atrial and ventricular arrhythmias. The characteristic positive inotropic response to increasing heart rate (the Bowditch phenomenon) is lost in the failing heart. Recent research has attempted to identify some of the specific myocardial mechanisms that account for the above observations.18 It has been proposed that there may be activation of processes that lead to programmed death of myocytes (apoptosis), which may account for ongoing loss of contractile elements within the heart19. In association, activation of enzymes (matrix metalloproteinases) that degrade the supporting extracellular skeleton of the heart may contribute to the slippage of myocytes, thereby facilitating chamber enlargement.


Chronic Heart Failure Clinical Practice Guidelines


Neurohormonal activation

Practice Point In CHF decreased cardiac output activates many neurohormonal compensatory systems that, in the short Decreased cardiac output in term, act to preserve circulatory homeostasis and CHF activates many maintain arterial pressure.17 However, when present in neurohormonal chronic excess, these compensatory systems play a compensatory systems that role in the development and progression of CHF. Early act to preserve circulatory compensatory mechanisms include activation of the homeostasis in the short sympathetic nervous system and the renin-angiotensin term but, when activated for system, leading to elevated levels of noradrenaline, longer periods, play a role angiotensin II and aldosterone. In advanced CHF, in the development and levels of vasopressin and endothelin also rise.17 20 progression of CHF. Chronic activation of vasoconstrictors contributes to deteriorating cardiac function through increased peripheral resistance and effects on cardiac structure, causing hypertrophy and fibrosis, myocyte necrosis and/or apoptosis, as well as down-regulation of adrenergic receptors and endothelial dysfunction (Figure 2). In early CHF, the adverse effects of endogenous vasoconstrictors are balanced by elevated levels of the natriuretic peptides, which cause vasodilation and also inhibit the secretion of noradrenaline, renin and vasopressin. In advanced CHF, the actions of vasodilator systems are attenuated, resulting in unopposed vasoconstrictor systems and consequent systemic and pulmonary vasoconstriction, cardiac hypertrophy and ischaemia, oedema and hyponatraemia. The clinical importance of activation of neurohormones in CHF is two-fold: Circulating levels reflect LV function and predict prognosis. Blockade of the actions of angiotensin and noradrenaline slows progression of myocardial dysfunction, alleviates symptoms and reduces morbidity and mortality.

Studies are underway to assess the efficacy of inhibition of constrictors, such as endothelin and vasopressin; and cytokines, such as tumour necrosis factor. Enhancement of endogenous vasodilator systems by inhibiting the breakdown of natriuretic peptides is also under investigation. Figure 2. The vicious cycle of CHF pathophysiology Chamber dilation Wall stress

Ventricular dysfunction
Heart rate arrhythmia Neurohormones Vasoconstriction (afterload) Renal vasoconst riction (Na +, H 2O, preload) Toxic effects

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Chronic Heart Failure Clinical Practice Guidelines


Vascular function in chronic heart failure

Major alterations in regional blood flow have been consistently observed in CHF. To a large extent these changes reflect the combined influences of increased vasoconstrictor system activity (as outlined previously) and reduced activity of endothelium-dependent vasodilatory processes, most notably the nitric oxide pathway. Structural changes, including vascular wall oedema and reduced vascular density, may also occur.


Skeletal muscle in chronic heart failure

While the conventional view is that reduced muscle blood flow is largely responsible for exercise intolerance, a number of recent studies have identified changes in muscle metabolism that could contribute to exercise intolerance. Studies using 31P NMR spectroscopy have shown rapid depletion of phosphocreatine, increased ADP concentrations and acidification of muscle during exercise. These changes are independent of blood flow and are probably caused by a reduction in the mitochondrial content of skeletal muscle. Exercise training ameliorates these metabolic changes. Cardiac cachexia, sometimes a prominent feature of severe CHF, includes loss of muscle mass as well as adipose tissue. Cardiac cachexia may be caused by increased production of tumour necrosis factor (TNF)-, plasma levels of which are elevated in severe CHF.21

6 6Diagnosis
6.1 Symptoms of chronic heart failure

A full medical history is important, both in determining the cause/s of CHF and assessing the severity of the disease. In patients with LV dysfunction, symptoms of CHF may develop relatively late. Furthermore, many patients claim to be asymptomatic, largely due to their sedentary lifestyle. The classic symptom of CHF is exertional dyspnoea. Initially it is felt with more strenuous exertion, but later dyspnoea progresses to occur on level walking and eventually at rest. As patients symptoms progress they are troubled by orthopnoea, and frequently have to prop themselves up on a number of pillows at night to sleep. They may also have attacks of breathlessness at night, called paroxysmal nocturnal Practice Point dyspnoea (PND). Clinical diagnosis of CHF A dry, irritating cough (due to LV failure) is a is often unreliable, frequent symptom, particularly at night. Patients especially in obese may be mistakenly treated for asthma, bronchitis or patients, those with ACE-inhibitor-induced cough. pulmonary disease and the elderly. Many of the Fatigue and weakness, due to reduced cardiac signs and symptoms of output, are prominent symptoms, sometimes more CHF lack specificity and prominent than exertional breathlessness. These sensitivity. symptoms may be exacerbated by some of the drug therapy that patients are prescribed. Dizzy spells or palpitations may indicate intermittent or established arrhythmias.

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Chronic Heart Failure Clinical Practice Guidelines Patients with more advanced CHF will have problems with symptoms related to fluid retention such as abdominal distension, ascites and sacral and peripheral oedema.

Symptom levels vary with the degree of medical control of CHF. Patients often relapse due to precipitating causes such as atrial fibrillation, broncho-pulmonary infection or non-compliance with medicationsometimes requiring urgent hospital admission.


Symptom classification

New York Heart Association grading The traditional system for symptom classification in CHF is the New York Heart Association (NYHA) grading system (see Table 1). Physicians may differ in their interpretation of grades. Table 1. New York Heart Association grading (NYHA) NYHA Grading Class I No limitations. Ordinary physical activity does not cause undue fatigue, dyspnoea or palpitations (asymptomatic LV dysfunction) Slight limitation of physical activity. Ordinary physical activity results in fatigue, palpitation, dyspnoea or angina pectoris (mild CHF) Marked limitation of physical activity. Less than ordinary physical activity leads to symptoms (moderate CHF) Unable to carry on any physical activity without discomfort. Symptoms of CHF present at rest (severe CHF) Metabolic *Equivalent >7

Class II

Class III


Class IV


MET (Metabolic Equivalent) is defined as the resting VO2 for a 40-year-old 70 kg man. 1 MET=3.5ml O2/min/kg body weight

The Specific Activities Scale (Appendix III), a more objective and activity-specific method of determining symptom class, may be easily used in the primary care setting.22


Physical examination

A careful physical examination is important, both for initial diagnosis of CHF and ongoing evaluation of disease status. There may be no abnormal physical signs initially, especially if the apex beat is not palpable. Patients with more severe CHF may appear obviously tachypnoeic at rest and need to sit in an upright position to obtain symptomatic relief. The jugular venous pulse is often elevated and may show a prominent V wave and steep Y descent, indicative of secondary tricuspid regurgitation. As the left ventricle dilates, the apex beat will be displaced laterally. Auscultation may reveal evidence of underlying valvular disease, which may be the primary cause of CHF or secondary to dilatation of the AV ring and papillary
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Chronic Heart Failure Clinical Practice Guidelines muscle dysfunction; for example, mitral regurgitation. A third heart sound is typically heard in more advanced LV dysfunction or during periods of symptomatic decompensation. Soft fine crepitations may be heard in the bases of the lung fields. The liver enlarges and is palpable below the costal margin. It may be tender owing to stretching of its capsule. Further fluid retention may also manifest as peripheral oedema, especially in dependent areas such as the ankles and, in recumbent patients, the sacral area. Ascites may also occur in more advanced cases.


Functional evaluation

Six-minute walk The six-minute walk test is a simple, safe and non-invasive measure of the distance covered in consecutive 25-metre laps, over a 6-minute period. Repeated determinations are useful to monitor progress. The ability to walk the distance strongly and independently predicts morbidity and mortality.23,24,25,26 Peak maximal oxygen utilisation (MVO2) This highly specialised test determines maximal oxygen uptake during exercise (in ml/kg/minute) and the point at which the anaerobic threshold occurs (when aerobic metabolism switches to anaerobic). It is used to determine functional capacity and the results of this test correlate closely with prognosis. Readings are affected by age, gender, airways and muscle diseases, and its usefulness is limited where there are other impediments to exercise.27,28,29 Exercise testing Treadmill or bicycle exercise testing are not considered as relevant in the CHF population as in those with near-normal ventricular function. CHF patients do not always perform well on usual robust test schedules so, when exercise testing is used, a modified Bruce or Naughton protocol with reduced speed and gradient increments is preferred. Metabolic equivalents and work capacity Metabolic equivalents (METs) can be used to assess functional disability. It is also helpful to use the METs diagram correlating exercise testing, symptom classification and clinical status (Appendix IV) to assess the likely functional effects of a patients disease in terms of work and lifestyle disability.


Diagnostic investigations

The purpose of investigating CHF is to: confirm the clinical diagnosis; identify a cause; identify exacerbating factors; guide therapy; determine prognosis.

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Chronic Heart Failure Clinical Practice Guidelines

Initial investigations Electrocardiogram (ECG) The ECG is seldom normal but abnormalities are frequently non-specific. The most common are non-specific repolarisation abnormalities (ST-T wave changes). Conduction abnormalities include: Left bundle branch block; First degree heart block; Left anterior hemi-block; Non-specific intraventricular conduction delays. Other abnormal findings include: Left ventricular hypertrophy and evidence of previous Q wave MI in patients with a history of IHD; Sinus tachycardia (due to increased activity of the adrenergic nervous system); Atrial fibrillation (prevalence increases with increasing age in patients with CHF). Chest X-Ray Cardiomegaly and pulmonary venous redistribution with upper lobe blood diversion are common. With increasing CHF, evidence of interstitial oedema may be present. This is seen particularly in the peri-hilar region, with prominent vascular markings and, frequently, small basal pleural effusions obscuring the costo-phrenic angle. Kerley B lines, indicative of lymphatic oedema due to raised left atrial pressure, may be present. Patients with diastolic heart failure usually have a normal heart size in contrast to those with primarily systolic failure. Peripheral markers Full blood count Mild anaemia may occur in patients with CHF and may worsen as the severity of CHF progresses. Severe anaemia, in itself, may uncommonly be a cause of CHF. Anaemia should be investigated. Mild thrombocytopenia may occur due to secondary chronic liver dysfunction or as an adverse effect of drugs, such as diuretics. The erythrocyte sedimentation rate (ESR) is usually normal or low, especially in patients with more advanced CHF. However, the ESR may be elevated due to associated conditions, such as infection.

Electrolytes The electrolytes in mild and moderate CHF are usually normal. However, in more advanced CHF, the following changes may occur: Dilutional hyponatraemia, exacerbated by high-dose diuretic therapy. Elevated potassium in the presence of impaired renal function or as a result of the use of potassium-retaining diuretics or ACE inhibitors. Hypokalaemia is more common and is often secondary to diuretic therapy, both thiazide and loop diuretics.
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Chronic Heart Failure Clinical Practice Guidelines

Serum magnesium levels may be reduced due to the effects of diuretic therapy. Magnesium replacement to normal levels reduces ectopy and helps normalise potassium levels. Renal blood flow and globular filtration rate (GFR) may fall as CHF progresses, with a rise in serum creatinine. This may be worsened by drug therapy, including diuretics and ACE inhibitors.

Iron Serum iron and ferritin levels are usually normal. However, in advanced CHF levels these may be reduced due to poor food intake (cardiac cachexia), malabsorption and the use of aspirin. Liver Function Tests Congestive hepatomegaly results in abnormal liver function tests with elevated levels of AST, ALT and LDH. There may be a rise in serum bilirubin, particularly in severe CHF. In long-standing CHF albumin synthesis may be impaired with resulting hypoalbuminaemia. The latter finding may also indicate cardiac cirrhosis.

Urinalysis Increased urine specific gravity and proteinuria are common. Thyroid Function Hyperthyroidism is an uncommon cause of CHF. Thyroid function tests should be considered, especially in older patients without pre-existing heart disease who develop atrial fibrillation. Viral Studies A number of viruses, the most common being Coxsackie, have been associated with clinical evidence of myocarditis. A four-fold rise in convalescent serum-neutralising antibodies occurs only in the minority of patients with suspected myocarditis. More recently, newer biological techniquesespecially PCRhave been used to detect viral products in endomyocardial biopsies taken from patients with suspected myocarditis. The reported variation in the incidence of positive biopsies is from 045%. Echocardiography Practice Point All patients with a suspected diagnosis of CHF should be considered for measurement of ventricular function. The preferred test is the transthoracic echocardiogram. The echocardiogram can make the all-important distinction between patients with systolic dysfunction (typically a LV ejection fraction < 40%) and those with normal resting systolic function but abnormal diastolic filling. It is non-invasive, safe and relatively cheap compared with other imaging modalities. All patients with a suspected diagnosis of CHF should be considered for measurement of ventricular function. The preferred investigation is the transthoracic echocardiogram.

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Chronic Heart Failure Clinical Practice Guidelines

The echocardiogram gives information about: Left and right ventricular systolic function The global ejection fraction as well as regional wall motion analysis in patients with CAD is readily performed in most patients. Left and right ventricular diastolic function Doppler echocardiography in patients in sinus rhythm yields distinctive diastolic filling patterns in patients with normal or abnormal diastolic function. Both the LV inflow Doppler and pulmonary vein Doppler can reliably predict patients with elevated ventricular diastolic filling pressures. Left and right ventricular size, volumes and ventricular wall thickness. Intracardiac spontaneous echo contrast or thrombus, particularly at the left ventricular apex or in the left atrial appendage in patients in atrial fibrillation (Figure 3). Valvular structure and function, including valve gradients. Intracardiac pressures, pulmonary pressures and indirect measures of the pulmonary capillary wedge pressure. Pericardial disease.

Figure 3. Echocardiograph showing large LV thrombus 3 months post extensive anterior infarct

Coronary angiography Coronary angiography should be considered in CHF patients with a history of exertional angina or suspected ischaemic LV dysfunction, including those with a strong risk factor profile for CAD. Although the majority of patients with ischaemic LV dysfunction will have a clear history of previous MI, occasionally patients may present with clinical features of CHF without obvious angina or prior history of
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Chronic Heart Failure Clinical Practice Guidelines ischaemic events. Coronary angiography may also have therapeutic implications, since selected patients with ischaemic CHF may benefit from myocardial revascularisation.30,31,32,33 Haemodynamic testing Invasive measurement of haemodynamics may be particularly helpful in patients for whom: CHF appears refractory to therapy; The diagnosis of CHF is in doubt; Diastolic heart failure is recurrent and difficult to confirm by other means.

Haemodynamic measurements are typically made at rest but pressure recordings can be made during exercise for patients with exertional symptoms but normal resting haemodynamics and in whom secondary pulmonary hypertension is suspected. Haemodynamic measurements also provide prognostic information; the ability to normalise filling pressures with tailored therapy carries a better prognosis than inability to optimise pressures.34 Endomyocardial biopsy Endomyocardial biopsy may be indicated in cardiomyopathy with recent onset of symptoms (<3 months) where any reasonable expectation of CAD has been excluded by angiography. While subacute lymphocytic infiltrate occurs in 10% of patients with otherwise idiopathic cardiomyopathy, histological evidence of fulminant myocarditis likely to respond to immunosuppression tends to be rare (2% of cases) except where there is other evidence for myocarditis, such as fever, elevated ESR, relatively preserved wall thickness with reduced LV contraction or concomitant viral illness35. Biopsy may also be specific for sarcoidosis, giant cell myocarditis, amyloidosis or haemochromatosis. Right ventricular biopsy is generally performed via the right internal jugular vein or right femoral vein and is generally considered to be representative of LV histology. Nuclear cardiology Gated radionuclide angiocardiography provides a reproducible measure of left and right ventricular ejection fraction as well as regional wall motion analysis. It requires the administration of a radionuclide tracer and is generally performed when echocardiography is either not available or non-diagnostic due to poor acoustic windows. Nuclear imaging plays an important role in the assessment of patients with myocardial dysfunction and coronary disease because it can provide information about the presence of significant inducible ischaemia, as well as the extent of viable myocardium. Inducible ischaemia can be assessed with numerous stress protocols using either technetium-labelled agents or thallium-based protocols. Many patients have limited exercise capacity and therefore pharmacological stress testingsuch as dipyridamole (Persantin) or dobutamine-thalliumis more appropriate. Stress echocardiography may be another alternative. While thallium imaging may demonstrate myocardial viability, it is less sensitive than Positron Emission Tomography (PET), which remains the gold standard for detecting viability but is not widely available. Prospective randomised trials of PET imaging in
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Chronic Heart Failure Clinical Practice Guidelines IHD and CHF are not available, but retrospective studies demonstrate that PET viability is an excellent discriminator of outcome post-revascularisation. Viability of myocardium may also be assessed by fluorodeoxyglucose (FDG) scan, interpreted in the context of results of scans for reversibility. Natriuretic peptides Atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP) relate to the severity of CHF, risk of hospitalisation and survival. A BNP level of >200 pg/ml is highly sensitive and specific for the presence or absence of LV dysfunction determined by echocardiography and for differentiating CHF from respiratory diseases in the emergency room situation. It is more useful in systolic than in diastolic dysfunction. Titration of drug therapy to plasma BNP level reduces the rate of adverse outcomes and guides adequacy of CHF management,36,37 but this is not yet standard clinical practice. Spirometry and respiratory function testing These are useful to exclude concomitant smoking-related or other causes of airways limitation. The FEV1 may be reduced, with reversibility demonstrable in reaction to an elevated wedge pressure ('cardiac asthma'). The gas transfer will be reduced in moderate CHF, generally down to 50% of predicted.38,39,40,41 Recommendations relating to the diagnostic investigation of CHF are shown in Table 2. Table 2. Recommendations for diagnostic investigation of CHF Level of Evidence* All patients with suspected CHF should be considered for an objective measurement of ventricular function, preferably by transthoracic echocardiogram. Coronary angiography should be considered in CHF patients with a history of exertional angina or suspected ischaemic LV dysfunction. Haemodynamic measurements may be particularly helpful in patients with refractory CHF, recurrent diastolic CHF or in whom the diagnosis of CHF is in doubt. Endomyocardial biopsy may be indicated in cardiomyopathy with recent onset of symptoms, where CAD has been excluded by angiography, or where systolic ventricular dysfunction is suspected. Nuclear cardiology, stress echocardiography and Positron Emission Tomography can all be used to assess reversibility of ischaemia and viability of myocardium in CHF patients with myocardial dysfunction and coronary disease. Thyroid function tests should be considered, especially in older patients without pre-existing heart disease who develop atrial fibrillation. EO =expert opinion EO





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Chronic Heart Failure Clinical Practice Guidelines

7 7.1

Non-pharmacological management
Exercise and rehabilitation
CHF patients may develop physical deconditioning and regular physical activity is recommended.42,43,44,45 When medically stable, all CHF patients should be considered for referral to an exercise program specifically designed for CHF patients.46,47,48,49,50,51,52,53 If such a program is unavailable, CHF patients may undertake a modified cardiac rehabilitation program. If patient co-morbidities prevent attendance at a rehabilitation program, clinically stable CHF patients should be encouraged to keep as active as possible. Exercise training has been shown to improve functional capacity, symptoms and neurohormonal abnormalities in CHF.43 Exercise should be tailored to individual patients following assessment.46,47,48,49,50,51,52,53,54 Exercise training may include walking, exercise bicycle, light weights and stretching exercises as well as daily walking at home for 1030 minutes/day, 5-7 days/week. Patients should not exercise to a level beyond which they cannot carry out a normal conversation.46,47,48,49,50,51,52,53,54 Patients should be educated so that realistic and sustainable levels of exercise are achieved. Elderly patients should not be excluded from exercise as they have also been shown to benefit.46,47,48,49,50,51,52,53,54 Isometric exercise with heavy straining should be avoided as it may increase LV afterload.55 Isokinetic muscle strengthening exercise has been used safely in CHF patients.55 Patients with angina pectoris should be encouraged to exercise below the anginal threshold.42,43,44,45,46,47,48,49,50,51,52,53,54,55 Practice Point People with CHF may develop physical deconditioning. Regular physical activity, if possible through a rehabilitation program designed for CHF patients, is therefore recommended.

Rest Patients who have an acute exacerbation of CHF, or who are unstable, should have a period of bed rest until their condition improves. Strict bed rest may improve diuresis and cardiac function.56 Adequate bed rest is advisable for all CHF patients.56

Sexual function There is little information about sexual activity in patients with CHF. Sexual activity may be associated with worsening arrhythmias in patients with preexisting arrhythmia, but this is probably rare. Sexual activity is likely to be safe in CHF patients who are able to achieve approximately 6 metabolic equivalents of exercisethat is, able to climb 2 flights of stairs without stopping due to angina, dyspnoea or dizziness.

Male CHF patients frequently suffer from erectile dysfunction.57,58,59 Sildenafil is contraindicated in patients receiving nitrate therapy, or who have hypotension, arrhythmias or angina pectoris.60 Studies to specifically address the safety of sildenafil in patients with LV dysfunction are currently ongoing and, at present, caution should be exercised in prescribing sildenafil in patients with CHF. There is little information about the use of intracavernosal injections in men with CHF and they are not recommended.
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Chronic Heart Failure Clinical Practice Guidelines


Lifestyle modification

Diet CHF patients who are overweight place increased demands upon their heart, both during exercise and daily living. Weight loss may improve exercise tolerance and quality of life and is recommended in all CHF patients who exceed the healthy weight range. Saturated fat intake should be limited in all patients, but especially in those who suffer from IHD.61 Due to relative gastrointestinal hypoperfusion, constipation is common in CHF and a high fibre diet is recommended.61 This will also avoid straining at stool, a situation that may provoke angina, dyspnoea or arrhythmia. In patients with severe CHF, more frequent, small meals may avoid shunting of the cardiac output to the gastrointestinal tract, thus reducing the risk of angina, dizziness, dyspnoea or bloating.61 Salt and fluid restriction Dietary sodium should be limited to below 2000 mg/day. This will help reduce fluid retention, diuretic requirements and potassium excretion.61 CHF patients should avoid processed and high salt foods and the addition of salt during cooking or at the table. CHF and diuretics may both increase thirst, but fluid intake should generally be limited to 1.5 litres/day in mild to moderate CHF and 1 litre/day in severe CHF62 to limit hyponatraemia and diuretic requirements. Fluid restrictions may be liberalised in warmer weather. Smoking Patients with CHF should not smoke. Smoking is atherogenic, reduces the oxygen content of blood, provokes vasoconstriction, impairs endothelial and respiratory function61 and is arrhythmogenic. Alcohol Patients who suffer from alcohol-related cardiomyopathy should abstain from alcohol as this may slow progression of the disease or even improve LV function. In other CHF patients, alcohol intake should not exceed 1020 grams of alcohol (12 standard drinks) a day. Alcohol is a direct myocardial toxin and may impair cardiac contractility.61,62 Alcohol also contributes to total fluid intake and may increase body weight due to its caloric load.61,62 Patients who have a history of heavy alcohol intake and poor nutrition may benefit from vitamin supplementation, particularly thiamine. Caffeine Excessive caffeine intake may exacerbate arrhythmia, increase heart rate and increase blood pressure. Caffeine also contributes to the total fluid intake and may alter electrolyte levels in patients taking diuretics. It should be limited in CHF patients to 12 cups of coffee per day.


Self management

CHF patients should be advised to weigh themselves daily and to consult their doctor if their weight increases by more than 1.5 kg in a 24-hour period.63,64,65,66 Patients who have a more labile fluid status are given a flexible action plan to adjust diuretic dosage according to changes in body weight. Patients should be taught the warning signs of dyspnoea, oedema, abdominal bloating or a change in their status and to promptly report this to their doctor before their condition deteriorates.

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Chronic Heart Failure Clinical Practice Guidelines

Patient education Patients should be educated about: their underlying condition; beneficial lifestyle changes; the function of their medications; possible side effects of therapy; signs of deterioration in their condition; the importance of adherence to therapy.

An understanding of the condition by both the patient and his/her carers may reduce the possibility of non-adherence to diet, fluid restriction or medication and allow early detection of change in clinical status.63,64,65,66 A good, consistent relationship with the patient, coupled with an active role for the patient and the family, is essential. Written information and audio-visual educational material are helpful tools in patient education.


Patient support

Practice Point When managing CHF, a good, consistent relationship with the patient, coupled with an active role for the patient and his/her family, is essential.

Support mechanisms help prevent deterioration in CHF status. Regular review by the treating doctor, to assess change in clinical status and adjust therapy, is very important.

Patients who are hospitalised for an exacerbation of CHF are at greatest risk of readmission to hospital and poor outcome. Review by a CHF nurse prior to hospital discharge, followed by a home visit within one week of discharge, has been shown to reduce hospital readmission rates and improve survival by improving compliance and directing patients to medical and allied health services appropriate to their clinical status. Further home visits at one month for high-risk patients may be necessary. Telephone follow-up may be appropriate for more geographically-isolated patients.63,64,65,66

Because patients with CHF commonly have complex co-morbidities and are usually on multiple medications, communication between the patient's general practitioner, the hospital and the specialist is very important to Practice Point improve patient care and reduce errors. Patients from non-English speaking background or Aboriginal and When managing CHF, Torres Strait Islander people may have cultural or communication between the language barriers and have been shown to have patient's GP, the hospital and poorer outcomes than other patients. These patients the specialist is very important may require special attention to improve outcomes. to improve patient care and Regular communication between the patient and reduce errors.69,70,71,72 health care team may also reduce hospital Patients from a non-English readmission rates.63,64,65,66 speaking background and


Psychosocial aspects

There is only a very weak association between LV function, functional capacity and quality of life67 as an important clinical outcome.

Aboriginal people have special communication needs. These groups have been shown to have a poorer outcome than other patients.69

Approximately one third of all patients experience depression after acute coronary syndromes (MI or unstable angina). Depression is also a powerful independent predictor of mortality as depressed patients generally have a 3-fold increase in mortality.68 In CHF patients, a low LV ejection fraction (<

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Chronic Heart Failure Clinical Practice Guidelines 20%) predicts major depression events and the presence of major depression predicts increased mortality.69 Social support, while not being an independent predictor of mortality, buffers the effect of depressed mood on mortality.70 In CHF patients, the severity of depressed mood is associated with both functional capacity and CHF symptoms, even though there is no relationship between the latter two factors.71 This suggests that the degree of depressed mood has contributions from different sources. Exercise training has been demonstrated to be as effective as antidepressant medication in non-cardiac patients.72 Cognitive behavioural therapy has been shown, in a randomised controlled trial, to reduce depressed mood in cardiac patients.73 Trials using cognitive behaviour therapy or anti-depressant medication are currently underway in cardiac patientsboth with or without impaired LV functionto examine the effect on mortality from treating depression.



Sleep apnoea Two varieties of sleep apnoea occur commonly in patients with CHF. Obstructive sleep apnoea occurs due to upper airway collapse and is likely to aggravate any underlying CHF. Weight reduction and nasal continuous positive airway pressure (CPAP) are effective treatments and are also likely to augment cardiac function; CPAP may do this via its intrathoracic pressure effects on the heart and alveoli.74 By contrast, central sleep apnoea (also known as Cheyne-Stokes respiration) can occur both independently of CHF and as a result of high sympathetic activation and pulmonary congestion due to severe CHF. Central sleep apnoea is best treated with optimisation of medical treatment. If persistent, a trial of nasal oxygen should be considered. Vaccination CHF patients are at increased risk of respiratory infection and should be vaccinated against influenza and pneumococcal disease.61,62 Pregnancy and contraception CHF greatly increases the risk of maternal and neonatal morbidity and mortality. Pregnancy and delivery may cause deterioration in women with moderate to severe CHF. Pregnancy in those with mild CHF may be considered on an individual basis for a fully informed patient and her partner. Many of the medications used to treat CHF are contraindicated in pregnancy. Low-dose oral contraceptive pills appear to have a small risk of causing hypertension or thrombogenicity62 but these risks needs to be weighed against those of pregnancy.

Travel Short-distance air travel appears to be of low risk in mild CHF. Long flights may predispose to accidental omission of medications, lower limb oedema, dehydration and venous thrombosis, but are not necessarily contraindicated.62 High altitude destinations should be avoided because of relative hypoxia. Travellers to very humid or hot climates should be counselled on dehydration and modification of diuretic doses.

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Chronic Heart Failure Clinical Practice Guidelines

Recommendations relating to the non-pharmacological management of CHF are shown in Table 3. Table 3. Recommendations for non-pharmacological management of CHF Level of evidence*
Regular physical activity is recommended. All CHF patients should be considered for referral to an exercise program specifically designed for 43,44,45 patients with CHF, if available. Patient support by doctor, pre-discharge nurse review and/or home visit 63,64 is critical to prevention of deterioration in CHF status. Sleep apnoea frequently co-exists with CHF. CHF patients with obstructive sleep apnoea may benefit from nasal continuous positive 75 airway pressure. CHF patients who have an acute exacerbation or are clinically unstable 56 should have a period of bed rest until their condition improves. Dietary sodium should be limited to below 2000 mg/day.
64. 42




Fluid intake should generally be limited to 1.5 litres/day in mild to moderate CHF and 1 litre/day in severe CHF, especially if there is 65 coexistent hyponatraemia. Alcohol intake should generally be nil but should not exceed 10-20 65 grams/day. Smoking should be strongly discouraged. CHF patients should be advised to weigh themselves daily and to consult their doctor if their weight increases by more than 1.5 kg in a 24hour period or if they experience dyspnoea, oedema or abdominal bloating. CHF patients should be vaccinated against influenza and pneumococcal disease. High altitude destinations should be avoided. Travel to very humid or hot climates should be undertaken with caution and fluid status should be carefully monitored. Evidence levels adapted from NHMRC Guidelines EO = expert opinion



8 Specific pharmacological therapy

8.1 Prevention of chronic heart failure and treatment of asymptomatic left ventricular dysfunction

Angiotensin converting enzyme (ACE) inhibitors ACE inhibitors have been shown to prevent development of symptomatic CHF in patients without known ventricular dysfunction, as well as in patients with asymptomatic LV dysfunction.76,77 Administration of ramipril (10 mg daily) has been shown to reduce the risk of development of CHF, in comparison to placebo, in patients at high risk of

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Chronic Heart Failure Clinical Practice Guidelines cardiovascular disease but without known LV dysfunction at the time of randomisation.78 In a study of patients with asymptomatic LV dysfunction (LV ejection fraction <40%), treatment with enalapril (10mg twice daily) prevented development of symptomatic CHF77 and lowered the risk of both death from, and hospitalisation for, CHF. These data are complemented by results from a number of studies of the immediate post-MI period. Beta blockers Limited data exists on the use of beta-blockers to prevent progression to symptomatic CHF in patients with asymptomatic LV dysfunction remote from MI. A subset (30%) of patients, in a trial of mild CHF patients, was asymptomatic at time of randomisation to carvedilol or placebo.79 Although not statistically significant, the relative risk reduction (RRR) in death and all-cause hospitalisation in this asymptomatic subset was similar to that observed in patients with symptoms. It should be emphasised that these were patients with IHD as the only cause of their LV dysfunction. Beta-blockers, when given in the early post-MI period, have been found to reduce the subsequent development of CHF in patients with preserved ventricular function and reduce the progression of CHF in patients with impaired ventricular function.80 81 A large prospective study recently investigated the use of beta-blockade, additional to background standard management, during the post-MI period in patients with LV dysfunction. This study demonstrated that the frequency of all-cause and cardiovascular mortality, and recurrent, non-fatal myocardial infarction was reduced with carvedilol compared with placebo thereby supporting the use of beta-blockade in this setting.82 Other agents Hypertension is a major risk factor for the subsequent development of CHF. There has been a clear demonstration in a number of major trials that lowering blood pressure dramatically reduces the incidence of CHF.8,83,84 There is no evidence that newer agents, such as ACE inhibitors or calcium channel blockers, achieve this to a greater extent than older agents, such as diuretics and beta-blockers.85,86,87 Table 4. Recommendations for prevention of CHF and treatment of asymptomatic LV dysfunction Level of Evidence* All patients with asymptomatic systolic LV dysfunction should be commenced on an ACE inhibitor and this maintained indefinitely, unless intolerant.76,77 Anti-hypertensive therapy should be used to prevent subsequent CHF in patients with elevated blood pressure levels.8,83,84,85,86,87 Commencement of an ACE inhibitor in patients at high risk of ventricular dysfunction (but without current evidence of ventricular impairment) may be considered in individual patients.78 -blockers should be commenced early after a MI, whether or not the patient has systolic ventricular dysfunction.83,84 Statin therapy should be used as part of a risk factor management strategy to prevent ischaemic events and subsequent CHF in patients who fulfil criteria for commencement of lipid-lowering therapy.33,88
Evidence levels adapted from NHMRC Guidelines
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Chronic Heart Failure Clinical Practice Guidelines


Treatment of symptomatic systolic heart failure

Many drug groups have been trialled in the treatment of patients with symptomatic CHF. Data supporting the use of these agents in systolic heart failure are described below with recommendations summarised in Table 5. Management of the patient with CHF and diastolic dysfunction is summarised below. ACE Inhibitors Because of the major importance of renin-angiotensin system activation in progression of CHF, blockade of this system has become the cornerstone of successful therapy for systolic ventricular dysfunction. ACE inhibitors have been shown to: prolong survival in patients with NYHA Class II, III and IV CHF, compared to placebo.89,90 improve patient symptom status, exercise tolerance and hospitalisation for worsening CHF91 (in some but not all studies). increase ejection fraction compared to placebo in many studies.89

The optimal dose of ACE inhibitor therapy has not been definitively determined, with one study showing no difference in the combined endpoint of death, CHF hospitalisation or worsening CHF with three different doses of enalapril92 ,while another found a non-significant reduction in mortality and a significant but small reduction in the combined Practice Point endpoint of death and all-cause hospitalisation93 with All patients with systolic LV higher doses of lisinopril. These data have been dysfunction, both asymptomatic interpreted in many ways; however there is general and symptomatic, should be agreement that all patients should be established on established on at least low at least low doses of ACE inhibitors, with an effort doses of ACE inhibitors with an made to up-titrate to higher doses if possible, but not effort made to up-titrate to higher at the expense of introduction, where appropriate, of doses if possible. beta-blockade.

Beta-Blockers As with ACE inhibitors, beta-blockers inhibit the adverse effects of chronic activation of a key neurohormonal system (in this case, the sympathetic nervous system acting on the myocardium). The adverse effects of this sympathetic activation are mediated via 1-receptors, 2-receptors and/or 1-receptors. Three beta-blockerscarvedilol (1, 2 and 1 antagonist),94 bisoprolol (1-selective antagonist, not available in Australia)95 and metoprolol extended release,96 (1selective antagonist, formulation not currently available in Australia)have been shown to prolong survival in patients with mild to moderate CHF already receiving background ACE inhibitor therapy. More recently, carvedilol has been shown to prolong survival in patients with severe CHF symptoms97 who did not have overt volume overload or recent acute decompensation. Patients with minimal symptoms (New York Heart Association Class II)22 derive little symptomatic benefit from beta-blocker therapy. In contrast, symptomatic benefits are observed in patients with more advanced disease.94,95,96 Symptomatic benefit is delayed with beta-blockade and this may be an important issue in decision-making about starting beta-blockers in severely symptomatic patients with limited life expectancy.

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Chronic Heart Failure Clinical Practice Guidelines Beta-blockers should not be initiated during a phase of CHF decompensation but only after the patients condition has stabilised. Adverse effects of beta-blockade in the setting of CHF may be observed and include symptomatic hypotension, worsening of underlying disease due to withdrawal of sympathetic drive, and bradycardia. However, side effects are often transitory and do not usually necessitate cessation of the drug. Diuretics Combination therapy with an ACE inhibitor and a diuretic is often necessary in CHF management, as an ACE inhibitor alone often does not provide adequate relief from congestive symptoms. Diuretics have been shown to increase urine sodium excretion and decrease the physical signs of fluid retention in patients with CHF, thus rapidly improving symptom status. In fluid-overloaded patients the aim is to achieve an increase in urine output and weight reduction of 0.51 kg daily, generally with loop diuretics, until clinical euvolemia is achieved. At this point, diuretics should be down-titrated, if possible. The dose of diuretic should be regularly reassessed, as dosage may need to be adjusted based on volume status. Patients should also be monitored for hypokalaemia when treated with a loop diuretic. Loop and thiazide diuretics are often given together in clinical practice although objective data supporting this combination is limited. Spironolactone Although traditionally considered a potassium-sparing loop diuretic, spironolactone has a number of other properties that make it an important agent in the treatment of CHF. Aldosterone receptors within the heart mediate fibrosis, hypertrophy and arrhythmogenesis. Blockade of these receptors with spironolactone may theoretically provide benefit in CHF. This hypothesis has recently been supported by the observation of a reduction in allcause mortality and symptomatic improvement in patients with advanced CHF receiving spironolactone (average dose 25mg per day) compared with placebo.98 The risk of the potentially lethal adverse effect of hyperkalaemia, particularly in the setting of concomitant renin-angiotensin system blockade and/or renal impairment, mandates vigilance when using spironolactone. Spironolactone is also an androgenreceptor antagonist and thus may be associated with feminisation-type side effects, such as gynaecomastia. Digitalis The cardiac glycoside, digoxin, acts to inhibit sodium-potassium ATPase in patients with ventricular dysfunction; blockade of this enzyme has been associated with improved inotropic responsiveness. Digoxin may also sensitise cardiopulmonary baroreceptors, reduce central sympathetic outflow, increase vagal activity and has been shown to reduce renin secretion. There have been a number of studies in patients in sinus rhythm supporting the favourable effect of digoxin on symptoms and ejection fraction. In about 30% of patients, withdrawal of digoxin in the presence of an ACE inhibitor leads to progressive clinical deterioration in symptom status as well as exercise tolerance.99 In contrast, the only placebo-controlled trial of mortality with digoxin yielded a neutral outcome in comparison to placebo.100 A reduction in deaths due to worsening CHF with digoxin therapy was offset by an increase in sudden death. However, digoxin therapy was accompanied by a reduction in hospitalisation for worsened CHF and

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Chronic Heart Failure Clinical Practice Guidelines patients with more severe symptoms appeared to obtain symptomatic benefit from the introduction of digoxin. Digoxin remains valuable therapy in CHF patients with concomitant atrial fibrillation. Other Drugs Hydralazine/Isosorbide Dinitrate This combination of vasodilator drugs has demonstrated marginal superiority compared with placebo for overall mortality101 but no benefit with respect to hospitalisation rates. The ACE inhibitor, enalapril, was clearly shown to be superior to hydralazine and isosorbide dinitrate in decreasing mortality by reducing the rate of sudden death.102 Angiotensin II Receptor Antagonists It is uncertain whether angiotensin II (AII) receptor antagonists offer additional benefits in comparison to ACE inhibitors. AII receptor antagonists are generally better tolerated than ACE inhibitors because of lack of kinin-mediated side effects, such as dry cough. On the other hand, inhibition of kinin breakdown by ACE inhibitors may be an important component of the beneficial mechanism of these agents (that is, bradykinin-induced nitric oxide synthesis). Comparative studies of ACE inhibitors versus AII antagonists have demonstrated equivalence between the two agents, however there was a significant mortality benefit conferred by the combination of ACE inhibitor and beta-blocker compared to the AII receptor antagonist and beta-blocker combination.103 It is possible (but not, as yet, confirmed) that combination therapy with ACE inhibitors and AII antagonists may maximise the benefits of blockade of the renin-angiotensin system.104 At present, however, AII receptor antagonists are only recommended for use as an alternative to ACE inhibitors for patients who are ACE-intolerant due to kinin-mediated adverse effects, such as a cough.104 Calcium Antagonists Calcium antagonists have been studied in patients with LV dysfunction because of their vasodilating and anti-ischaemic effects. Non-dihydropyridine calcium antagonists that are direct negative inotropes, such as verapamil and diltiazem, are contraindicated in patients with systolic heart failure; however diltiazem may occasionally be used to reduce excessive exercise-related heart rate acceleration in patients with CHF and atrial fibrillation. Dihydropyridine calcium antagonists have not shown survival benefits in patients with CHF105,106,107 but may be used to treat co-morbidities, such as hypertension and ischaemic heart disease, in these patients.


Treatment of symptomatic diastolic heart failure

Diastolic heart failure is typically seen in patients with hypertensive or valvular heart disease, as well as hypertrophic and/or restrictive cardiomyopathies. The prognosis for diastolic heart failure is usually better than that for systolic dysfunction. Although studies on several classes of agents have been performed, no specific agent has yet been demonstrated to directly improve left ventricular diastolic function. Strategies employed in the management of diastolic heart failure include: reduction of elevated left ventricular filling pressures (with the use of diuretics and/or nitrates);
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Chronic Heart Failure Clinical Practice Guidelines slowing of heart rate (with the use of beta-blockers and/or rate-limiting calcium channel blockers); control of blood pressure in patients with hypertension.

ACE inhibitors and/or angiotensin II receptor blockers are frequently used in diastolic heart failure, although the evidence to support their use is limited. Further clinical trials with both of these classes of agents will help address their role in this setting.

Table 5. Recommendations for treatment of symptomatic CHF Level of evidence* First Line Agents ACE inhibitors, if tolerated, are mandatory in all patients with systolic heart failure (LV ejection fraction <40%), whether symptoms are mild, moderate or severe.89,90 Every effort should be made to up-titrate to the highest tolerated dose of ACE inhibitor.92,93. If this is not possible, a lower dose of ACE inhibitor is preferable to none at all. Diuretics should be used if necessary to achieve euvolaemia in fluid-overloaded patients. In patients with systolic LV dysfunction, diuretics should never be used as monotherapy but should always be combined with an ACE inhibitor to maintain euvolaemia. Beta-blockers are recommended therapy, unless not tolerated or contra-indicated, for all patients with systolic CHF who remain mildly to moderately symptomatic despite appropriate doses of ACE inhibitors and diuretics.94,95,96,97 Beta-blockers can also be recommended for patients with symptoms of advanced CHF.97 Spironolactone is recommended for patients who remain severely symptomatic despite appropriate doses of ACE inhibitors and diuretics.98 AII receptor antagonists may be used as an alternative to ACE inhibitors for patients who are ACE-intolerant due to kininmediated adverse effects e.g. cough.104 Second Line Agents Digoxin can be considered in patients with advanced CHF for relief of symptoms and reduction of hospitalisation.100 It remains valuable therapy in CHF patients with atrial fibrillation. Hydralazine-isosorbide dinitrate should be reserved for patients who are truly intolerant of ACE inhibitors or for whom these agents are contraindicated and no other therapeutic option exists.101 Other agents Amlodipine and felodipine can be used for the treatment of comorbidities in patients with systolic CHF, as they have been shown not to increase mortality.105,106,107
* Evidence levels adapted from NHMRC Guidelines EO = expert opinion
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Chronic Heart Failure Clinical Practice Guidelines


Treatment of advanced systolic heart failure

Positive inotropic agents Oral positive inotropic agents (excluding digoxin) Despite favourable haemodynamic effects, long-term oral therapy with positive inotropic agents has not been demonstrated to reliably improve symptoms or clinical status and has been associated with a significant increase in mortality.108,109,110 Intermittent intravenous outpatient infusions Intermittent (212 hours for 25 days/week) intravenous outpatient infusions are associated with increased mortality for dobutamine (mortality is related to total dose given) and are not recommended. Data on the use of intermittent milrinone are insufficient for any recommendation at present. Inpatient 35 day intravenous infusions These have been found to be safe and are the mechanism for haemodynamic optimisation in many patients with severe CHF. This treatment may achieve clinical stability, thereby enabling introduction of beta-blockade. Continuous home ambulatory inotrope infusion Continuous home infusion of positive inotropes may have a role in improving quality of life in patients who cannot be weaned from inotropic support and would otherwise be unable to be discharged from hospital.111 This therapy can also be used as palliation or as a bridging strategy to transplantation.


Treatment of associated disorders

CHF and cardiac arrhythmia Atrial fibrillation and atrial flutter Paroxysmal or sustained atrial flutter or fibrillation occur frequently in patients with CHF. Atrial fibrillation, in particular, worsens symptomatic status and markedly increases the risk of thromboembolic complications. While electrophysiological ablation prevents recurrence of atrial flutter in about 50% of cases, pharmacotherapy remains the mainstay of treatment of atrial fibrillation. Efforts should be made to restore and maintain sinus rhythm in patients with atrial fibrillation, especially in those with diastolic dysfunction. This may require episodic electrical cardioversion while patients are warfarinised or heparinised. If it is apparent that sinus rhythm cannot be maintained for prolonged periods, therapy should be directed at controlling ventricular response rate (with digoxin, beta-blockers or amiodarone) and reducing thromboembolic risk with warfarin. Prophylactic anti-arrhythmic therapy for patients with CHF includes beta-blockers, amiodarone (for serious tachyarrhythmias such as ventricular tachycardia and some cases of paroxysmal atrial flutter) or sotalol where LV function is only mildly impaired.

Ventricular tachycardia and ventricular fibrillation Although the incidence of ventricular fibrillation increases as LV function worsens, there is still a significant risk in patients with mild to moderate CHF. In many patients ventricular tachycardia is present intermittently as a non-sustained phenomenon and implies increased risk of ventricular fibrillation.

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Chronic Heart Failure Clinical Practice Guidelines Patients with severe systolic dysfunction should be screened for the spontaneous presence of ventricular tachycardia; and the use of amiodarone should be considered in patients with frequent symptomatic ventricular tachycardia, and as a component of therapy in patients at high risk of ventricular fibrillation. Therapy with Class I anti-arrhythmic agents (flecainide, encainide, ethmozin) is generally contra-indicated in the presence of systolic heart failure. Implantable cardioverter defibrillator (ICD) is first-line therapy for patients who have experienced sudden cardiac death (SCD) where LV function is only moderately depressed but CHF has not occurred. The risk of SCD for such patients is reduced within two years of ICD therapy but benefits in total mortality over and above those of drug therapy may take five years to be realised. However, overall survival benefit may not be large compared with amiodarone. ICD therapy has been shown, in terms of survival rates, to be superior to drug therapy in those with LV ejection fraction of 2034%, while there may be no added benefit of ICD for those with an ejection fraction >35%. For those with an ejection fraction <20%, the effect of ICD over medication is marginal; therefore, before recommending an ICD in such patients, consideration must be given to the possibility that mortality from progressive CHF may overwhelm any benefit from the ICD. In these patients amiodarone may prove to be as effective in reducing total mortality.112 Drug therapy may still be required in 2070% of ICD recipients to decrease shock number, reduce battery depletion, suppress confounding arrhythmias and slow ventricular tachycardia rate, making it more amenable to pace termination. CHF and valvular heart disease CHF symptoms are a common cause of presentation in patients with mitral or aortic valve disease. Surgical treatment often normalises cardiac function; however, some patients have residual failure after surgery and a minority are unsuitable surgical candidates. Patients with severe aortic stenosis, an increasing cause of CHF in older people, respond poorly to medical therapy. Arterial vasodilators, including ACE inhibitors are relatively contra-indicated in these patients because of the risk of coronary hypoperfusion. Appropriate medical therapy should therefore include digoxin and diuretics. CHF and ischaemic heart disease Reversible myocardial ischaemia may occur with little or no discomfort (for example, in older people and those with diabetes) and prolonged ischaemia may lead to apparently fixed dysfunction of the left ventricle (myocardial hibernation). For these reasons, revascularisation may represent the primary therapeutic option in selected patients presenting with symptoms of CHF. CHF patients with demonstrable reversible ischaemia should be considered for myocardial revascularisation procedures. Practice Point Calcium antagonists should probably be Drugs to avoid in CHF: avoided as anti-anginal therapy in patients with LV ejection fractions below 40%. 1. Anti-arrhythmic agents (apart from betablockers and amiodarone). Beta-blockers represent a major component of anti-anginal therapy in CHF, and should 2. Calcium antagonists that are direct be used whenever tolerated. negative inotropic agents, such as Prophylactic nitrate therapy should usually be a component of anti-anginal therapy in CHF. verapamil and diltiazem. 3. Tricyclic anti-depressants. 4. Non-steroidal anti-inflammatory drugs and COX-2 inhibitors.

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Chronic Heart Failure Clinical Practice Guidelines Patients with severe angina and inoperable disease, together with systolic heart failure, should be considered for prophylactic therapy with perhexiline, as long as regular monitoring of plasma drug levels is performed to prevent toxicity. Decubitus angina (nocturnal angina associated with orthopnoea) should be treated essentially as CHF. Useful specific measures include prescribing loop diuretic in the afternoon (to minimise filling pressures overnight) and prophylactic nitrate therapy at night.

CHF and arthritis CHF patients with severe systolic dysfunction and/or hyponatraemia should not be treated with large doses of COX inhibitors (both non-selective and COX-2-selective) for arthritis, as they will increase the risk of worsening CHF.113 Low-dose aspirin (up to 150 mg/day) appears to be well-tolerated in patients with CHF. Higher doses should probably be avoided.114 There is controversy at present regarding a possible interaction between aspirin and ACE inhibitors that might decrease the efficacy of the latter agents.115 CHF and chronic renal dysfunction The presence of renal dysfunction and/or renovascular disease should be considered in all CHF patients who are elderly or have a past history of hypertension. During initiation of therapy with ACE inhibitors, creatinine concentrations may increase markedly in patients with renovascular disease. While this increase is occasionally hazardous, ACE inhibitors may be safely used in the majority of patients with minor degrees of renal functional impairment. Renal dysfunction is also associated with impaired clearance of digoxin; to avoid toxicity the maintenance dosage should be reduced. Risk of spironolactone-induced hyperkalaemia is also increased in the presence of renal dysfunction, even with very low doses of the drug.

Malignant disease Cancer chemotherapy, with anthracycline derivatives in particular, may lead to the development of CHF; the risk is directly related to cumulative anthracycline dosage. Pre-existent impairment of LV systolic function represents a relative contraindication to aggressive chemotherapy with such agents.

9 9Ancillary therapies
9.1 Pacing
Practice Point Only a minority of highly selected patients are suitable for cardiac surgery for the primary indication of CHF. Careful evaluation, generally by cardiologists specialising in the management of CHF, is essential. All patients with severe CHF and angina require a specialist consultation.

Pacing may be needed to treat symptomatic bradyarrhythmias. The pacing mode is determined by the atrial rhythm but, whenever possible, atrioventricular synchrony should be maintained in view of the significant contribution of atrial filling to cardiac output in CHF. Consideration should be given to upgrading a ventricular pacemaker to a dual-chambered device in patients with CHF who have ECG evidence of organised atrial activity. Rate-responsiveness may also be a useful pacing characteristic in CHF patients. The use of biventricular pacing to resynchronise cardiac contraction in patients with systolic heart failure and left bundle branch block is currently the
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Chronic Heart Failure Clinical Practice Guidelines subject of several international trials. Early to medium-term results are promising, with symptomatic benefit in patients programmed in biventricular mode.116 Longerterm and mortality data are awaited.


Surgery (other than revascularisation)

Surgical management of mitral regurgitation can produce significant improvement in both symptoms and LV function. Left ventricular aneurysmectomy may benefit patients with CHF in whom a large aneurysm can be excised, particularly if the remaining myocardium is functionally normal and there is minimal residual coronary artery disease. Left ventricular free-wall excision (frequently with concomitant mitral valve repair/replacement) aims to restore normal mass/volume ratio in patients with severe LV dilatation. This procedure has not yet been subjected to the clinical trials needed to define its place (if any) in the management of CHF117 and has largely been abandoned in favour of attention to mitral regurgitation. Cardiomyoplasty via stimulated skeletal muscle wraps have been used to augment the function of the failing left ventricle in patients with NYHA Class III symptoms and only modest LV dilatation.118 Because of disappointing results with this approach, non-stimulated synthetic wraps, which passively restrict LV dilatation, have more recently been evaluated.119 Left ventricular assist devices (LVADs) are most often used as a temporary bridge to cardiac transplantation or for recovery of the heart post-cardiac surgery.120 While they have occasionally been used as a medium-term alternative to cardiac transplantation, no device is approved for this indication. The prohibitive cost, large size, lack of total implantability and risk of complications (especially infection and thromboembolism) limit the widespread use of currently available LVADs in patients with end-stage CHF. Cardiac transplantation is an accepted form of therapy for certain patients with refractory CHF.121 Five-year survival is 6575%, but donor shortage means it is only available to a very small subset of patients. Generally accepted indications for transplantation are listed in Table 6 and contraindications in Table 7. Patients with NHYA Class IV symptoms, who are candidates for transplantation and who are not responding to manipulation of medical therapy, should be referred early for assessment as the development of end-organ dysfunction may exclude them as recipients.

Table 6. Indications for cardiac transplantation

Definite: Persistent NYHA class IV symptoms VO2 max <10 mls/kg/min Severe ischaemia not amenable to revascularisation Recurrent, uncontrollable ventricular arrhythmias NYHA class III VO2 max <14 mls/kg/min + major limitation Recurrent unstable angina with poor LV function EF <20% without significant symptoms Past history of NYHA class III or IV symptoms VO2 max >14 mls/kg/min without other indication



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Chronic Heart Failure Clinical Practice Guidelines Table 7. Contraindications to cardiac transplantation
Age > 65 Active infection Untreated malignancy or treated malignancy in remission and <5 years follow-up Fixed high pulmonary pressures (pulmonary vascular resistance >4 Wood units or mean transpulmonary gradient >12mmHg or PA systolic pressure >60mmHg) Current substance abuse (including tobacco and alcohol) Co-existing systemic illness likely to limit survival Severe and irreversible major organ dysfunction Adverse psycho-social factors limiting compliance with medical therapy Recent pulmonary embolism (<6 weeks) Diabetes mellitus with severe or progressive end-organ damage Morbid obesity Unhealed peptic ulceration

10 1-Palliative support in chronic heart failure

The quality of life of patients with CHF can be poor and comparable to that of a cancer sufferer.122,123,124 In particular, patients with Class IV CHF have both significant symptoms and one-year mortality rate.125 Many of these patients, therefore, may benefit from symptom palliation, psychosocial support and referral to community support services.123 Some patients may require assistance in negotiating the change of their goals of care, from prolongation of life to a primary emphasis on improving quality of life by maximising comfort and dignity. Treating doctors should discuss with their patients the level of intervention appropriate and/or desirable during this phase of their illness, so that unwanted, traumatic interventions are prevented in the last few days of life.126 Both the patient and their family and carers may need significant emotional support during this process.

10.1 Symptom control

Dyspnoea Dyspnoea is a common symptom, affecting approximately 65% of people with CHF. It may be mediated by numerous pathophysiological mechanisms127, including: afferent signals from ventilatory muscles and mechanoreceptors in the upper airways, bronchi, epithelium or alveolar walls; hypercapnia and hypoxia (via chemoreceptors).

Patients may therefore have no dyspnoea even when hypoxic/hypercapnic or, conversely, be very dyspnoeic without either. The palliative goal is to improve the patients subjective sensation rather than correct abnormal parameters. Dyspnoea can be palliated by various approaches such as:

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Chronic Heart Failure Clinical Practice Guidelines

Oxygen The use of oxygen may reverse hypoxia and allow increased activity. However, it may tie the patient to the oxygen source, cause a persistent dry mouth, impede communication between patients and their carers, and exacerbate claustrophobia. The cost of home oxygen is a concern for patients with financial constraints. As there may be a significant placebo response with the administration of oxygen, it is important to determine if the patient requires oxygen continuously, or only during exacerbations of their symptoms. Benzodiazepines These are given regularly to relieve the anxiety associated with dyspnoea. Benzodiazepines can also be used to manage panic attacks arising from the anxietydyspnoea cycle. Opioids It is thought that opioids have their effect by increasing patients exercise tolerance, resulting in lowered ventilation requirements and, thus, lowered perception of breathlessness for a given workload.128 Opioids should be titrated against symptomatic response. The optimum route and dose regimen remains unclear but it appears that opioids do improve dyspnoea.129,130 Frequent bolus doses may be more effective than slow-release formulations or continuous infusions.130 The role of nebulised opioids remains unclear.131,132,133, 134 Parenteral Diuretics If the patient is unable to take diuretics orally and intravenous access is unavailable, they can be given subcutaneously. Other Measures Advice on posture, relaxation techniques and having a flow of air across the face (from a fan or an open window) may all provide comfort. The beneficial effect of a flow of air is thought to be due to the action of inhibitory fibres from facial receptors.127 Uraemia Rather than develop dyspnoea, patients sometimes choose to continue with diuretics and/or other medications, knowing that this will result in progressive renal impairment. The resulting uraemic nausea, mediated via the chemoreceptor trigger zone, can be palliated using a subcutaneous infusion of haloperidol or another antiemetic. Uraemic itch may respond to steroids and agitated delirium may be treated with neuroleptics such as haloperidol. Morphine-metabolite accumulation occurs in patients with renal impairment, resulting in clinical features of neuroexcitation such as agitated delirium and frequent myoclonus.135,136,137. Opioids with less evidence of this phenomenon138, such as fentanyl, should therefore be considered.139 Lower limb oedema When severe this is associated with serous exudate, requiring good nursing care to prevent trauma to the skin. Elevation of the lower limbs, when resting or sleeping, can improve the degree of oedema to a limited extent.

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Chronic Heart Failure Clinical Practice Guidelines

Cardiac cachexia Cachexia should be managed with an unrestricted calorie intake and dietary supplements (protein milks, Sustagen etc.). Other symptoms The symptoms of terminal heart disease can also include pain, nausea, constipation and lowered mood.123,140

Practice Point Treating doctors should discuss with their patients the level of intervention appropriate and/or desirable during this phase of their illness, so that unwanted, traumatic interventions are prevented in the last few days of life129. Both the patient and their family and carers may need significant emotional support during this process.

10.2 Community palliative support

Many patients and their carers are unaware of the possibility of receiving palliative care support at home but, when informed of these services, some patients wish to die at home with these supports in place. Many of these services also provide counsellors who can give emotional support, to patients and carers, during the terminal phase of the patients illness as well as bereavement support to carers following the patients death.141,142,143

Literature regarding palliation of chronic heart failure Much of the literature quoted regarding dyspnoea is from study populations with advanced cancer or chronic airways disease. Although the same principles probably apply, some caution should be shown in translating these findings to people with CHF.

Support Agencies and Services Cardiomyopathy Association of Australia Ltd.

The aims of the association are: To provide the opportunity for individuals and their families to share their experiences and to support one another. To provide accurate and up to date information about Cardiomyopathy, when it is available, to the members, their families and those in the medical profession. To increase public awareness of Cardiomyopathy. To foster medical research in this area.

The Cardiomyopathy Association of Australia Ltd has contact people in most states. For details of your nearest contact person please phone Heartline: 1300 36 27 87 Or Website: Heart Support Australia

The aims of the organisation are to: To provide free-of-charge peer support, lay counselling and other support assistance to persons with any form of heart condition, their carers and their families.

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Chronic Heart Failure Clinical Practice Guidelines To support medical and health professionals in providing local and national rehabilitation and education programs for such persons to ensure their physical, psychological and social wellness so that they may attain their optimum potential. To encourage members and clients in such a manner that they are motivated to comply with the advice of their consulting medical and health professionals so that they may commit themselves to a lifetime maintenance program. To engage in any other work or program which will benefit Heart SupportAustralia, its members, clients and the general public. For details of your nearest Heart Support Australia group please phone Heartline: 1300 36 27 87 Hospitals

Some metropolitan and regional hospitals have heart failure clinics or specialist services for heart failure patients. Contact your local hospital for details of any services near you.

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Chronic Heart Failure Clinical Practice Guidelines

11 Management flowcharts
11.1 Diagnostic algorithm for chronic heart failure
Suspected heart failure Shortness of breath Fatigue Oedema

Clinical history Physical examination Initial investigations

Confirmed clinical diagnosis of heart failure


Structural diagnosis e.g. myopathic, valvular

Pathophysiological diagnosis Systolic dysfunction (LVEF <40%) Diastolic dysfunction

Consider specialist referral re further investigation Clinical history Symptoms of heart failure Dyspnoea Orthopnoea PND Fatigue Oedema Palpitations/syncope Past cardiovascular disease Angina/MI Hypertension Diabetes Murmur/valvular disease Cardiomyopathy Alcohol/tobacco use Medications

Proceed to treatment algorithm

Physical examination Pulse rate and rhythm Blood pressure Elevated JVP Cardiomegaly Cardiac murmurs Lung crepitations Hepatomegaly Oedema Ascites

Initial investigations Blood tests Full blood count Electrolytes Renal function Liver function Thyroid function ECG CXR

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Questions the specialist must answer

Questions the specialist must answer

What is the underlying cause? What is the predominant pathophysiology?

What is the precipitating cause?

Is it surgically correctable? Predominant systolic heart failure Predominant diastolic heart failure

Is it reversible/ preventable?

Mixed systolic/diastolic

Proceed to Section 11.3 Specialist advanced diagnostic algorithm Proceed to treatment algorithm (Section 11.7 management of diastolic heart failure)

Proceed to treatment algorithms (Sections 11.4 asymptomatic LV dysfunction 11.5 systolic CHF NYHA Class II and III 11.6 systolic CHF NYHA Class IV)

Proceed to treatment algorithms (Sections 11.4 asymptomatic LV dysfunction 11.5 systolic CHF NYHA Class II and III 11.6 systolic CHF NYHA Class IV)

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Specialist advanced diagnostics algorithm

Is there surgically correctable disease?

Coronary heart disease

Valvular heart disease

Congential heart disease

Pericardial disease

Clinical indicators of myocardial viability e.g. Angina No documented MI No/few pathological Q waves on ECG Further non-invasive investigation depending on lesion identified on transthoracic echocardiography Further non-invasive investigation depending on lesion identified on transthoracic echocardiography

Thoracic CT scan* MRI scan

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Is there hibernating myocardium*? Dobutamine stress echo Nuclear imaging PET imaging

Cardiac catheterisation +/Coronary angiography

Cardiac catheterisation +/Coronary angiography

Cardiac catheterisation +/Coronary angiography

Cardiac catherisation Coronary angiography Valve repair/ replacement

Catheter/ surgical correction

Pericardial drainage/ resection


* The choice of imaging modality will vary according to local availability and institutional expertise

Chronic Heart Failure Clinical Practice Guidelines

11.4 Treatment of asymptomatic LV dysfunction

Treatment of systolic heart failure (LVEF < 40%) Asymptomatic LV dsyfunction (NYHA Class I)

Non-pharmacologic management Exercise/conditioning program Risk factor modification e.g. smoking/alcohol cessation, diet

Pharmacological management ACE inhibitor Beta-blocker

Disease-specific treatment e.g. IHD - aspirin, beta-blocker, statin HT - second agent if needed

11.5 Treatment of systolic heart failure (NYHA Class IV)

Treatment of systolic heart failure (NYHA Class II and III) (LVEF < 40%)
Mild-moderate symptomatic heart failure


Correct/Prevent acute precipitants e.g. non-compliance acute ischaemia/infarction arrhythmia**

Pharmacological management

Non-pharmacological management General counselling* Exercise/conditioning program Low salt diet * General counselling regarding prognosis, importance of compliance, exercise & rehabiliation, lifestyle modification, self-monitoring, patient education and support, smoking cessation and limitation of alcohol. ** Patients in AF should be anticoagulated with target INR of 2.0 --3.0. Amiodarone may be used to control AF rate or attempt cardioversion. Electrical cardioversion may be considered after 4 weeks if still in AF. Digoxin will slow resting AF rate. *** Most commonly prescribed first choice diuretic is a loop diuretic e.g. frusemide, however there is no evidence that loop diuretics are more effective or safer than thiazides. Diuretic dose should be reduced when symptom status improves. **** Or AII receptor antagonist if patient is ACE-intolerant.

fluid overload Yes Diuretic*** + ACE inhibitor**** No ACE inhibitor****

Persistent oedema


Beta blocker

Add spironolactone +/- Digoxin

Beta blocker


Beta blocker

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Chronic Heart Failure Clinical Practice Guidelines


Treatment of systolic heart failure (NYHA Class IV)

Treatment of systolic heart failure (LVEF < 40%)

Severe symptoms (NYHA Class IV)

Identify/treat acute precipitant e.g.acute ischaemia/infarction arrhythmia non-compliance

Non-pharmacological treatment Salt/fluid restriction Exercise/conditioning program

Pharmacological treatment

Diuretic + ACE inhibitor * Patients with NYHA Class IV heart failure should be challenged with beta blockers provided they have been rendered euvolaemic and do not have any contra-indication to beta blockade. ** Pallative care options may include use of multiple diuretics, hydralazine, nitrates and/or short term use of inotropic agents to control intractable heart failure symptoms.

No improvement


Add spironolactone +/Digoxin

Add beta blocker

Add beta blocker (irrespective of NYHA Class*)

No improvement/ not tolerated


Consider heart transplantation if age < 65 years + no major co-morbidity

Palliative care if unsuitable for for heart transplantation**

Continue medical treatment

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Management of diastolic heart failure

Management of diastolic heart failure (heart failure with preserved systolic function)

Is there fluid overload**?

Is there an identifiable cause?

Yes Hypertension Ischaemic heart disease

Yes Diuretic

No No Treat cause


Anti-hypertensive therapy***

Investigate suitability for revascularisation

Hypertrophic CM Investigate family history

Restrictive CM

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** With rare exception, patients with diastolic heart failure present with symptoms and signs of fluid overload, either pulmonary or systemic congestion or both.

Pharmacological treatment ACE inhibitor Beta blocker Calcium antagonist

Pharmacological treatment Beta blocker Calcium antagonist

Endomyocardial biopsy for infiltrative diseases e.g. sarcoidosis amyloidosis

*** Choice of therapy will vary according to clinical circumstances eg. thiazide diuretic - elderly, systolic hypertension ACE inhibitor - LVH, diabetes, IHD Beta blocker - angina.

If no specific cause found consider constrictive pericarditis

Surgical pericardiectomy

Chronic Heart Failure Clinical Practice Guidelines

12 Supporting people with CHF

Each year around 30% of people with CHF are hospitalised because of their condition6. People with CHF are able to reduce the likelihood and frequency of hospitalisation by understanding how changes in their health may be related to CHF, and by understanding the actions they can take to limit symptoms. Multidisciplinary care for people with CHF will provide support and information to: help improve the understanding of people with CHF and their families and carers about their CHF and its potential interaction with other health conditions; aid understanding about how they can reduce its impact upon their lives; support people in adjusting to, and sustaining, any lifestyle changes required; help people understand what the treatment options are; inform people about the possible course of their disease, and support people in communicating and making decisions with health advisers.

Self-management implies that the person is taking responsibility for his or her own health. In order for this to be effective, the following information should be discussed and reviewed openly and often with each person with CHF, and his or her carers and family when appropriate.
Lifestyle Rehabilitation participation, including exercise and activity in the long term. Food (esp. salt intake), fluid intake via foods and liquids, alcohol. Quitting smoking. Personal energy conservation, sleep disturbance, sexual function changes. Depression, coping with change/emotions and changes in family roles. Changes in activity (temporary/permanent), ability to work/study/travel. Pregnancy, contraception, genetic predispositions. Practical measures e.g. alert bracelet, diary for daily weights/medications. Selecting appropriate medical assistance for CHF/other health conditions. Accessing support services such as Heart Support Australia (HSA), Cardiomyopathy Association of Australia (CMAA), home help, financial assistance.

Personal issues Medical issues Support

Each person with CHF needs to become well practised at: monitoring weight changes (alert doctor if weight increases by 1.5 kg in 24 hrs or take diuretic if part of management plan); monitoring other symptoms, noting questions for doctor visits, and understanding the effects of different medications, taking medications correctly and practically, and being aware of medication interactions.

Information for people with CHF, including a set of frequently asked questions (FAQs), based on these guidelines, is accessible through the Heart Foundations information service Heartline - phone 1300 36 27 87 and the Heart Foundation website Check your local phone directory for contact details for Heart Support Australia and the Cardiomyopathy Association of Australia in each state.

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Chronic Heart Failure Clinical Practice Guidelines



Appendix I: NHMRC Designation of Levels of Evidence (1995)1

Levels of evidence
Level I Explanation Evidence obtained from a systematic review of all relevant randomised controlled trials. Evidence obtained from at least one properly designed randomised controlled trial. Evidence obtained from any of the following: Well-designed pseudo-randomised controlled trials (alternate allocation or some other method). Comparative studies with concurrent controls and allocation not randomised (cohort studies), case-control studies, or interrupted time series with a control group. Comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group.




Evidence obtained from case series, either post-test or pre-test and post-test. Opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees.

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Chronic Heart Failure Clinical Practice Guidelines

Appendix II: Writing Panel Members

Chair NHF CSANZ RACGP Medical specialists

Heart Support Australia Cardiomyopathy Association of Australia NHF Program Managers Medical Editor Peer Review Panel

A/Prof Henry Krum Prof Andrew Tonkin A/Prof Michael Jelinek Dr Mark Harris Prof John McNeil, Dr David Hunt, Dr David Kaye, A/Prof Louise Burrell, A/Prof Leonard Arnolda, A/Prof Anne Keogh, Dr Peter Bergin, Dr Warren Walsh, A/Prof Andrew Sindone, Dr David Hare, Ms Di Holst, Dr Gerry ODriscoll, Prof John Horowitz, Dr Meroula Richardson, Dr Julian Smith, Dr Phil Spratt, Prof Leon Piterman, Dr Ian Cameron, A/Prof Peter Macdonald, Dr Andrew Galbraith, Dr Alan Henderson, Ms Kylie Oliver, Dr Peter Martin, Dr Jack Minas Mr Gerry Atkinson Ms Bev Motteram

Ms Helen Egan Ms Sueann Case Dr Jacinta Halloran Dr Michael Feneley, National Heart Foundation Cardiovascular Heart Advisory Committee Dr Mark Harris, UNSW, Royal Australian College of General Practitioners (RACGP) National Preventive Care Committee Prof Terry Campbell, Royal Australian College of Physicans (RACP) nominee, President, CSANZ President A/Prof Michael Jelinek, Cardiac Society of Australia and New Zealand (CSANZ) Continuing Education and Recertification Committee Dr Ken Hossack, Cardiac Society of Australia and New Zealand (CSANZ) Continuing Education and Recertification Committee Dr Mariell L. Jessup, ACC/AHA Task Force on Practice Guidelines, American College of Cardiology /American Heart Association Mr James Dunne, Flinders Medical Centre, Cardiac nurse (research) Prof Hamid Ikram, Christchurch Hospital (NZ), Cardiac Society of Australia and New Zealand (CSANZ) Prof Norman Sharpe, Auckland Hospital, NZ Guideline Group Prof Paddy Phillips, Flinders Medical Centre, Levels of Evidence oversight Prof Michel Komajda, European Society of Cardiology Working Group on Heart Failure, Chairman Dr Leslie E. Bolitho, Australian College of Rural and Remote Medicine (ACRRM)

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Chronic Heart Failure Clinical Practice Guidelines

Appendix III: Specific activities scale of functional capacity22 Any Yes 1. Can you walk down a flight of steps without stopping? 2. Can you carry something up a flight of 8 steps without stopping? Or can you: (a) have sexual intercourse without stopping? (b) garden, rake, weed? (c) walk at 6km/hr on level ground? 3. Can you carry at least 10 kgs up 8 steps? Or can you: (a) carry objects that are at least 36 kgs? (b) ski, play basketball, squash? 4. Can you shower without stopping? Or can you: (a) mop floors? (b) hang out wet clothes? (c) clean windows? (d) walk 4km/hr ? (e) play golf walk and carry clubs? (f) push power lawn mower? 5. Can you dress without stopping? go to 2 go to 3 No go to 4 Class III

Class I

Class II

Class III

go to 5

Class III

Class IV

Appendix IV: Metabolic equivalents diagram


METS Speed % Grade* Speed % Grade* Speed % Grade** METS MI.O2/kg/min CLINICAL STATUS


1.0 0 1.6 5.6

9 10 11 12 13 5.47 kms per hour 2 4 6 8 10 12 14 16 18 20 4.83 kms per hour 0 2.5 5 7.5 10 12.5 15 17.5 20 22.5 3.22 kms per hour 0 3.5 7 10.5 14 17.5 2 3 4 5 6 7 8 9 10 11 12 13 7 14 21 28 35 42 Symptomatic Patients Diseased, Recovered Sedentary Healthy Physically Active Subjects III II I and Normal

14 22

15 24

16 26

14 49


16 56



* Balke ** Naughton

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Chronic Heart Failure Clinical Practice Guidelines

Appendix V: Glossary (Adapted from Your Guide to CHF, Alfred Hospital, 1998143) ACE inhibitor

medication that blocks an enzyme which, in turn, dilates the blood vessels and reduces stress on the heart.

Antiarrhythmic medication that controls the heart rhythm. Cardiac catheterisation (cardiac cath or angiogram) a test in which a small tube (catheter) is inserted into an artery in the arm or leg and guided towards the heart. Contrast dye is injected into the coronary arteries and the heart chambers. The dye is filmed as it moves through the heart valves, coronary arteries and chambers. Cardiac rehabilitation a program of education, counselling and activity to support lifestyle changes and provide peer support. Cardiomyopathy a condition that directly weakens the heart muscle. Chronic heart failure (CHF, heart failure or congestive heart ailure) a condition where the heart muscle weakens and cannot pump blood efficiently through the body. Diabetes mellitus a condition in which the body does not produce or respond to insulin (a hormone, produced by the body, which allows blood sugar or glucose to enter the bodys cells). Diastolic heart failure related to stiffness of the heart muscle. The most common cause is high blood pressure. Diuretic (fluid tablet) medication which helps remove extra fluid from the tissues and the blood stream. Dyspnoea breathlessness or difficulty breathing. (echo) Echocardiogram

a picture of the heart valves and chambers, produced from ultrasound waves that come from a hand piece placed on the chest. Electrocardiogram (ECG) a picture of the electrical impulses travelling through the heart muscle, captured through a trace on graph paper. Fatigue tiredness, lethargy. Inotropic agent medication that improves that hearts pumping ability.

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Chronic Heart Failure Clinical Practice Guidelines

Myocardial infarction (heart attack, infarct, coronary) an area of heart muscle is damaged and scarred as a result of a blocked coronary artery. Orthopnoea breathlessness when lying flat. Paroxysmal nocturnal dyspnoea (PND) intense shortness of breath that awakens a person from sleep. Systolic heart failure heart failure that occurs when the pumping action of the heart is weakened. The most common cause is ischaemic heart disease. Vasodilator medication that relaxes the blood vessels in order to decrease the hearts work or reduce blood pressure.

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. National Health and Medical Research Council of Australia (NHMRC) Quality of Care and Health Outcomes Committee: Guidelines for the development and implementation of clinical practice guidelines. 1995. Australian Government Publishing Service, Canberra. 2. Yamani M, Massie BM. Congestive heart failure: insights from epidemiology, implications for treatment. Mayo Clin Proc 1993; 68:1214-18. 3 . Kannel WB, Cupples A. Epidemiology and risk profile of cardiac failure. Cardiovasc Drugs Ther 1988; 2 (Suppl 1): 387-95. 4. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med 1971; 285(26): 1441-6. 5. Australian Institute of Health and Welfare (AIHW). Heart, Stroke and Vascular Diseases, Australian facts. AIHW and Heart Foundation of Australia (Cardiovascular Disease Series No.10). AIHW Cat No CVD 7, Canberra 1999. 6. Krum H, Tonkin AM, Currie R, Djundjek R, Johnston CI. Frequency, awareness and pharmacological management of chronic heart failure in Australian general practice. The Cardiac Awareness Survey and Evaluation (CASE) Study. Med J Aust 2001; 174: 439-444. 7 . Kelly DT. Paul Dudley White International Lecture. Our future society. A global challenge. Circulation 1997; 95(11): 2459-2464. 8 . Kostis JB, Davis BR, Cutler J et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group. JAMA 1997; 278: 212-216. 9 . Devereux RB, Agabiti-Rosie E, Dahlof B, Gosse P. Hahn RT, Okin PM, Roman MJ. Regression of left ventricular hypertrophy as a surrogate end-point for morbid events in hypertension treatment trials. J Hypertens Suppl 1996 Sep;14(2):S95-101. 10 . Shepherd J, Cobbe SM, Ford I, Isles CG, Loriner AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333(20): 1301-7. 11 . The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339(19): 1349-57. 12 . Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 1996; 335(14):1001-9. 13 . Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet 1994; 344(8934): 13893-9. 14 . American College of Cardiology/American Heart Association guidelines for the management of patients with acute myocardial infarction, 1999. 15 . UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853. 16 . 1999 Guide to Management of Hypertension for Doctors. National Heart Foundation of Australia, 1999. 17 . Schrier RW, Abraham WT. Mechanisms of Disease: Hormones and Hemodynamics in Heart Failure. N Engl J Med 1999; 341(8): 577-585. 18 . MacLellan WR. Advances in the molecular mechanisms of heart failure. Curr Opin Cardiol 2000; 15(3): 128-135. 19 . Narula J, Lolodgie FD, Virmani R. Apoptosis and cardiomyopathy. Curr Opin Cardiol 2000; 15(3): 183-188.

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. Suersh DP, Lamba S, Abraham WT. New developments in heart failure: role of endothelin and the use of endothelin receptor antagonists. J Card Fail 2000; 6(4): 359-368. 21 . Blum A, Miller H. Pathophysiological role of cytokines in congestive heart failure. Ann Rev Med 2001; 52: 15-27. 22 . Goldman L, Hasimoto B, Cook EF, et al. Comparative reproducibility and validity of systems for assessing cardiovascular functional class; advantages of a new specific activity scale. Circulation 1981; 64(6): 1227-1234. 23 . Lipkin DP, Scriven AJ, Poole-Wilson PA. Six-minute walking test for assessing exercise capacity in chronic heart failure. BMJ 1986; 292: 653-655. 24 Bittner V, Weiner DH, Yusef S et al. Prediction of mortality and morbidity with a 6-minute walk test in patients with left ventricular dysfunction. JAMA 1993; 270: 1702-1707. 25 . Guyatt GH, Sullivan MJ, Thompson PJ et al. The six-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J 1985; 132: 919923. 26 . Poole-Wilson PA. Six minute walk predicts prognosis in patients with heart failure. Eur Heart J 2000; 21: 507-8. 27 . Mancini D, Eisen H, Kussmaul W et al. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991; 83: 78-86. 28 . Stelken AM, Younis LT, Jennison SH et al. Prognostic value of cardiopulmonary exercise testing using percent achieved of predicted peak oxygen uptake for patients with ischemic and dilated cardiomyopathy. J Am Coll Cardiol 1996; 27: 345-352. 29 . Metra M, Faggiano P, DAloia A et al. Use of cardiopulmonary exercise testing with hemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure. J Am Coll Cardiol 1999; 33: 943-950. 30 . Tjan TD, Krondruweit M, Scheld HH et al. The bad ventricle-revascularization versus transplantation. Thorac Cardiovasc Surg 2000; 48: 1-6. 31 . Louie HW, Hillel L, Milgalter E et al. Ischaemic cardiomyopathy criteria for coronary revascularization and cardiac transplantation. Circulation 1991; 84[Suppl III]: lll-290-lll-295. 32 . Elefteriades JA, Tolis G, Levi E et al. Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state. J Am Coll Cardiol 1993; 22: 1411-7. 33 . Marwick TH, Shan K, Go RT et al. Use of positron emission tomography for prediction of perioperative and late cardiac events before vascular surgery. Am Heart J 1995; 130: 1196-1202. 34 . Stevenson LW, Tillisch JH, Hamilton M et al. Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or non-ischemic dilated cardiomyopathy. J Am Coll Cardiol 1990; 66(19): 13481354. 35 . Mc Carthy RE, Boehmer JP, Hruban RH et al. Long-term outcome of fulminant myocarditis as compared with acute (non-fulminant) myocarditis. N Engl J Med 2000; 342: 690-695. 36 . Troughton RW, Frampton CM, Yandle TG et al. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000; 355: 1126-1130. 37 . Hobbs RE, Miller LW, Bott-Silverman C et al. Hemodynamic effects of a single intravenous injection of synthetic human brain natriuretic peptide in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy [congestive heart failure]. Am J Cardiol 1996; 78(8): 896-901. 38 . Chua TP, Coats AJS. The lungs in chronic heart failure. Eur Heart J 1995; 16(7): 882887. 39 . Guazzi M, Agostino P, Natturri M et al. Pulmonary function, cardiac function and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol. Am Heart J 1999; 138: 460-467.


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Chronic Heart Failure Clinical Practice Guidelines


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Chronic Heart Failure Clinical Practice Guidelines

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Chronic Heart Failure Clinical Practice Guidelines

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Chronic Heart Failure Clinical Practice Guidelines

. Pitt B, Poole-Wilson PA, Segal R et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial-the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582-1587. 104 . Pitt B, Segal R, Martinez FA et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE) Lancet 1997; 349: 747-752. 105 . Packer M, OConnor CM, Ghali JK et al. Effect of Amlodipine on Survival Evaluation Study Group. N Engl J Med 1996; 335: 1107-1114. 106 . Packer M. Primary results of the PRAISE II Study. Presented at Annual Scientific Meeting of the American College of Cardiology, 2000, Anaheim, CA, USA. 107 . Cohn JN, Ziesche S, Smith R et al. Effect of the calcium antagonist, felodipine, as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group. Circulation 1997; 96(3): 856-863. 108 . Packer M, Carver JR, Rodeheffer RJ et al for the PROMISE Study Research Group: Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991; 325: 1468-1475. 109 . Hampton JR, van Veldhuisen DJ, Kleber FX et al for the Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators: Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Lancet 1997; 349: 971-977. 110 . The Xamoterol in Severe Heart Failure Study Group: Xamoterol in severe heart failure. Lancet 1990; 336(8706): 1-6. 111 . Sindone AP, Keogh AM, Macdonald PS, McCosker CJ, Kaan AF. Continuous home ambulatory intravenous inotropic drug therapy in severe heart failure: safety and cost efficacy. Am Heart J 1997; 134(5, part 1): 889-900. 112 . The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmics-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997 Nov 27; 337(22): 1576-83. 113 . Page J, Henry D. Consumption of NSAIDS and the development of congestive heart failure in elderly patients: an under-recognized public health problem. Arch Intern Med 2000; 160(6): 777-784. 114 . Cleland JG, Bulpitt CJ, Falk RH et al. Is aspirin safe for patients with heart failure? Br Heart J 1995; 74(3): 215-219. 115 . Hall D. The aspirin-angiotensin-converting enzyme inhibitor trade-off: to halve and halve not. J Am Coll Cardiol 2000; 35: 1808-1812. 116 . Hauer RN, Aliot E, Block M, Capucci A, Luderitz B, Santini M, Vardas PE. Indications for implantable cardioverter defibrillator (ICD) therapy. Study Group on Guidelines on ICDs of the Working Group on Arrhythmias and the Working Group on Cardiac Pacing on the European Society of Cardiology. Eur Heart J 2001; Jul 22(13): 1074-1081. 117 . Dreyfus G, Mihealainu S. The Batista procedure. Heart 2001; 85: 1-2. 118 . Jessup M. Dynamic cardiomyoplasty: expectations and results. J Heart Lung Transplant 2000; 19(8 Suppl): S68-S72. 119 . Raman JS, Power JM, Buxton B et al. Ventricular containment as an adjunctive procedure in ischaemic cardiomyopathy: early results. Ann Thorac Surg 2000; 70(3): 11241126. 120 . Jaski BE, Lingle RJ, Reardon LC et al. Left ventricular assist device as a bridge to patient and myocardial recovery. Prog Cardiovasc Dis 2000; 43(1): 5-18. 121 . Dabol R, Edwards NM. Cardiac transplantation and other therapeutic options in the treatment of end-stage heart disease. Compr Ther 2000; 26(2): 109-113. 122 . Hinton JM. The physical and mental stress of dying. Q J Med 1963; 32: 1-21. 123 . Gibbs LM, Addington-Hall J, Gibbs SJ. Dying from heart failure: lessons from palliative care. BMJ 1998; 317: 961-962.


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Chronic Heart Failure Clinical Practice Guidelines

. Stewart Al, Greenfield S, Hays RD et al. Functional status and well being of patients with chronic conditions. Results from the Medical Outcomes Study. JAMA 1989; 262: 907913. 125 . Watson RD, Gibbs CR, Lip GY. ABC of heart failure: clinical features and complications. BMJ 2000; 320(7229): 236-239. 126 . Lynn J, Teno JM, Phillips RS et al. Perceptions by family members of the dying experience of older and seriously ill patients. Ann Intern Med 1997; 126: 97-106. 127 . Manning HL, Schwartzstein RM. Pathophysiology of dyspnoea. New Engl J Med 1995; 333(23):1547-1552. 128 . Light RW, Muro JR, Sato RI et al. Effects of oral morphine on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. Am Rev Resp Dis 1989; 139: 126-133. 129 . Bruera E, Macmillan K, Pither J et al. Effects of morphine on the dyspnoea of terminal cancer patients. J Pain Symptom Manage 1990; 5(6): 341-344. 130 . Allard P, Lamontagne C, Bernard P et al. How effective are supplementary doses of opioids for dyspnoea in terminally ill cancer patients? A randomized continuous sequential clinical trial. J Pain Symptom Manage 1999; 17(4): 256-265. 131 . Davis C. The role of nebulised drugs in palliating respiratory symptoms of malignant disease. European Journal of Palliative Care 1995; 2: 9-15. 132 . Leung R, Hill P, Burdon J. Effect of inhaled morphine on the development of breathlessness during exercise in patients with chronic lung disease. Thorax 1996; 51: 596-600. 133 . Enck RE. The role of nebulized morphine in managing dyspnea. The American Journal of Hospice & Palliative Care 1999; 16(1): 373-374. 134 . Chandler S. Nebulized opioids to treat dyspnea. The American Journal of Hospice & Palliative Care 1999 (January/February): 418-422. 135 . Milne RW, Nation R, Somogi L, Somogi AA. The deposition of morphine and its 3- and 6- glucuronide metabolites in humans and animals, and the importance of the metabolites to the pharmacological effects of morphine. Drug Metabolism Reviews 1996; 28(3): 345472. 136 . Mercadante S. The role of morphine glucuronides in cancer pain. Palliative Medicine 1999; 13: 95-104. 137 . Ashby MA, Fleming B, Wood M et al. Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients. J Pain Symptom Manage 1997; 14:157-167. 138 . Clotz MA, Nahata MC. Clinical uses of fentanyl, sufentanil and alfentanil. Clinical Pharmacy 1991; 10: 581-593. 139 . Ashby M, Martin P, Jackson K. Opioid substitution to reduce adverse effects in cancer pain management. Med J Aust 1999; 170: 68-71. 140 . Addington-Hall JM, McCarthy M. Regional study of care for the dying. Palliative Medicine 1995; 9: 27-35. 141 . Cushin M. Palliative care in severe heart failure. BMJ 1994; 308: 717. 142 . Gannon C. Palliative care in terminal cardiac failure. BMJ 1995; 310: 1410-1411. 143 . Your Guide to CHF. Alfred Hospital, Melbourne, 1998.


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