Cardiovascular diseases

In reply: The guidelines were published to provide clinicians with the most contemporary information on the management of acute coronary syndromes based on the international literature, and may include treatments which are not currently available, officially licensed or available through the Pharmaceutical Benefits Scheme in Australia. In the context of adjuvant therapy for patients with ST-segment-elevation myocardial infarction (STEMI), the guidelines recommend that antithrombin therapy should be used with fibrin-specific fibrinolytic agents.1 Based on the best evidence available at the time, the guidelines mention two antithrombins, unfractionated heparin and enoxaparin, to be considered for use in this setting. The recommendation for enoxaparin is based on comprehensive evidence of clinical benefit with the regimen of an initial intravenous (IV) bolus dose followed by subcutaneous injections every 12 hours. It is up to individual practitioners to determine whether the IV dose should be provided “off-label” or omitted, based on the evidence and the circumstances of the individual patient and setting. The issue of superiority of enoxaparin over unfractionated heparin as adjuvant therapy for patients with STEMI is currently being evaluated in light of recent evidence,2 and will be included in a future update of the guidelines.

Constantine N Aroney · Philip Aylward

In Australia, many deaths and significant cardiac disability result from delayed response to symptoms of heart attack. Although delays due to transport and initiation of reperfusion therapy in hospital may contribute to late treatment, the major component of delay is the time patients take in deciding to seek help. A critical examination of campaigns to shorten patient delay concludes that they were based on a factual, short-term, non-targeted approach that included education and mass media strategies. They achieved equivocal results. One randomised controlled trial has been conducted. Although this showed an improved understanding of heart attack symptoms, it did not shorten pre-hospital delays. The implications of these findings are that future campaigns to shorten patient delay are likely to be more effective if they address the psychosocial and behavioural blocks to action, are ongoing rather than short term, and focus on people at highest risk, including those with known or high risk of coronary heart disease, those in rural locations, and Indigenous Australians. The National Heart Foundation of Australia proposes a comprehensive strategy to incorporate this approach into its future campaigns to reduce patient delay for suspected heart attack.

on behalf of the National Heart Foundation of Australia Chest Pain Every Minute Counts Working Group

Postural syncope is a transient loss of consciousness secondary to a reduction in cerebral blood flow and is typically precipitated by standing. It is the commonest cause of recurrent transient loss of consciousness. Recurrent unexplained postural syncope is most often due to one of the five disorders of circulatory control: vasovagal syncope, postural tachycardia syndrome, chronic autonomic failure, initial orthostatic hypotension, or persistently low supine systolic blood pressure. Failure to identify the underlying cause of postural syncope can result in ongoing morbidity, impaired quality of life and high health care costs. With a detailed history, examination, blood pressure assessment and electrocardiography, most disorders of circulatory control can be diagnosed. In difficult cases, analysis of sympathetic nervous system and circulatory responses during head-up tilting can aid diagnosis. Treatment is challenging and compounded by a lack of evidence. Most patients can be managed in an outpatient setting, and hospital admission or emergency department assessment is rarely warranted.

Gautam Vaddadi MB BS, BMedSci, FRACP · Elisabeth Lambert BSc, PhD · Susan J Corcoran MB BS, FRACP · Murray D Esler MB BS, FRACP, PhD

To the Editor: Clark et al have claimed to map the distribution of services for people with chronic heart failure (CHF) against the distribution of these people.1 An examination will show that they have mapped the distribution of people likely to have CHF, using age and Aboriginality as surrogate markers. The stated mapping of the services shows the services probably available to these people. A map is drawn to show us what the cartographer wants us to see.2 The authors note that high prevalence in remote regions has been shown on the maps, but they have not considered different mapping methods to provide a better representation of their results.3 This has led to an anomaly so that, when calculating numbers of people with CHF, the maps show remote areas with giant households containing between 24 and 300 people. CHF programs were located by a snowball sampling technique, which by its nature will miss isolated examples. Isolation is a feature of rural and remote practice, so this method is biased to finding metropolitan examples. In my own rural practice in Griffith, I found a local program that had been operating in 2004 and a distance program run by a health fund, neither of which had been identified by Clark et al. On the medical front, the authors asserted that access to a CHF management program is a mark of equity in health services. This is based on a metro-centric model looking at admission with CHF to a major teaching hospital, and showing that rates of readmission and death were reduced where a nurse and a pharmacist made a single visit to someone with CHF in their home after hospital discharge. The relevance of this activity to a rural person with a single community pharmacist who may make a home visit, a single point of contact with medical services in their general practitioner, and the possible availability of a community nurse to visit them regularly is unproven. Perhaps the city folk were copying the principles of the services we already had?

Elizabeth A Dodd

In reply: We thank Dodd for her commentary on our article.1 We concur with many of the highlighted issues relating to our suboptimal response to the burden and management of chronic heart failure (CHF) in rural and remote Australia. These include the lack of rigorous epidemiological data and lack of specialist services “beyond city limits”. Unfortunately, we have limited space to respond fully. However, we re-emphasise that, although our previous estimates2 complement that of the Canberra Study,3 neither can replace an Australia-wide study of CHF that samples metropolitan, regional, rural and Indigenous communities. We also stand by (within the context of the stated limitations) the accuracy of our mapping of the CHF programs and the location of general practice services in Australia for the study period. Our geo-mapping approach and data have been well validated by the National Centre for Social Applications of Geographic Information Systems (GISCA).4 For example, Jenks’ (natural breaks) classification is used for all sociodemographic thematic mapping at GISCA. Overall, we identified only four CHF programs which were located in regional areas. Other rural programs were excluded as they did not meet our prespecified definition of a CHF program. In summary, we acknowledge the need for better data to describe the burden of CHF throughout Australia. We also explicitly acknowledge the need for a less “metro-centric” approach to CHF service: perhaps by using remote monitoring techniques.5

Robyn A Clark · Andrea Driscoll · Justin Nottage · Skye McLennan · David M Coombe · Errol J Bamford · David Wilkinson · Simon Stewart

To the Editor: Walker and colleagues recently reported a series of patients with interstitial pneumonitis following use of statin cholesterol-lowering drugs.1 They state that other investigators have previously reported biopsy findings resembling amiodarone-induced pulmonary toxicity in pneumonitis associated with statin therapy. We believe this observation is pivotal to understanding the authors’ findings. Amiodarone produces mitochondrial toxicity, which is recognised to be a potential initiating event in amiodarone-induced pulmonary toxicity.2 Statins also produce mitochondrial toxicity in vulnerable individuals. Adverse effects of statins on muscle have been linked to mitochondrial abnormalities,3 and other clinical manifestations of statin mitochondrial toxicity have been reported. Mitochondrial respiratory chain disease is famously protean in its manifestations, but most classically produces a mitochondrial encephalomyopathy — with muscle, brain, or both affected. Consistent with this, muscle and cognitive symptoms are the most widely reported adverse effects in our reporting database of statin adverse effects (comprising 2478 patients to date), and these symptoms frequently occur together, consistent with a common mechanism. Statin–amiodarone combinations have produced heightened toxicity relative to each agent alone. Interference with cytochrome P450 metabolism has been the presumed mechanism,4 but additive or synergistic mitochondrial toxicity may also be a factor. The occurrence of amiodarone-like interstitial pulmonary disease in statin users adds to concerns that a range of clinical presentations of mitochondrial toxicity may ultimately be reported with statins in susceptible individuals, with mitochondrial heteroplasmy and threshold effects determining the specific manifestations.5

Beatrice A Golomb · Marcella A Evans

CABG offers a cost-effective and better long-term clinical outcome for many patients Coronary artery disease is still the single largest cause of premature death in Australia, according to the Australian Institute of Health and Welfare.1 Also documented is the dramatic decline in age-related mortality from heart disease, which is largely attributed to reductions in smoking and better intervention for hyperlipidaemia and elevated blood pressure.2 As many as 85% of elective percutaneous coronary intervention (PCI) procedures are done in patients with stable coronary artery disease.3 However, the only data showing prognostic benefit of intervention in reducing death and infarction in such patients come from subgroup analyses in old surgical trials,4-6 which showed benefits for patients with left main, triple vessel or proximal left anterior descending stenoses, especially if there was additional left ventricular damage. These benefits lasted up to 11 years, but the surgery was compared with medical therapy that did not include aspirin, β-blockers or lipid-lowering therapy for most patients. The surgical group did not receive arterial conduits. Subsequently, 11 randomised trials comparing PCI with coronary artery bypass graft (CABG) surgery for patients with multivessel coronary artery disease showed that the frequency of death and myocardial infarction was similar in both arms.7 These results cannot be used to claim an outcome benefit for PCI, as the trials entered only about 5% of screened patients, and the patients were not equivalent in the severity of their coronary artery disease to those in the original CABG trials. Further, analysis of the comparative trials shows that the highest-risk group (those with diabetes) showed benefit with CABG over PCI.8 Outcomes after CABG now show that, despite this surgery being performed in increasingly sick and complex patients, the overall mortality is less than 2%.9 Average length of hospital stay is now 3–5 days and return to work is usual in less than 2 months. Improved techniques have reduced the problem of cognitive impairment, and comparative studies have shown no difference with PCI in this respect.10 Long-term outcomes of CABG have improved due to the increased use of arterial conduits. Repeat CABGs now make up only 3%–4% of total CABG surgery, although this low figure may reflect a preference for PCI in repeat procedures. PCI has flourished since its introduction 30 years ago, with its offer to patients of a sound and timely intervention for coronary artery disease — but it has not been without problems. Recoil restenosis with balloon angioplasty was largely solved by the introduction of bare-metal stents. Acute stent thrombosis is less of a problem with better anticlotting agents, and drug-eluting stents have significantly reduced the problem of late restenosis. Despite these improvements, no reported studies have shown convincing evidence that PCI reduces the finite end points of death or myocardial infarction for patients with stable coronary artery disease. Controversy has recently arisen over the finding that patients with drug-eluting stents have an ongoing excess risk of late stent thrombosis of around 0.5% a year, presumably due to failure of endothelialisation of the stent. These events are usually associated with acute myocardial infarction, which carries a 50% mortality rate. It is now recommended that patients with drug-eluting stents stay on combined treatment with clopidogrel and aspirin for at least 12 months after implantation, and possibly permanently.11 This adds to patients’ financial costs and places them at extra risk of bleeding. Two recent reports provoke additional comment. First, Griffin et al used a complicated analysis of previous data to assess the cost-effectiveness of PCI and CABG in patients with multivessel disease considered suitable for revascularisation. CABG reached the accepted level of cost-effectiveness (US$60 000 per quality-adjusted year of life gained) but PCI did not, mainly due to the ongoing need for repeat procedures in PCI patients.12 Second, Boden et al reported a randomised trial comparing PCI with medical therapy in patients with stable coronary artery disease, which found no difference in the rate of death or non-fatal myocardial infarction at a median follow-up of 4.6 years. The PCI group initially had a reduced rate of angina, but this difference had disappeared at 5 years, largely because the medical therapy group had improved.3 The best interpretation of currently available data is that, for patients with severe coronary artery disease, the more invasive procedure with a longer recovery time (CABG) has a better long-term clinical outcome and is more cost-effective than the less invasive fast-recovery procedure (PCI). Three ongoing randomised clinical trials (CARDia, SYNTAX and FREEDOM) should further clarify the roles of PCI and CABG in treating severe coronary artery disease. The question then arises of whether, in current practice, PCI is being used in patients with severe coronary artery disease who would be more appropriately treated with CABG. Surgeons and cardiologists have argued that patients are not being adequately advised of the surgical option.13 Indeed, use of CABG is in such decline that training programs for young surgeons are at risk.14 In practice, the patient decides between CABG and PCI following discussion with a cardiologist, often while still in the angiography suite. This arrangement bypasses one of the recommendations on self-referral issues: to undertake consultation with other providers.15 It has been suggested that the technical suitability of a lesion for angioplasty determines the advice given to patients, rather than the relative benefits of CABG, PCI or even medical treatment alone.16 Smoking cessation and treatment to lower lipids and blood pressure are remarkably effective in improving the outlook for patients with stable coronary artery disease. Both CABG and PCI will provide benefits if revascularisation is performed for relief of symptoms, and patients may be influenced in their choice by both the less invasive nature of PCI and by the fewer recurrent procedures offered by CABG. However, for patients with prognostically important stable coronary artery disease (ie, severe left main or triple vessel disease), current evidence indicates that CABG offers a better long-term outcome.

Keith V Woollard MRCP, FRACP · Mark A J Newman DS, FRACS

To the Editor: Awareness about atypical and malignant modes of presentation of a clinical condition can avoid catastrophic outcomes, assist in correct diagnosis in the appropriate clinical setting and, as typified by the following case, offer complete cure. A 39-year-old woman presented with a 5-year history of intermittent, recurrent brief syncopal episodes. During an episode at presentation, telemetry showed torsade de pointes with ventricular fibrillation (Box), and external defibrillation was required to restore sinus rhythm. Amiodarone infusion was initiated at a local hospital before the patient was referred to our institution for further investigation and management. On presentation, her heart rate was 50 beats/min and her blood pressure was 170/95 mmHg. No other abnormalities were detected on examination. A resting electrocardiogram (ECG) showed prominent U waves, with a long QT interval (QTc of 540 ms). As the patient had mild hypokalaemia (serum potassium level, 3.1 mmol/L), mild hypocalcaemia (serum calcium level, 2.10 mmol/L) and a prolonged QT interval, the amiodarone infusion was discontinued, and supplementation with potassium and calcium was initiated. In view of the hypertension and hypokalaemia, primary aldosteronism was suspected. Serum cortisol, 24-hour urinary cortisol and 24-hour urinary catecholamine levels were normal. The plasma aldosterone/renin ratio was markedly elevated (1920/1.2 = 1595; normal, < 99). Failure of aldosterone suppression after acute saline loading was also noted. Computed tomography of the abdomen showed a right adrenal ovoid mass (1.9 × 1.2 cm). Adrenal vein sampling confirmed right lateralisation (right to left ratio, 40 : 1; aldosterone level in the right vein was 224 000 pmol/L while that in the left vein was 5570 pmol/L). Despite initial potassium supplementation, the hypokalaemia persisted and only improved after initiating diuretic therapy with amiloride. Two weeks later, laparoscopic right adrenalectomy was performed, and adrenocortical adenoma was confirmed histologically. After surgery, plasma aldosterone and renin levels normalised to 106 pmol/L and 8.9 mU/L, respectively. Nine months later, the patient was normotensive (without treatment) and had a normal ECG with no further recurrence of arrhythmias. This was a case of primary aldosteronism presenting as aborted sudden cardiac death and malignant syncope secondary to hypokalaemia-induced torsade de pointes. Most patients with primary aldosteronism are either asymptomatic or have symptoms related to hypertension or hypokalaemia (eg, polyuria, cramps, paraesthesia or muscle weakness); the diagnosis is often missed because of the non-specific clinical features. Primary aldosteronism presenting with cardiovascular collapse caused by hypokalaemic torsade de pointes and recurrent ventricular fibrillation is extremely rare, as is presentation as sudden cardiac death secondary to ventricular fibrillation.1 A prolonged QT interval has been reported in cases of primary aldosteronism,2 with values normalising after adrenalectomy.3 Torsade de pointes noted on telemetry in a 39-year-old woman

Aditya Kapoor · Timothy A Wells · Daniel Wong · John P O’Shea

Objective: To assess the management of patients with type 2 diabetes mellitus in the primary care setting, with respect to risk factors associated with coronary heart disease.Design: Retrospective cross-sectional audit.Setting: Specialised diabetes assessment clinic in a tertiary referral teaching hospital.Participants: 328 patients with type 2 diabetes mellitus (mean age, 58.3 years [95% CI, 57.5–59.1]) and no existing coronary heart disease (CHD) referred to the clinic by general practitioners during 2004–2005.Main outcome measures: Comparison of glycated haemoglobin (HbA1c), systolic blood pressure and total cholesterol levels and smoking frequency with current RACGP (Royal Australian College of General Practitioners) targets (< 7.0%; < 130/80 mmHg; < 4 mmol/L; and smoking cessation, respectively). Estimation of patients’ 10-year absolute risk of CHD events using the United Kingdom Prospective Diabetes Study risk engine, and its relation to primary prevention of CHD.Results: 42%, 61% and 43% of patients were receiving medication to treat hyperglycaemia, hypertension and hypercholesterolaemia, respectively; 46%, 29% and 15% of patients, respectively, had achieved the recommended RACGP target values for HbA1c, blood pressure, and total cholesterol; and 22% of patients were current smokers. The mean 10-year absolute risk of CHD was 16.8% (95% CI, 15.7%–17.9%), and 48% of patients were classified as “high risk” (absolute risk, > 15%). Based on the 10-year absolute risk, there was no difference between high- and low-risk groups with respect to prescription of aspirin, statins or angiotensin-converting enzyme inhibitors. If all the recommended RACGP goals were achieved, the mean 10-year absolute risk would decrease to 12.6% (95% CI, 11.8%–13.4%).Conclusions: Recommended treatment targets are not being uniformly achieved. Medication for primary CHD prevention is not being preferentially directed at those patients at highest risk, based on the estimated 10-year absolute risk of CHD events. Our findings suggest new initiatives are required in the way target goals and primary CHD prevention measures are set for patients with type 2 diabetes mellitus.

Tuck Y Yong MB BS · George Phillipov BSc(Hons), MSc, PhD · Patrick J Phillips MB BS, MA, FRACP

“First responders” are people trained in advanced first aid who can respond at the same time as, and often more quickly than, ambulance services to suspected medical emergencies. Hatzolah is a volunteer First Responder group, based on halakhic (Jewish legal) principles, in a localised area of metropolitan Melbourne with the highest density of Holocaust survivors outside Israel. Low numbers of “call-outs” to Victoria’s Metropolitan Ambulance Service (MAS) from this community suggested that many were reluctant to make contact with a “uniformed” external agency. Hatzolah is an autonomous organisation operating under adapted MAS clinical practice guidelines and clinical governance processes. Hatzolah responders undergo an 18-month MAS training course comprising first aid, cardiopulmonary resuscitation, the use of semiautomated defibrillators, and oxygen therapy. We describe the first 11 years (1995–2005) of the Hatzolah service. The number of patients attended to annually has risen steadily, peaking at 867 in 2005. The most frequent reasons for call-outs were falls (19.4%), chest pain (9.7%), or respiratory distress (7.6%). Hatzolah’s median response times were 2 or 3 min for all cases. They attended 35 patients with cardiac arrest (median response time, 2 min), and arrived before the MAS to 29 call-outs (83%). Nineteen patients (54%) with cardiac arrest were resuscitated and transported from the scene alive. Among those transported, significantly more had a shockable cardiac rhythm (50% v 13%, P = 0.03). Five (14%) survived to hospital discharge. Hatzolah has evolved into an organisation providing a complementary service to the MAS. It serves as a model for the establishment of other metropolitan community First Responder groups.

Tony Chan MB BS · George Braitberg MB BS, FACEM · Danny Elbaum BBus(Accounting) · David McD Taylor MD, MPH, FACEM

Objective: To describe the outcome of valve surgery, for rheumatic heart disease (RHD) and non-RHD, in residents of Cape York Peninsula and the Torres Strait Islands referred to the Cairns Base Hospital specialist outreach service.Design and participants: Retrospective review of medical records on all patients residing in the outreach area who had surgery for valvular heart disease between 1 January 1992 and 31 December 2004.Main outcome measures: Operation type and perioperative characteristics; 5- and 10-year survival rates; reoperation rates; complications.Results: Forty-seven patients met the selection criteria; the median age was 40 years (range, 4–76 years); and 39 patients were Indigenous. RHD was the predominant cause of valve dysfunction (30/47 patients). Thirty-seven patients had valve replacements, six had valve repair and four had balloon valvotomy as the initial procedure. There were three bleeding complications, two episodes of operated valve endocarditis, and six embolic complications. There were nine valve-related deaths (six in the first 5 years). At 5 years, all seven patients who had had valve repair or balloon valvotomy were alive. Seven of the 47 patients required reoperation. Survival analysis showed freedom from valve-related deaths to be 83% (95% CI, 66%–92%) at 5 years and 61% (95% CI, 33%–80%) at 10 years. Freedom from reoperation at 5 years was 88% (95% CI, 71%–95%). Among the 30 patients with RHD, freedom from valve-related death was 80% (95% CI, 60%–92%) at 5 years and 52% (95% CI, 21%–75%) at 10 years. In patients with RHD, freedom from reoperation at 5 years was 87% (95% CI, 65%–96%).Conclusion: Valvular heart disease results in substantial morbidity and mortality, despite intervention. Efforts need to focus on prevention of rheumatic fever and closer follow-up.

Anna McLean MB BS · Michael Waters MB BS(Hons) · Emma Spencer MB BS · Clive Hadfield MB BS

To the Editor: We report an exceptional case of a woman who underwent emergency “finger fracture valvuloplasty” (FFV) in 1954 to treat rheumatic mitral stenosis and required no further surgical intervention for 51 years. The woman presented in 1954 with pulmonary oedema due to mitral stenosis during the first trimester of her second pregnancy. She underwent FFV at Lewisham Hospital in Sydney. She had a prolonged convalescent period, was discharged after 5 months, and delivered a healthy child. She was one of two pregnant patients reported in the Medical Journal of Australia by Hall and Windsor.1 She remained well and active until 2005, when she presented with New York Heart Association Class III symptoms of dyspnoea on exertion, and ultimately underwent mitral valve replacement that year. She made a good recovery postoperatively and remains well. In the 1920s, 10 patients with mitral valve stenosis were treated surgically.2 In 1923, Cutler and associates from Boston operated on seven patients using a cardiovalvulotome (through the left ventricle) and, in the same year, Duff and Evarts from Washington used a cardioscope (through the left atrium) on one patient. In 1925, Soutter from London and Pribram from Germany used a “finger fracture method” and a valvulotome, respectively, on one patient each. However, of the 10 patients, only two survived, one of Soutter’s and one of Cutler’s. The procedure was subsequently successfully revived in 1948 by Harken in Boston, Bailey in Philadelphia, Blalock in Baltimore, Brock in London, and others, who performed various procedures including valvuloplasty and commissurotomy. However, the so-called FFV (Harken) became the favoured procedure. It evolved from using the forefinger, to using the little finger, to eventually using a knife. Most surgeons had difficulty in using the mitral knife to divide the medial commissure and thus developed their own instrument.2 There are few successful case reports of FFV in pregnancy. In the United Kingdom, Brock reported three, Logan and Turner, six, and Marshall and Pantridge, 18.3 Hall and Windsor in Sydney performed FFV in two of seven pregnant women who were being considered for FFV, including our patient. One of the other five, who were managed conservatively, died.1 In 1963, Windsor said, “Eleven years’ experience in the surgery of the mitral valve has brought with it a great respect for the ability of the mitral commissures to resist finger, knife and dilator”. He reported follow-up of 90 patients who underwent FFV. No more than 40 patients (45%) obtained good results. Sixteen patients in this group have since been reoperated upon by the more effective transventricular route using a mechanical expanding dilator.4 It should be noted that mitral stenosis in young women is rarely accompanied by calcification, and this may allow a more complete and successful valvuloplasty. All the procedures mentioned above occurred before the development of cardiopulmonary bypass and open heart surgery in 1954. Early pioneers in surgery faced many challenges and disappointments, as well as condemnation, criticism and ridicule from colleagues. Some, like Soutter and Bailey (the latter nicknamed the “butcher of Hahnemann Hospital [Philadelphia]” after his first four FFV patients died) lost their practices.5 We would like to pay homage to all surgical pioneers and conclude with a comment from Harken: “He who would not learn from the past is condemned to relive it”. Finger fracture mitral valvuloplasty technique (Hall and Windsor1)

John S Murala · Hugh D Wolfenden · George S Youssef · Daniel Friedman

Prediabetes, the presence of impaired fasting glucose/glycaemia and/or impaired glucose tolerance, affects about 16.4% of Australian adults. People with prediabetes are at increased risk of developing diabetes, and cardiovascular and other macrovascular disease. Management includes reducing cardiovascular disease risk factors, specifically lipid and blood pressure abnormalities, and smoking-cessation counselling. To help prevent progression to diabetes, people with prediabetes who are overweight or obese require intensive lifestyle intervention. Medication to help prevent diabetes may also be used, but only after a minimum of 6 months of lifestyle intervention. In people with prediabetes, there is no role for routinely testing: capillary blood glucose; glycated haemoglobin (HbA1c) levels; serum insulin or pancreatic C-peptide levels; or testing for ischaemic heart disease or the microvascular complications of diabetes. Follow-up assessment of glycaemia in prediabetes requires a formal 75 g oral glucose tolerance test, initially performed annually, with subsequent individualised testing frequency.

Stephen M Twigg MB BS, FRACP, PhD · Maarten C Kamp FRACP, MHA · Timothy M Davis FRACP · Elizabeth K Neylon DAA, CDE · Jeffrey R Flack FRACP, MMed

Objective: To assess whether a diagnosis of the metabolic syndrome (MetS) improves the prediction of cardiovascular disease or total mortality beyond that already provided by conventional risk factors.Design and setting: A longitudinal cohort study conducted in Dubbo, New South Wales.Participants: 2805 men and women aged 60 years and older living in the community, first assessed in 1988–1989 and followed for 16 years.Main outcome measures: Coronary heart disease (CHD) events, ischaemic stroke events, and total mortality.Results: MetS was present in 31% of men and 34% of women. Crude CHD, ischaemic stroke, and total mortality rates were higher in the presence of MetS in men and women. In proportional hazards models that included conventional risk factors, but excluded variables used to define the presence of MetS, MetS was a significant predictor of CHD, stroke and total mortality. In men, the respective hazard ratios were 1.64 (95% CI, 1.37–1.96), 1.31 (95% CI, 0.97–1.77), and 1.53 (95% CI, 1.30–1.79). In women, the respective hazard ratios were 1.70 (95% CI, 1.43–2.02), 1.37 (95% CI, 1.04–1.82), and 1.35 (95% CI, 1.15–1.59). The use of MetS variables on an ordinal scale produced broadly similar conclusions.Conclusions: A diagnosis of MetS provides additional prediction of CHD events, stroke events, and total mortality beyond that provided by other conventional risk factors.

Leon A Simons MD, FRACP · Judith Simons MACS · Yechiel Friedlander PhD · John McCallum DPhil

Objective: To assess the prevalence of obesity in patients undergoing coronary artery bypass grafting, heart valve surgery, or both procedures, and its association with postoperative outcomes.Design and setting: Retrospective analysis of data, collected by the Australasian Society of Cardiac and Thoracic Surgeons Victorian Cardiac Surgery Database Project, on patients undergoing coronary artery bypass grafting, heart valve surgery, or both procedures, between 1 June 2001 and 31 January 2006.Participants: 11 736 patients divided into four groups: underweight (body mass index [BMI], < 20), normal weight (BMI, 20–30), obese (BMI, > 30 to < 40), and morbidly obese (BMI, ≥ 40).Main outcome measures: Prevalence of obesity (compared with the age- and sex-matched adult Australian population); associations between obesity and morbid obesity in cardiac patients and adverse postoperative outcomes.Results: 30.4% of patients had a BMI > 30 (28.6% obese, 1.8% morbidly obese) compared with an expected prevalence of 21.2%. Morbid obesity was associated with prolonged ventilation (adjusted odds ratio [OR], 2.4; 95% CI, 1.6–3.7), readmission to intensive care (adjusted OR, 2.2; 95% CI, 1.2–4.1), and length of stay > 14 days (adjusted OR, 2.1; 95% CI, 1.4–3.3). Both obesity and morbid obesity were associated with renal failure (adjusted ORs, 1.4 [95% CI, 1.1–1.7] and 2.9 [95% CI, 1.7–4.9], respectively) and deep sternal wound infection (adjusted ORs, 2.4 [95% CI, 1.5–3.8] and 7.2 [95% CI, 2.8–18.7], respectively).Conclusions: Obesity is 1.4 times more prevalent in patients having coronary artery bypass grafting or heart valve surgery in Victoria compared with the general adult Australian population. Both obesity and morbid obesity are associated with early morbidity, but not mortality, after operation.

Cheng-Hon Yap MB BS, MS · Morteza Mohajeri FRACS · Michael Yii FRACS, MS

A 55-year-old woman was admitted to hospital with a 1-year history of recurrent haemoptysis. A chest radiograph showed a well defined, rounded left hilar mass with surrounding air-space shadowing (Box, A). Contrast-enhanced computed tomography revealed a thrombosed aneurysm of the left main pulmonary artery that extended into its branches, with surrounding lung consolidation (Box, B). Echocardiography excluded any valvular lesions or shunt. Tests for tuberculosis and HIV were negative, and antinuclear antibody levels were not raised. The aneurysm was thought to be idiopathic. It was surgically resected, and the postoperative course was uneventful. A: Chest radiograph showing a left hilar mass. B: Contrast-enhanced computed tomography of the thorax showing an aneurysm of the left pulmonary artery extending distally into its branches with evidence of curvilinear thrombus (1), patent vessels (left pulmonary artery [2], right pulmonary artery [3], ascending aorta [4], superior vena cava [5] and descending aorta [6]), and consolidation of lung parenchyma adjoining the thrombus, with pleural thickening (7).

Zubair Ahmad MD, FCCP · Imrana Masood MB BS · Saurabh K Singh MB BS

There are two types of coronary stents: bare-metal stents (BMS) that cost about $800 each, and drug-eluting stents (DES) that cost about $3300 each. DES reduce the rate of restenosis but have a higher incidence of late stent thrombosis, particularly if dual antiplatelet therapy with aspirin and clopidogrel is interrupted. Stent thrombosis has a myocardial infarction rate of 70% and a mortality rate of 31%–45%. Randomised studies of BMS versus DES show no increase in myocardial infarction or death with DES in simple coronary lesions, but in clinical practice, DES are mainly used in complex coronary disease where the rate of stent thrombosis is higher. Registry data suggest an increased rate of death and myocardial infarction of 0.5%–1.0% per annum with DES. Clinicians need to be aware of the risks associated with prematurely ceasing dual antiplatelet therapy in patients with DES.

Richard W Harper MB BS, FRACP, FACC

The incidence and prevalence of atrial fibrillation are increasing because of both population ageing and an age-adjusted increase in incidence of atrial fibrillation. Deciding between a rate control or rhythm control approach depends on patient age and comorbidities, symptoms and haemodynamic consequences of the arrhythmia, but either approach is acceptable. Digoxin is no longer a first-line drug for rate control: β-blockers and verapamil and diltiazem control heart rate better during exercise. Anti-arrhythmic drugs have only a 40%–60% success rate of maintaining sinus rhythm at 1 year, and have significant side effects. The selection of optimal antithrombotic prophylaxis depends on the patient’s risk of ischaemic stroke and the benefits and risks of long-term warfarin versus aspirin, but is independent of rate or rhythm control strategy. Ischaemic stroke risk is best estimated with the CHADS2 score (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, 1 point each; prior Stroke or transient ischaemic attack, 2 points). For patients with valvular atrial fibrillation or a CHADS2 score ≥ 2, anticoagulation with warfarin is recommended (INR 2–3, higher for mechanical valves) unless contraindicated or annual major bleeding risk > 3%. Aspirin or warfarin may be used when the CHADS2 score = 1. Aspirin, 81–325 mg daily, is recommended in patients with a CHADS2 score of 0 or if warfarin is contraindicated. Stroke rate is similar for paroxysmal, persistent, and permanent atrial fibrillation, and probably for atrial flutter.

Caroline Medi BMed · Graeme J Hankey MD, FRCP, FRACP · Saul B Freedman FRACP, FACC, FESC

Over a 3-year period, seven patients who were taking HMG-CoA reductase inhibitors (statins) presented to our respiratory service with interstitial pneumonitis. Clinical course varied, with the condition responding to prednisolone treatment and cessation of statins in three patients, and progressing slowly despite this management in another three, while one patient died of associated cardiac disease. While a causative role cannot be confirmed, clinicians should be aware of the possible association. Two patients who presented with interstitial lung disease to our hospital’s respiratory service in 2000 prompted us to research a possible association between this disease and therapy with statins (hydroxymethylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors). A literature review revealed several isolated cases of pneumonitis in the setting of statin therapy.1-3 Thereafter, we prospectively recorded patients referred to our unit who had interstitial lung disease and were undergoing statin therapy, where no other clear cause of the pneumonitis was evident. All cases have been reported to the Adverse Drug Reactions Advisory Committee. Clinical recordsBetween January 2000 and December 2003, our service saw 58 new presentations of interstitial lung disease, including the two patients discussed above. Data on these patients were retrieved from an ambulatory care database of newly presenting patients kept prospectively by our service. Their diagnoses are shown in Box 1. Eight cases were thought to be drug-associated: five of these were potentially linked to statin therapy, two to nitrofurantoin and one to amiodarone. Another two patients were referred to our service during hospital admissions in other specialties not included in our database. Details of these patients were retained from consultation records. Clinical details of the seven patients taking statin therapy are shown in Box 2. Most patients presented with dyspnoea and non-specific examination findings consistent with interstitial lung disease, such as bilateral crepitations on chest auscultation. None had clubbing. Some patients had a background of smoking and mild chronic obstructive airways disease, while others had no specific risk factors. Statins potentially implicated were atorva-statin (10–40 mg daily), pravastatin (40 mg daily) and simvastatin (10–40 mg daily). No patients were taking other medications known to be implicated in interstitial lung disease. Pneumonitis was diagnosed based on clinical assessment, along with demonstration of interstitial infiltrates on high-resolution computed tomography and reduced transfer factor for carbon monoxide diffusion on lung function testing (Box 3). Management comprised prednisolone or other immune-modifying treatment and/or withdrawal of the statin. In three patients treated with both prednisolone and statin withdrawal, pneumonitis decreased (Patients 3, 5 and 7). In another three, the condition progressed slowly: one of these (Patient 1) did not take prednisolone, and another (Patient 2) initially continued statin therapy and experienced respiratory failure necessitating home oxygen therapy before it was ceased. He died 18 months later of respiratory failure. The third (Patient 4) experienced slow progression despite statin withdrawal and treatment with prednisolone and azathioprine. The remaining patient (Patient 6) was treated with prednisolone but continued statin therapy, and died from coexisting cardiac disease, probably exacerbated by interstitial lung disease. DiscussionStatins are the most often prescribed class of medication for treating hypercholesterolaemia. They act primarily by inhibiting HMG-CoA reductase, thereby inhibiting cholesterol biosynthesis and improving lipid profiles. However, recent research has revealed multiple immunomodulatory, vascular endothelial, antioxidant and other effects of statins.4 These so-called “pleiotrophic” effects have led to statins being studied in a host of unrelated clinical settings, including osteoporosis, multiple sclerosis and Alzheimer’s disease. While research is ongoing, it appears that statins have profound multisystem effects that extend well beyond lipid metabolism. Statins are, on the whole, well tolerated, with the most commonly reported adverse effects being gastrointestinal upset, headache, rash and a dose-dependent elevation in serum levels of liver transaminases. The best characterised rare, but potentially serious, adverse effects are myopathy and polyneuropathy. These adverse effects are probably dose-related and may occur more often in patients taking medications known to inhibit statin metabolism.5 There are also a few reports of lupus-like syndromes, polymyositis/dermatomyositis with lung involvement, and hypersensitivity pneumonitis associated with statin therapy.1-3,6-9 The timing of onset appears unpredictable, with many patients having been taking statin therapy for many months or years before symptoms develop. Clinical features varied in severity from mild dry cough and rash through to severe and progressive respiratory failure. Low-titre antinuclear antibody (ANA) positivity and a raised erythrocyte sedimentation rate were also described in some patients. There are only four reports of open lung biopsy in these cases, two showing hypersensitivity pneumonitis with granuloma formation, one showing diffuse alveolar damage and the other showing non-specific interstitial pneumonitis. Most — but not all — patients responded to drug cessation and therapy with prednisolone or other potent immunosuppressive agents.2,8,9 Our patients shared many features with these patients. However, we did not observe rash of a dermatomyositic, lupoid or urticarial type, or lupus or polymyositis-like syndromes in our patients. Instead, all presented with respiratory symptoms — shortness of breath with or without dry cough — generally of insidious onset. Two out of six patients tested were positive for ANA with no other clinical features of connective tissue disease. The findings on transbronchial biopsy, when performed, were non-specific. Radiological appearances varied between alveolitis and fibrosis, but none showed the characteristic subpleural basal honeycombing that is common in usual interstitial pneumonia. The occurrence of alveolar eosinophilia in two out of the four patients who underwent bronchoalveolar lavage, which has previously been described in drug-hypersensitivity pneumonitis, and the response in several patients to drug cessation and/or corticosteroid therapy also point to a potential drug-induced pneumonitis. One previous case of pneumonitis has been reported in the setting of statin therapy, which was confirmed by open lung biopsy, and where the findings closely resembled those in amphiphilic drug toxicity, such as that reported with amiodarone. The authors hypothesised that a toxic mechanism, possibly mediated by statin effects on lipid metabolism, led to the observed intralysosomal lamellar inclusions in pneumocytes and interstitial cells.9 Thus, while not fully characterised, there is a putative mechanism through which statins may cause interstitial pneumonitis. Detecting rare side effects of commonly prescribed medications has always been a challenging task for the clinician. It is even more difficult when symptoms present insidiously, months or years after medication has been commenced, and the disease process has multiple potential aetiologies, which are not fully characterised. Similarly, interstitial lung disease remains a challenging diagnostic area even for experts in the field. Failure to recognise an under-lying cause of the pneumonitis often leads to the diagnosis of usual interstitial pneumonia being accepted. With continuation of the causative agent, the expected clinical pattern is progressive deterioration leading to respiratory failure and death, which also closely resembles the expected course of usual interstitial pneumonia. We hope that our description of our patients and review of the possible role of statins in interstitial lung disease will raise awareness of the potential association between statin therapy and this uncommon and often fatal condition. The effects of withdrawal of statin therapy on development of interstitial lung disease in patients taking this class of medication require further study. 1 New presentations of interstitial lung disease, 2000–2003 Diagnosis Number of patients Sarcoidosis 26 Usual interstitial pneumonitis 10 Non-specific interstitial pneumonitis 9 Drug-associated 8 Hypersensitivity pneumonitis 2 Asbestosis 2 Connective tissue disease-associated 1 2 Clinical details of seven patients with interstitial lung disease receiving statin (HMG-CoA reductase inhibitor) therapy Patient Sex, age Presentation Comorbidities Medications at presentation Investigations* Treatment Outcome 1 F, 78 Progressive dyspnoea, dry cough Hypertension, type 2 diabetes, hyperlipidaemia, non-smoker Atorvastatin (10 mg, 1 year), fosinopril, sertraline HRCT: extensive bilateral fibrosis TLCO: 46% No lavage or biopsy ANA-positive (1/40) Colchicine, atorvastatin withdrawn Slow progression: lung function deteriorated but clinical condition stable, little dyspnoea on 3-year follow-up 2 M, 78 Progressive dyspnoea (3 weeks), no cough or fever Chronic obstructive airways disease, IHD, atrial fibrillation, stroke, hyperlipidaemia, depression, ex-smoker Pravastatin (40 mg, 10 years), aspirin, frusemide, isosorbide mononitrate, perindopril, sertraline HRCT: extensive mid and upper zone emphysema, coarse bilateral basal fibrosis TLCO: 14%, mildly obstructed flow volume loop No lavage No biopsy (as poor respiratory reserve) ANA-positive (1/640) Prednisolone (50 mg), pravastatin withdrawn Progression, discharged with home oxygen, died 18 months later (respiratory failure) 3 F, 74 Cough and fever (3 days) (consistent with pneumonia) on background of worsening exertional dyspnoea Chronic obstructive airways disease, IHD, congestive cardiac failure, hyperlipidaemia, ex-smoker Simvastatin (10 mg for 2 years, then 20 mg for 1 year), aspirin, thyroxine, frusemide, diltiazem, nicorandil, long-acting nitrates HRCT: diffuse ground glass left upper lobe and bilateral lower zone No TLCO Lavage: 78% macrophages, 12% neutrophils, 9% lymphocytes Biopsy: non-specific interstitial pneumonitis No ANA test Prednisolone (50 mg), simvastatin withdrawn Gradual reduction in infiltrative change on imaging, lung function stable at 9-month follow-up 4 M, 83 Progressive dyspnoea (6 months) IHD, CABG and aortic valve replacement, atrial flutter, hyperlipidaemia, ex-smoker Pravastatin (40 mg, 1 year), aspirin, digoxin, frusemide, ramipril, ranitidine HRCT: scattered bilateral fibrosis TLCO: 33% Lavage: 68% neutrophils, 26% macrophages, 3% lymphocytes, 1% eosinophils Biopsy: non-diagnostic ANA-negative Prednisolone (40 mg), azathioprine, pravastatin withdrawn Slow progression 5 F, 67 Chronic mild dyspnoea (9 months), dry cough (6 months) Hyperlipidaemia, atypical chest pain, non-smoker Simvastatin (40 mg, 5 years), aspirin HRCT: patchy bilateral upper and lower zone ground glass TLCO: 22% No lavage or biopsy Negative for ANA, ANCA, normal ACE Prednisolone (25 mg, reduced to 10 mg after 3 months), simvastatin withdrawn Marked improvement (TLCO: 51% after 1 month, then 65% after 1 year) 6 M, 68 Progressive dyspnoea and hypoxia IHD, CABG and aortic valve replacement (10 years before), gastro-oesophageal reflux disease, hyperlipidaemia, ex-smoker Simvastatin (10 mg, 2 years), atenolol, candesartan, esomeprazole, frusemide, warfarin HRCT: bilateral fibrosis TLCO: 46%, mild restrictive defectLavage: 19% eosinophils, 19% neutrophils Biopsy: mixed inflammatory and fibrotic change ANA-negative Prednisolone (37.5 mg), azathioprine, simvastatin continued Progressive cardiac failure, died 9 months after presentation 7 M, 64 Progressive dyspnoea, dry cough IHD, CABG and aortic valve replacement (11 years before), peptic ulcer disease, hyperlipidaemia, ex-smoker Atorvastatin (20 mg for 3 years, then 40 mg for 2 years), fosinopril HRCT: bilateral ground glass infiltrates, fibrosis, some traction bronchiectasis TLCO: 44%, mildly obstructed flow volume loop Lavage: 38% eosinophils, 15% lymphocytes, 5% neutrophils Biopsy: thickened alveolar walls with interstitial fibrosis, minimal inflammation ANA-negative Prednisolone (initially 50 mg, then 10 mg maintenance), atorvastatin withdrawn Slight initial improvement (TLCO: 52% at 2-month follow-up), then stable disease HMG-CoA = hydroxymethylglutaryl-coenzyme A. IHD = ischaemic heart disease. CABG = coronary artery bypass graft surgery. HRCT = high-resolution computed tomography. TLCO = transfer factor for carbon monoxide diffusion. ANA = antinuclear antibody. ANCA = antineutrophil cytoplasmic antibody. ACE = angiotensin-converting enzyme. * All patients underwent HRCT and TLCO measurement, while most underwent bronchoscopy with broncho-alveolar lavage and transbronchial biopsy. 3 Investigations in two patients with interstitial lung disease High-resolution computed tomography in Patient 7 at presentation showed bilateral interstitial infiltrates with an area of honeycombing. Transbronchial biopsy specimen from Patient 7 showed a lymphocytic interstitial infiltrate and intra-alveolar macrophages (haematoxylin and eosin stain; original magnification, × 100). Transbronchial biopsy specimen from Patient 6 showed thickened alveolar walls with a low grade inflammatory infiltrate (haematoxylin and eosin stain; original magnification, × 400).

Tim Walker MB BS(Hons) · Joe McCaffery MB BS · Chris Steinfort FRACP

To the Editor: In a recent observational study, Krum et al concluded that the treatment of heart failure after myocardial infarction in Australian teaching hospitals is suboptimal because angiotensin-converting enzyme (ACE) inhibitors, β-blockers and aldosterone antagonists are underutilised.1 We believe that another explanation, mentioned by the study’s authors, is worth exploring further — for valid clinical reasons, it was not appropriate for certain patients to start or continue taking some of these medications. An understanding of the enrolment criteria of relevant clinical trials is informative. The large, long-term ACE inhibitor trials quoted by Krum et al — SAVE,2 TRACE and AIRE4 — between them screened 34 037 patients with myocardial infarction and left ventricular dysfunction. Only 5986 patients (18%) met the inclusion/exclusion criteria to be enrolled in one of the trials. Unfortunately, the CAPRICORN5 (β-blocker) and EPHESUS (aldosterone antagonist) trials did not publish the number of patients screened versus the number randomised, but a glance at their exclusion criteria explains why, for some patients, it may not have been appropriate to start these medications during their hospital stay. Some of the exclusion criteria for CAPRICORN were: unstable angina, ongoing therapy with antiarrhythmics (except amiodarone), secondary or tertiary heart block or sick sinus syndrome unless paced, uncontrolled hypertension (> 160/95 mmHg), bradycardia (heart rate, < 60 beats/min), hypotension (systolic blood pressure, < 80 mmHg), requirement for intravenous diuretics or inotropes, chronic obstructive pulmonary disease with ongoing inhaled β2-agonist or steroid therapy, and unstable insulin-dependent diabetes. Is there any harm in prescribing outside the inclusion/exclusion criteria for clinical trials? A population-based, time-series analysis linking prescription-claims data and hospital admission records of 1.3 million adults in Canada6 showed that hyperkalaemia-related deaths in hospital doubled after the RALES trial (spironolactone) was published in 1999. There was no reduction in re-hospitalisation for heart failure or all-cause mortality. The authors speculated that part of the reason for this was prescription of spironolactone to patients who would have been excluded from the RALES trial. While we would not advocate prescribing strictly within the boundaries of the inclusion/exclusion criteria of clinical trials, it is important to understand these criteria, so that prescribing in “real world” patients is done with care. We are reassured that Krum et al’s study suggests there is discretion in the prescribing of drug therapy. Presumably, during ongoing medical assessment, it will be appropriate for some patients to commence some of these medications (potential benefit outweighs potential harm), while others may need to have their medications reviewed because of adverse events.

Lauren J Bailey · Vasi Naganathan

In reply: We thank Bailey and Naganathan for their thoughtful viewpoint regarding prescribing according to clinical trial criteria. We agree that prescribing in the real world often involves complex decision making, taking into account age, comorbidities, concomitant medications and other factors, whereby guidance regarding individual patients cannot readily be extracted from clinical trial literature. This may certainly contribute to underutilisation of evidence-based drug treatment.1 Nevertheless, several analyses support the contention that physicians who more closely adhere to evidence-based guidelines (which in turn are derived from randomised clinical trials) produce better outcomes for their patients.2,3 Therefore, we would still advocate prescribing as closely as possible to guideline recommendations, while acknowledging that these recommendations may not always be readily applicable to every patient.

Henry Krum

To the Editor: The guidelines for managing acute coronary syndromes, published in a supplement to the Journal in 2006, provide a readily accessible tool for clinicians to enhance patient care.1 However, unfortunately the recommendations concerning adjunctive anticoagulation in patients with acute coronary syndromes (ACS) are suboptimal. The 2006 guidelines recommend that high-risk patients with non-ST-segment-elevation ACS should be treated with aggressive medical management, including unfractionated heparin or the low molecular weight heparin (LMWH) enoxaparin, based on evidence from randomised trials showing that these agents reduce the risk of non-fatal myocardial infarction (MI).1 However, neither unfractionated heparin nor enoxaparin have been shown to reduce mortality in patients with non-ST-segment-elevation ACS, even when compared against placebo, and enoxaparin increases the risk of bleeding when compared with unfractionated heparin.2-4 By contrast, the OASIS-5 study, presented at the European Society of Cardiology Meeting in September 2005 and published in early 2006, showed that fondaparinux (a pentasaccharide inhibitor of factor Xa) compared with enoxaparin reduced death and stroke rates, and reduced the risk of bleeding by one half.5 Updating the recommendation so that enoxaparin was replaced with fondaparinux for patients with non-ST-segment-elevation ACS would save six Australian lives at 30 days for every 1000 patients treated, and would cause 19 fewer bleeds. The recommendations of the 2006 ACS guidelines concerning the management of patients with ST-segment-elevation MI are similarly suboptimal. There are now convincing data from randomised trials that enoxaparin is more effective than unfractionated heparin for preventing recurrent MI in patients with ST-segment-elevation MI who have been treated with fibrinolytic therapy.4,6 However, as in the case with non-ST-segment-elevation ACS, enoxaparin has never been shown to reduce mortality in ST-segment-elevation MI. By contrast, both the LMWH reviparin, and fondaparinux, reduce mortality,7,8 and fondaparinux does so without increasing the risk of bleeding.8 We appreciate that rapid advances in the management of ACS make it increasingly difficult for evidence-based guidelines to reflect the best evidence from clinical trials. However, when new evidence becomes available that is clinically relevant at the individual and population level, we believe the guidelines working group and the Journal have a responsibility to update the readers.

John W Eikelboom · Graeme J Hankey · Paul E Langton

In reply: We thank Eikelboom et al for presenting new data on acute coronary syndrome (ACS) management. In this field of rapid advances, another recent study, ACUITY, has also been published, which examined bivalirudin in ACS.1 The Australian guidelines2 are based on peer reviewed published reports, and neither OASIS-53 nor ACUITY1 were released at the conclusion of the formulation of the guidelines. Also, fondaparinux is only available on the Pharmaceutical Benefits Scheme (PBS) in Australia for thromboembolic prophylaxis, and bivalirudin is currently only approved by the PBS for therapy during percutaneous coronary interventions. The Australian guidelines are consistent with international guidelines for both unfractionated heparin and low molecular weight heparin considered as Grade A recommendations for treating non-ST-segment-elevation ACS, based on Level 1 evidence (American College of Cardiology/American Heart Association guidelines). For example, the FRISC trial showed a significant reduction in mortality and myocardial infarction with dalteparin (compared with placebo; 1.8% v 4.8%; P = 0.001) at 6 days, which persisted at 40 days.4 The Australian ACS guidelines are a living document, and new evidence, such as the OASIS-5 (fondaparinux)3 and ACUITY (bivalirudin)1 findings, will be considered on their relative merits in future updates of the guidelines (available on the National Heart Foundation Australia website at http://www.heartfoundation.com.au).

Constantine N Aroney · Philip Aylward

Objective: To document the risk-factor profile and risk-factor knowledge of patients with an acute coronary syndrome (ACS) not attending standard cardiac rehabilitation.Design and setting: Cross-sectional comparison in a tertiary hospital.Participants: Patients admitted to hospital with an ACS, residing within 20 km of the hospital, and without severe comorbidity who did not access cardiac rehabilitation (NCR) were compared with a group about to commence standard cardiac rehabilitation (SCR).Main outcome measures: Risk-factor profile, knowledge of risk factors via face-to-face assessment, quality of life.Results: Of the 446 patients eligible for cardiac rehabilitation, 208 attended for assessment (NCR: n = 144; SCR: n = 64). The NCR group had higher mean (± SEM) low-density lipoprotein (LDL) cholesterol levels (2.6 ± 0.1 v 2.3 ± 0.1; P = 0.02), and were more likely than the SCR group to have a total cholesterol level of > 4.0 mmol/L (78% v 53%; P < 0.001) and an LDL cholesterol level > 2.5 mmol/L (47% v 25%; P = 0.01). They were more likely than the SCR group to be physically inactive (77% v 22%; P < 0.001); obese (46% v 33%; P = 0.04); depressed (21% v 5%; P < 0.001); or current smokers (21% v 1%; P < 0.001). Compared with the SCR group, the NCR group also had higher risk scores (LIPID risk score) (4.5 v 2.1; P < 0.001); lower quality of life (Medical Outcome Short Form [SF-36] Health Survey); and significantly poorer knowledge of risk factors. Among patients with at least two modifiable cardiac risk factors, the NCR group were less likely than the SCR group to be able to state at least one risk factor (24% v 38%; P < 0.001).Conclusions: Patients not participating in cardiac rehabilitation after an ACS have more adverse risk profiles and poorer knowledge of risk factors compared with those about to commence cardiac rehabilitation. Alternate models for secondary prevention are required to improve health outcomes in patients not attending cardiac rehabilitation.

Julie Redfern BAppSc, BSc · Elizabeth R Ellis MHealthLaw, MSc, PhD · Tom Briffa BPhysEd, MPhysEd, PhD · S Ben Freedman MB BS,PhD, FRACP

Chronic heart failure (CHF) is found in 1.5%–2.0% of Australians. Considered rare in people aged less than 45 years, its prevalence increases to over 10% in people aged ≥ 65 years. CHF is one of the most common reasons for hospital admission and general practitioner consultation in the elderly (≥ 70 years). Common causes of CHF are ischaemic heart disease (present in > 50% of new cases), hypertension (about two-thirds of cases) and idiopathic dilated cardiomyopathy (around 5%–10% of cases). Diagnosis is based on clinical features, chest x-ray and objective measurement of ventricular function (eg, echocardiography). Plasma levels of B-type natriuretic peptide (BNP) may have a role in diagnosis, primarily as a test for exclusion. Diagnosis may be strengthened by a beneficial clinical response to treatment(s) directed towards amelioration of symptoms. Management involves prevention, early detection, amelioration of disease progression, relief of symptoms, minimisation of exacerbations, and prolongation of survival.

on behalf of the CHF Guidelines Core Writers