Guidelines for management of patients with chronic heart failure in Australia

Note: This document has now been superseded by the 2006 edition. Click here to access the 2006 edition.

Abstract

• Chronic heart failure (CHF) affects approximately 1% of people aged 50-59 years, and this high prevalence increases dramatically with age.
  
• CHF is a common reason for hospital admission and general practitioner consultation in the elderly.
  
• Common causes of CHF are ischaemic heart disease, hypertension and idiopathic dilated cardiomyopathy.
  
• Diagnosis of CHF is based on clinical features and objective measurement of ventricular function (eg, echocardiography).
  
• Management is directed at prevention, retarding disease progression, relief of symptoms and prolonging survival.
  
  • Non-pharmacological approaches include exercise, home-based support and risk-factor modification.
    
  • Angiotensin-converting enzyme (ACE) inhibitors are the cornerstone of pharmacological therapy to prevent disease progression and prolong survival.
    
  • ß-Blockers prolong survival when added to ACE inhibitors in symptomatic patients.
    
  • Diuretics provide symptom relief and restoration or maintenance of euvolaemia.
    
  • Spironolactone, angiotensin II receptor antagonists and digoxin may be useful in some patients.
    
  • Surgical approaches in highly selected patients may include myocardial revascularisation, insertion of devices and cardiac transplantation.

Most of the current information on the epidemiology of chronic heart failure (CHF) is derived from seven major overseas epidemiological studies published since 1985.¹ There have been several consistent findings, including a sharp increase in prevalence with age and a marked male preponderance.² The prevalence of CHF is approximately 1% in people aged 50 to 59 years, but over 50% in people 85 years and older.

Information on the overall incidence and prevalence of CHF in Australia is derived mainly by extrapolation of overseas information. Based on data from the United States,³ it is likely that at least 300 000 Australians are affected with CHF and about 30 000 new cases are diagnosed annually. There are more reliable Australian data regarding hospitalisation for CHF -- in 1996 and 1997, 41 000 hospitalisations reported CHF as a principal diagnosis, and CHF accounted for 0.8% of all hospitalisations in Australia in these two years, with patients 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.⁴

CHF also constitutes a common reason for consultations with general practitioners. A recent survey of 341 Australian general practitioners estimated that, for every 100 patients aged 60 years and over seen in general practice, 11 had known CHF and two would be newly diagnosed as having CHF based on clinical features and known aetiological factors.⁵

The cost burden associated with CHF is expected to increase markedly⁶ because of a number of factors, including:

• ageing of the population;

• the projected increase in the number of older people with coronary heart disease and hypertension;

• the decrease in case-fatality rates associated with acute coronary syndromes; and

• improved diagnosis of CHF because of increased use of sensitive techniques, such as echocardiography.

There are no precise data for Australia relating to the economic burden associated with CHF. However, direct health costs for cardiovascular disease in 1993-94 were estimated at $3719 million (12% of total health care costs), and CHF has been estimated to account for $411 million of these costs, including $140 million per annum for costs of hospitalisation and $135 million per annum for nursing home costs.

Causes and diagnosis

Although systolic and diastolic CHF often coexist, the distinction between them is relevant to the therapeutic approach. Causes of chronic heart failure are shown in Box 1.

Diagnosis is based on well-known clinical features and appropriate investigations, not only to confirm or exclude the diagnosis of CHF, but also to establish underlying causes for which particular treatment is necessary.

Recommendations relating to the diagnosis of CHF are shown in Box 2.

Management of chronic heart failure

General non-pharmacological measures are important in the management of CHF and are summarised in Box 3, and recommendations for therapy in asymptomatic patients or to prevent CHF are summarised in Box 4.

Details supporting the use of drugs in systolic CHF are summarised in Box 5 and the management of diastolic CHF is summarised in Box 6.

Angiotensin-converting enzyme (ACE) inhibitors

Because of the major importance of renin-angiotensin system activation in the 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 (compared with placebo) in patients with New York Heart Association Class II, III and IV CHF;^31,32

• improve patient symptom status, exercise tolerance and reduce hospitalisation for worsening CHF⁴⁵ (in some but not all studies); and

• increase ejection fraction compared with placebo in many studies.

The optimal dose of ACE inhibitor has not been definitively determined. In one study that examined ACE inhibitor dosage, there was no difference in the combined endpoint of death, CHF hospitalisation or worsening CHF whether enalapril was used at 2.5 mg, 5 mg or 10 mg twice daily.⁴⁶ In a study comparing lisinopril at doses of 2.5-5 mg and 32.5-35 mg daily, there was a marginal, non-significant reduction in mortality, with a significant but rather small (12%) reduction in the combined endpoint of death and all-cause hospitalisation with the higher dose.³⁴ These data have been interpreted in many ways, but there is general agreement that all patients with CHF should be established on therapy with at least low doses of ACE inhibitors, and that an effort should be made to up-titrate to higher doses if possible.

ß-Blockers

As with ACE inhibitors, ß-blockers inhibit the adverse effects of chronic activation of a key neurohormonal system (in this case, the sympathetic nervous system) on the myocardium. These adverse actions may be mediated via ß₁-receptors, ß₂-receptors, and/or α₁-receptors.

Three ß-blockers — carvedilol (ß₁-, ß₂- and α₁-antagonist),³⁵ bisoprolol (ß₁-selective antagonist, not currently available in Australia)³⁶ and metoprolol extended release (ß₁-selective antagonist, formulation not currently available in Australia)³⁷ — 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 (35% relative reduction in risk of death)³⁹ in a prospective study of patients with severe CHF symptoms who did not have overt volume overload or recent acute decompensation. Similar observations have been made from post-hoc analyses of subgroups with advanced heart failure symptoms in the above trials of metoprolol and bisoprolol.

ß-Blocker therapy should not be initiated during a phase of decompensation, but only after the patient's condition has stabilised. ß-Blockers should be started at very low initial doses, then up-titrated slowly to target dose, with the expectation that it may take some months before clinical benefits occur. Adverse effects of initiation of ß-blockade in CHF are commonly observed and include symptomatic hypotension, worsening of underlying disease because of withdrawal of sympathetic drive, and bradycardia. However, side effects are usually transitory and rarely necessitate cessation of ß-blocker therapy.

Patients with minimal symptoms (New York Heart Association Class II) derive little symptomatic benefit from ß-blocker therapy,⁴⁷ while clinically significant improvements in symptom status are observed in those with more advanced disease. Symptomatic benefit is delayed with ß-blockade, and this may be an important issue in decision-making about starting the drug in severely symptomatic patients with limited life expectancy.

Diuretics

Diuretics are used to improve symptoms. They have been shown to increase urine sodium excretion and to decrease the physical signs of fluid retention in patients with CHF, thus rapidly improving symptom status. In patients with fluid overload, the aim is to achieve an increase in urine output and weight reduction of 0.5-1 kg daily, generally with loop diuretics, until euvolaemia (evaluated from clinical symptoms and signs as well as the patient's bodyweight) is achieved. Combined use of loop and thiazide diuretics is often used in clinical practice, although objective data supporting this combination are limited.

The dose of diuretic should be regularly reassessed, as dosage may need to be adjusted based on whether the patient is considered to be volume overloaded or underloaded on clinical evaluation.

Spironolactone

Although traditionally considered a potassium-sparing loop diuretic, spironolactone has a number of other potential properties that make it an important agent in the treatment of CHF. Aldosterone receptors within the heart mediate fibrosis, hypertrophy and arrhythmogenesis. Thus, blockade of these receptors with spironolactone may theoretically provide benefit in CHF.

This hypothesis has recently been supported by the observation of a 30% reduction in all-cause mortality and symptomatic improvement in advanced CHF patients receiving spironolactone (average, 25 mg per day) compared with placebo.⁴⁰

The risk of the potentially lethal adverse effect of hyperkalaemia, particularly in the setting of concomitant renin-angiotensin system blockade and/or renal impairment, makes careful monitoring mandatory when using spironolactone.

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 with CHF and sinus rhythm that support the favourable effect of digoxin on symptoms and ejection fraction. Withdrawal of digoxin in the presence of an ACE inhibitor leads to progressive clinical deterioration in symptom status as well as exercise tolerance.⁴²

In contrast, the only placebo-controlled trial of mortality with digoxin yielded a neutral outcome.⁴³ While deaths from worsening CHF were reduced with digoxin therapy, this was offset by an increase in sudden deaths. However, digoxin therapy was accompanied by a reduction in hospitalisation for worsened CHF and patients with more severe symptoms appeared to benefit symptomatically from the introduction of digoxin.

Digoxin remains valuable therapy in CHF patients with concomitant atrial fibrillation (AF).

Other drugs

• Hydralazine and isosorbide dinitrate — This combination of vasodilator drugs has shown marginal superiority compared with placebo in terms of overall mortality,⁴⁸ and no benefit for hospitalisation. The ACE inhibitor enalapril was clearly shown to be superior to hydralazine and isosorbide dinitrate by reducing sudden deaths.⁴⁴

• Angiotensin II receptor antagonists — It is uncertain whether angiotensin II (AII) receptor antagonists offer additional benefits over ACE inhibitors. They are generally better tolerated than ACE inhibitors because they do not produce 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 their beneficial mechanism (ie, bradykinin-induced nitric oxide synthesis).

Comparative studies of ACE inhibitors versus AII antagonists have tested these hypotheses,^49,50 but have shown no evidence for superiority of AII receptor antagonists; indeed, there was a significant mortality benefit with the combination of ACE inhibitor and ß-blocker compared with the AII receptor antagonist and ß-blocker combination.⁵⁰

It is possible (but not yet confirmed) that combination therapy with ACE inhibitors and AII antagonists may maximise the benefits of renin-angiotensin system blockade.⁴¹ There may also be an adverse interaction of this combination with ß-blockers.⁴¹

Based on the above findings, AII receptor antagonists may be considered as an alternative to ACE inhibitors for patients who are truly ACE-inhibitor intolerant as a result of kinin-mediated adverse effects such as cough.⁴¹

Drugs to avoid in chronic heart failure

• Anti-arrhythmic agents (apart from ß-blockers and amiodarone) should be avoided because of their pro-arrhythmic potential, negative inotropic effects, and a tendency to increase mortality.

• Calcium antagonists that are direct negative inotropic agents, such as verapamil and diltiazem, are absolutely contraindicated in patients with systolic CHF. Dihydropyridine calcium antagonists such as amlodipine and felodipine offer no survival benefit in systolic CHF.^51-53

• Tricyclic antidepressants should be avoided because of their pro-arrhythmic potential.

• Non-steroidal anti-inflammatory drugs (NSAIDs)⁵⁴ should be avoided, as they can inhibit the effects of diuretics and ACE inhibitors and can worsen both cardiac and renal function. Cyclooxygenase (COX)-2 inhibitors appear to have similar adverse effects on salt and water retention as do standard NSAIDs.⁵⁵

Pharmacological therapies reserved for advanced chronic heart failure

Positive inotropic agents can improve cardiac performance during short-term and long-term therapy. -Adrenergic agonists (eg, dobutamine) and phosphodiesterase inhibitors (eg, milrinone) enhance cardiac contractility by increasing myocardial levels of cyclic adenosine monophosphate. However, despite favourable short-term haemodynamic and clinical effects, long term oral therapy with positive inotropic agents has not been shown to reliably improve symptoms or clinical status and has been associated with a significant increase in mortality.^56-58 For similar reasons, long term intermittent infusions of positive inotropic therapy are not recommended.

A small proportion of patients can not be weaned from inotropes despite repeated attempts, but are well enough with inotrope therapy to be managed at home with the aid of a portable pump and long-term IV access. This can be used as a bridging strategy to heart transplantation, or as palliation.

Treatment of associated disorders

CHF and cardiac arrhythmia

• Efforts should be made to restore and maintain sinus rhythm in patients with atrial fibrillation (AF). This may require episodic electrical cardioversion while patients are anticoagulated with warfarin. If sinus rhythm can not be maintained for prolonged periods, therapy should be directed at controlling the ventricular response rate (with digoxin, -blockers or amiodarone) and reducing thromboembolic risk by anticoagulation with warfarin.⁵⁹

• Use of amiodarone should be considered in patients who have frequent episodes of symptomatic ventricular tachycardia (VT), and as a component of therapy in patients at high risk of ventricular fibrillation (VF).

• Therapy with Class I anti-arrhythmic agents (eg, flecainide) is generally contraindicated in the presence of systolic CHF.

CHF and ischaemic heart disease

• Specific treatment of ischaemia may represent the primary therapeutic option in selected patients presenting with symptoms of CHF.

• CHF patients with demonstrably reversible ischaemia should be considered for myocardial revascularisation procedures.

• Calcium antagonists should generally be avoided as anti-anginal therapy in patients with left ventricular ejection fractions below 40%.

• -Blockers represent a major component of anti-anginal therapy in CHF, and should be used whenever tolerated.

• Prophylactic nitrate therapy should usually be a component of anti-anginal therapy in CHF.

• Patients with severe angina and inoperable disease, together with systolic CHF, may be considered for prophylactic therapy with perhexiline, as long as plasma drug levels are monitored regularly to prevent toxicity.

CHF and arthritis

CHF patients with severe systolic dysfunction, hyponatraemia, or both, should not be treated with large doses of COX inhibitors (both non-selective and COX-2-selective) for arthritis, as these drugs will increase the risk of worsening CHF.^54,55

Low-dose aspirin (up to 150 mg/day) appears to be well tolerated in patients with CHF. Higher doses should probably be avoided.⁶⁰ There is controversy at present about a possible interaction between aspirin and ACE inhibitors which might decrease the efficacy of the ACE inhibitors.⁶¹

Ancillary therapies

Pacing

Pacing may be needed to treat symptomatic bradyarrhythmias. Whenever possible, atrioventricular synchrony should be maintained in view of the significant contribution of atrial filling to cardiac output in CHF. Upgrading a ventricular pacemaker to a dual-chamber device should be considered in patients with CHF who have electrocardiographic 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 CHF and left bundle branch block is currently the subject of several international trials. Results so far are promising, with symptomatic benefit in patients programmed in biventricular mode.⁶² Longer-term and mortality data are awaited.

Surgery (other than revascularisation)

Surgical management of mitral regurgitation can produce significant improvement in both symptoms and left ventricular 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 or replacement) aims to restore a normal myocardial mass-to-volume ratio in patients with severe left ventricular dilatation. This procedure has not yet been subjected to the clinical trials needed to define its place (if any) in managing CHF.⁶³

Cardiomyoplasty via stimulated skeletal muscle wraps has been used to augment the function of the failing left ventricle in patients with New York Heart Association Class III symptoms and only modest left ventricular dilatation.⁶⁴ Because of disappointing results with this approach, non-stimulated synthetic wraps, which passively restrict LV dilatation, have more recently been evaluated, with promising initial results.⁶⁵

Left ventricular assist devices (LVADs) are most often used as a temporary bridge to cardiac transplantation or for recovery of the heart after cardiac surgery.⁶⁶ While they have occasionally been used as a long-term alternative to cardiac transplantation, no device is approved for this indication. The prohibitive cost, large size, the fact that only part of the device is implantable 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 therapy for certain patients with refractory CHF who meet eligibility criteria.⁶⁷ The five-year survival is 65%-75%, but a shortage of donors means it is available only for a very small subset of patients.

Diastolic heart failure

Diastolic heart failure is common and may account for up to 40% of patients with heart failure. A proposed schema for management of diastolic heart failure is summarised in Box 6. It is important to note that these recommendations for therapy represent expert opinion only, as no randomised controlled trial has yet been completed with any agent specifically for diastolic CHF.

Disclosure

Many members of the Writing Panel have received paid honoraria for work performed on behalf of manufacturers of therapies described in these guidelines. However, no members of the Writing Panel stand to gain financially from their involvement in these guidelines and no conflicts of interest exist for Writing Panel members, the National Heart Foundation or the Cardiac Society of Australia & New Zealand.

Reference

1. Yamani M, Massie BM. Congestive heart failure: insights from epidemiology, implications for treatment. Mayo Clin Proc 1993; 68: 1214-1218.
2. Kannel WB, Cupples A. Epidemiology and risk profile of cardiac failure. Cardiovasc Drugs Ther 1988; 2 Suppl 1: 387-395.
3. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med 1971; 285: 1441-1446.
4. Australian Institute of Health and Welfare. Heart, stroke and vascular diseases, Australian facts. Canberra: AIHW and Heart Foundation of Australia, 1999. (AIHW Catalogue no. CVD 7; Cardiovascular Disease Series No.10.)
5. Krum H, Tonkin AM, Currie R, et al. 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.
6. Kelly DT. Paul Dudley White international lecture. Our future society. A global challenge. Circulation 1997; 95: 2459-2464.
7. Mancini DM, Walter G, Reichek N, et al. Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation 1992; 85: 1364-1373.
8. Coats AJS, Adamopolous S, Meyer TE, et al. Effects of physical training in chronic heart failure. Lancet 1990; 335: 63-66.
9. Bellardinelli R, Georgiou D, Cianci G, et al. Randomised, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, capacity, quality of life, and clinical outcome. Circulation 1999; 99: 1173-1182.
10. Keteyian SJ, Levine AB, Brawner CA, et al. Exercise training in patients with heart failure. A randomised, controlled trial. Ann Intern Med 1996; 124: 1051-1057.
11. Rich MW, Beckham V, Wittenberg C, et al. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995; 333: 1190-1195.
12. Stewart S, Vandenbroek A, Pearson S, et al. Prolonged beneficial effects of a home-based intervention on unplanned readmissions and mortality among patients with congestive heart failure. Arch Intern Med 1999; 159: 257-261.
13. Naughton MT. Impact of treatment of sleep apnoea on left ventricular function in congestive heart failure. Thorax 1998; 53 Suppl 3: S37-S40.
14. McDonald CD, Burch GE, Walsh JJ. Prolonged bed rest in the treatment of idiopathic cardiomyopathy. Am J Med 1972; 52: 41-50.
15. The National Heart Foundation of New Zealand, Cardiac Society of Australia and New Zealand and the Royal New Zealand College of General Practitioners Working Party. New Zealand guidelines for the management of chronic heart failure. N Z Med J 1997; 110: 99-107.
16. The Task Force of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Eur Heart J 1997; 18: 736-753.
17. A guide to the development, implementation and evaluation of clinical practice guidelines. Canberra: NHMRC 1999.
18. Nicklas JM, Pitt B, Timmis G, et al. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992; 327: 685-691.
19. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement Trial. N Engl J Med 1992; 327: 669-677.
20. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145-153.
21. 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.
22. MRC Working Party Medical Research Council. Trial of treatment in older adults: principal results. BMJ 1992, 304: 405-412.
23. Dahlof B, Lindholm JH, Hansson L, et al. Morbidity and mortality in the Swedish trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991, 338: 1281-1285.
24. Hansson L, Lindholm LH, Niskanen L, et al. Principal results of the Captopril Prevention Project (CAPP) randomised trial. Lancet 1999, 353: 611-616.
25. Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the international nifedipine GITS study: intervention as a goal in hypertension treatment. Lancet 2000; 356: 366-372.
26. Hansson L, Hedner T, Lund-Johansen P, et al Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet 2000; 356: 359-365.
27. Psaty BM, Smith NL, Siscovick DS, et al. Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. JAMA 1997; 277: 739-745.
28. Dargie HJ. Design and methodology of the CAPRICORN trial -- a randomised double blind placebo controlled study of the impact of carvedilol on morbidity and mortality in patients with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail 2000; 2: 325-332.
29. Freemantle N, Cleland JGF, Young P, et al. Beta-blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999; 318: 1730-1777.
30. Kjekshus J, Pedersen TR, Olsson AG, et al. The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail 1997; 3: 249-254.
31. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 1991; 325: 293-302.
32. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316: 1429-1435.
33. Armstrong PW, Moe GW. Medical advances in the treatment of congestive heart failure. Circulation 1993; 88: 2941-2952.
34. Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation 1999; 100: 2312-2318.
35. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996; 334: 1349-1355.
36. CIBIS II investigators and committees. The cardiac insufficiency bisoprolol study II (CIBIS II): a randomised trial. Lancet 1999; 353: 9-13.
37. MERIT Investigators. Effect of metoprolol CR/XL in chronic heart failure. Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353: 2001-2007.
38. Carson PE. Beta-blocker treatment of heart failure. Prog Cardiovasc Dis 1999; 41: 301-321.
39. Packer M, Coats AJS, Fowler MB, et al, for the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group. Effect of carvedilol on the survival of patients with severe chronic heart failure. New Engl J Med 2001. In press.
40. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709-717.
41. Thackray SD, Witte KK, Khand A, et al. Clinical trials update: highlights of the scientific sessions of the American Heart Association year 2000: Val HeFT, COPERNICUS, MERIT, CIBIS-II, BEST, AMIOVIRT, V-MAC, BREATHE, HEAT, MIRACL, FLORIDA, VIVA and the first human cardiac skeletal muscle myoblast transfer for heart failure. Eur J Heart Fail 2001; 3: 117-124.
42. Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med 1993; 329: 1-7.
43. Digitalis Intervention Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336: 525-533.
44. Cohn JN, Johnson G, Ziesche S, et al A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991; 325: 303-310.
45. Pflugfelder PW, Baird MG, Tonkon MJ, et al. Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind placebo-controlled study of quinapril. J Am Coll Cardiol 1993; 22: 1557-1563.
46. The NETWORK Investigators. Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison. Eur Heart J 1998; 19: 481-489.
47. Australia/New Zealand Heart Failure Research Collaborative Group. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Lancet 1997; 349: 375-380.
48. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986; 314: 1547-1552.
49. 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.
50. 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.
51. Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on survival. Evaluation Study Group. N Engl J Med 1996; 335: 1107-1114.
52. Thackray S, Witte K, Clark AL, Cleland JG. Clinical trials update: OPTIME-CHF, PRAISE-2, ALL-HAT. Eur J Heart Fail 2000; 2: 209-212.
53. 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: 856-863.
54. Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. Arch Intern Med 2000; 160: 777-784.
55. Swan SK, Rudy DW, Lasseter KC, et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial. Ann Intern Med 2000; 133: 1-9.
56. 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.
57. 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.
58. The Xamoterol in Severe Heart Failure Study Group. Xamoterol in severe heart failure. Lancet 1990; 336: 1-6.
59. Mackstaller LL, Alpert JS. Atrial fibrillation: a review of mechanism, etiology, and therapy. Clin Cardiol 1997; 20: 640-650.
60. Cleland JG, Bulpitt CJ, Falk RH, et al. Is aspirin safe for patients with heart failure? Br Heart J 1995; 74: 215-219.
61. Hall D. The aspirin-angiotensin-converting enzyme inhibitor tradeoff: to halve and halve not. J Am Coll Cardiol 2000; 35: 1808-1812.
62. Barold SS. Biventricular cardiac pacing : promising new therapy for congestive heart failure. Chest 2000; 118: 1819-1812.
63. Dreyfus G, Mihealainu S. The Batista procedure. Heart 2001; 85: 1-2.
64. Jessup M. Dynamic cardiomyoplasty: expectations and results. J Heart Lung Transplant 2000; 19 (8 Suppl): S68-S72.
65. Raman JS, Power JM, Buxton BF, et al. Ventricular containment as an adjunctive procedure in ischemic cardiomyopathy: early results. Ann Thorac Surg 2000; 70: 1124-1126.
66. Jaski BE, Lingle RJ, Reardon LC, Dembitsky WP. Left ventricular assist device as a bridge to patient and myocardial recovery. Prog Cardiovasc Dis 2000; 43: 5-18.
67. Dabol R, Edwards NM. Cardiac transplantation and other therapeutic options in the treatment of end-stage heart disease. Compr Ther 2000; 26: 109-113.

Authors' details

National Heart Foundation of Australia, Melbourne, VIC.
Henry Krum, MB BS, PhD, Associate Professor, Department of Epidemiology and Preventive Medicine, and Department of Medicine, Monash University, Alfred Hospital, Melbourne, VIC.

Correspondence: Associate Professor H Krum, Clinical Pharmacology Unit, Department of Epidemiology and Preventive Medicine, and Department of Medicine, Monash University, Alfred Hospital, Prahran, 3181 VIC.
henry.krumATmed.monash.edu.au
* See background and evidence basis of recommendations box at the end of the article.

Background and evidence basis of recommendations This article is a summary of evidence-based clinical practice guidelines on the best practice management of chronic heart failure (CHF) in the Australian setting recently developed by the National Heart Foundation of Australia (NHF) and the Cardiac Society of Australia & New Zealand (CSANZ). Financial and administrative support was drawn from both organisations. These guidelines were written by a multi-disciplinary panel comprising Associate Professor Henry Krum (Chair); Professor Andrew Tonkin (NHF); Associate Professor Michael Jelinek (CSANZ); Dr Mark Harris (Royal Australian College of General Practitioners); Professor John McNeil, Dr David Hunt, Dr David Kaye, Associate Professor Louise Burrell, Associate Professor Leonard Arnolda, Associate Professor Anne Keogh, Dr Peter Bergin, Dr Warren Walsh, Associate Professor Andrew Sindone, Dr David Hare, Ms Di Holst, Dr Gerry O'Driscoll, Professor John Horowitz, Dr Meroula Richardson, Dr Julian Smith, Dr Phil Spratt, Professor Leon Piterman, Dr Ian Cameron, Associate Professor Peter Macdonald, Dr Andrew Galbraith, Dr Alan Henderson, Ms Kylie Oliver, Dr Peter Martin; Mr Gerry Atkinson (Heart Support Australia); Ms Bev Motteram (Cardiomyopathy Association of Australia); Ms Helen Egan (NHF Program Manager); Dr Jacinta Halloran (medical writer). These guidelines were externally reviewed by the European Society of Cardiology Working Group on Heart Failure, American College of Cardiology/American Heart Association, Royal Australasian College of Physicians, Royal Australasian College of General Practitioners and New Zealand Guidelines Group. The aim was to develop recommendations towards achieving the best health outcomes for people with CHF. Current relevant literature was reviewed, with assessment of the quality of evidence for each recommendation adapted from the NHMRC 1999 Designation of Levels of Evidence.17

1: Causes of chronic heart failure Systolic (impaired ventricular contraction) Common causes: Ischaemic heart disease and prior myocardial infarction Hypertension Less common causes: Non-ischaemic idiopathic dilated cardiomyopathy Uncommon causes: Valvular heart disease Alcoholic cardiomyopathy Inflammatory cardiomyopathy, or myocarditis (traditionally associated with a history of viral infections such as enteroviruses, especially Coxsackie B virus) HIV-related cardiomyopathy Drug-induced cardiomyopathy, especially anthracyclines (eg, daunorubicin and doxorubicin, cyclophosphamide, paclitaxel and mitoxantrone) Peripartum cardiomyopathy Chronic arrhythmia Diastolic (impaired ventricular relaxation) Common causes: Hypertension Ischaemic heart disease Less common causes: Valvular disease, especially aortic stenosis Uncommon causes: Hypertrophic cardiomyopathy Restrictive cardiomyopathy

2: Recommendations for diagnosis of chronic heart failure (CHF) Level of evidence All patients with suspected CHF should have an objective measurement of ventricular function, preferably by transthoracic echocardiography EO Coronary angiography should be considered in patients with CHF who have a history of exertional angina or suspected ischaemic left ventricular dysfunction EO Haemodynamic measurements may be particularly helpful in patients with refractory CHF, recurrent diastolic CHF or in whom the diagnosis of CHF is in doubt EO Endomyocardial biopsy may be indicated in patients with cardiomyopathy with recent onset of symptoms, in whom coronary artery disease has been excluded by angiography, or in whom systolic ventricular dysfunction is suspected EO Nuclear cardiological testing, 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 EO Thyroid function tests should be considered, especially in older patients who develop atrial fibrillation, and who have pre-existing heart disease EO EO=expert opinion.

3: Recommendations for non-pharmacological management of chronic heart failure (CHF) Level of evidence Regular physical activity is recommended.7 All patients with CHF should be referred to an exercise program specifically designed for patients with this condition, if available.7-10 II Patient support by doctor, pre-discharge nurse review with or without home visit is crucial for preventing deterioration in CHF status.11,12 II Sleep apnoea frequently coexists with CHF; patients with obstructive sleep apnoea may benefit from nasal continuous positive airway pressure.13 III CHF patients who have an acute exacerbation or are clinically unstable should have bed rest until their condition improves.14 IV Dietary sodium should be limited to below 200mg daily.15 IV Fluid intake should generally be limited (1.5 litres daily in mild to moderate CHF and 1 litre daily in severe CHF), especially if coexistent with hyponatraemia.16 IV Alcohol intake should generally be nil, but should not exceed 10-20g/day.16 IV Smoking should be strongly discouraged. EO Patients with CHF should be advised to weigh themselves daily and to consult their doctor if their weight increases by more than 1.5kg in a 24-hour period, or if they experience dyspnoea, oedema or abdominal bloating. EO Patients with CHF should be vaccinated against influenza and pneumococcal disease. EO Long flights may predispose to an exacerbation of CHF and should be undertaken with caution. 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. EO EO=expert opinion. Remaining evidence levels adapted from National Health and Medical Research Council Guideines.17

4: Recommendations for prevention of chronic heart failure (CHF) and treatment of asymptomatic left ventricular (LV) dysfunction Level of evidence All patients with asymptomatic systolic LV dysfunction should be treated with an angiotensin-converting enzyme (ACE) inhibitor and maintained on this therapy indefinitely, unless they are intolerant.18-20 I Antihypertensive therapy should be used to prevent subsequent CHF in patients with elevated blood pressure levels.21-27 I Commencement of therapy with an ACE inhibitor in patients at high risk of ventricular dysfunction (but without current evidence of ventricular impairment) may be considered in individual patients.20 II ß-Blockers should be used early after myocardial infarction (whether or not the patient has systolic ventricular dysfunction).28,29 II 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.30 II Evidence levels adapted from National Health and Medical Research Council Guidelines.17

5: Recommendations for treatment of symptomatic chronic heart failure (CHF) Level of evidence First-line agents Angiotension-converting (ACE) enzyme inhibitors, if tolerated, are mandatory in all patients with systolic heart failure (left ventricular ejection fraction, <40%), whether symptoms are mild, moderate or severe.31-33 Every effort should be made to up-titrate to highest tolerance dose of ACE inhibitors.34 If this is not possible, a lower dose of ACE inhibitor to none at all. Diuretics should be used if necessary to achieve euvolaemia in fluid-overloaded patients. In patients with systolic left ventricular dysfunction, diuretics should never be used as monotherapy, but should always be combined with an ACE inhibitor to maintain euvolaemia. EO β-Blockers are recommended therapy, unless not tolerated or contraindicated, for patients with systolic CHF who remain mildly to moderately symptomatic despite appropriate doses of ACE inhibitors, as well as use of diuretics to optimise fluid status.35-38 I β-Blockers can also be recommended for patients with advanced symptoms of CHF.39 II Spironolactone is recommended for patients who have severe heart failure despite appropriate doses of ACE inhibitors and diuretics.40 II Angiotensin II receptor antagonists may be used as an alternative to ACE inhibitors for patients who are truly ACE-intolerant because of kinin-mediated adverse effects (eg, cough).41 II Second-line agents Digoxin can be considered in patients with advanced CHF for relief of symptoms and to reduce hopitalisation.42,43 It remains valuable therapy in CHF patients with atrial fibrillation. II Hydralazine and isosorbide dinitrate should be reserved for patients who are truly intolerant of ACE inhibitors, or for whom ACE inhibitors are contraindicated and no other therapeutic option exists.44 II EO=expert opinion. Remaining evidence levels adapted from National Health and Medical Research Guideines.17

Box 6 * With rare exceptions, patients with diastolic heart failure present with symptoms and signs of fluid overload, either pulmonary or systemic congestion, or both. † Choice of therapy will vary according to clinical circumstances (eg, thiazide diuretics in elderly patients or those with systolic hypertension; angiotension-converting enzyme [ACE] inhibitors in patients with left ventricular hypertrophy, diabetes or ischaemic heart disease; β-Blockers in patients with agina).