Volume 174 Issue 9

Henry Krum, Andrew M Tonkin, Robert Currie, Robert Djundjek and Colin I Johnston MJA 2001; 174: 439-444 For editorial comment, see Horowitz & Stewart; see also Krum Abstract - Methods - Results - Discussion - Acknowledgements - Reference - Authors' details - - More articles on Cardiology and cardiac surgery Abstract Objectives: To investigate the frequency and general practitioner awareness of patients with chronic heart failure (CHF), and to evaluate a cardiac algorithm and document cardiac investigations performed in establishing this diagnosis. Design and setting: Between March and August 1998, consecutive patients aged 60 years and older presenting to their GP were assessed. In patients previously diagnosed with CHF, aetiology and diagnostic assessments were documented. In patients with suspected CHF (by a standardised algorithm, based on World Health Organization guidelines), further investigations and GP diagnosis were recorded. Patients: 80 consecutive patients were assessed by each of 341 GPs throughout Australia, reflecting the Australian metropolitan/rural population mix of 1996. This provided a total of 22 060 evaluable patients. Main outcome measures: Estimated numbers of patients with CHF in general practice (previously and newly diagnosed); major aetiological factors; use of ancillary diagnostic tests; drugs prescribed. Results: CHF was diagnosed in 2905 of 22 060 patients (13.2%) (2485 previously diagnosed and 420 newly diagnosed). Major aetiological factors were ischaemic heart disease and hypertension. Echocardiography had been performed in 64% of previously diagnosed patients, but was performed in only 22% of possible CHF patients. Angiotensin-converting enzyme (ACE) inhibitors were prescribed in 58.1% of patients with CHF. Patients with evidence of left ventricular dysfunction were more likely to have received ACE inhibitors. Conclusions: CHF appears to be very common in the elderly, based on GP diagnosis of the condition. Of 100 patients aged 60 years and over presenting to their GP, two new cases of CHF will be detected using a simple clinical algorithm in conjunction with appropriate diagnostic tests. ACE inhibitors appear to be underutilised. Chronic heart failure (CHF) is a debilitating condition with high morbidity and mortality, and is a major public health burden. Its prevalence is increasing,1 despite a reduction in age-standardised mortality associated with cardiovascular diseases such as myocardial infarction and stroke.2 Factors implicated in this increased prevalence include the ageing of the population, decreased mortality rates following myocardial infarction, and more frequent diagnosis of CHF after investigations such as echocardiography.3The epidemiology of CHF in Australia has been assumed to be similar to that in the United States,4-6 the United Kingdom7-10 and Europe.11,12 However, substantive data have been lacking, and the approach taken to diagnosis of patients with suspected CHF in general practice in Australia is also unknown. Similarly, although international studies have suggested marked underutilisation of angiotensin-converting enzyme (ACE) inhibitors and β-blockers,4-11,13-17 no evaluation of use of drug therapies for CHF in Australia has been reported. Accordingly, the aims of the Cardiac Awareness Survey and Evaluation (CASE) Study were: to investigate the frequency, awareness, and aetiology of heart failure in general practice in Australia; to document cardiac investigations used by general practitioners in establishing the diagnosis of CHF; and to determine prescribing patterns in the treatment of CHF by Australian GPs. As the prevalence of heart failure increases steeply with age, the study focused on people aged 60 years and older. Methods Recruitment into the CASE study GPs were recruited solely on the basis of interest in participating in the study. Interest was first ascertained by the local pharmaceutical representative of the study sponsor (see Acknowledgements). The CASE steering committee then sent interested GPs a formal letter of invitation to participate in the study. GPs agreeing to participate attended a local education and information session. These sessions were spread across all Australian States and Territories with a mix of metropolitan, rural and remote regions in an effort to recruit a sample of GPs (and thus patients) representative of their distribution. Each GP was asked to assess 80 consecutive patients aged 60 years or older for the possibility of heart failure. GPs were recruited from March 1998, data were collected prospectively and the study was completed in August 1998. Assessment for CHF New patients: Patients not previously diagnosed as having CHF were assessed for that possibility using modified World Health Organization criteria (Box 1).18 Alternative conditions that may have contributed to these symptoms and signs were recorded. In patients suspected of having CHF based on the above criteria, further investigations (chest x-ray [CXR], electrocardiogram [ECG], and echocardiogram) were suggested (but not mandated). GPs were also asked to note any investigations that had been performed in the previous 12 months. For patients who had an echocardiogram, the GP was asked to indicate whether there was evidence of systolic or diastolic ventricular dysfunction (or both) from the echocardiogram report. At the conclusion of this process, the GPs assessed whether they thought the patient had CHF. Previously diagnosed patients: For patients who had previously been diagnosed as having CHF by their GP, records were retrospectively analysed for clinical and diagnostic criteria that contributed to that diagnosis. These included use of ECG, CXR and echocardiography, hospital admission for heart failure, and specialist referral for CHF. Pharmacotherapy For patients with previously diagnosed CHF, GPs were asked to document current drug therapy specifically prescribed for this condition (name of drug, daily dose, and frequency of administration). For patients with newly diagnosed CHF, GPs were asked whether they instituted pharmacotherapy immediately and what that pharmacotherapy comprised. A dosage equivalence table of commonly prescribed ACE inhibitors was compiled, and prescribing was divided into low, medium and high doses. To determine prescribing according to decade of life, prescribing was assessed in patients aged 60-69 years (n = 569), 70-79 years (n = 1360), and 80 years and older (n = 976). GP prescribing in patients with echocardiographic evidence of systolic or diastolic left ventricular dysfunction was specifically determined. Initial pharmacotherapy prescribed for patients diagnosed with CHF as part of the CASE study was evaluated. Because of the cross-sectional nature of the assessment in CASE, most of these patients did not have the opportunity to be up-titrated to target doses of drugs. For this reason, newly diagnosed patients were not included in the analysis of dose of ACE inhibitor prescribed. Results Of 523 GPs who originally expressed interest in participating, 341 completed the study. Their geographical distribution (78% metropolitan, 22% rural or remote) was similar to that observed for all Australian GPs (77% metropolitan, 23% rural or remote). In all, 23 845 patients were entered into the study. Of these, 1785 were excluded from analysis because of patient refusal or missing data, leaving 22 060 who made up the baseline population. Baseline demographics The distribution of the CASE patient population by area (capital city, 58.7%; metropolitan, 10.7%; rural, 21.4%; remote, 1.2%; 8% unclassified) was similar to the 1996 Australian population aged 60 years or older.19 However, there were fewer rural patients among the CASE cohort than in the census population. The total CASE study population comprised 45% men and 55% women; 8612 (39%) were aged 60-69 years (48% men), 9371 (42.5%) were aged 70-79 years (45% men) and 4077 (18.5%) were aged 80 years or older (39% men). Patients not previously diagnosed with CHF Box 2 shows the assessment process and results for the 22 060 patients. In the 4807 patients assessed as having possible CHF, at least one further investigation was performed in 2903 (60.4%). To determine whether the CASE audit itself may have prompted further investigation of these patients, the tests were divided into those ordered within the previous 12 months and those ordered subsequent to the CASE audit. Investigations ordered within the 12 months before the CASE audit were ECG in 1953 (40.6%), CXR in 1894 (39.4%), and echocardiogram in 366 patients (7.6%). Investigations subsequent to the CASE clinical assessment were performed in 488 patients who had ECGs (10.2%), 493 who had CXR (10.2%), and 466 who had echocardiograms (9.7%). The diagnosis of CHF was based on symptoms in 73%, signs in 66%, causative factors in 61%, and investigations in 49% (not mutually exclusive). Presence of at least one symptom and one causative factor had the highest sensitivity for detection of new heart failure (323 of the 420 [76.9%] new cases of heart failure). The sensitivity of the other diagnostic groupings for possible heart failure were > 2 symptoms, 68.6%; > 2 signs, 47.3%; > 1 symptom and > 1 sign, 68.6%; > 1 sign and > 1 causative factor, 66.9%. Possible false negative diagnoses: Of the 4807 patients who met diagnostic criteria for suspected CHF, 466 underwent echocardiography after the CASE audit (when systolic, diastolic or no dysfunction was specifically noted). Of these 466 patients, 108 had an echocardiographic report of left ventricular systolic or diastolic dysfunction. However, despite this objective evidence of ventricular dysfunction, GPs diagnosed CHF for only 77 of these 108 patients. Possible false positive diagnoses: Of the 420 patients newly diagnosed as having CHF, 162 underwent echocardiography. Nineteen of these 162 patients (11.7%) had no evidence of left ventricular systolic or diastolic dysfunction on this test, yet were still classified as having CHF by their GP. Patients previously diagnosed as having CHF CHF had been previously diagnosed in 2485 of the baseline population of 22 060 (11.3%). Both electrocardiograms and CXRs had been performed in 96% of the patients previously diagnosed as having heart failure, and 64% had had echocardiography performed. For these patients, in the previous 12 months: 1640 patients (66%) had been referred to a specialist; 1744 patients (70%) had either not been admitted to hospital with CHF or their hospitalisation status was unknown; and of the 741 patients admitted for CHF, 459 (62%) had one admission, 165 (22%) had two admissions, and 58 (8%) had three admissions. Six patients (1%) had been admitted 10 or more times for CHF. CHF patients in the CASE study At the end of the study, 2905 of the 22 060 baseline population (13.2%) were considered to have CHF: 2485 (11.2%) with a previous diagnosis, and 420 (1.9%) with a new diagnosis. The prevalence of CHF in these patients was closely related to age group (Box 3). The cardiovascular diagnoses that may be contributing to CHF in these patients are summarised in Box 4. Hypertension and ischaemic heart disease were major comorbidities and potential aetiological factors in both the new and previously diagnosed cohorts. Pharmacotherapy Specific CHF pharmacotherapy for the 2905 patients with CHF is summarised in Box 5. Most patients were receiving diuretics and ACE inhibitors. Alternatives to ACE inhibitors in patients who can not tolerate this medication include nitrates and hydralazine (prescribed for 0.6%) and/or angiotensin II receptor antagonists (prescribed for 4.3%). β-Blockers were prescribed for 12% of patients. Less than 50% of β-blocker prescribing was of the non-selective, vasodilating β-blocker carvedilol, approved for CHF in Australia. The dose of ACE inhibitor was determined in patients previously diagnosed as having CHF (Box 6). Based on our dosage equivalence table, prescribed doses were low in 60%, medium in 31%, and high in 9% of patients. Prescribing according to echocardiographic findings: Pharmacotherapy prescribed for CHF according to left ventricular (LV) systolic (found in 932 patients) or diastolic (found in 376 patients) dysfunction is summarised in Box 5. The presence of LV dysfunction on echocardiography resulted in higher prescribing of ACE inhibitors than in the overall patient cohort. However, the frequency of ACE inhibitor prescribing was not different between the systolic and diastolic LV dysfunction groups. Furthermore, there were very few differences among other agents in these groups according to systolic or diastolic LV dysfunction. Prescribing according to decade of life: Prescribing of drug therapy specifically for CHF according to decade of life is summarised in Box 5. ACE inhibitor prescribing was unaltered in the very elderly (≥ 80 years). Prescribing of β-blocker demonstrated an age-dependent decrease, whereas prescribing of digoxin and diuretics (thiazide and loop) demonstrated an age-dependent increase. Prescribing in patients with newly diagnosed CHF: Use of pharmacotherapy among newly diagnosed CHF patients was less than that observed in patients with previously diagnosed CHF. In particular, only 51% of newly diagnosed patients were prescribed ACE inhibitors, 37% diuretics, 17% received calcium-channel blockers, 10% digoxin and 8% β-blockers. Discussion We undertook a clinical algorithm approach to the possible diagnosis of CHF. By identifying possible CHF based on the grouping of symptoms, signs and causative factors, we demonstrated an 8.7% rate of identification of CHF (420 of 4807 patients). Although this approach resulted in a relatively low rate of successful diagnosis of CHF, the algorithm used was entirely clinical with a very simple screening process. Our results suggest that, of 100 patients aged 60 years or older presenting to a GP, two will have previously undetected CHF that can be simply diagnosed by attention to clinical symptoms and signs in conjunction with appropriate diagnostic tests. Prevalence of CHF We found somewhat higher rates of CHF patients (13.2%) than in earlier general practice based studies.4,7-9 Specifically, reported prevalence of CHF among patients aged 65 years or older in UK general practice ranged from 2.8%9 to 8.0%.7 The higher rate in the CASE study may reflect the differing methods by which the diagnosis of CHF was made (eg, patient file review,4,9 morbidity registry8), greater use of objective testing (ie, echocardiography in our patient cohort), or our study being a more representative sample of the true CHF population than previous geographically restricted studies performed in the US or UK. In contrast to the above assessments of CHF frequency, population studies where echocardiographic ventricular dysfunction was the main criterion for diagnosis detected fewer CHF patients within these age groups than in the CASE study.10,12 Numbers of CHF patients in the CASE Study increased dramatically with each decade of life — more than 20% of patients aged 80 years or older were diagnosed with CHF. Given the ageing of the population, these findings have important implications for resource allocation. Aetiology The aetiology of CHF was as expected, with a major contribution from ischaemic heart disease and previous myocardial infarction, as well as hypertension. Hypertension was a major contributor to CHF in the Framingham study,20,21 but less so in analysis of the Studies of Left Ventricular Dysfunction (SOLVD)22 and other, more recent data.23 The major contribution of hypertension in the CASE cohort may reflect the advanced age of the population studied, in which hypertension is a frequent comorbidity. Investigations Use of ECG and CXR was high, and echocardiography was used in more than half the patients. The lower use of echocardiography (despite recommendations by major organisations such as WHO)18 may reflect lack of full knowledge of the sensitivity and specificity of this diagnostic test, concerns regarding expense, and difficulty with access. Pharmacotherapy Use of ACE inhibitors: ACE inhibitor prescribing by Australian GPs ranges from 51%-71% of CHF patients, depending on the specific population studied. Prescribing of ACE inhibitor was more likely in patients in whom ventricular dysfunction had been objectively documented. These findings are consistent with international studies, in which prescribing of ACE inhibitors ranges from 10% to 60%.5,6,8-10,14-17 ACE inhibitors reduce morbidity and mortality across the entire spectrum of CHF severity, including in patients with asymptomatic systolic left ventricular dysfunction.24-26 Therefore, all patients with systolic left ventricular dysfunction should be receiving ACE inhibitors unless contraindicated or intolerant. Lack of compliance with these prescribing recommendations may relate to contraindications to ACE inhibitor therapy (ie, bilateral renal artery stenosis) or observed side effects such as hyperkalaemia or cough. Furthermore, ACE inhibitors are not of proven benefit in patients with diastolic CHF. Definitive diastolic dysfunction on echocardiography comprised only a small percentage in the CASE study, although the true percentage is undoubtedly considerably higher. Potential alternatives to ACE inhibitors in patients who are ACE intolerant or have contraindications include angiotensin II receptor antagonists and hydralazine (the latter as part of the hydralazine/nitrate combination). However, only 4.3% of patients were taking angiotensin II receptor antagonists and 0.6% were taking hydralazine. Our findings suggest that, despite the definitive data supporting the use of ACE inhibitors in CHF, these agents are still being underutilised. Dose of ACE inhibitors: Submaximal doses of ACE inhibitors were prescribed for those patients who are taking these drugs. The major clinical trials conducted in patients with CHF (SOLVD,24 CONSENSUS25) and LV dysfunction post-MI (SAVE27) used much higher doses (150 mg of captopril or 20-40 mg of enalapril) than the median and mean doses prescribed in this study. Doses prescribed by Australian GPs were generally lower than both the target and achieved ACE inhibitor doses used in these major trials. There are a number of reasons why the recommended target doses may not be achieved in general practice. First, patients may not tolerate the highest dosage because of hypotension, particularly if up-titration is rapid. Second, because these agents improve symptomatology, patients may become asymptomatic at lower doses of drug and the need to go to higher doses not be entertained in an asymptomatic patient. Finally, until recently, there has been no clear evidence that higher doses offer substantial clinical benefits over and above the use of ACE inhibitors at lower doses. The ATLAS study28 demonstrated a reduction in the combined endpoint of death/heart failure related hospitalisation with lisinopril 32.5-35 mg daily compared with lisinopril 2.5-5 mg daily. Mortality alone was reduced by 8% in the high-dose lisinopril subgroup. Although this reduction is modest, it does suggest that an attempt should be made to maximise ACE inhibitor dosage in every patient. β-Blockers: Prescribing of β-blockers was low, despite overwhelming evidence supporting the benefits of these agents in patients with New York Heart Association (NYHA) Class II-III symptoms.29-31 However, much of this evidence has only been published subsequent to the completion of the CASE study.30,31 Prescribing of the β-blocker vasodilator carvedilol occurred in fewer than half the patients receiving β-blockers. As carvedilol is the only β-blocker approved in Australia for CHF, this suggests that much of the prescribing of β-blockers for the CASE cohort was for indications other than CHF (eg, ischaemic heart disease and hypertension). As GPs in Australia are not permitted to prescribe carvedilol, our observed rate of use of β-blockers reflects specialist prescribing. Factors affecting prescribing: In patients with a definitive diagnosis of ventricular dysfunction by echocardiography, prescribing of ACE inhibitor therapy was higher than for the overall CASE CHF cohort. This may reflect more confidence with the cause of patient symptomatology as being related to CHF. Alternatively, it may be that a GP who is more likely to perform echocardiography to diagnose CHF is also more likely to prescribe best-practice pharmacotherapy. It was also noteworthy that the difference in overall prescribing for systolic versus diastolic dysfunction in these patients appeared similar, although many of the agents (eg, ACE inhibitors) are not of proven benefit in diastolic CHF. Furthermore, some drugs, such as non-dihydropyridine calcium-channel blockers, are relatively contraindicated in patients with systolic heart failure, yet prescribing rates were similar for the entire patient cohort. Conversely, these agents may be of particular benefit in diastolic heart failure, but again prescribing rates appeared similar to the entire patient cohort. There was no reduction in prescribing of ACE inhibitor with each decade of life, suggesting that GPs supported the use of these agents in CHF management in the very elderly (≥ 80 years). Very few data exist to support the use of ACE inhibitors in this group of patients, although studies are currently being conducted. In contrast, β-blocker use declined with each decade of life, suggesting less comfort in prescribing these agents for older patients. Increased digoxin and diuretic use with advanced age may reflect the need to increasingly prescribe these agents for comorbidities such as atrial fibrillation and oedema of other causes. Study limitations The CASE study had a number of potentially significant limitations. Selection of GPs was not random, but was based on interest in undertaking the study. This could introduce significant bias, and therefore we have not classified our evaluation as a prevalence or incidence study. Nevertheless, every effort was undertaken to ensure a representative distribution of general practices according to State, regional area and metropolitan versus rural practice. The study has also demonstrated the difficulty in making a clinical diagnosis of CHF. Diagnosis of CHF was left to the clinical judgement and decision of the GP. We noted a significant false positive and negative rate using documented left ventricular dysfunction on echocardiogram as the "gold standard" of CHF in conjunction with relevant signs, symptoms and causative factors. This is a limitation of many surveys of this type, in which the diagnosis is made based on subjective clinical criteria.4,9 A further limitation may have been the algorithm used to assist the GP in making the diagnosis. This clinical algorithm approach has not been used previously in the diagnosis of CHF. Therefore, the possibility exists of patients being wrongly assigned as having CHF using this approach. This is particularly true as echocardiography was not mandated for all patients. Nevertheless, this algorithm did yield an extra two new CHF patients for every 100 patients aged 60 years and older studied in this way. Acknowledgements The CASE study was supported by the National Heart Foundation of Australia and the Royal Australasian College of General Practitioners. The CASE Management Committee wish to thank all 341 GPs who participated in the CASE study and Servier Laboratories, Australia, who provided input into the study design as well as financial and logistical assistance in the conduct of the study. Servier Laboratories were not involved in the analysis of data. In addition, the Committee acknowledges the expert statistical assistance provided by Dr Chris Reid and Mr Stephen Lim (Baker Medical Research Institute, Prahran, VIC). References Bonneaux L, Barendregt J, Meeter K, et al. Estimating clinical morbidity due to ischemic heart disease and congestive heart failure: the future risk of heart failure. Am J Public Health 1994; 84: 20-28. Waters A-M, Bennett S. Mortality from cardiovascular disease in Australia. Cardiovascular Disease Series No. 3. Canberra: Australian Institute of Health and Welfare, 1995. McGovern PG, Pankow JS, Shahar E, et al. Recent trends in acute coronary heart disease. Mortality, morbidity, medical care and risk factors. N Engl J Med 1996; 334: 884-890. Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993; 22: 6A-13A. Gardin JM, Siscovick D, AntonCulver H, et al. Sex, age and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly: the Cardiovascular Health Study. Circulation 1995; 91: 1739-1748. Lauer MS, Evans JC, Levy D. Prognostic implications of subclinical left ventricular dilatation and systolic dysfunction in men free of overt cardiovascular disease (the Framingham Heart Study). Am J Cardiol 1992; 70: 1180-1184. Mair FS, Crowley TS, Bundred P. Prevalence, aetiology and management of heart failure in general practice. Br J Gen Pract 1996; 46: 77-79. Morbidity statistics from general practice. 4th National Survey, 1991-92. Royal College of General Practitioners, Office of Population Census and Survey and Department of Health and Social Security. London: HMSO, 1995. Parameshwar J, Shackell MM, Richardson A, et al. Prevalence of heart failure in three general practices in west London. Br J Gen Pract 1992; 42: 287-289. McDonagh TA, Morrison CE, Lawrence A, et al. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population. Lancet 1997; 350: 829-833. Ambrosio GB, Riva LM, Casiglia E. Prevalence, clinical features and prognosis of congestive heart failure (CHF) in the elderly. A survey from a population in Veneto region. Acta Cardiologica 1994; 49: 324-325. Mosterd A, Bruijne de MC, Hoes AW, et al. Usefulness of echocardiography in detecting left ventricular systolic dysfunction in population based studies (The Rotterdam Study). Am J Cardiol 1997; 79: 103-104. Hillis GS, Trent RJ, Winton P, et al. Angiotensin-converting enzyme inhibitors in the management of congestive heart failure: are we ignoring the evidence? Q J M 1995; 89: 145-150. Mosterd A, Hoes AW, de Bruijne MC, et al. Prevalence of heart failure and (a) symptomatic left ventricular dysfunction in the general population. The Rotterdam Study. Eur Heart J 2001; in press. Bart BA, Gattis WA, Diem SJ, O'Connor CM. Reasons for underuse of angiotensin-converting enzyme inhibitors in patients with heart failure and left ventricular dysfunction. Am J Cardiol 1997; 79: 1118-1120. Newman J, Ahmed O, Hyngstrom T, et al. Heart failure treatment with angiotensin converting enzyme inhibitors in hospitalized Medicare patients in 10 large states. Arch Int Med 1997; 157: 1103-1108. Stafford RS, Saglam D, Blumenthal D. National patterns of angiotensin converting enzyme inhibitor use in congestive heart failure. Arch Intern Med 1997; 157: 2460-2464. World Health Organization/Council on Geriatric Cardiology Task Force on Heart Failure Education. Concise guide to the management of heart failure. Geneva: WHO/CGC, 1997; 6-9. Available at <http://www.who.int/ncd/cvd/concguid.pdf>. Rural, remote and metropolitan areas classification. 1991 Census Edition. Canberra: AGPS, 1994. 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. Kannel WB, Belanger JA. Epidemiology of heart failure. Am Heart J 1991; 121: 951-956. Bangdiwala SI, Weiner DH, Bourassa MG, et al. Studies of Left Ventricular Dysfunction (SOLVD) Registry: rationale, design, methods and description of baseline characteristics. Am J Cardiol 1992; 70: 347-353. Teerlink JR, Goldhaber SZ, Pfeffer MA. An overview of contemporary etiologies of congestive heart failure. Am Heart J 1991; 121: 1852-1853. 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. 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; 3161: 1429-1435. 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. 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: 821-828. 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. 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. CIBIS II investigators and committees. The cardiac insufficiency bisoprolol study II (CIBIS II): a randomised trial. Lancet 1999; 353: 9-13. 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. (Received 24 Dec 1999, accepted 28 Oct 2000) Authors' details Alfred Hospital, Melbourne, VIC. Henry Krum, PhD, FRACP, Associate Professor, Clinical Pharmacology Unit, Department of Epidemiology and Preventive Medicine, and Department of Medicine, Monash University. National Heart Foundation of Australia, Melbourne, VIC. Andrew M Tonkin, MD, FRACP, Director, Health, Medical and Scientific Affairs. North East Valley Division of General Practice, Melbourne, VIC. Robert Currie, MB BS, FRACGP, Director. Servier Laboratories, Melbourne, VIC. Robert Djundjek, BSc, Manager, Scientific Projects. Austin and Repatriation Medical Centre, Melbourne, VIC. Colin I Johnston, MD, FRACP, Professor and Head, Department of Medicine, University of Melbourne. Reprints will not be available from the authors. Correspondence: Professor C I Johnston, Baker Medical Research Institute, Prahran, VIC 3181. Make a comment 1: Modified World Health Organization18 criteria for assessment of possible chronic heart failure Symptoms: Dyspnoea, chronic fatigue, oedema, and exercise intolerance. Signs: Third or fourth heart sounds, heart murmur, cardiomegaly, pulmonary crackles, raised jugular venous pressure, and dependent oedema. Causative factors: Angina, previous myocardial infarction, hypertension, valvular heart disease/rheumatic fever, and cardiomyopathy. Patients were considered to have possible CHF if they had: > 2 symptoms, > 2 signs, > 1 symptom and > 1 sign, or > 1 symptom and > 1 causative factor. Back to text Back to text Back to text 4: Cardiovascular comorbidities that may be contributing to chronic heart failure Percentage of patients New CHF Previous CHF Hypertension 69.1% 63.6% Angina 44.2% 53.4% Previous MI 28.1% 39.3% Valve disease 15.2% 23.0% Cardiomyopathy 5.2% 11.8% MI = myocardial infarction. Back to text 5: Percentage (95% CI) of patients with chronic heart failure prescribed each class of drug, by evidence of left ventricular dysfunction, and by age group Left ventricular dysfunction* All patients (n = 2905) Systolic (n = 932) Diastolic (n = 376) Diuretics (thiazide, loop) 63.3 (62.4-64.2) 60.3 (58.7-61.9) 62.2 (59.7-64.7) ACE inhibitor 58.1 (57.2-59.0) 70.7 (69.2-72.2) 70.5 (68.1-72.9) Digoxin 31.3 (30.4-32.2) 35.0 (33.4-36.6) 33.2 (30.8-35.6) beta-Blocker 11.8 (11.2-12.4) 13.9 (12.8-15.0) 17.8 (15.8-19.8) CCB-DHP 10.1 (9.5-10.7) 11.1 (10.1-12.1) 12.0 (10.3-13.7) CCB-NDHP 10.0 (9.4-10.6) 10.3 (9.3-11.3) 11.2 (9.6-12.8) Aspirin 10.3 (9.7-10.8) 9.3 (8.3-10.3) 9.6 (8.1-11.1) Warfarin 7.7 (7.2-8.2) 8.2 (7.3-9.1) 8.8 (7.3-10.3) Spironolactone 8.1 (7.6-8.6) 6.9 (6.1-7.7) 1.0 (0.5-1.5) Hydralazine 0.6 (0.5-0.7) 0.2 (0.1-0.3) 0.0 (0.0-0.0) AIIA 4.3 (3.9-4.7) 6.4 (5.6-7.2) 7.7 (6.3-9.1) Age group (years) 60-69 (n = 569) 70-79 (n = 1360) ≥80 (n = 976) Diuretics (thiazide, loop) 57.1 (55.0-59.2) 62.1 (60.8-63.4) 68.4 (66.9-69.9) ACE inhibitor 58.7 (56.6-60.8) 58.0 (56.7-59.3) 58.1 (56.5-59.7) Digoxin 24.8 (23.0-26.6) 29.9 (28.7-31.1) 37.2 (35.7-38.7) beta-Blocker 14.1 (12.6-15.6) 13.2 (12.3-14.1) 8.4 (7.5-9.3) CCB-DHP 9.5 (8.3-10.7) 11.0 (10.2-11.8) 9.0 (8.1-9.9) CCB-NDHP 10.2 (8.9-11.5) 11.0 (10.2-11.8) 11.2 (10.2-12.2) Aspirin 10.0 (8.7-11.3) 11.4 (10.5-12.3) 8.9 (8.0-9.8) Warfarin 9.5 (8.3-10.7) 8.8 (8.0-9.6) 5.0 (4.3-5.7) Spironolactone 6.7 (5.7-7.7) 8.8 (8.0-9.6) 8.0 (7.1-8.9) Hydralazine 1.1 (0.7-1.5) 0.6 (0.4-0.8) 0.3 (0.1-0.5) AIIA 3.5 (2.7-4.3) 5.4 (4.8-6.0) 3.4 (2.8-4.0) * According to echocardiography. ACE = angiotensin-converting enzyme. CCB-DHP = calcium-channel blocker - dihydropyridine. CCB-NDHP = calcium-channel blocker - non-dihydropyridine. AIIA = angiotensin II receptor antagonist. Back to text 6: Dosage equivalence table for angiotensin-converting enzyme (ACE) inhibitors, and median and mean doses prescribed for patients with diagnosed chronic heart failure Dosage equivalence (mg) Low Medium High Captopril ≤ 50 ≤ 100 ≤ 150 Enalapril ≤ 10 ≤ 20 ≤ 40 Perindopril ≤ 2 ≤ 4 ≤ 8 Lisinopril ≤ 10 ≤ 20 ≤ 40 Ramipril ≤ 5 ≤ 10 ≤ 20 Fosinopril ≤ 10 ≤ 20 ≤ 40 Trandolopril ≤ 2 ≤ 4 ≤ 8 Quinapril ≤ 10 ≤ 20 ≤ 40 Dose (mg) Media Mean SD n Captopril 50 67.5 44.1 383 Enalapril 10 15.6 12.0 308 Perindopril 4 3.6 2.2 223 Lisinopril 10 12.6 9.7 218 Ramipril 5 5.1 4.3 98 Fosinopril 10 14.3 7.1 81 Trandolopril 1 1.9 1.8 76 Quinapril 10 11.6 9.1 74 Back to text

Henry Krum · Andrew M Tonkin · Robert Currie · Robert Djundjek · Colin I Johnston

Liang Han Ling, Colin Marchant, Nicholas A Buckley, Michael Prior and Rod J Irvine MJA 2001; 174: 453-455 Abstract - Methods - Results - Discussion - Acknowedgements - Authors' details - - More articles on Pharmacology - More articles on Drugs and alcohol Abstract Objective: To describe the clinical features of paramethoxyamphetamine (PMA; "death") poisoning and to compare these with those of people with self-reported "ecstasy" poisoning. Design: Retrospective casenote review. Participants and setting: 22 patients who presented to the Emergency Department of the Royal Adelaide Hospital (RAH), a major metropolitan teaching hospital, between 1 January 1996 and 31 December 1998 with PMA poisoning identified through urine drug screens; and 61 patients with self-reported ecstasy poisoning between 1 September 1997 and 31 December 1998 found through the hospital databases. Results: Patients with PMA poisoning presented with tachycardia (64%), hyperthermia (temperature > 37.5ºC; 36%), coma (41%), seizures (32%), arrhythmias (23%), and QRS intervals ≥ 100 ms (50%) with greater frequency and often greater severity than those with self-reported ecstasy poisoning. Two patients with PMA poisoning presented with severe hypoglycaemia (blood glucose level, < 1.5 mmol/L) accompanied by hyperkalaemia (K+ concentration, > 7.5 mmol/L). Conclusions: At our hospital, PMA poisonings accounted for most of the severe reactions among people who believed they had taken ecstasy. Hypoglycaemia and hyperkalaemia may be specific to PMA poisoning. PMA toxicity should be suspected with severe or atypical reactions to "ecstasy", and confirmed by chromatographic urine drug screens. The recreational use of amphetamine derivatives among young people is common, particularly at dance clubs and dance parties ("raves"). 3,4- Methylenedioxymethamphetamine (MDMA), popularly known as "ecstasy", was first identified in street use in 1972.1 Another amphetamine derivative, paramethoxyamphetamine (PMA), also appeared in recreational use during the 1970s. PMA, and other amphetamine derivatives, such as 3,4-methylenedioxyethylamphetamine (MDEA) and 3,4-methylenedioxyamphetamine (MDA), are known to have been sold on the street as ecstasy.2,3 Within a few years, PMA was associated with several fatalities in Canada and earned the street-name "death".4 Further fatalities associated with PMA toxicity have only been reported in significant numbers in South Australia,2,5,6 where at least eight deaths have occurred since September 1995, while no deaths from MDMA alone were reported in the same period (P D Felgate, Scientist, Forensic Science Centre, South Australia, personal communication). The toxic effects of MDMA are well described,7-10 and the few previous case reports of PMA poisoning showed similar toxic effects.2,4,5 Serotonergic and sympathomimetic symptoms include anxiety, agitation, nausea, and palpitations. Life-threatening adverse effects of MDMA include severe hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, multiorgan failure, arrhythmias, intracerebral haemorrhage, seizures, and hyponatraemia leading to cerebral oedema.3,11 While case reports of PMA deaths collectively suggest that PMA is more toxic than MDMA, the clinical effects of PMA have not yet been studied systematically. Here, we report a series of non-fatal, confirmed PMA poisonings, all in patients presenting to the emergency department of a metropolitan hospital in South Australia. Methods We conducted a retrospective casenote review of all PMA poisonings identified through urine drug screens of patients presenting to the Royal Adelaide Hospital (RAH) Emergency Department between 1 January 1996 and 31 December 1998. We included PMA poisonings involving the coadministration of MDMA or other substances. Urine drug screens had been performed by enzyme immunoassay, with confirmation of positive results by gas chromatography and mass spectrometry, according to Australian Standard 4308 (1995). Data were retrieved from casenotes by means of standardised forms and entered into a computer database. Findings were compared with those for all other patients presenting to the RAH between 1 September 1997 and 31 December 1998 because of adverse effects after the self-reported use of "ecstasy". These patients were identified by reviewing casenotes of all stimulant drug poisonings through admission diagnosis-related group coding and recorded in the RAH Emergency Department database; a few additional cases that had been wrongly coded were identified through urine drug screens. Confirmation of MDMA exposure by urine drug screens was not available for most patients in this comparison group. Ethical approval for this study was granted by the Royal Adelaide Hospital ethics committee. Results Twenty-two PMA poisonings were confirmed by urine drug screens between 1 January 1996 and 31 December 1998. These occurred in the first eight months and last eight months of the study period, with 16 months of no confirmed PMA poisonings in between. The casenotes of 15 of these 22 patients recorded that they believed they had taken ecstasy. No patient's records showed that he or she knowingly took PMA. Sixty-one patients with self-reported ecstasy (MDMA) poisoning presented to RAH between 1 September 1997 and 31 December 1998. Their characteristics and clinical features are compared with the PMA group in the Box. Eleven patients with PMA poisoning had only relatively minor symptoms (anxiety, agitation, delirium, hallucinations, headache, involuntary movements, vomiting). Frequent signs recorded in these patients included tachycardia (heart rate > 100 bpm), mild hyperthermia (temperature, > 37.5ºC) and a prolonged QRS interval on electrocardiogram, often with a right bundle branch block pattern. A much larger proportion of patients with ecstasy poisoning presented with relatively minor symptoms. The other 11 patients with PMA poisoning had life-threatening toxicity with coma, generalised seizures, severe hyperthermia (temperature, > 40ºC) or hypothermia (temperature, < 34.5ºC), and some had arrhythmias (atrial fibrillation [2], multifocal ventricular ectopic beats [2], supraventricular tachycardia [1]). Two patients with PMA poisoning presented with severe hypoglycaemia (blood glucose level, < 1.5 mmol/L; normal range, 3.8-5.5 mmol/L), accompanied by hyperkalaemia (K+, > 7.5 mmol/L; normal range, 3.1-4.2 mmol/L). Discussion PMA and MDMA are structurally and pharmacologically similar, producing their effects through serotonergic, dopaminergic, and noradrenergic mechanisms. The recent case reports of PMA-related deaths in South Australia5,6 suggest that PMA is more toxic than MDMA, but do not provide a clinical explanation for this difference. Our retrospective study showed that most people with PMA poisoning present with clinical features that are qualitatively similar to those of people with ecstasy poisoning (ie, hyperthermia, coma, and seizures), but that these symptoms occur more frequently and are more severe in those who took PMA. Certain features, such as QRS interval prolongation, hypoglycaemia and hyperkalemia, appear unique to PMA poisoning, suggesting there may be toxicological mechanisms different from those of MDMA contributing to PMA's adverse effects. Our patients with PMA poisoning did not have significant acidosis, haemolysis or tissue damage to explain the hyperkalaemia. The high frequencies of prolonged QRS intervals and seizure suggest that PMA may have sodium-channel-blocking properties. Severe hypoglycaemia has never previously been reported as an adverse effect of PMA. The affected patients did not have liver failure at the time, nor were other drugs detected that might explain the hypoglycaemia. However, PMA is a monoamine oxidase (MAO) inhibitor,12 and other MAO inhibitors have been reported to stimulate insulin release.13 There are only two human studies on PMA, neither of which provides an explanation for serious toxic effects. Sustained blood pressure elevation of up to 240/130 mmHg occurred in some people taking PMA at a dose of 1 mg/kg bodyweight,4 and PMA was found to be three times as potent as the amphetamine derivative MDA as a hallucinogen.14 Our retrospective study design makes direct comparison between PMA and MDMA impossible. As urine drug screens were not routinely performed in presentations involving stimulant use, it is impossible to determine the exact frequency of PMA and MDMA poisonings presenting over the study period, or to identify a large enough cohort of people poisoned with MDMA alone to serve as a control group. Coadministration of other drugs and inconsistencies in casenote reporting are further factors which would have confounded the comparison of PMA and MDMA poisonings. However, the coronial data and the unique toxicological features of the known PMA poisonings we identified are sufficient to demonstrate that PMA accounts for most severe adverse events after apparent ecstasy ingestion in Adelaide. As PMA does not account for the majority of ecstasy use, this implies that PMA is substantially more toxic than MDMA. The serious acute toxic effects of MDMA are generally related to hyperthermia, which results from a combination of temperature deregulation, excessive physical activity and high ambient temperatures.3 This knowledge has led to moderately successful public health and education programs to highlight these dangers and encourage users of MDMA at "rave" parties to ensure adequate hydration and to take breaks to cool down. However, much of the serious toxicity we describe with PMA, such as sudden collapse and seizures, may not be amenable to such harm-minimisation approaches. Although the actual doses ingested by our patients are not known, only one person reported taking more than two tablets and none were deliberate overdoses. Estimates of dose are unreliable, not only because of the difficulty in obtaining a reliable history of illicit drug use, but also because of variations in tablet strength. However, analysis of recently confiscated ecstasy capsules and tablets shows similar mean concentrations of the active ingredient in those containing PMA (73 mg) and MDMA (106 mg) (P D Felgate, Forensic Science Centre, South Australia, personal communication). Thus, the apparent greater toxicity of PMA is unlikely to be explained by the dose received. Despite the poor reputation of PMA, its use remains a continuing health concern in Australia. Deaths from PMA use have been reported most frequently in Adelaide, but also in Queensland and Western Australia.2 PMA toxicity should be suspected in patients presenting with severe or atypical reactions to ecstasy and the diagnosis can be confirmed by chromatographic urine drug screens. Acknowledgements We thank Dr Christopher Angley, Staff Consultant, RAH, for assistance with database searching, and the South Australian Forensic Science Centre for figures on illicit stimulant deaths in South Australia. References Buchanan JF, Brown CR. "Designer drugs". A problem in clinical toxicology. Med Toxicol Adverse Drug Exp 1988; 3: 1-17. Felgate HE, Felgate PD, James RA, et al. Recent paramethoxyamphetamine deaths. J Analyt Toxicol 1998; 22: 169-172. Milroy CM. Ten years of "ecstasy". J R Soc Med 1999; 92: 68-71. Cimbura G. PMA deaths in Ontario. CMAJ 1974; 110: 1263-1267. Byard RW, Gilbert J, James R, Lokan RJ. Amphetamine derivative fatalities in South Australia -- is "Ecstasy" the culprit? Am J Forensic Med Pathol 1998; 19: 261-265. Byard RW, James RA, Gilbert JD, Felgate PD. Another PMA-related fatality in Adelaide. Med J Aust 1999; 170: 139-140. Green AR, Cross AJ, Goodwin GM. Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy"). Psychopharmacol 1995; 119: 247-260. McCann UD, Slate SO, Ricaurte GA. Adverse reactions with 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"). Drug Safety 1996; 15: 107-115. Rochester JA, Kirchner JT. Ecstasy (3,4-methylenedioxymethamphetamine): history, neurochemistry, and toxicology. J Am Board Family Pract 1999; 12: 137-142. Steele TD, McCann UD, Ricaurte GA. 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"): pharmacology and toxicology in animals and humans. Addiction 1994; 89: 539-551. Henry JA, Jeffreys KJ, Dawling S. Toxicity and deaths from 3,4-methylenedioxymethamphetamine ("ecstasy"). Lancet 1992; 340: 384-387. Ask AL, Fagervall I, Ross SB. Selective inhibition of monoamine oxidase in monoaminergic neurons in the rat brain. Naunyn Schmiedebergs Arch Pharmacol 1983; 324: 79-87. Stockley IH. Drug interactions. 4th ed. London: The Pharmaceutical Press; 1996. Galloway G, Shulgin AT, Kornfeld H, Frederick SL. Amphetamine, not MDMA, is associated with intracranial hemorrhage. J Accident Emerg Med 1995; 12: 231-232. (Received 20 Sep 2000, accepted 15 Feb 2001) Authors' details Department of Clinical and Experimental Pharmacology, Faculty of Medicine, University of Adelaide, SA. Liang Han Ling, 5th Year Medical Student; Colin Marchant, 6th Year Medical Student; Nicholas A Buckley, FRACP, MD, Senior Consultant; Rod J Irvine, PhD, Research Fellow. Institute of Medical and Veterinary Science, Adelaide, SA. Michael Prior, BAppSc, FAIMS, Senior Scientist, Toxicology. Reprints will not be available from the authors. Correspondence: Dr N A Buckley, Department of Clinical and Experimental Pharmacology, Faculty of Medicine, University of Adelaide, SA 5000. nbuckleyATmail.rah.sa.gov.au Make a comment Demographic and clinical data for patients confirmed to have ingested paramethoxyamphetamine (PMA) compared with others who reported ingesting "ecstasy" PMA (n=22) "Ecstasy" (n=61) % Difference (95% CI) P* Median age (range) 23 (18-32) 22 (17-35) 0.1115 Males 15 (68%) 33 (54%) 14% (-10% to 38%) 0.3176 Cardiovascular effects Median pulse (range) 118 (52-218) 88 (46-160) 0.0156 No. (%) with: Pulse ≥100bpm QRS interval ≥100ms Arrhythmias 14 (64%) 11 (50%) 5 (23%) 25 (41%) 3 (5%) 3 (5%) 23% (-1% to 46%) 45% (23%-67%) 18% (-1% to 36%) 0.0842 0.0278 Metabolic effects Median temperature Range 37°C 32-42°C 36°C 32-38°C 0.1185 No. (%) with: Temperature >37.5°C Temperature >40.0°C 8 (36%) 4 (18%) 3 (5%) 0 31% (11%-52%) 18% (2%-34%) 0.0008 0.004 Neurological effects Median Glasgow coma score Range 12.5 3-15 15 4-15 0.0018 No. (%) with: Glasgow coma score Seizures 9 (41%) 7 (32%) 4 (7%) 2 (3%) 34% (13%-56%) 29% (9%-49%) 0.0005 0.001 No. (%) with life-threatening toxicity† 11 (50%) 4 (7%) 43% (22%-65%) *Fisher's exact test or Mann-Whitney U test. †Seizures, temperature >40°C or Glasgow coma score <6. 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Colin Marchant · Nicholas A Buckley · Michael Prior · Rod J Irvine

Medicine and the Community Economic costs of urinary incontinence in community-dwelling Australian women Christopher M Doran, Pauline Chiarelli and Jill Cockburn MJA 2001; 174: 456-458 For editorial comment, see Moore Abstract - Methods - Results - Discussion - References - Authors' details - - More articles on Obstetrics & gynaecology and women's health - More articles on Urology - More articles on Economics Abstract Objective: To estimate the economic cost of urinary incontinence in community-dwelling Australian women aged 18 years and over for the year 1998. Design: Extrapolation of data from studies of women with incontinence to the Australian population of women aged 18 years and over in 1998. Main outcome measures: Estimated prevalence of urinary incontinence in 1998, and estimated cost in Australian dollars of resource use and personal costs related to management of incontinence. Results: An estimated 1 835 628 community-dwelling women over the age of 18 years had urinary incontinence in 1998. The total annual cost of this urinary incontinence is estimated at $710.44 million, or $387 per incontinent woman, comprising $338.47 million in treatment costs and $371.97 million in personal costs. An estimated 60% of women with incontinence in 1998 were aged 40 years or over. Assuming the prevalence of incontinence remains constant and, allowing for inflation, we project that the total annual cost in 20 years' time will be $1267.85 million, 93% ($1.18 billion) of which will constitute costs associated with women aged over 40 years. Conclusions: Urinary incontinence imposes a considerable drain on Australian healthcare resources. More research is needed to understand the magnitude of the problem and potential gains from continence promotion. Urinary incontinence is a major clinical problem that has a profound effect on quality of life and activities of daily living.1-3 Women with urinary incontinence report fear, shame and humiliation, and worry about the odour of urine from pads and wet underclothing.4 Urinary incontinence is physically debilitating and socially incapacitating, and is associated with loss of self-confidence, feelings of helplessness, depression and anxiety.3Studies of the prevalence of urinary incontinence suggest that it is widespread among women of all ages.5 Australian community-based studies have reported incontinence in 19% of women aged 10-29 years, 40% of women aged 30-44 years, 50% of women aged 45-59 years, 30% of women aged 60-74 years, and 42% of women aged over 75 years.6 Recent data from the Women's Health Australia (WHA) project, a longitudinal study of three age cohorts (18-23 years, 45-50 years and 70-75 years), conducted by staff of the universities of Newcastle and Queensland and funded by the Commonwealth Department of Health and Aged Care, support these findings.7,8 The probability of incontinence increases with age,9-11 and the nature of incontinence changes from stress incontinence to urge incontinence12 as a result of an increasing prevalence of multiple disorders and organ dysfunction with age. This change has significant implications for clinical management.13 While stress incontinence is typically managed with strengthening exercises for pelvic floor muscles, with or without neuromuscular electrostimulation and surgery, management of urge incontinence might also include a bladder-training program, transcutaneous electrostimulation aimed at the spinal micturition reflex centre and drugs.14 Urinary incontinence has a considerable financial impact on both individuals and the healthcare system. One United States study has reported costs of US$26.3 billion in 1995 for individuals aged 65 years and over, or US$3565 per incontinent individual.15 Little is known of the economic impact of urinary incontinence in Australia, but the Australian National Women's Health Policy Statement estimated that individuals may pay up to $1200 a year for incontinence pads, and that 25% of nursing time in nursing homes was spent managing incontinence, at an annual cost of $450 million.16 A recent study of 100 community-dwelling Australian women aged between 25 and 85 years reported a median total direct cost (including personal and treatment costs) of $12.89 per week.17 Our aim was to comprehensively examine the economic costs of urinary incontinence in community-dwelling women in Australia for the year 1998. Methods We used a similar approach to that used by Hu et al in the US,15,18,19 in that we used information from a variety of sources in our estimates. However, rather than using national utilisation figures19 and a "top-down" approach, we used a "bottom-up" approach, taking estimates derived from relevant studies and extrapolating them to the 1998 population of Australian women aged over 18 years. We estimated the cost of urinary incontinence as the total value of all resources used or lost by ill individuals, treatment providers or others as a result of the illness.15 Direct costs include resources used for diagnosis, treatment and care of urinary incontinence, while indirect costs include the value of lost earnings and time spent by carers. Intangible costs20 related to psychological, physical and social effects were not included. Estimating prevalence The WHA project provides the most comprehensive information on the prevalence of urinary incontinence in Australian women.7,8 It reported incontinence in 12.8% of women aged 18-23 years, 36.1% of women aged 45-50 years and 35% of women aged 70-75 years, and a prevalence of help-seeking among incontinent women in each cohort of 22.9%, 45.5% and 44.6%, respectively.21We assumed that the prevalence of incontinence and help-seeking in the three age cohorts could be applied to broader age groups of 18-39 years, 40-69 years and over 70 years, and used Australian Bureau of Statistics (ABS) figures for the resident population in these age groups22 to estimate the total number of incontinent Australian women who did and did not seek help in 1998. Resource use and personal costs A recent study developed the Dowell-Bryant Incontinence Cost Index (DBICI) to measure the total direct costs of urinary incontinence.17 This study applied the DBICI to 100 consecutive community-dwelling women attending continence clinics for treatment of their urinary incontinence. Personal cost estimates included weekly expenditure on pads, incontinence-related laundry and miscellaneous costs (such as dry cleaning, replacement of urine-soaked carpets and clothing), while treatment-cost estimates included visits to healthcare professionals, surgical procedures, medications and costs associated with travel and time off work in the previous year. We costed these resources by using standard fees from the Medical Benefits Schedule and Pharmaceutical Benefits Scheme or by actual costs incurred if women had private health cover. We used the data from this study17 in conjunction with the prevalence estimates from the WHA project to estimate the resource implications and personal cost of urinary incontinence among women aged 18 years and over in Australia in 1998. Results We estimate that 1 835 628 community-dwelling women over the age of 18 years in Australia had urinary incontinence in 1998, and that 60% (1 109 506) of these women were aged 40-69 years (Box 1). An estimated 742 348 women sought help for their incontinence, of whom 68% were aged 40-69 years. Box 2 shows that we estimate total annual treatment costs at $338.47 million, 48% of which was for visits to health professionals, and 25% of which was for investigations. Further, we estimate that total personal costs in 1998 were $371.97 million, 56.5% of which was borne by women who did not seek help (Box 3). The total annual cost of urinary incontinence in 1998 is estimated at $710.44 million, or $387 per woman with urinary incontinence. Up to 90% ($640.98 million) of the total annual costs were incurred by women aged over 40 years. Given Australia's ageing population, assuming the same prevalence and taking inflation into account, the total cost of urinary incontinence in community-dwelling women is projected to be $1267.85 million in 20 years' time; 93% of this ($1.18 billion) will constitute costs associated with women aged over 40 years. Discussion Our estimates represent the first attempt to quantify the total economic impact of urinary incontinence in community-dwelling Australian women. However, our analysis has some limitations that need to be kept in mind when interpreting the results. Importantly, our data sources differ in methodological rigour and comparability, so we have had to make a number of assumptions. Prevalence rates of incontinence reported from the WHA project have been extrapolated to a wider age range than originally measured.7 We applied the data of Dowell et al on treatment resource use universally to all age groups in our analysis, and without considering socioeconomic and demographic variations. Given that the type and severity of incontinence varies with age,9-12 this assumption may not provide an accurate picture. We also applied the personal costs reported in Dowell et al17 to slightly different age groups. Finally, although the sample of 100 women used in Dowell et al represented a wide spectrum of age and severity of leakage, it may not have been representative of all community-dwelling women.17 Despite these limitations, our analysis is the most comprehensive assessment of the annual costs of urinary incontinence in community-dwelling women conducted in Australia to date. The total cost of $710.44 million is a conservative estimate of the cost of resources used in treatment and care of women with urinary incontinence. If we were to consider the reduced quality of life, lost earnings and the burden imposed on family, friends and carers, the total cost would be considerably higher. From a woman's perspective, there are substantial personal costs involved in managing incontinence; research has found that women are willing to pay considerable amounts to reduce the symptoms of urinary incontinence.23,24 From a health system perspective, the high cost of treatment and care of urinary incontinence clearly demonstrates that this is a serious medical condition that imposes a considerable drain on scarce healthcare resources. We need more and better information on the consequences of urinary incontinence so that we do not have to make as many assumptions to estimate economic impact. In particular, we need to know the resource implications of the different types of incontinence, the effect on quality of life and the potential benefits from reducing the prevalence of urinary incontinence among Australian women. We also need to alert women to the risk factors for incontinence, strategies that may minimise or prevent incontinence, and the support and treatment options available. Given the demographic shift towards an older population and the escalating costs of healthcare provision and technology, this is an urgent need. References Wyman J. The psychiatric and emotional impact of female pelvic floor dysfunction. Curr Opin Obstet Gynecol 1994; 6: 336-339. Hollywood B, O'Dowd T. Female urinary incontinence: another chronic illness. Br J Gen Pract 1998; 48: 1727-1728. Grimby A, Milson I, Molander U, et al. The influence of urinary incontinence on the quality of life of elderly women. Age Ageing 1993; 22: 82-89. Lam G, Foldspang A, Elving LB, Mommsem S. Social context, social abstention, and problem recognition correlated with adult female urinary incontinence. Dan Med Bull 1992; 39: 565-570. Hunskar S, Arnold EP, Burgio K, et al. Epidemiology and natural history of urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2000; 11: 301-319. Millard R. The prevalence of urinary incontinence in Australia. Aust Continence J 1998; 4: 92-99. Chiarelli P, Brown W. Leaking urine: prevalence and associated factors in Australian women. Neurourol Urodyn 1999; 18: 567-577. Brown W, Bryson L, Byes J, et al. Women's Health Australia: recruitment for a national longitudinal cohort study. Womens Health 1998; 28: 23-40. Thomas T. Prevalence of urinary incontinence. BMJ 1980; 281: 1243-1245. Outlander J. Urinary incontinence in nursing homes. J Am Geriatr Soc 1990; 3: 289-291. Milos I, Eke Lund P, Molander U, et al. The influence of age, parity, oral contraception, hysterectomy and menopause on the prevalence of urinary incontinence in women. J Urol 1993; 149: 1459-1462. Herzog A, Fultz N. Prevalence and incidence of urinary incontinence in community dwelling populations. J Am Geriatr Soc 1990; 38: 273-281. Whishaw M. Urinary incontinence in the elderly: establishing a cause may allow a cure. Aust Fam Physician 1998; 27: 1087-1090. Wall L, Norton P, Delaney J. Practical Urodynamics. Baltimore: Williams and Wilkins, 1993. Wagner T, Hu T. Economic costs of urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 1998; 9: 127-128. National policies and priorities for women's health. Canberra: National Women's Health Policy, 1989. Dowell C, Bryant C, Moore K, Simons A. Calculation of the direct costs of urinary incontinence: the DBICI. Br J Urol 1999; 83: 596-606. Hu T. The economic impact of urinary incontinence. Clin Geriatr Med 1986; 2: 673-687. Hu T. Impact of urinary incontinence on health care costs. J Am Geriatr Soc 1990; 38: 292-295. Drummond M. Methods for the economic evaluation of health care programmes. Oxford: Oxford University Press, 1997. Chiarelli P, Brown W. Leaking urine in Australian women: prevalence and associated conditions. Womens Health 1999; 29: 1-13. Population by age and sex, Australian States and Territories. Canberra: Australian Bureau of Statistics, 1998. (Catalogue no. 3201.0.) Johannesson M, O'Conor R, Kobelt-Nguyen G, Mattiasson A. Willingness to pay for reduced incontinence symptoms. Br J Urol 1997; 80: 557-562. O'Conor R, Johannesson M, Hass S, Kobelt-Nguyen G. Urge incontinence: quality of life and patients' valuation of symptom reduction. Pharmacoeconomics 1998; 14: 531-539. (Received 28 Jun, accepted 18 Dec, 2000) Authors' details School of Population Health Sciences, Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, NSW. Christopher M Doran, PhD, Research Fellow. Pauline Chiarelli, MMedSci, Doctoral candidate. Jill Cockburn, PhD, Professor of Behavioural Science in Relation to Medicine. Reprints will not be available from the authors. Correspondence: Professor J Cockburn, Locked Bag 10, Wallsend, NSW 2287. jillcATmail.newcastle.edu.au Make a comment 1: Estimated numbers of women aged 18 years and over with urinary incontinence and those who sought help for their incontinence in Australia, 1998 Age group No. of women in Australia No. of women with incontinence No. of women with incontinence who sought help 18-39 years 40-69 years 70+ years Total 3114215 3073424 935720 7123359 398620 (12.8%) 1109506 (36.1%) 327502 (35.0%) 1835628 91424 (22.9%) 504798 (45.5%) 146175 (44.6%) 742348 Back to text 2: Estimated cost of resource use for management of urinary incontinence in community-dwelling Australian women aged 18 years and over in 1998 Resource % Of women with incontinence using resource Average annual cost Annual total cost of resource Health professionals General practitioner 54% $48.56 $19465060 Urogynaecologist, Nurse continence advisor, Urologist 53% $327.70 $127960547 Physiotherapist 3% $334.00 $7438324 Other (herbalist, acupuncturist) 2% $18.50 $27466 Travel/parking 75% $12.24 $6813837 Subtotal $161705234 Investigations Midstream urine culture 8% $89.92 $5340078 Urodynamics (cystometry) 29% $359.02 $77288109 Urinary tract ultrasonography 1% $98.75 $733068 Intravenous pyelogram 1% $128.25 $952061 Subtotal $84313316 Medications Hormone replacement therapy (for bladder symptoms only) 19% $33.91 $4782794 Anticholinergics 17% $58.34 $7145837 Laxatives (for anticholinergic-related constipation) 2% $134.05 $1990160 Antibiotics (for urinary tract infection) 19% $28.77 $4057503 Urinary antiseptics 2% $15.22 $225896 Other (for bladder symptoms only) 6% $77.97 $3472702 Subtotal $21674892 Surgery Colposuspension 4% $2200.00 $65326603 Cystoscopy 3% $132.51 $2950980 Phenol injection 2% $168.85 $2506908 Subtotal $70784491 Total treatment costs $338477933 Back to text 3: Personal costs of urinary incontinence for community-dwelling Australian women aged 18 years and over, 1998 Annual cost Average weekly personal costs* Women who sought help Women who did not seek help Age group 18-39 years 40-69 years 70+ years $1.34 $3.38 $8.76 $6370453 $88714515 $66585778 $21405354 $106292270 $82597933 Subtotal $161670746 $210295557 Total personal costs $371966303 *Includes costs of pads, protection, laundry and miscellaneous items. Note that average personal costs reported in Dowell et al were for age groups 24-39, 40-64 and 65-88 years.17 These average rates have been applied to the age groups used in this analysis. Back to text

Christopher M Doran · Pauline Chiarelli · Jill Cockburn

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.54,55Low-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 Yamani M, Massie BM. Congestive heart failure: insights from epidemiology, implications for treatment. Mayo Clin Proc 1993; 68: 1214-1218. Kannel WB, Cupples A. Epidemiology and risk profile of cardiac failure. Cardiovasc Drugs Ther 1988; 2 Suppl 1: 387-395. 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. 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.) 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. Kelly DT. Paul Dudley White international lecture. Our future society. A global challenge. Circulation 1997; 95: 2459-2464. 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. Coats AJS, Adamopolous S, Meyer TE, et al. Effects of physical training in chronic heart failure. Lancet 1990; 335: 63-66. 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. 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. 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. 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. Naughton MT. Impact of treatment of sleep apnoea on left ventricular function in congestive heart failure. Thorax 1998; 53 Suppl 3: S37-S40. McDonald CD, Burch GE, Walsh JJ. Prolonged bed rest in the treatment of idiopathic cardiomyopathy. Am J Med 1972; 52: 41-50. 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. 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. A guide to the development, implementation and evaluation of clinical practice guidelines. Canberra: NHMRC 1999. 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. 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. 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. 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. MRC Working Party Medical Research Council. Trial of treatment in older adults: principal results. BMJ 1992, 304: 405-412. 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. Hansson L, Lindholm LH, Niskanen L, et al. Principal results of the Captopril Prevention Project (CAPP) randomised trial. Lancet 1999, 353: 611-616. 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. 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. 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. 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. Freemantle N, Cleland JGF, Young P, et al. Beta-blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999; 318: 1730-1777. 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. 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. 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. Armstrong PW, Moe GW. Medical advances in the treatment of congestive heart failure. Circulation 1993; 88: 2941-2952. 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. 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. CIBIS II investigators and committees. The cardiac insufficiency bisoprolol study II (CIBIS II): a randomised trial. Lancet 1999; 353: 9-13. 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. Carson PE. Beta-blocker treatment of heart failure. Prog Cardiovasc Dis 1999; 41: 301-321. 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. 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. 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. 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. Digitalis Intervention Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336: 525-533. 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. 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. The NETWORK Investigators. Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison. Eur Heart J 1998; 19: 481-489. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. The Xamoterol in Severe Heart Failure Study Group. Xamoterol in severe heart failure. Lancet 1990; 336: 1-6. Mackstaller LL, Alpert JS. Atrial fibrillation: a review of mechanism, etiology, and therapy. Clin Cardiol 1997; 20: 640-650. Cleland JG, Bulpitt CJ, Falk RH, et al. Is aspirin safe for patients with heart failure? Br Heart J 1995; 74: 215-219. Hall D. The aspirin-angiotensin-converting enzyme inhibitor tradeoff: to halve and halve not. J Am Coll Cardiol 2000; 35: 1808-1812. Barold SS. Biventricular cardiac pacing : promising new therapy for congestive heart failure. Chest 2000; 118: 1819-1812. Dreyfus G, Mihealainu S. The Batista procedure. Heart 2001; 85: 1-2. Jessup M. Dynamic cardiomyoplasty: expectations and results. J Heart Lung Transplant 2000; 19 (8 Suppl): S68-S72. 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. 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. 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).

National Heart Foundation of Australia and Cardiac Society of Australia