Cardiovascular diseases

Objective: To compare rates of percutaneous coronary interventions (PCI) and bypass surgery after acute myocardial infarction (AMI) in Indigenous and non-Indigenous patients.Design: Cohort study of public-sector patients who were followed up for 1 year using administrative hospital data.Participants and setting: We followed up 14 683 public-sector patients admitted to Queensland hospitals for AMI between 1998 and 2002. Of these, 558 (3.8%) identified as Indigenous.Outcome measures: Rates of PCI and bypass surgery, adjusted for differences between the Indigenous and non-Indigenous cohorts according to age, sex, socioeconomic status, remote residence, hospital characteristics, and comorbidities.Results: The adjusted rate for PCI during the index admission was significantly lower by 39% (rate ratio [RR], 0.61; 95% CI, 0.38–0.98) among Indigenous versus non-Indigenous patients with AMI; the adjusted rate for subsequent PCI was significantly lower by 28% (RR, 0.72; 95% CI, 0.54–0.96). Adjusted rates for bypass surgery were similar in the two cohorts. For any coronary procedure (ie, PCI or bypass surgery), the adjusted rate was significantly lower by 22% (RR, 0.78; 95% CI, 0.64–0.94) among Indigenous patients with AMI. Diabetes, chronic renal failure, pneumonia, and chronic rheumatic fever were at least twice as common among Indigenous patients with AMI as in the rest of the cohort, and chronic bronchitis and emphysema and heart failure were at least 60% more common. If a patient had at least one comorbidity, then their probability of having a coronary procedure was reduced by 40%.Conclusions: There are likely to be several reasons for the lower rates of coronary procedures among Indigenous patients, but their high rates of comorbidities and the association of comorbidities with lower procedure rates was an important finding. As investment in primary care can reduce the prevalence and severity of comorbidities, we suggest that adequate primary health care is a prerequisite for effective specialist care.

Michael D Coory PhD, FAFPHM · Warren F Walsh FRACP, FACC

Patients with acute coronary syndromes represent a clinically diverse group and their care remains heterogeneous. These patients account for a significant burden of morbidity and mortality in Australia. Optimal patient outcomes depend on rapid diagnosis, accurate risk stratification and the effective implementation of proven therapies, as advocated by clinical guidelines. The challenge is in effectively applying evidence in clinical practice. Objectivity and standardised quantification of clinical practice are essential in understanding the evidence–practice gap. Observational registries are key to understanding the link between evidence-based medicine, clinical practice and patient outcome. Data elements for monitoring clinical management of patients with acute coronary syndromes have been adapted from internationally accepted definitions and incorporated into the National Health Data Dictionary, the national standard for health data definitions in Australia. Widespread use of these data elements will assist in the local development of “quality-of-care” initiatives and performance indicators, facilitate collaboration in cardiovascular outcomes research, and aid in the development of electronic data collection methods.

Derek P B Chew MB BS, MPH, FRACP · Roger M Allan MB BS, FRACP Chair · Constantine N Aroney MD, FRACP · Noella J Sheerin RN, BAppSc (HMvt)

They reduce rates of restenosis but not mortality or infarction — so are they worth it? The development of drug-eluting coronary stents has proven to be a quantum advance in interventional cardiology, rivalling the impact of stenting itself. Drug-eluting coronary stents deliver effective local concentrations of antiproliferative drugs (thus avoiding systemic toxicities), without substantially modifying the technique of percutaneous coronary intervention (PCI). Two of the drugs used are sirolimus and paclitaxel. Sirolimus is an inhibitor of the G1-phase of the cell cycle, while paclitaxel inhibits microtubule formation, both of which are necessary for cell division. Thus, they inhibit the natural healing mechanisms — endothelial cell migration and extracellular matrix formation — that produce intimal hyperplasia, resulting in restenosis. Randomised clinical trials of patients with stents that elute these agents have demonstrated reduced angiographic restenosis rates when compared with patients with bare-metal stents.1,2 These individual trials are supported by a recent meta-analysis of 11 randomised clinical trials involving 5103 patients; this showed that, in patients with drug-eluting stents (compared with those receiving bare-metal stents), there was a significant reduction in the proportion of patients requiring target lesion revascularisation (Box).3 Thus, within the context of randomised trials, and when all other things are equal, drug-eluting stents are clearly superior in preventing restenosis, which is the most significant late morbidity associated with coronary intervention. But, not all things are equal — these stents come at an approximately threefold increase in economic cost. As a consequence of this cost differential, the benefits of this new technology need to be considered critically. While the meta-analysis confirmed that drug-eluting stents decrease rates of restenosis and target lesion revascularisation,3 there was no evidence that they reduced deaths and myocardial infarction rates. However, given the nature of the innovation, this would not be expected. Furthermore, from the patient’s perspective, the impact of drug-eluting stents on the more relevant endpoint of “any” coronary revascularisation (as opposed to “target lesion” revascularisation) has not been highlighted and will be eroded by the development of de novo disease in other areas of the coronary vasculature.6 Among cardiologists and patients, this technology has been embraced with substantial enthusiasm. Drug-eluting stents are now being implanted in patients in subgroups and with lesion types beyond those evaluated by randomised trials.7 Some clinicians have also proposed that multi-vessel PCI using drug-eluting stents provides a comparable alternative to coronary artery bypass grafting.8 This preference is best illustrated by the disparate rates of drug-eluting stent implantation in the private and public sectors, estimated at > 75% and < 25%, respectively, reflecting the difference in who is paying for this technology. Several issues make it difficult to compare the cost-effectiveness of the two types of stents. First, without a benefit in terms of mortality, assessment of cost-effectiveness by cost-per-life-year saved is precluded. To circumvent this issue, a published cost-effectiveness analysis from the SIRIUS trial of sirolimus-eluting stents in elective PCI used quality-adjusted life-year (QALY) data drawn from a trial of bare-metal stenting for reperfusion therapy after myocardial infarction.4 Whether these QALY data are applicable to the patients in the SIRIUS trial, and to Australian patients, is uncertain. Given the potential lack of generalisability of clinical trial data to clinical practice, the use of QALY data from patients treated within a different clinical context may lead to a cost-effectiveness extrapolation not relevant to our local context. The time has come for the Australian cardiology community to develop national systems that routinely assess the long-term clinical outcomes of all patients undergoing PCI and coronary artery bypass grafting. Such data should yield several benefits. First, actual local data on effectiveness are essential for locally relevant cost-effectiveness estimates. Second, data on specific patient and lesion subsets inadequately studied in randomised trials will allow us to apply this innovation to patients most likely to benefit from it.9 Such data are vital to the rational development of practice guidelines and reimbursement strategies for optimal patient outcomes and health care expenditure. Third, as with any emerging therapy or technology, routine evaluation of long-term safety remains a priority; this has been highlighted by the recent report of very late stent thrombosis associated with drug-eluting stents.10 Routine systems of evaluation would provide an effective infrastructure for surveillance of unexpected adverse events occurring after a new technology has been approved, and would be less reliant on physicians for recognition and reporting. Problems relating to the costs of data collection and the difficulties of risk adjustment remain to be solved before nationwide registries can be implemented. However, the clinical and economic consequences of inappropriate application of this and other technologies would exceed these costs, potentially by orders of magnitude. The resource burden associated with assessing implementation of a new technology should not be used as an argument against its conduct, but rather should encourage the incorporation of this activity into routine clinical practice and funding. It has been argued that, with time, the cost of drug-eluting stents will fall, clinical experience will grow, and the application of this technology to clinical practice will be optimised.11 Over the past 10 years, the cost of bare-metal stents has declined by approximately 60%. Yet, interventional practice remains heterogeneous, and outcomes remain uncertain. Registries designed to assess practice, outcomes and cost will offer essential objective data to inform rational choices — until the time when all things become equal. Summary of evidence related to drug-eluting stents A Bayesian meta-analysis* of 11 randomised controlled trials comparing drug-eluting stents with bare-metal stenting3 showed the former had: — No effect on mortality rates (odds ratio, 1.11; 95% credible interval*, 0.61–2.06)3 — No effect on rates of myocardial infarction (odds ratio, 0.92; 95% credible interval*, 0.66–1.25)3 — Substantially lower rates of target lesion revascularisation (odds ratio, 0.26; 95% credible interval*, 0.14–0.45)3 — Fewer major adverse cardiac events when death, myocardial infarction, and target vessel revascularisation are combined (odds ratio, 0.42; 95% credible interval*, 0.32–0.53)3 In a randomised comparison of sirolimus-eluting versus bare-metal stents in elective percutaneous coronary intervention, the incremental cost-effectiveness ratio was estimated to be US$27 540 per quality-adjusted life-year gained.4 This reflects the money that needs to be spent to gain a benefit of one quality-adjusted life-year with this technology. Up to 50% of patients undergoing percutaneous coronary intervention have characteristics that would have led to their exclusion from clinical trials of drug-eluting stents in the US Dynamic Registry, a comprehensive angioplasty registry sponsored by the National Heart, Lung and Blood Institute.5 * In a Bayesian meta-analysis, “credible interval” corresponds to confidence interval.

Derek PB Chew MB BS, MPH, FRACP

Objective: To identify variation in the rates of use of key evidence-based therapies and in clinical outcomes among patients hospitalised with acute coronary syndromes (ACS).Design: Retrospective analysis of data on care processes and clinical outcomes of representative patient samples recorded by the Queensland Health Cardiac Collaborative registry.Setting: 18 public hospitals (3 tertiary, 15 non-tertiary) in Queensland, August 2001 to December 2003.Study population: 2156 patients who died or were discharged after troponin-positive ACS.Main outcome measures: Comparison of proportions of highly eligible patients receiving indicated care and in-hospital mortality between subgroups categorised by age, sex, comorbidities (diabetes, renal failure, chronic obstructive pulmonary disease and mental disorder), type of admitting hospital (tertiary or non-tertiary), and cardiologist involvement (transfer or non-transfer to cardiology unit).Results: Patients aged ≥ 65 years were less likely than younger patients to receive heparin (79% v 87%), β-blockers (79% v 87%), lipid-lowering agents (78% v 87%), coronary angiography (51% v 66%), and referral to cardiac rehabilitation (17% v 33%). Patients with diabetes were less likely than others to receive coronary angiography (50% v 63%), while those with moderate to severe renal failure were less likely to receive thrombolysis (52% v 84%), heparin (71% v 83%), β-blockers (69% v 84%), lipid-lowering agents (61% v 84%), in-hospital cardiac counselling (46% v 64%) and referral to cardiac rehabilitation (9% v 25%). Patients admitted to tertiary hospitals were more likely than those admitted to non-tertiary hospitals to receive coronary angiography (85% v 55%) and referral to cardiac rehabilitation (36% v 21%). Risk-adjusted mortality was highest in patients with moderate to severe renal failure (15% v 3%) and older patients (6% v 2%).Conclusions: Variations exist in the provision of indicated care to patients with ACS according to age, diabetic status, renal function and type of admitting hospital. Excess mortality in elderly patients and in those with advanced renal disease may be partially attributable to failure to use key therapies.

Ian A Scott FRACP, MHA, MEd · Mark A Jones BSc(Hons) · Andy B Duke · Irene C Darwin BSpThy, GradCertManagement · Kathy H Harvey GradCertManagement

Objectives: To determine population-based rates and outcomes of hypertensive disorders in pregnancy.Design: Cross-sectional study using linked population databases.Setting and participants: All women, and their babies, discharged from hospital following birth in New South Wales, between 1 January 2000 and 31 December 2002.Main outcome measures: Rates of hypertensive disorders in pregnancy, maternal and infant morbidity and mortality, and level of hospital care for the birth admission.Results: 250 173 women and their 255 931 infants were included in the study. Overall, 24 517 women (9.8%) had a hypertensive disorder in pregnancy, including 1411 (0.6%) with chronic hypertension, 10 379 (4.2%) with pre-eclampsia, 731 (0.3%) with chronic hypertension with superimposed pre-eclampsia, and 10 864 (4.3%) with gestational hypertension. Women with, and infants exposed to, hypertension were more likely to suffer death or major morbidity than those without hypertension. Infants of mothers with hypertension were more likely to be to born preterm and small for gestational age. Just over half the women with major morbidity or mortality delivered in hospitals with a high level of medical care. In contrast, most infants with major morbidity or mortality were delivered in hospitals with neonatal intensive care units.Conclusions: Hypertension is a common complication of pregnancy, and adverse outcomes are increased among hypertensive women and their babies. Clinicians appear to be better at identifying and seeking an appropriate level of care for pregnancies where the infant is at risk of a poor outcome than when the mother is at risk. More specific antenatal indicators of poor maternal outcome would help guide the referral of hypertensive women to higher levels of care.

Christine L Roberts MB BS, DrPH · Jane B Ford BA(Hons), PhD · David J Henderson-Smart FRACP, PhD · Charles S Algert BSc, MPH · Jonathan M Morris FRANZCOG, PhD

A 58-year-old man of British descent presented in 2003 with chest pain, facial flushing and elevated jugular venous pressure but no leg oedema. He had been exposed to tuberculosis in childhood, had a strongly positive tuberculin test and had been followed up in the tuberculosis surveillance program with regular chest x-rays, but had never been diagnosed with tuberculosis. Chest x-ray on presentation showed calcified plaques and masses in the pericardium and mediastinum (Box 1). Computed tomography revealed extensive calcification of the pericardium (Box 2). Coronary angiography showed 70% stenosis in the left anterior descending artery. Cardiac catheterisation showed equalisation of diastolic pressures in all four chambers, with a positive square root sign (pattern of ventricular diastolic pressure characteristic of constrictive pericarditis). Pericardiectomy with left internal mammary bypass graft to the left anterior descending artery was performed. Severe constrictive pericarditis with a thick (up to 4 mm) layer of calcium plaque was found. Two large cystic masses within a thick calcified shell were present in the posterolateral aspect of the right side of the heart and the left posterior atrioventricular groove. Both contained creamy caseous material, which was drained (Box 3). Histopathological examination was consistent with chronic calcific pericarditis with no granuloma. Microbiological examination and culture did not show any organisms. The patient was treated with a 6-month regimen for Mycobacterium tuberculosis based on his known previous exposure to tuberculosis, strongly positive tuberculin test, and the operative and pathological findings. Corticosteroid therapy, which is sometimes recommended in the treatment of tuberculosis,1,2 was not considered as the patient did not have effusive pericarditis or active tuberculosis. At 12-month follow-up, he was fully active, without angina or shortness of breath. In Australia, the annual incidence of tuberculosis is 5–6 cases per 100 000.3,4 Tuberculous pericarditis is seen in 1%–2% of all cases of pulmonary tuberculosis.5 Extensive tuberculous pericarditis is rare in Anglo–Celtic populations. 1 Chest x-ray showing calcified mass along the diaphragmatic surface of heart (A) and calcified pericardium (B). 2 Pre-operative computed tomography scan showing large calcified masses (5 cm × 4 cm) in the left posterior atrioventricular groove (A) and right atrioventricular groove posterior to the tricuspid annulus (B), with calcification throughout. 3 Intraoperative photograph showing the opened large cystic mass posterior to the right atrioventricular groove, with caseous contents (arrow).

Shiromani Goyal M Ch · Kang-Teng Lim MB BS · Cheng-Hon Yap MB BS · Elizabeth W Ryan FRACP · Morteza Mohajeri FRACS

Alexandra A Bennett,* Jo-anne E Brien,† Peter S Macdonald‡ * PhD Candidate, † Professor of Clinical Pharmacy, University of Sydney, Sydney, NSW (address for correspondence: Therapeutics Centre, St Vincent's Hospital, Darlinghurst, NSW 2010); ‡ Associate Professor of Medicine, and Cardiologist, St Vincent's Hospital, Sydney, NSW. sashabATpharm.usyd.edu.au To the Editor: We wish to add our perspective to the article by Phillips et al. 1 Needs identified by GPs included education about the effectiveness and target dosing of angiotensin-converting enzyme (ACE) inhibitors and β-blockers, and improved communication. We wish to highlight the potential roles hospital and community pharmacists have in supporting GPs caring for patients with heart failure. It is expected that by 2010 there will be at least 25 patients with heart failure per GP and 100 per community pharmacy in Australia. A recent review of 100 patients with heart failure discharged from St Vincent’s Hospital (SVH) in New South Wales showed they were taking an average of 9.5 regular medications, two-thirds of which were cardiac medications. 2 Their average age was 70.5 years. They had an average of 7.3 diagnoses, including ischaemic heart disease, atrial fibrillation and osteoarthritis. They were commonly taking amiodarone, warfarin and digoxin. Six per cent of patients had taken cyclooxygenase-2 (COX-2) inhibitors before they were admitted to hospital. 2 While rates of ACE inhibitor (or angiotensin-II-receptor antagonist) and β-blocker use at discharge were high in patients with systolic dysfunction (84% and 65%, respectively), only a minority of patients were taking target doses (27% and 15%, respectively). This highlights the need for good communication between healthcare providers. Discharge letters are often illegible and do not necessarily prioritise issues or detail future management, such as stating whose responsibility it is to up-titrate the dose of ACE inhibitor or β-blocker. Electronic entry of medical information, including e-prescribing (currently being trialled in some hospitals), may assist. Some patients have typed medication cards from a pharmacist on discharge. However, this is not routine practice. Ideally, all patients should receive such cards with supporting information. Copies of this information should be provided for the GP and pharmacist. Such a system would support Australian Pharmaceutical Advisory Council guidelines for continuity of care. Since 2002, a pharmacist has consulted with patients in the SVH Heart Failure Clinic regarding medication and lifestyle issues. Problems identified are referred to the treating cardiologist. A pilot study of this service showed high patient satisfaction (T Hargraves, Pharmacist, St Vincent’s Hospital, personal communication). Such a service could also be provided by community pharmacists, perhaps linked to home medicines review. A pharmacist is also employed by the community multidisciplinary heart failure service based at SVH. These positions support patients and their carers as well as healthcare providers, including GPs, community and hospital pharmacists and nurses. Evidence for such roles for pharmacists is supported by US and UK data. 3 We propose that designs for future models of care for patients with heart failure should incorporate pharmacists.

Alexandra A Bennett · Jo-anne E Brien · Peter S Macdonald

Congenital heart disease is often regarded as a chance occurrence affecting only a small number of children. In fact, it affects nearly 1 in 100 newborn infants1,2 and is the leading non-infectious cause of death in this age group. A third of those affected will need surgical or catheter-based intervention in the first year of life. In 2002, congenital heart disease accounted for 224 deaths in Australian children.2 In the United States there are more than 35 000 new cases each year and over 1 million survivors of congenital heart disease in the community.3 Studies of gene expression in animal models have provided a window into how the human heart is constructed . . . Diagnosis and treatment of congenital heart disease has improved dramatically over the past 15 years. The mortality rate for surgical repair of some common conditions, such as tetralogy of Fallot, is currently less than 3%,4 and innovative catheter-based therapies, including closure of certain septal defects, have been developed. Preservation of ventricular function, avoidance of repeat surgery and freedom from arrhythmias are the next goals to be achieved. The first question affected families usually ask is: “What is the risk of having an affected offspring or another affected sibling?”. Population studies suggest that the risk is relatively small (2%, or double the background risk). The reason the risk is relatively modest may be that most congenital heart disease is the result of multiple gene defects and/or an interaction between single or multiple defective genes and the fetal environment. As the genotype and experience of each individual is unique, the occurrence of congenital heart disease in most individuals will not be in the context of a strong familial trait. However, there are many rare examples of families in which congenital heart disease is strongly inherited, and apparently caused by single-gene defects. Even in these families, cardiologic phenotypes can vary enormously, presumably because of the effects of modifier genes and/or influences other than genetic. Such families, if large enough, can be studied using classical genetic techniques (such as linkage analysis), but so far only a small number of clinical cases can be matched to a specific mutation. Thus, family genetic studies are currently not indicated for isolated, non-syndromal cases of congenital heart disease. With the advent of high-throughput genetic screening technology and improved cost benefit, indications for screening may be extended in the future. Recently, cardiac developmental and molecular biologists and geneticists have started to unravel the molecular circuitry underpinning heart formation. Significant progress has come about partly because we can now dissect the morphological and genetic basis of human congenital heart disease in animal models from zebra fish to mice. Aspects of cardiac development are, in fact, highly conserved through evolution, and many of the regulators that transform embryonic mesoderm to myocardium are similar across species. One example is the cardiac regulatory gene NKX2.5, which was first isolated because of its similarity to a gene present in the fruit fly, a laboratory model for genetic studies. The developmental approach has defined a number of key cardiac regulatory genes subsequently found by conventional linkage studies to underpin familial congenital heart disease.5 Mutations in NKX2.5 itself cause atrial septal defect and conduction abnormalities, while TBX5 mutations underpin heart and hand malformations of the Holt–Oram syndrome, and mutations in GATA4 cause atrial septal defect and more complex congenital heart disease. In clear cases of familial inheritance, genetic screening for mutations in these genes may be beneficial. Studies of gene expression in animal models have provided a window into how the human heart is constructed, and recent insights have led to a revision of traditional concepts of how cardiac chambers and valves develop. The heart begins as a rudimentary vascular tube,6 which, cardiologists are taught, is composed of anatomical segments that develop into chambers. Yet mapping of the cardiac precursor cell populations in the embryo has revealed a more complex picture. Gene expression patterns now show us that chambers arise from discrete zones, not segments, and that non-chamber myocardium gives rise to the central conduction system.7,8 Another significant advance is the discovery of a second distinct pool of cardiac precursor cells in the embryo that migrate into the forming heart tube from the region of the developing pharyngeal arches. These cells, the so-called “secondary heart field”, contribute importantly to the right ventricle, outflow tracts and atria.9 Characterisation of the secondary heart field has unified genetic, developmental and clinical observations in congenital heart disease. Abnormal development and/or deployment of the secondary heart field cells causes underdevelopment and malpositioning of the outflow tracts over the ventricles. This occurs in velocardiofacial syndrome (VCFS, incorporating DiGeorge syndrome), which is caused by microdeletions in chromosome 22q11.10 The TBX1 transcription factor gene is expressed in the secondary heart field and is deleted in VCFS. Its loss in mice has been causally related to abnormalities of the outflow tract that can arise in VCFS. One such abnormality is tetralogy of Fallot, in which unequal partitioning of the rudimentary outflow vessel produces a large aorta and a right ventricular outflow tract obstruction, with subsequent complications. Malalignment of the outflow vessels over the interventricular septum causes a large ventricular septal defect. Although fewer than a third of cases of tetralogy of Fallot are associated with the 22q11 microdeletion, single-gene mutations may prove to be a significant cause. In the case of interrupted aortic arch type B and truncus arteriosus, however, more than 50% of cases are associated with the 22q11 microdeletion. Recent developments in genome-wide screening technology have the power to detect microdeletions in individual patients on an unprecedented scale. This may revolutionise the detection of congenital heart disease genes. Pathological circumstances also provide deep insights into development. In the fetus, even simple primary structural disease (eg, a pulmonary valve that fails to develop) can cause complex secondary disorders as a result of disturbed blood-flow patterns. In heart development, function (flow) dictates form, and loss of normal blood-flow patterns can contribute to underdevelopment of chambers. In these circumstances, it is often difficult to predict from primary lesions the extent to which abnormal development and remodelling will occur as the fetus grows — this is one of the challenges of fetal echocardiography. Now, surgical correction during fetal life, long taboo, is being explored experimentally for valve correction,11 as this would allow more time for normal ventricular development. While only a small proportion of congenital heart lesions currently have identifiable gene markers, the number is growing rapidly. The next decade of research into congenital heart disease will see an exciting convergence of the disciplines of developmental biology, genetics and paediatric cardiology, and, we hope, will not only go further towards answering the question “Why did this happen to us?”, but also provide more secure grounds for genetic counselling and intervention.

David S Winlaw MB BS, MD, FRACS · Gary F Sholler MB BS, FRACP · Richard P Harvey PhD

Objective: To determine the extent to which the Framingham function predicts the risk of coronary heart disease (CHD) in Aboriginal people.Design and setting: Cohort study in an Aboriginal community in the Northern Territory.Participants: 687 Aboriginal people aged 20–74 years were followed up from a baseline examination in 1992–1995 through to 31 December 2003.Main outcome measure: First CHD events were identified through hospital and death records during the follow-up period.Methods: An original Framingham function was used to predict CHD risk according to the duration of follow-up and the values of traditional risk factors, which included age, sex, total cholesterol level, high-density lipoprotein (HDL) cholesterol level, blood pressure, the presence of diabetes, and smoking status. The predicted CHD incidence using the Framingham function was 4.4 per 1000 person-years, while the observed incidence was 11.0 (95% CI, 8.7–13.9) per 1000 person-years. The observed number of CHD events (68) was 2.5 times the number predicted (27) using the Framingham function. The observed incidence was about four and three times the predicted incidence for age groups < 35 and 35–44 years, respectively, and about twice the predicted incidence for those over 45 years of age. The Framingham function was a particularly unreliable predictor for women, especially younger women, in whom the observed CHD rate was 30 times the predicted rate.Conclusions: The Framingham function substantially underestimates the actual risk of CHD observed in Aboriginal people in a remote community, especially for women and younger adults. This implies that traditional risk factors have different degrees of impact and/or that other factors are contributing to risk. A population-specific risk function is needed.

Zhiqiang Wang PhD, MSc, MB · Wendy E Hoy MB BS, BScMed, FRACP

Given fundamental differences in the recommendations in guidelines from major national and international committees, we cannot rely on them unquestioningly. Different antihypertensive agents are known to have differing effects according to age and race. Exchanging (rather than following guideline recommendations of adding to) an ineffective first-line antihypertensive drug can result in control of hypertension with monotherapy. Conclusions about a preferable first-line antihypertensive agent are limited by trial protocols with varying drug doses and questionable drug combinations. Guidelines are often based on meta-analyses of drugs of a particular class, which could ignore important differences between drugs within a class. Trials of 3–5 years cannot determine the long-term effects of drugs which patients often take for decades.

Roger E Peverill PhD, FRACP

We report two elderly women who presented with hypertensive crisis and acute pulmonary oedema, which responded poorly to antihypertensive therapy. The patients were later diagnosed as having hepatitis C virus-related cryoglobulinaemia. Acute pulmonary oedema is a well-known complication of severe hypertension,1 but, to our knowledge, has never been reported in association with mixed cryoglobulinaemia. We report two patients with severe hypertension who presented with pulmonary oedema which was not controlled until cryoglobulinaemia was diagnosed and treated with plasmapheresis and methylprednisolone. Clinical recordsPatient 1Presentation: A 66-year-old woman presented to our emergency department in late February (winter) with severe dyspnoea of 2 hours’ duration. She had a 10-year history of hypertension, and had had a stroke 3 months before, but had recovered. Over the previous month, her blood pressure had been over 210/120 mmHg, and she had intermittent dyspnoea, orthopnoea and leg oedema. On examination, she was orthopnoeic, with blood pressure of 218/124 mmHg, regular pulse of 126 bpm, and respiratory rate of 36 breaths per minute. She had engorged jugular veins, bilateral chest crackles, hyperpigmentation of the legs and marked bipedal pitting oedema. A chest radiograph showed diffuse haziness over both lungs. Electrocardiography (ECG) showed inverted T waves in leads V4 to V6. Oxygen saturation was 77% while breathing 100% O2 (reference range [RR], 95%–100%). Initial management: The patient was intubated and mechanically ventilated. Her central venous pressure was 13 cmH2O (RR, 3–11 cmH2O), and pulmonary wedge pressure was 19 mmHg (RR, 6–12mmHg). She was treated with intravenous glyceryl trinitrate and diuretics, but over the next 48 hours her blood pressure fluctuated between 300/130 mmHg and 200/90 mmHg, and pulmonary oedema persisted. After 2 days, the patient was extubated. Over the next 24 hours, she developed massive bilateral pleural effusions and numerous petechiae over the legs. Echocardiography revealed a normal left ventricular (LV) ejection fraction (72%) and diastolic dysfunction. Radionuclide angiography confirmed these findings. Laboratory tests showed hypoalbuminaemia, proteinuria (daily protein loss, 9.3 g), haematuria with granular casts, impaired renal function, anaemia and thrombocytopenia (Box 1). Nephrotic syndrome was diagnosed. Further tests revealed a decreased serum concentration of complement components C3 and particularly C4, and markedly raised concentration of rheumatoid factor. However, tests were negative for antinuclear (ANA), anti-double-strand-DNA (anti-ds-DNA), antiglomerulo-basement-membrane and antineutrophil-cytoplasmic antibodies. A cryoglobulin test was positive (Box 2). Immunofixation electrophoresis of the cryoprecipitates showed monoclonal IgM/kappa and polyclonal IgG. A test for hepatitis C virus antibodies (anti-HCV) was then performed and was positive. Diagnosis: On Day 27 of admission, the patient was diagnosed with type II mixed cryoglobulinaemia associated with HCV infection. At that time, her blood pressure was still fluctuating between 230/130 mmHg and 180/100 mmHg, and pulmonary oedema and massive pleural effusions persisted, despite vigorous antihypertensive therapy with frusemide, intravenous glyceryl trinitrate, an α-adrenergic blocker and angiotensin-converting enzyme inhibitors. Repeated thoracocentesis was required to release massive effusions (initially transudative, but later haemorrhagic). Renal biopsy revealed diffuse glomerulonephritis with crescent formation. Management: Plasmapheresis was started on Day 27, along with pulse therapy of intravenous methylprednisolone (500 mg daily for 3 days). After five courses of plasmapheresis in 12 days, the hypertension and pulmonary oedema were controlled. The patient was discharged from hospital on Day 57 of admission. At discharge, serum creatinine level was 141 μmol/L (reference range [RR], 53–106 μmol/L), and she was taking prednisolone (25 mg), diltiazem (180 mg), spironolactone (75 mg) and doxazosin (8 mg) per day. Patient 2Presentation: In February, 2 years after Patient 1, a 77-year-old woman presented to our emergency department with a 1-day history of severe dyspnoea and orthopnoea. She had had hypertension for 3 years. On several occasions during the previous month, her blood pressure had risen to 200/120 mmHg. On examination, she was stuporous, with blood pressure of 200/110 mmHg, regular pulse of 112 bpm, and respiratory rate of 36 breaths per minute. She had engorged jugular veins, bilateral chest crackles, hepatomegaly, ascites and bipedal oedema. A chest radiograph showed bilateral diffuse haziness, and ECG showed a generalised low QRS complex. Blood gas analysis showed pH, 7.43 (RR, 7.35–7.45); Paco2, 3.9 kPa (RR, 4.7–5.3 kPa) and Pao2, 11.2 kPa (RR, 12.7–13.3 kPa) while breathing oxygen through a mask. Initial management: The patient was intubated and mechanically ventilated. Central venous pressure was 12 cmH2O. Echocardiography revealed concentric LV hypertrophy, normal LV ejection fraction, but impaired LV diastolic function. Blood pressure fell to 170–200/90–100 mmHg in 2 days, after diuretic and nitroprusside therapy, but pulmonary oedema and respiratory failure did not decrease, even after haemodialysis. She had massive ascites, bilateral pleural effusions, hypoalbuminaemia, proteinuria (daily protein loss, 3.5 g), haematuria, poor renal function, anaemia and thrombocytopenia (Box 1). Nephrotic syndrome was diagnosed. Levels of both C3 and C4 were markedly low. ANA and anti-ds-DNA antibodies were negative, but rheumatoid-factor titre was markedly high. Cryoglobulin tests on Days 14 and 16 of admission were positive. Immunofixation electrophoresis of serum cryoprecipitates showed polyclonal IgG. HCV tests were negative for anti-HCV antibody but positive for serum HCV RNA. Diagnosis: The diagnosis of type III mixed cryoglobulinaemia associated with HCV infection was thus established on Day 16 of admission. At that time, the patient was still being mechanically ventilated and needed repeated thoracocentesis (effusions were initially yellow, but later became haemorrhagic). Computed tomography of the head showed multiple ischaemic infarcts. Management: Plasmapheresis and methylprednisolone pulse therapy (1 g intravenously daily for 3 days) were started on Day 17 of admission. The patient was extubated the next day and discharged from hospital 2 weeks later, after two courses of plasmapheresis. Serum creatinine level at discharge was 291.5 μmol/L. DiscussionHypertensive crisis with rapid-onset pulmonary oedema has been associated with coronary artery disease,2 renal artery stenosis3,4 and phaeochromocytoma,5 but a search of English-language articles in PubMed revealed no previous reports of an association with mixed cryoglobulinaemia. The latter is characterised by the presence of cold-precipitable cryoglobulins in serum. Underlying diseases include autoimmune and infectious diseases, especially hepatitis C.6-9 “Mixed” indicates that the cryoglobulins in these patients contain either monoclonal plus polyclonal immunoglobulins (type II cryoglobulinaemia), or polyclonal immunoglobulins (type III cryoglobulinaemia).7 In hepatitis C, cryoglobulins usually contain anti-HCV antibody, HCV RNA and IgM rheumatoid factor (ie, anti-IgG autoantibody).9 Cryoglobulins often trigger the formation of immune complexes, leading to immune-complex-type vasculitis, and produce cutaneous, vasomotor, renal and neurological symptoms.7-9 In our patients, factors precipitating the acute pulmonary oedema included hypertensive crisis, renal insufficiency and probably coronary insufficiency. The hypertensive crisis and pulmonary oedema had abrupt onset, progressed rapidly to respiratory failure, were accompanied by nephrotic syndrome, and responded poorly to antihypertensive and diuretic therapy. Our patients had had moderate hypertension for 3–10 years before their blood pressure suddenly rose markedly 2 to 3 months before the development of pulmonary oedema. Hypertension has been found in 37% of patients with cryoglobulinaemia.6 When the underlying disease of cryoglobulinaemia (eg, hepatitis C) flares up, levels of cryoglobulins (which contain HCV-RNA) increase, resulting in higher levels of circulating immune complexes, acute vasculitis and raised blood viscosity. These factors all precipitate the abrupt rise in blood pressure and pulmonary oedema, and explain the failure of conventional antihypertensive agents. Treating cryoglobulinaemia in our patients decreased renal vasculitis and ischaemia, fluid overload, and ultimately hypertension and pulmonary oedema. Coronary vasculitis, found at autopsy in 22% of patients with mixed cryoglobulinaemia,6 could contribute to pulmonary oedema. However, both our patients had a normal LV ejection fraction, suggesting that neither had significant coronary vasculitis. In both patients, acute pulmonary oedema developed in winter. Whether cold weather worsens hypertension by precipitating more cryoglobulins and increasing viscosity awaits further observation. In our patients, the initial features that led to the suspicion of vasculitis were petechiae, proteinuria and haematuria. Further testing revealed decreased complement levels (especially C4). These and other manifestations, including oedema, ascites, recurrent pleural effusions, cerebral infarction and glomerulonephritis, were caused by circulating cold-precipitable immune complexes and resulting vasculitis.6-9 Chronic HCV infection stimulates B-cell clones to proliferate and produce cryoprecipitable IgM antibody with rheumatoid-factor activity10 — an important laboratory index of HCV-related mixed cryoglobulinaemia. However, Patient 2 was negative for anti-HCV antibody, possibly because the sensitivity of the anti-HCV immunoassay, although high, is still suboptimal,11 or because the anti-HCV antibodies were concentrated in cryoprecipitates, and therefore not detectable by the serum assay.7 In both patients, the refractory hypertension and pulmonary oedema responded to plasmapheresis and methylprednisolone therapy. Conventional treatment of mixed cryoglobulinaemia aims to reduce circulating immune complexes through immunosuppression and plasmapheresis.8 Although immunosuppressive therapy alone could ameliorate vasculitis,12 plasmapheresis has shown hypotensive effect in immune-complex nephritis, including mixed cryoglobulinaemia.13 It also reduces plasma viscosity and improves perfusion of the affected organs,14 thus helping in patients with hypertension, encephalopathy or severe renal impairment. Neither patient had a history of blood transfusion, surgery, intravenous drug use or tattooing. They probably acquired HCV infection through non-sterile injections or acupuncture in local clinics, the most common source of HCV infection in Taiwan.15,16 With the increasing prevalence of hepatitis C,17 knowledge of its extrahepatic manifestations is important. Our two patients illustrate the association with mixed cryoglobulinaemia presenting with hypertensive crisis and acute pulmonary oedema. 1 Blood test results before diagnosis of cryoglobulinaemia Test Patient 1 Patient 2 Reference range Serum albumin (g/L) 24 24 32–45 Serum urea nitrogen (mmol/L) 13.9 36.8 2.9–8.2 Serum creatinine (μmol/L) 230 412 53–106 Haemoglobin (g/L) 59 98 120–160 Platelet count (× 109/L) 105 69 150–450 Complement 3 (g/L) 0.62 0.30 0.79–1.19 Complement 4 (g/L) 0.02 0.07 0.17–0.37 Rheumatoid factor 1:10 240 > 1:20 480 < 1:40 2 Cryoglobulin test Cryoglobulin particles float in the serum and precipitate at the bottom of the test tube at 4°C. The particles dissolve on rewarming of serum to body temperature.

Li-Na Lee MD, PhD · Shyh-Chyi Lo MD · Fu-Chi Lin BS · Hon-Ping Lau MD · Jih-Shuin Jerng MD · Pan-Chyr Yang MD, PhD

Is there something wrong with the way CPR is presently practised? “That doctor — he should be sacked!” An elderly gentleman was talking about me, and he was doing it on the local television news! My crime was to make the observation in a letter to the MJA that “. . . regular involvement in cardiopulmonary resuscitation (CPR) makes me wish the technique had never been introduced.”1 I had waved a red rag in front of bulls. To disparage CPR creates fury in those who, professionally or otherwise, see it as the reason for their existence. My wife had warned me that I would be painted as the bad guy, and, when this happened, my daughter asked cheerfully, “Is Daddy going to be like Pauline Hanson?”. My first inkling of the coming storm was on the Monday the Journal appeared. A Perth radio personality wanted to interview me. I was not told that, immediately before me, he would be interviewing the head of St John’s Ambulance in Western Australia. “Doctors Give CPR Shock Treatment” was the headline in The Australian. A flurry of phone calls from journalists followed. The local paper picked up the story, and over the next few days a local general practitioner, the local ambulance chief, a surf-lifesaving identity and an editorial in the paper all attacked my purported position. I had several conversations with the medical superintendent of the hospital where I was working: I was free to express an opinion in the MJA, and I was not being reprimanded — as some in the media wished. But, he indicated that he was going to publicly distance the hospital from my remarks, and reaffirm hospital policy — to commence CPR in an emergency whenever a person has stopped breathing or has no pulse. (I am grateful to this medical superintendent, who expended time and effort publicly defending the hospital, and defending me for opinions which — like those expressed here — are mine alone, and not those of the hospital.) The local television station made the topic their main story, and repeatedly replayed the clip of the elderly gentleman who had survived two cardiac arrests and wanted me sacked. The story finished with the words, “Dr Mackay declined to be interviewed”. I did not know I had been invited. Someone had received and declined the invitation for me! An advanced healthcare directive Should I have my cardiac arrest while going about my duties in the emergency department — immediate defibrillation please! And maybe a whiff of oxygen. (If I don’t survive, I will be quite surprised.2) Should I arrest in the hospital dining room, forgo the mouth- to-mouth (I am squeamish about these things). I may (grudgingly) accept some chest compression, until the defibrillator arrives. But if you have not got me back after three shocks — call off the circus. Go back and finish your lunch. If I arrest in the street, you will do what you will. But I won’t be happy. I doubt you will be able to get a defibrillator to me quickly enough. If I arrest at home, I know it will be very difficult for you to do nothing. But it will be 15 minutes before the ambulance arrives. And to end up brain damaged on a ventilator is something I do not want. (But if you are clever enough to call the ambulance so that I arrest after it arrives, by all means use the defibrillator.) When I am in a bed in a hospital ward “old and grey and full of sleep”, do not use your hands to commit violence upon me — use them to comfort me. I became a member of a hospital cardiac arrest team in 1973. Formally or informally, I have been part of such teams ever since. Two things I have learnt from this: there are things I do to patients that I do not want done to me; and, an advanced healthcare directive can never be found when you want one — so I hope I will be forgiven for placing mine here (Box). I would have attended at least a couple of hundred cardiac arrests. My guess is that, sadly, only a dozen or so of these people survived to leave hospital. (A meta-analysis of 39 studies involving 33 124 out-of-hospital cardiac arrests has shown a survival rate of 6.4%.3) Some of the survivors I remember well. While one middle-aged man was telling me about his chest pain, I noticed the cardiac rhythm on the monitor change to ventricular fibrillation. I charged the defibrillator as he continued to talk. I waited until he lost consciousness and then shocked him. In seconds, he was asking me what happened. Such episodes are not unusual in emergency departments (or in the back of ambulances). Of the vast majority who have not survived, I have a clear memory of only a few. I was visiting a patient at his home. He was telling me about his “gallbladder pain” when he had a cardiac arrest. His wife phoned an ambulance while I began resuscitation. When the ambulance arrived, his wife and I had a pink patient with small pupils. At that time ambulances did not carry defibrillators. By the time we arrived at the hospital, which was only a hundred yards away, the patient was blue, his pupils were fixed and dilated, and he could not be revived. It is difficult to maintain effective and continuous external cardiac massage while loading and unloading an ambulance, and while the ambulance is in motion. An editorial in the MJA in 2003 bemoaned the fact that “cardiac arrest is more successfully treated in Chicago or Heathrow airport, on an American Airlines or Qantas jet, or in a Boston post office, than in the vestibules, corridors or general wards of Australia’s premier hospitals”.4 A review of 28 cardiac arrests occurring at the Melbourne Cricket Ground (MCG) revealed a quite extraordinary survival rate of 71%,5 compared with a 3% survival rate from out-of-hospital resuscitation reported, at about the same time, in metropolitan Melbourne as a whole.6 Each minute from the onset of ventricular fibrillation to the use of a defibrillator results in a 10% reduction in survival.7,8 Thus, there is every reason to encourage anything that can shorten the time between the onset of cardiac arrest and defibrillation.9 But there is a big difference between the population of the MCG and that of a general hospital ward. The former has been able to get to the MCG, whereas the latter may be unable to get to the bathroom. Patients in a general medical ward may have failing hearts, lungs, kidneys and brains; they may be dying of cancer, they may be failing to respond to treatment for severe infection, or they may be otherwise very unwell. Most MJA readers will be familiar with the following scene, which takes place regularly in hospital wards. The curtains are barely closed around the bed of an elderly woman; two people are taking it in turns to rhythmically compress her chest; three doctors are attacking her oedematous limbs with needles, unsuccessfully attempting to insert them into veins; a fourth is poking around her groin trying to cannulate her femoral vein; and a fifth has a laryngoscope in her throat. But on this occasion, I notice something rather unusual (though I have seen it before). As I ventilate her lungs through the endotracheal tube, her eyes are wide open, her pupils are small, she blinks, she seems to be looking straight at me. Someone remarks, “She has a dying heart”. Eventually, we allow the rest of her to follow. In the past, nurses used experience and common sense when deciding not to use CPR in most patients when they died. Now, they are expected to start CPR on anyone who collapses and does not have a “not-for-resuscitation” order. This order is supposed to be discussed with the patient. This exceptionally difficult task may fall to the most inexperienced doctor on the ward. The results of CPR in this ward population are likely to be poor, even if immediate defibrillation is available (which it is not10). If cardiac arrest in a general medical ward is to be treated, could management be limited to prompt defibrillation, oxygen by bag and mask, and little else? The management of out-of-hospital cardiac arrest seems particularly prone to controversy. During the 1990s, ambulances regularly arrived at emergency departments carrying patients on whom cardiac massage was being performed. Subsequent discussion with relatives revealed that many of these patients had not had a witnessed cardiac arrest. They had been found dead. It was treating these patients that made me wish that the technique of CPR had never been introduced. In the five years since I wrote those words (and while the notes for this piece were gathering dust), it has become accepted that “. . . survival for the victim of cardiac arrest not resuscitated by a determined trial of advanced cardiac life support at the scene is negligible and not improved by further emergency department efforts”.11 Ambulance officers now have authority to cease resuscitation at the scene when it has clearly failed. This has reduced the incidence of futile resuscitation being performed in ambulances, which then has to be continued for a respectable period of time in the emergency department. But it may not prevent futile resuscitation efforts being performed in patients’ living rooms. An 85-year-old woman may phone “triple 0” after finding her husband collapsed on the floor. She may be advised to commence CPR. Sometimes, mightn’t it be quite reasonable for her to disregard this advice, and, when the ambulance arrives, to ask the paramedics to let her husband remain undisturbed? One hundred and five paramedics, emergency nurses, and emergency physicians who regularly took part in CPR were asked at what point they would like CPR stopped if they were the patient.12 Ten per cent did not wish to have CPR started at all; and only 3% wished to complete a full CPR protocol based on standard American Heart Association guidelines. Does not this suggest that there might be something wrong with the way CPR is presently practised? I was explaining to an elderly woman that her dying brother would be unlikely to last the hour. I asked if she wished to be with him when he died. Her husband turned to her and said, “ No. You don’t want to be there when they put the paddles on.” The assumptions behind this remark startled me. Should cardiopulmonary resuscitation be a futile deathbed ritual — a secular last right? There are many ways to die. To die without fuss, here one minute gone the next — that is the best.

Michael J Mackay MB ChB, MHA, FACRRM

An 80-year-old woman with a history of hypertension presented to the emergency department with a 3-hour history of dyspnoea and precordial discomfort. Serum concentrations of troponin T, creatine kinase and creatine kinase MB isoenzyme were normal. An electrocardiogram (Box 1) showed changes consistent with myocardial ischaemia. When the patient developed haemodynamic instability, cardiac catheterisation was performed (Box 2). The patient’s condition improved after an intra-aortic balloon pump (a catheter-mounted balloon positioned in the descending aorta and timed to inflate during diastole) was placed for the management of cardiogenic shock. An echocardiogram 3 weeks later showed normal left ventricular size and function. The patient had acute transient apical ballooning with normal coronary arteries (“Takotsubo” cardiomyopathy). First described in 1990,1 the presentation is similar to that of acute transmural myocardial ischaemia, with chest symptoms and electrocardiographic changes ranging from ST-segment elevation to T-wave inversion without ST shifts.2,3 Postulated triggering factors for transient apical ballooning have included onset or exacerbation of systemic disorders (eg, cerebrovascular accident, asthma, acute abdomen) and extreme emotional distress.2 Women are 6–12 times more likely to be affected than men.2-4 The in-hospital mortality rate is less than 1%,2 and there is usually complete functional recovery of the left ventricle within 2 weeks.3,4 The 2-year recurrence rate is less than 3%.2 The optimal therapy for this condition is unknown. 1 Electrocardiogram, showing delayed R-wave progression and inverted T waves in the anterolateral leads 2 Images from cardiac catheterisation A. End-diastolic left ventriculogram. B. End-systolic left ventriculogram, showing akinesia/dyskinesia of the apical and mid portions of the left ventricle and hyperdynamic motion at the base. The left ventricular ejection fraction was 30%, with elevated left ventricular end-diastolic pressure of 35 mmHg. C. Normal end-systolic left ventriculogram (from a different patient). D. Left coronary angiogram, showing a normal left anterior descending artery.

Constantin B Marcu MD · Kristen M Andresen MD · Thomas J Donohue MD, FACC

Hypothermia is now standard care for some types of cardiac arrest Out-of-hospital cardiac arrest is a leading cause of unexpected death in the developed world, occurring in about 1 in 1500 adults each year.1 Successful recovery from out-of-hospital cardiac arrest depends on the rapid activation of the “chain of survival”: an immediate call to the ambulance service, bystander delivery of external cardiac massage and expired-air breathing, defibrillation and the provision of advanced life support by paramedics.2 Unfortunately, survival with good neurological outcome at hospital discharge is rare after out-of-hospital cardiac arrest. Studies in Perth and Melbourne show that less than 5% of these patients survive to hospital discharge.3,4 As the average response time of ambulances in most Australian cities is between 7 and 12 minutes, considerable neurological injury occurs during this prolonged period of cardiac arrest, even with bystander cardiopulmonary resuscitation. While paramedics may restore spontaneous circulation and transport some patients alive to an emergency department, most remain comatose because of the severe anoxic brain injury.4 To improve outcome, considerable emphasis has been placed on shortening the time between cardiac arrest and defibrillation. As decreasing ambulance response times towards 5 minutes would be prohibitively expensive, alternative approaches to earlier defibrillation have been proposed. These include fire-fighters co-responding with ambulance services to patients with suspected cardiac arrest,5 or installation of automatic defibrillators in public places.6 On the other hand, recent data from Canada have cast doubt on the effectiveness of paramedic advanced life-support programs, which did not improve survival rates when introduced.7 What therapies are available after arrival at the hospital? In most cases, no immediate cardiology intervention is required, and treatment has therefore been largely supportive until the neurological outcome could be determined. Common intensive care practice has been to defer neurological assessment for at least 3 days, to allow more accurate clinical assessment.8 Recently, an “old” therapy for anoxic brain injury — therapeutic hypothermia — has been re-introduced into clinical practice. In this issue of the Journal, Williamson and colleagues (page 500) describe the use of this therapy in a patient who was comatose after near-drowning.9 The use of mild therapeutic hypothermia after cardiac arrest was first described in the 1950s, but later abandoned without being formally tested in clinical trials.10 Interest in hypothermia was revived in the early 1990s when animal studies and preliminary clinical studies suggested benefit. Subsequently, two prospective, randomised, controlled clinical trials have been conducted.11,12 In a recent Australian trial, patients who remained comatose after resuscitation from out-of-hospital cardiac arrest were treated with either 12 hours of therapeutic hypothermia (33°C) or standard care.11 At hospital discharge, 49% of those treated with hypothermia were discharged home or to rehabilitation, compared with 24% of those treated with standard care. In a European study, 55% of patients treated with hypothermia (33°C for 24 hours) had a favourable outcome at 6 months, compared with 39% of those treated with standard care.12 Subsequently, the International Liaison Committee on Resuscitation (which includes the Australian Resuscitation Council) endorsed the use of therapeutic hypothermia for patients with anoxic brain injury after out-of-hospital cardiac arrest, particularly when the initial cardiac rhythm is ventricular fibrillation (Box).13 Therefore, this treatment should now be regarded as a standard of care for this condition. However, a number of issues require further consideration if therapeutic hypothermia is to be applied more widely. Firstly, uncertainty remains about the effectiveness of this therapy in patients with out-of-hospital cardiac arrest due to causes other than ventricular fibrillation. Patients with asystolic out-of-hospital cardiac arrest have a dismal prognosis,14 as do those with coma after near-drowning, hanging, or other causes of asphyxia. Clinical data on the effects of therapeutic hypothermia in these groups are lacking. The role that therapeutic hypothermia played in the recovery of the patient reported by Williamson and colleagues is uncertain. Secondly, a protocol needs to be established in the emergency department for the rapid induction of hypothermia in patients who are unconscious after out-of-hospital cardiac arrest. In most hospitals, this will require consensus to be reached between emergency physicians, intensive care physicians and cardiologists on the indications for the provision of this treatment. Finally, there are technical issues to be considered in the rapid induction of hypothermia. In previous studies, hypothermia was induced through surface cooling with ice packs and/or refrigerated air blankets.11,12 This approach is slow and logistically difficult in busy emergency departments. Other technologies for the rapid induction of hypothermia are therefore under investigation.10 Currently, we are exploring the use of a rapid intravenous infusion of large-volume (30 mL/kg), ice-cold crystalloid fluid to induce hypothermia. Preliminary data suggest that this is relatively simple, effective, inexpensive and not associated with pulmonary complications.15 As there is often a delay between resuscitation and emergency department initiation of hypothermia, cooling in the ambulance would be ideal. In a study supported by the National Heart Foundation, paramedics in Melbourne are now infusing large-volume (2000 mL), ice-cold crystalloid fluid, together with a muscle relaxant, immediately after out-of-hospital cardiac arrest to induce hypothermia as soon as possible after resuscitation. If this is confirmed as feasible, further studies are planned which will examine the use of therapeutic hypothermia after asystolic and asphyxial cardiac arrest. Recommendations on therapeutic hypothermia from the International Liaison Committee on Resuscitation In October 2002, the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation recommended: Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C–34°C for 12–24 hours when the initial rhythm was ventricular fibrillation. Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest. Preliminary data from clinical trials of perinatal asphyxia indicate that induced hypothermia is feasible and safe, but data on long-term neurological morbidity are not yet available. Until additional paediatric data become available, clinicians should tailor therapy for individual patients based on their assessment of the risks and benefits of hypothermia.

Stephen A Bernard MD, FACEM, FJFICM

A 74-year-old woman presented to hospital with dyspnoea of sudden onset. She was in cardiogenic shock, with blood pressure of 90/50 mmHg, and pulse rate of 115 bpm. The electrocardiogram (ECG) was difficult to interpret because of severe, persistent and inexplicable artefacts (Box 1A). Chest x-ray showed acute pulmonary oedema thought secondary to left ventricular failure. Echocardiography showed a left ventricular ejection fraction of 40% and anterior akinesia. Coronary angiography confirmed a proximal occlusion of the left anterior descending coronary artery, which was successfully treated by direct angioplasty and stenting. Review of the patient’s previous medical records revealed, on a thoracoabdominal image derived from computed tomography data, a foreign body in the central abdominal region (Box 2). Questioning of the patient after the angioplasty revealed that this was an electrostimulator (Itrel II, Medtronic, Minneapolis, USA) implanted a few years earlier as part of a dynamic graciloplasty to treat faecal incontinence. An ECG performed 12 hours after the angioplasty with the device deactivated (by the patient’s control programmer) produced an ECG tracing free of artefacts (Box 1B). Persistent and inexplicable ECG artefacts should raise the suspicion of interference from a device generating high frequency electrical impulses. Such devices may include minute ventilation rate-responsive pacemakers1 and central or transcutaneous neurostimulators (eg, deep brain neurostimulators used in Parkinson’s disease,2 and spinal neurostimulators used in chronic back pain3). Occasionally, when the vector of impulses is perpendicular to an ECG lead, the tracing from that lead may be free of artefacts (eg,Box 1A, lead I). Intrathoracic devices are usually discovered on physical examination or standard chest x-ray, but devices in other parts of the body may not be obvious. In dynamic graciloplasty to treat anal incontinence, the gracilis muscle is transposed around the anal canal and electronically stimulated by a device placed in a subcutaneous pocket in the abdominal wall.4 In our case, this device led to ECG artefacts potentially interfering with the ability to diagnose the acute myocardial infarction. Implanted electrostimulation devices are being used increasingly in medicine and should be considered as a possible source of ECG artefacts, especially by frontline clinicians confronted daily with such life-threatening conditions as acute coronary syndromes. Electrocardiograms in a patient with an electrostimulation device A. On presentation, showing artefacts. B. After temporary deactivation of the device. 2 Thoracoabdominal image calculated from computed tomography data, showing the device (arrow)

Robert F Bonvini MD · Edoardo Camenzind MD

More than 170 clinicians from diverse healthcare backgrounds attended the National Institute of Clinical Studies (NICS) “Heart Failure Forum 2004: improving outcomes in chronic care”, held in Canberra, 7–8 June 2004. The purpose of the forum was to raise awareness of the growing burden of heart failure, engage with Australian and international experts in heart failure and chronic care management, and explore strategies for improving outcomes in chronic care. Successful models of careGeoffrey Tofler (Chair of the NICS Heart Failure Advisory Group and Professor of Preventive Cardiology, University of Sydney) set the scene by highlighting gaps in the current medical treatment of heart failure. These gaps are most notable in the use of evidence-based drug therapies, such as angiotensin-converting enzyme (ACE) inhibitors and β-blockers, that reduce symptoms and hospital admissions and improve survival.1 Chronic care expert Ed Wagner (Director, MacColl Institute for Healthcare Innovation, Group Health Cooperative, Seattle, Washington, US, and leader of the Robert Wood Johnson Foundation Improving Chronic Illness Care Program) argued that the current care system is not working adequately for either patients or healthcare professionals,2 and emphasised the importance of redesigning care systems around the needs of patients with chronic illnesses. He described the essential elements of the chronic care model (Box 1),3 and illustrated how the model, combined with the Institute of Healthcare Improvement collaborative improvement method, enabled over 1000 US healthcare organisations to improve quality of care for patients with asthma, diabetes and chronic heart failure.4 Peter Didsbury (Chairman, New Zealand Guidelines Group, and Deputy Head and Manager of Integration, ProCare Health Ltd, Wellington, NZ) reported increased prescribing of ACE inhibitors, β-blockers and spironolactones following multifaceted intervention strategies, such as improved access to echocardiography, rapid access to cardiology advice, funding for β-blocker titration, access to a cardiac nurse specialist and 24-hour telephone triage. The results of an unpublished randomised trial he conducted involving patients with chronic obstructive pulmonary disease led him to suggest that improving the effectiveness of patient adherence through more structured care processes (such as holistic assessments, education about the condition, lifestyle therapy, action plans and active follow-up) may have greater effect. The vital role played by nursing staff was highlighted by Simon Stewart (Chair, Cardiovascular Nursing, and Director of the Centre for Innovation in Health, University of South Australia). He presented evidence from a recent systematic review of randomised trials of multidisciplinary strategies for the management of patients with heart failure at high risk for admission. This review showed that programs that incorporate follow-up by a specialised multidisciplinary team (in either a clinic or a non-clinic setting) reduce mortality, heart failure hospitalisations and all-cause hospitalisations.5 Stewart emphasised the need for a more systematic implementation of specialist nurse-led, home-based, follow-up services after discharge for patients with heart failure. Such services are currently available to less than 10% of those needing them. Whether this form of care is applicable in rural and remote locations is not certain, according to Henry Krum (Director, NHMRC Centre of Clinical Research Excellence in Therapeutics, Monash University), who described the computerised, telephone-based patient support system (“Telewatch”) his research group is trialling in Australia. The system allows healthcare providers to closely monitor symptoms of patients with chronic heart failure and to track progress, respond to deterioration and make suggestions to improve overall management. Specific questions relate to diet, exercise, alcohol use, smoking, use of drugs for chronic heart failure, use of prescribed and over-the-counter medications unrelated to chronic heart failure, mood state and current coping. Results are expected by the end of 2005. The role of GPs in management of heart failureAlthough heart failure is a leading medical cause of hospital admissions in older people, Justin Beilby (Head, Department of General Practice, University of Adelaide) noted that patients with heart failure represent a low proportion of the total patients that each general practitioner treats. Of concern to GPs is the need to identify people with early heart failure, who would benefit from more aggressive intervention. This point was reinforced by Michael Feneley (Chair, Cardiac Society of Australia and New Zealand Echocardiography Working Group), who stressed that new shortness of breath with no other obvious cause is often a symptom of early heart failure and should trigger investigation. He believes echocardiography is the most useful investigation in confirming or ruling out heart failure and is critical for determining the underlying cause and guiding therapy.6 Mark Harris (Professor, General Practice, University of New South Wales) detailed the important role of Divisions of General Practice in providing support and feedback to practices in the collection and analysis of data and in the use of patient registries — key elements of proactive chronic care patient management. The forum heard from Judith Mackson (Prescribing Program Coordinator, National Prescribing Service [NPS]) that the NPS, the National Heart Foundation of Australia (NHFA) and the NICS have formed a collaboration to improve targeted elements of heart failure diagnosis and management in general practice. This joint program will deliver key messages on drug use for treating heart failure and will emphasise the importance of echocardiography to confirm the diagnosis and guide treatment. Current government initiatives in chronic careThe importance of adopting a more systematic approach to chronic care management in Australia was reinforced by Andrew Tonkin (Director, Health, Medical and Scientific Affairs, NHFA), who argued that the effective management of heart failure represents an excellent paradigm for improving the care of people with other chronic conditions. The value and cost-effectiveness of management programs that can support patients with heart failure in the home and community and prevent hospitalisation have been demonstrated. Programs and information systems for patients with heart failure, once established, could be easily adapted to the needs of other chronically ill patients. Jane Halton (Secretary, Australian Government Department of Health and Ageing) highlighted recent Budget initiatives. Funding is provided for 1600 more primary care nurses and a new Medicare Benefits Schedule item number linked to the Enhanced Primary Care multidisciplinary care plan for services provided by allied health professionals. Ms Halton outlined the government’s plans for a national chronic disease strategy, following development and consultations by the National Health Priority Action Council’s Chronic Disease Strategy Group. The forum heard about different state heart failure programs. Craig White (Deputy Chair, Victorian Hospital Admission Risk Prevention Program, and Executive Director, Clinical Services, Austin Health) and Kym Scanlon (Assistant Director, Chronic Care Program, NSW Health) presented figures showing encouraging reductions in hospital admissions for chronic heart failure since the commencement of statewide chronic care programs, such as the Victorian Hospital Admission Risk Prevention Program and the NSW Chronic and Complex Care Program.7,8 Clearly, more patients need to access these programs, with only an estimated 15% of eligible patients enrolled in Victoria (Andrea Driscoll, Deakin University). NSW Health is currently addressing implementation and spread of issues through a statewide chronic care collaboration that focuses on heart failure and chronic obstructive pulmonary disease. The change principles of the collaboration are based on the key elements of Wagner’s chronic care model, as well as policy components from the World Health Organization’s Innovative Care for Chronic Conditions Framework.9 Conclusion and the way forwardIn the concluding plenary session, Didsbury and Wagner suggested strategies that would facilitate implementation of the chronic care model in Australia. They emphasised the need to reward care planning, support efforts to encourage practice system change, and make patients a part of the planning. Using the patient journey as a framework, Geoffrey Tofler presented a matrix of key strategies and interventions that patients, clinicians and governments should consider to improve outcomes and quality of life for patients with heart failure (Box 2). The matrix indicates areas where best-practice models of care are known, such as cardiac nurse specialists for post-discharge heart failure patients, and areas where more research is needed, such as the best use of practice nurses in chronic diseases. Finally, the matrix suggests areas where enhanced government support is needed (such as in creating mechanisms for funding comprehensive care programs and in further funding for practice nurses). The range of participants at the forum reinforced the broad approach needed to improve outcomes in heart failure. Furthermore, strategies adopted successfully with heart failure could have major effects when extrapolated to other chronic conditions. The forum presentations and a more detailed report are available on the National Institute of Clinical Studies website (www.nicsl.com.au). 1 The chronic care model Source: Ed Wagner keynote address, NICS Heart Failure Forum 2004. Available at www.nicsl.com.au. For more information on the chronic care model, see reference 3. 2 Matrix of key strategies and interventions for a patient with heart failure Stage Prevention Early stage Acute exacerbation Ongoing care Palliative care Issues Identification of high-risk patients Recognition of early signs and symptoms, when and whom to refer for echocardiography Use and availability of echocardiography, particularly in rural areas Use of BNP in primary care to be further defined In-hospital initiation of appropriate therapy and discharge to community with management plan, including dose titration schedules Comorbidities, diagnostic issues, systematic patient education and support Need research on the education of practice nurses in chronic care management and effectiveness in improving patient outcomes Changing roles in general practice Need research on access to palliative care services and how to extend these to patients with heart failure Model Prevention and management of coronary artery disease and hypertension Consumer Education (NICS Online directory of quality information for patients with heart failure) Appropriate use of echocardiography in diagnosis and assessment of heart failure in primary care (NICS education module in preparation) Clinician-led quality improvement programs Heart failure nurse-led, home-based management programs (Alternatives include hospital-based rehabilitation, heart failure clinics) Chronic care management model Study and implement self-management models Targeted interventions aimed at implementing best practice management of heart failure in primary care (NICS, NPS and NHFA joint heart failure program) Need research on appropriate palliative care model and extrapolation of palliative care and nursing principles Consumer role Awareness of risk factors (SNAP) Awareness of early symptoms and precipitants, especially in high risk individuals Working in partnership with healthcare professionals Access to self-management education and support, particularly post-discharge Self-management education and support, ongoing monitoring, adherence to treatment Heart Failure Action plan Consider advance directives Access to self-management and support Provider role Identification and treatment of high-risk patients by GPs, cardiologists, general physicians Assessment of patients with early signs and symptoms by GPs Referrals to cardiologists or general physicians, where appropriate Emergency physicians, cardiologists, general physicians, geriatricians, cardiac nurses, hospital pharmacists GPs, practice nurses with training in chronic care and support from cardiac nurses, allied health, community nurses and pharmacists GPs, community nurses, palliative care teams Government role Heart failure health promotion campaign, and systems in place to support this Access to echocardiography, access to cardiologists Need heart failure prevalence study and minimum heart failure dataset Need initiatives for improved outcomes for cardiovascular disease in primary care Ongoing resourcing for cardiac nurse role in acute settings and post-discharge (state) Testing and implementation of chronic care model in general practice and system redesign issues (Commonwealth) Mechanism for funding comprehensive care programs More practice nurses Capacity building for quality improvement Extend palliative care entitlements to patients with heart failure (eg, access to medicines, oxygen and home nursing services) BNP = Brain natriuretic peptide. NICS = National Institute of Clinical Studies. NPS = National Prescribing Service. NHFA = National Heart Foundation of Australia. SNAP = Smoking, Nutrition, Alcohol, Physical activity.

Susan M Phillips DPhil · Janice M Davies PhD · Geoffrey H Tofler MB BS, MD

Raised plasma homocysteine (tHcy) concentrations are caused by genetic mutations, vitamin deficiencies, renal and other diseases, numerous drugs, and increasing age. Raised tHcy concentrations are associated with laboratory evidence of atherogenesis (eg, endothelial dysfunction) and thrombosis, and epidemiological evidence of an increased risk of atherothrombotic vascular disease. An association between raised tHcy concentration and an increased risk of atherothrombosis is independent of other vascular risk factors, strong, dose-related and biologically plausible, but has not been proven to be causal in randomised controlled trials. A recent trial identified no significant benefit from lowering tHcy concentration by folic-acid-based multivitamin therapy among 3680 patients with recent ischaemic stroke, but did not reliably exclude a modest but important reduction in the relative risk of stroke of up to 20%; a difference of only 2 mmol/L in tHcy concentration between the two treatment groups was probably due to widespread vitamin use and fortification of grains and staple foods with folate in North America. There is currently insufficient evidence to recommend routine screening and treatment of high tHcy concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease.

Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MSc, FRACP, FRCPA · Wai Khoon Ho MB ChB, FRACP, FRCPA · Frank M van Bockxmeer PhD, FAHA

Cardiovascular disease is the leading cause of morbidity and mortality in Australia. It is therefore important that all medical practitioners are familiar with the well documented risk factors for cardiovascular disease, as well as the outcome benefits of pharmacological and other interventions. The large and ever-increasing body of clinical evidence, the range of patient groups at risk and the plethora of recommended interventions all make it increasingly difficult for busy doctors to adopt an integrated approach to prevention of vascular events. While absolute risk calculators, such as the Framingham Heart Study Prediction Score Sheets (www.nhlbi.nih.gov/about/framingham/riskabs.htm) or the New Zealand Cardiovascular Risk Factor Calculator (www.racp.edu.au/bp/resources/EBM_cardio.pdf), enable doctors to assign overall risk, guidelines for management are usually focused on single interventions. Moreover, the continual emergence of new data on vascular risk management redefines risk categories and approaches to risk management. Prevention of cardiovascular disease: an evidence-based clinical aid was developed by a multidisciplinary group of physicians to address this issue and was first published by the MJA in July 2003. We have revised and updated our evaluation of current best practice based on a rigorous analysis of available published evidence to March 2004, and formulated a concise and up-to-date guide for the prevention of cardiovascular disease. This consensus of opinions is summarised in this document (see Clinical aid, page F12) and provided as a single-page chart for use in clinical practice as a desktop reference. Patients were classified as being either at high or low risk of cardiovascular events (Box 1). It is widely considered that high-risk patients are those with clinically evident vascular disease, renal disease, diabetes or other risk factors conferring an annual risk of a future event of 2%–3% or greater. Risk can be calculated using an absolute risk-factor calculator (see above). The major interventions considered were: lifestyle changes; cessation of smoking; and treatment of hypertension and dyslipidaemia. Where new indications for treatment have been demonstrated in particular circumstances for a single product, this product is shown; otherwise, the class of agents is presented. We considered the results of recent trials that will potentially have a major impact on the management of high-risk patients. Such trials include the HOPE study,1 the PROGRESS study2 and the Heart Protection Study.3 Furthermore, the recognition that proteinuria imparts substantial risk warranted the inclusion of specific advice for the population with this risk factor. Although the importance of homocysteine, Lp(a) and fibrinogen as cardiovascular risk factors was recognised, the infrequent measurement of these parameters in usual practice, together with the lack of proven interventions, justifies their omission from this review. We anticipate further updates and revisions to the aid to maintain its currency in the context of a rapidly expanding cardiovascular evidence base. The management recommendations of this “living” document will continually evolve as new evidence is published. It should be noted that this clinical aid applies to the long-term management of cardiovascular risk in general practice or community-based physicians’ practice. It does not cover the medical management of acute coronary syndromes or heart failure. Glossary of abbreviations ACE inhibitor – angiotensin-converting enzyme inhibitor AIIRA – angiotensin II receptor antagonist AMI – acute myocardial infarction CCF – congestive cardiac failure CHD – coronary heart disease HDL cholesterol – high-density lipoprotein cholesterol LDL cholesterol – low-density lipoprotein cholesterol RCT – randomised controlled trial TIA – transient ischaemic attack Recommendations for all patientsHealthy lifestyleAdvice concerning the benefits of smoking cessation, physical activity and healthy dietary choices should be given at a population and individual level. These measures are considered as first-line in any management decisions. a) Cessation of smokingThere is extensive evidence that smoking is strongly related to mortality, largely because of an increased risk of CHD and stroke.4 Furthermore, smoking cessation has been shown to decrease this risk in patients with and without established CHD.5 In patients with peripheral vascular disease or stroke, smoking cessation is associated with improved exercise tolerance and survival, and decreased rates of limb amputation and recurrent stroke.5 b) ExerciseWhile there is limited evidence from RCTs of the value of exercise in primary prevention of cardiovascular disease, there is strong observational evidence that moderate, regular physical activity reduces the risk of both CHD6 and stroke,7 and that the risk is increased in people with a sedentary lifestyle.8 For secondary prevention after AMI, two meta-analyses of exercise-based rehabilitation in up to 14 RCTs have shown reductions in mortality of between 20% and 25% (absolute risk reduction [ARR], 3.1%) at 3-year follow-up, although many of the trials allowed other risk-factor intervention as well.9,10 While these data must be interpreted with caution, prescribing a moderate degree of regular physical exercise is consistent with published evidence. c) DietCohort studies have shown that eating fruit and vegetables reduces the risk of heart attack and stroke.11 One RCT showed that a Mediterranean diet decreased mortality by 30% at 27 months after AMI (ARR, 4.0%).12 In addition, a modest intake of fish (as little as 35 g daily) appears to decrease the relative risk of AMI.13 Following general advice to decrease the intake of saturated fats and cholesterol and increase the intake of polyunsaturated fats favourably affects serum lipid levels and decreases the likelihood of CHD.14 Finally, weight maintenance education should be part of routine advice for the general population, but is particularly important in patients at increased risk of cardiovascular events. d) StressRecently, an Expert Working Group of the National Heart Foundation of Australia undertook a review of the evidence relating to major psychosocial risk factors to assess whether these influenced the development of CHD and acute coronary events.15 They concluded that there was “no strong or consistent evidence for a causal association between chronic life events, work-related stressors (job control, demands and strain), type A behaviour patterns, hostility, anxiety disorders or panic attacks and CHD”.15 However, there was strong and consistent evidence of an independent and causal association between depression, social isolation and the prognosis of CHD and, importantly, the impact of these was of a similar order to conventional risk factors such as smoking.15 It is therefore crucial that these psychosocial factors are considered during individual CHD risk assessments. Recommendations for patients with established vascular disease1. Normotensive patients with a history of cardiovascular diseaseThe HOPE,1 PROGRESS2 and, more recently, EUROPA studies16 have examined the effects of preventive treatment with ACE inhibitors in normotensive high-risk patients. In the HOPE study, patients with CHD, peripheral vascular disease, stroke, or diabetes (types 1 or 2) and an additional risk factor were randomly allocated to receive ramipril 10 mg daily or placebo. Patients were included irrespective of a history of hypertension, but those with blood pressure greater than 140/90 mmHg or with a specific indication for treatment with an ACE inhibitor (eg, CCF) were excluded. The 3/1 mmHg lower blood pressure in the ramipril group at the end of the study was unlikely to explain the highly significant 22% reduction in the combined endpoint of cardiovascular death, stroke or heart attack (cardiovascular death [26% reduction; ARR, 2.0%], stroke [32% reduction; ARR, 1.5%], heart attack [20% reduction; ARR, 2.2%]; P < 0.05) or the 17% decrease in total mortality (P < 0.05).1 In the PROGRESS study,2 patients with a previous history of stroke or TIA were randomly allocated to perindopril 4 mg ± indapamide 2.5 mg versus placebo, whether there was a history of hypertension or not. When given together this combination reduced the risk of recurrent stroke (fatal or non-fatal) and major vascular events in both normotensive and hypertensive patients with this background.2 There was also a significant reduction in major coronary events (26%) and the development of heart failure (26%) in these patients with underlying cerebrovascular disease.17 The magnitude of blood pressure reduction in the active treatment group was greater in the PROGRESS study (9/4 mmHg) than in the HOPE study (3/1 mmHg), making it less clear as to how much of the benefit seen in the PROGRESS study was independent of blood pressure reduction alone. The recently published EUROPA study16 looked at patients with known ischaemic heart disease, and participants were randomly allocated to receive perindopril 8 mg or placebo, independent of whether or not they had a history of hypertension. At 5 years, there was a significant 20% reduction in cardiovascular mortality, infarction and cardiac arrest in patients who received perindopril, with a blood pressure difference of 5/2 mmHg between the groups. It appears that, in patients with a history of CHD or cerebrovascular disease, treatment with a high dose ramipril- or perindopril-based regimen will improve outcomes whether or not there is a history of hypertension, and that at least some of these benefits are independent of blood pressure reduction alone. In the immediate post-infarct management of normotensive patients, a mortality benefit in the short term has also been demonstrated with β-blockers18 and ACE inhibitors (particularly in patients with associated heart failure),19 with less robust evidence for calcium channel blockers, verapamil and diltiazem.20-22 2. Patients with elevated blood pressure and a history of cardiovascular diseaseWhile epidemiological studies have established that raised blood pressure is a major risk factor for cardiovascular events in patients with a history of AMI,23 until recently there has been no systematic review or RCT that specifically examines blood pressure reduction in patients with established CHD, nor in those with peripheral vascular disease; however, the results of the HOPE, PROGRESS and EUROPA studies are applicable to patients with hypertension. In our recommendations, and those of both the JNC-7 Report24 and the National Heart Foundation,25 the benefits of blood pressure lowering in patients with CHD have been extrapolated mostly from primary prevention trials and from studies of patients after AMI.1,18-22 Evidence of event reduction exists for patients taking calcium channel blockers,20-22,26-29 diuretics and β-blockers,29-35 and ACE inhibitors.1,28,35 In patients with elevated blood pressure and a history of stroke or TIA, the evidence is strongest for the use of ACE inhibitors (ramipril 10 mg; and perindopril 4 mg when given with indapamide 2.5 mg),1,2 diuretics and β-blockers.34-38 More recently, the INVEST study39 examined patients with hypertension and known ischaemic heart disease. This study found that event rates were similar in both subjects taking a verapamil-based regimen and in those receiving atenolol-based therapy. However, to achieve target blood pressures, most patients in both study groups were taking combination therapy that also included an ACE inhibitor and thiazide diuretic. As over 50% of patients in the ALLHAT study38 had a history of atherosclerotic cardiovascular disease, the result of this study should be considered when blood pressure lowering is contemplated for such patients.38 Specifically, the results of treatment with ACE inhibitors, diuretics or calcium channel blockers were comparable. It should be noted, however, that there was an increased rate of development of diabetes mellitus in the thiazide diuretic treatment arm. In view of the impact of diabetes on cardiovascular event rates, this finding may have implications for cardiovascular disease beyond the 5-year treatment period covered by the trial. 3. Patients with dyslipidaemia and a history of cardiovascular diseaseThere is strong RCT evidence that lowering cholesterol levels decreases cardiovascular mortality and morbidity in patients who have been diagnosed with an acute coronary syndrome or myocardial infarction,40 even if cholesterol levels are normal.3,41,42 The most substantial data are from studies of simvastatin and pravastatin,3,40-42 but, recently, results of the PROVE-IT study43 suggest that intensive lipid lowering with atorvastatin 80 mg improves outcomes more than moderate lipid lowering in patients with acute coronary syndromes and cholesterol levels less than 6.2 mmol/L.43 The Heart Protection Study3 provides the most complete information of the benefits of lowering cholesterol level in a wide range of circumstances. Both men and women with total cholesterol levels greater than 3.5 mmol/L and with a history of cardiovascular disease (including those with a history of coronary disease, cerebrovascular disease, or peripheral vascular disease) achieved a significant reduction in major vascular events (P < 0.001) irrespective of the starting cholesterol level. In men with low levels of HDL cholesterol and a history of CHD, gemfibrozil significantly reduced the risk of major cardiovascular events, in the absence of an effect on LDL cholesterol level.44 In patients with diabetes and CHD, the data are strongest for the use of statins,3,40-42 but, again, in patients with low levels of HDL cholesterol gemfibrozil is efficacious.44 To date, this evidence has been derived from subgroup analyses. In RCTs, it has been shown that both pravastatin and simvastatin reduce the incidence of stroke in patients with CHD,3,41,42,45 but in those without CHD the evidence is strongest for simvastatin.3 There are no “head-to-head” outcome studies of statins versus fibrates. Recommendations for patients with diabetes without known cardiovascular disease1. Patients with diabetes and “normal” blood pressureIn patients with diabetes, “normal” blood pressure is arbitrarily defined as being less than 130/85 mmHg and “ideal” blood pressure as less than 120/80 mmHg.25 As the HOPE study1 only included patients with diabetes if they had at least one cardiovascular risk factor, treatment of low-risk patients with diabetes (ie, those who have no additional cardiovascular risk factors) with an ACE inhibitor to prevent future CHD events is not supported by current data. Observation with repeated measurement of blood pressure at least annually is recommended.25,46 2. Patients with diabetes and elevated blood pressureA systematic review of RCTs has shown that ACE inhibitors, diuretics, calcium channel blockers and β-blockers are all effective in primary prevention of cardiovascular events in patients with diabetes and hypertension.47 There is no clear evidence that any of these classes is more effective than another in event reduction,26,28 and currently drugs of all of these classes are recommended to treat blood pressure in patients with diabetes.25 Despite this, an apparent greater reduction in major cardiovascular events (including heart failure) occurring with ACE inhibitors, compared with some calcium channel blockers,48-50 has led us to list calcium channel blockers as second-line therapy. In addition to reducing cardiovascular events, ACE inhibitors have a major role in renal protection in patients with type 1 diabetes and hypertension.51 Similar protection has recently been shown with the AIIRAs irbesartan52,53 and losartan,54 including patients with type 2 diabetes and left ventricular hypertrophy.55 3. Lowering cholesterol level in patients with diabetesIn the Heart Protection Study,3,56 patients with diabetes with a total cholesterol level greater than 3.5 mmol/L had significantly fewer major vascular events (P < 0.0001) when taking simvastatin 40 mg, whether or not they had a prior history of CHD. To date, this is the largest intervention trial of statin therapy in patients with diabetes and thus should be considered the definitive trial. These data support the use of a statin for both primary and secondary prevention of major vascular events in patients with diabetes. Furthermore, three large primary prevention RCTs using lovastatin,57 gemfibrozil58 and bezafibrate59 have each shown a benefit in preventing cardiovascular events. Thus, a predominant elevation of total or LDL cholesterol levels indicates a statin is appropriate initial therapy, whereas a fibrate could be an appropriate choice in patients with low levels of HDL cholesterol and raised triglyceride levels. When treating combined hyperlipidaemia, both classes of drug may be required, but there are no outcome data from using this approach and practitioners should exercise caution in prescribing this combination. Definitive trials on lipid management in patients with diabetes (eg, the FIELD study60) are still to be published. 4. Cardiovascular prevention with other therapiesAs the HOPE study included patients with diabetes and dyslipidaemia (total cholesterol level > 5.2 mmol/L and HDL cholesterol level 0.9 mmol/L),61 the use of ramipril in addition to other therapies should be advocated in diabetic patients with dyslipidaemia or other cardiovascular risk factors. Recommendations for patients with non-diabetic renal disease1. Patients with non-diabetic renal disease and “normal” blood pressureRenal insufficiency is a well described predictor of cardiovascular outcomes.62 Hypertension in patients with renal disease is defined as blood pressure greater than 130/85 mmHg,25 although observational studies suggest that even a lower blood pressure confers an increased risk. Despite this, there is no RCT of antihypertensive therapy showing treatment benefit if blood pressure is below this threshold. Ongoing observation with repeated measurement of blood pressure every 6 months is currently recommended for normotensive patients with non-diabetic renal disease.24,25,46 2. Patients with non-diabetic renal disease and hypertensionThe benefits of treating hypertension in patients with established renal disease have largely been studied with surrogate endpoints, and the effects of lowering blood pressure on cardiovascular outcomes have not been specifically assessed. Nevertheless, patients with renal dysfunction are at high risk of CHD and it is reasonable to extrapolate from this that aggressive blood pressure lowering will confer a substantial benefit.25 Published data support the use of ACE inhibitors as first-line treatment for hypertension, with greater demonstrated efficacy in reducing proteinuria than calcium channel blockers.51 Further, in a meta-analysis of a number of clinical trials, ACE inhibitors were more effective than other agents in delaying the development of end-stage renal disease; however, it could not be determined whether this was due to the lower blood pressure achieved with ACE inhibitors or to effects independent of blood pressure.63 β-Blockers and diuretics are also recommended.24,25 If calcium channel blockers are used they should be considered as second-line therapy after ACE inhibitors.51 More recent information in this patient group has been derived from the CATS64 and COOPERATE65 studies. The CATS study showed that, although renal function deteriorated markedly after a first AMI, it was significantly preserved by taking the ACE inhibitor captopril. Patients after a first anterior-wall AMI were allocated at random to receive captopril (up to 75 mg daily) or placebo, after completion of a streptokinase infusion. Renal function determined by calculating glomerular filtration rate was found to decline by 5.5 mL/min within 1 year versus only 0.5 mL/min in the captopril group (P < 0.05). The beneficial effects of captopril were most pronounced in patients with the most compromised renal function at baseline. The COOPERATE study65 aimed to assess the effects of ACE inhibitor and AIIRA therapy, both in combination as well as monotherapy at maximal dose. Participants were randomly assigned to receive losartan 100 mg daily or trandolapril 3 mg daily, or a combination of both drugs at equivalent doses. Survival analyses were done to compare the effects of each regimen on the primary combined endpoint of time to doubling of serum creatinine concentration or end-stage renal disease on an intention-to-treat basis. Eleven per cent of patients taking the combination treatment reached the combined primary endpoint, compared with 23% of patients taking trandolapril alone (hazard ratio, 0.38; 95% CI, 0.18–0.63; P = 0.018) and 23% of patients taking losartan alone (hazard ratio, 0.40; 95% CI, 0.17–0.69; P = 0.016). Combination treatment was found to safely retard the progression of non-diabetic renal disease compared with monotherapy; however, as some patients taking combined therapy reached the combined endpoint, further research on strategies for complete management of progressive non-diabetic renal disease is needed. 3. Lowering cholesterol level in patients with non-diabetic renal diseaseSpecific trials of lipid-lowering therapy have not been conducted in patients with non-diabetic renal disease. Thresholds for intervention have been derived by consensus and recommendations for the choice of agents have been based on the lipid-lowering characteristics of specific therapies. The approach for other high-risk patientsOver the past decade, it has been recommended that the intensity of risk-factor management be governed by a patient’s absolute risk of a CHD event. However, patients with mild levels of multiple risk factors may be at high risk because of the exponential additive contribution of each risk factor,66 whereas other patients may have an overall low risk even if they have one markedly abnormal risk factor (Box 1). 1. High-risk patients with raised blood pressureA number of systematic reviews have shown a reduction in total mortality, cardiovascular death, stroke, major coronary events and CCF in patients taking β-blockers, diuretics, ACE inhibitors or calcium channel blockers.25,62,67 One unblinded RCT in 6600 people aged 70–84 years, comparing diuretics and/or β-blockers versus calcium channel blockers versus ACE inhibitors, showed no significant difference in blood pressure control or cardiovascular morbidity and mortality.68 The ALLHAT study, involving hypertensive patients with at least one other CHD risk factor, supports these findings.38,69 When the primary outcome was considered (fatal CHD or non-fatal AMI), diuretic-based therapy (chlorthalidone) was of similar efficacy to either therapy with a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril). In fact, patients taking amlodipine had an increased risk of CCF (relative risk, 1.38; 95% CI, 1.25–1.52) and patients taking lisinopril had a higher risk of combined cardiovascular disease, stroke and CCF.38 As amlodipine is a dihydropyridine calcium channel blocker, it may not be possible to extrapolate these results to the non-dihydropyridine calcium channel blockers.69 2. Lowering cholesterol level in patients at high risk of a cardiovascular eventUntil recently, there was no evidence that lowering cholesterol level reduces total mortality in non-diabetic patients without cardiovascular disease, although systematic reviews and RCTs had shown that cholesterol reduction improves cardiovascular outcomes in high-risk populations.3,57,70-72 The benefit is related to baseline risk and extent of cholesterol reduction rather than initial cholesterol level (within the range studied). The lipid-lowering arm of the ASCOT study73 demonstrated the benefits of lipid reduction for hypertensive patients with multiple cardiovascular risk factors. ASCOT examined 10 305 patients with hypertension and at least three other cardiovascular risk factors (excluding previous AMI or current angina) who had non-fasting cholesterol levels less than 6.5 mmol/L. Treatment with atorvastatin 10 mg conferred a 36% reduction in fatal CHD and non-fatal AMI compared with placebo (P = 0.0005). The benefits of lipid reduction were also evident among non-diabetic patients. A total cholesterol level greater than 5 mmol/L is the current recommended threshold for treatment in patients with associated risk factors or vascular disease.74 The approach for patients at low risk of a cardiovascular eventPatients who are not in any of the above categories are at low risk of a cardiovascular event. There is a more liberal threshold for intervention in this group in the knowledge that the treatment benefits will be smaller, but the recommendations for choice of therapy to lower blood pressure and lipid levels are identical to those in higher-risk patients. 1. Blood pressure managementWe routinely adopt a more proactive approach for monitoring blood pressure than the current guidelines, which advocate that low-risk patients whose blood pressure is considered normal by current criteria should have blood pressure measurements either every 5 years (age < 60 years) or every 1–2 years (age > 60 years).25,67 Current clinical practice would also be at variance with the guideline recommendations that drug therapy and lifestyle modification for hypertension should only be introduced in patients under 60 years if their systolic blood pressure is greater than 180 mmHg or diastolic blood pressure greater than 100 mmHg,25,67 or in those over 60 years whose systolic blood pressure is greater than 160 mmHg.27,29 Despite our personal views, we have included the current published recommendations.25 In the ANBP-2 Study,75 6083 elderly subjects aged 65–84 years with hypertension were treated with either ACE inhibitors or diuretics and compared. Although a similar number of strokes occurred in each group, ACE inhibitor therapy was associated with better cardiovascular outcomes, particularly in men.75 2. Lipid managementPatients with normal lipid levels should be assessed every 5 years until middle age and then every 1–2 years. In the absence of other risk factors triggering a lower threshold for treatment, lipid-lowering therapy with a statin should be commenced for patients with predominant hypercholesterolaemia (total cholesterol > 8.0 mmol/L or total cholesterol : HDL cholesterol ratio > 8.0),76 or with a fibrate for patients with low HDL cholesterol and high triglyceride levels.74 (At present, the reimbursement criteria of the Pharmaceutical Benefits Schedule are at variance with National Heart Foundation guidelines). The approach for patients with macro- or microalbuminuria associated with diabetes or hypertensionThe finding of microalbuminuria (urinary albumin excretion 20–200 μg/min) or macroalbuminuria (urinary albumin excretion > 200 μg/min) should prompt a search for the presence of diabetes, hypertension or renal disease. If diabetes is present, the use of ramipril is appropriate for cardiovascular risk reduction.1,61 Furthermore, there is good evidence to support the use of ACE inhibitors for renal risk reduction in normotensive patients with diabetes (type 1 or type 2) and microalbuminuria1,77 and hypertensive patients with type 2 diabetes,51 and the use of AIIRAs (irbesartan and losartan) in patients with type 2 diabetes.52-54 Other interventions1. Antiplatelet therapies (aspirin, dipyridamole or clopidogrel)Aspirin (75–150 mg/day) has been shown to have significant benefit for patients at high risk of cardiovascular disease, particularly in secondary prevention,78,79 although blood pressure should be tightly controlled to minimise the risk of haemorrhagic stroke.80-82 It must be recognised, however, that the benefits of aspirin are not clear in older patients (> 70 years) with no previous cardiovascular events who, primarily due to age, remain at high risk of cardiovascular disease. This is highlighted by the recent FDA decision not to list primary prevention of cerebrovascular disease as an indication for aspirin in the elderly and to strongly support proposals for the conduct of such trials. The risks associated with gastrointestinal and cerebral bleeding in older patients may offset any cardiovascular protection benefits. The American Diabetes Association recommends the use of aspirin for patients with diabetes over the age of 30 years,83 but there is no evidence of benefit in primary prevention in low-risk subjects.80 Alternative or additional antithrombotic therapies such as clopidogrel or dipyridamole (stroke or TIA only) may be required if aspirin is not tolerated or the patient experiences recurrent cardiovascular events while taking aspirin.84-87 It is beyond the scope of this review of cardiovascular prevention measures to focus on the management of acute coronary syndromes. However, it is important to highlight the results of a recent trial using combination antiplatelet therapy in patients with acute coronary syndromes: initiating therapy during the acute management phase in hospital was shown to have benefits up to 1 year after the initial presentation. The CURE study88 showed that patients with acute coronary syndromes who were given a loading dose of 300 mg of clopidogrel followed by ongoing treatment with 75 mg daily for 9 months, in addition to their usual therapy (including aspirin), had a 20% reduction in the combined endpoint of cardiovascular death, AMI, and stroke (ARR, 2.1%).89 Thus, many patients who leave hospital after an admission with unstable angina or non-ST elevation myocardial infarction will be receiving clopidogrel in addition to aspirin as combined antiplatelet therapy for atherothrombosis, which should be continued as long-term therapy. The CREDO study showed a 27% relative risk reduction (ARR, 3.0%) in the combined endpoint of death, AMI and stroke at 1 year with the use of clopidogrel added to conventional therapy (including aspirin) after placement of a coronary stent.89 Once again, early treatment translates into long-term preventive therapy, and thus a case can be made for the use of combination antiplatelet therapy (aspirin and clopidogrel) for preventing ischaemic events in appropriate patients. Definitive long-term trials of this combination to prevent events in patients with cardiovascular disease (but who have not presented with an acute coronary syndrome), or to avoid the need for coronary artery stenting, are currently under way. 2. AnticoagulationLong-term anticoagulation to reduce thromboembolism may be required for patients with paroxysmal or chronic atrial fibrillation, proteinuria greater than 3 g/day, and those with a history of extensive anterior infarction or severe CCF.90,91 ConclusionPrevention of cardiovascular disease: an evidence-based clinical aid 2004 is based on a review of current evidence and practice, incorporating data from RCTs, as well as recommendations from local and international guidelines. This clinical aid consolidates current evidence and recommendations into a single source and provides a reference tool for the optimal treatment of “at-risk” patients to prevent vascular events and improve clinical outcomes. 1 Categories of patients based on future risk of a cardiovascular event High-risk patients are those with: Clinically evident coronary heart disease (prior acute myocardial infarction, angina, or history of a revascularisation procedure) Clinically evident vascular disease (cerebrovascular or peripheral vascular disease) Diabetes Renal disease A risk of a future vascular event ≥ 2%–3% per year, based on an aggregate of unfavourable risk characteristics* Low-risk patients are those with: A risk of a future vascular event < 2%–3% per year* * Determined using a calculation of the 5-year risk of any cardiovascular event and death, from a validated absolute-risk calculator such as the Framingham Heart Study Prediction Score Sheets or, in the case of type 2 diabetes, the UK Prospective Diabetes Study risk calculator (www.dtu.ox.ac.uk/index.html?maindoc=/riskengine/). 2 Competing interests Name Consultant fees Honoraria/fees for service Advisory/Steering Committee fees Investigator-initiated research grants Travel assistance Dr John V Amarena BMS, Boehringer Ingelheim, Novartis, Sanofi Abbott, Aventis, BMS, MSD, Servier, Solvay Aventis, BMS, Sanofi Boehringer Ingelheim, Pfizer, Sanofi Dr John F Beltame Alphapharm, Aventis, Bayer, BMS, MSD, Pfizer, Roche, Sanofi, Servier Aventis, BMS, Pfizer, Solvay Prof Stephen Colagiuri MSD, Novo Nordisk, Roche, Servier Member of MSD steering committee — unpaid Dr Greg W Conner Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Dr Greg R Fulcher Aventis, BMS, MSD, Novo Nordisk, Sanofi, Eli Lilly Aventis, GSK, MSD, Novo Nordisk, Sanofi, Aventis, MSD Prof Richard E Gilbert Aventis, AZ, BMS, MSD BMS AZ, Servier Prof Graeme Hankey BMS, Sanofi Aventis, BMS, MSD, Pfizer, Sanofi BMS, Pfizer, Sanofi Assoc Prof Anthony C Keech Laboratoires Fournier, MSD (contribution to department) BMS, Laboratoires Fournier, MSD Invited lectures only Prof Brian R McAvoy Aventis Prof Carol A Pollock Aventis, Sanofi, Servier BMS Prof Malcolm J West Aventis, BMS, MSD Aventis, BMS, MSD BMS, MSD BMS Aventis, BMS, MSD Abbott = Abbott Australasia; Aventis = Aventis Pharma; AZ = AstraZeneca; BMS = Bristol-Myers Squibb; GSK = GlaxoSmithKline; MSD = Merck Sharpe & Dohme/Amrad; Sanofi = Sanofi-Synthelabo

Practical Implementation Taskforce for the Prevention of Cardiovascular Disease

Cardiovascular disease is the leading cause of morbidity and mortality in Australia. It is therefore important that all medical practitioners are familiar with the well documented risk factors for cardiovascular disease, as well as the outcome benefits of pharmacological and other interventions. The large and ever-increasing body of clinical evidence, the range of patient groups at risk and the plethora of recommended interventions all make it ...

Practical Implementation Taskforce for the Prevention of Cardiovascular Disease

The prevalence of peripheral arterial disease (PAD) in people aged over 55 years is 10%–25% and increases with age; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Patients with PAD alone have the same relative risk of death from cardiovascular causes as those with coronary or cerebrovascular disease, and are four times more likely to die within 10 years than patients without the disease. The ankle–brachial pressure index (ABPI) is a simple, non-invasive bedside tool for diagnosing PAD — an ABPI less than 0.9 is considered diagnostic of PAD. About half of patients with PAD (defined by an abnormal ABPI) have symptomatic coronary or cerebral vascular disease. The ABPI is an independent predictor of coronary and cerebrovascular morbidity and mortality. Patients with PAD require medical management to prevent future coronary and cerebral vascular events. There are currently insufficient data to recommend routine population screening for asymptomatic PAD using the ABPI.

Paul E Norman DS, FRACS · John W Eikelboom MB BS, FRACP · Graeme J Hankey MD, FRACP

Clive D Hadfield Gastroenterologist, 30 Megan Street, Cairns, QLD 4870. chadfieldATaustarnet.com.au To the Editor: In their recent study, Scott and colleagues demonstrated benefit from a program to standardise clinical management of cardiac conditions in Queensland hospitals.1 They found differences in the effect on “low-intensity intervention” hospitals compared with “high-intensity intervention” hospitals. The former were, by and large, district-type hospitals and the latter tertiary hospitals. The study found that about 50% more patients in the larger hospitals had assessments of left ventricular function. Three times as many patients in the larger hospitals accessed rehabilitation. Nearly three times as many patients in the smaller hospitals were readmitted with a diagnosis of acute coronary syndrome within 30 days, perhaps a surrogate for angiography rates, which were not reported differentially. It may be that the most urgent intervention required is “high-intensity” funding of district hospitals, so that they can achieve rates of echocardiography, rehabilitation and coronary angiography approaching those of tertiary hospitals. This intervention would need no further justification than that the population served by the district hospitals has paid its share for these treatments. Let us hope that the remaining comparative outcome data are published.

Clive D Hadfield

Ian A Scott,* Irene C Darwin,† Kathy H Harvey,‡ Andy B Duke,§ Nicholas D Buckmaster,¶ John Atherton,** Hazel E Harden,†† Michael Ward,‡‡ for the CHI Cardiac Collaborative * Director of Internal Medicine, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102; † Program Manager, ‡ Project Manager, § Senior Analyst, Collaborative for Healthcare Improvement, Queensland Health; ¶ Director of Medicine, Caboolture Hospital; ** Director of Cardiology, Royal Brisbane Hospital; †† Program Manager, Integrating Strategy and Performance, Queensland Health; ‡‡ Program Director, Queensland Health Skills Development Centre, Royal Brisbane Hospital. ian_scottAThealth.qld.gov.au In reply: We agree with Hadfield that optimising cardiac care may require extra resources targeted at increasing access of patients in regional Queensland to specific interventions, such as coronary angiography, cardiac rehabilitation and echocardiography, in addition to the quality-improvement strategies used within our collaborative. We contend that both approaches are necessary, and that the magnitude of improvement achieved by either will depend on the intensity with which they are applied. Indeed, the “high-intensity” quality-improvement hospitals in our study were defined on the basis of more funding being made available to undertake quality-improvement activities at those sites. We concede that some of the differences in quality indicators between “high-intensity” and “low-intensity” quality-improvement hospitals may be attributable to inequities in capital expenditure on service delivery that we did not measure. However, some of the differences may have also arisen from variation in systems for identifying and referring those patients who have most to gain from receiving the care targeted by our collaborative.

Ian A Scott · Irene C Darwin · Kathy H Harvey · Andy B Duke · Nicholas D Buckmaster · John Atherton · Hazel E Harden · Michael Ward

Objective: To determine the incidence of congenital heart defects (CHD) in Aboriginal and non-Aboriginal infants in Central Australia and to compare this with the incidence elsewhere in Australia.Design and setting: Data on cases were obtained from patient records of the Alice Springs Hospital, Central Australia, the sole referral centre for paediatric and initial cardiac diagnostic services for the region.Participants: Patients with CHD proven by echocardiography reported between 1 January 1993 and 30 June 2000.Main outcome measures: Incidence of CHD using all live births in Central Australia as the denominator.Results: 108 patients with CHD were detected among 6156 live births (incidence, 17.5 per 1000; 95% CI, 14.9–21.7 per 1000); 57 of 2991 were Aboriginal (19.0 per 1000; 95% CI, 14.4–24.6 per 1000) and 51 of 3165 were non-Aboriginal (16.1 per 1000; 95% CI, 12.0–21.1 per 1000). The difference between the two groups was not statistically significant (relative risk, 1.18; 95% CI, 0.81–1.72). CHD incidence in Central Australia was significantly higher than that reported for other parts of Australia (4.3 per 1000 live births in New South Wales and the Australian Capital Territory, 1981–1984; 7.65 and 12 per 1000 total births in Western Australia, 1980–1989, and South Australia, 1993–2000, respectively).Conclusions: The high rates of CHD in Central Australia may partly reflect the high utilisation of echocardiography for assessing minor lesions. However, the incidence of both major and minor types of CHD was significantly higher than previously reported from other regions of Australia. The role of socioenvironmental factors in this high incidence should be explored.

Srinivas Bolisetty FRACP · Ameet Daftary MD · Dan Ewald FAFPHM · Brodie Knight FRACP · Gavin Wheaton FRACP

To the Editor: We report a case in which routine use of transesophageal echocardiography (TOE) during cardiac surgery almost certainly prevented a patient’s death. This is important, as the Australian Government Department of Health and Ageing has recently decided that TOE during routine coronary artery cardiac surgery should not attract a Medicare benefit as there is no Level 1 or 2 evidence of its efficacy.1 A 65-year-old man with critical aortic valve stenosis and severe left ventricular dysfunction, requiring an intra-aortic balloon pump, was scheduled for mechanical aortic valve replacement. He had been in atrial fibrillation intermittently, but was in sinus rhythm for the 24 hours before surgery and his heparin had been at therapeutic levels since balloon pump insertion 36 hours before. Like most cardiac anaesthetists in Australia, we routinely perform TOE during cardiac surgery. Following induction of anaesthesia, TOE examination confirmed severe aortic stenosis and poor left ventricular function, but the left atrial appendage was not specifically examined and a routine preoperative transthoracic echocardiogram had shown no other abnormalities. With the patient on cardiopulmonary bypass, the diseased valve was replaced. Before weaning the patient from bypass, a TOE examination showed a large free 2.5 × 2 cm mass in the left atrium resembling thrombus (Box [a]). The surgeon then reported having invaginated the left atrial appendage while de-airing. While the patient was still on bypass, a large organised clot was removed from the left atrium (Box [b]) — this had presumably developed sometime during the preoperative period. Subsequent separation of the patient from bypass was uneventful, and he made a good recovery. The thrombus would not have been suspected or found without the TOE, and almost certainly would have migrated from the left atrium into the left ventricle following the return of cardiac output, and would likely have precipitated a sudden cardiac arrest with acute valvular obstruction. Despite the lack of Level 1 or 2 evidence, most cardiac anaesthetists and surgeons consider TOE an invaluable diagnostic and monitoring tool, particularly for assessment of left ventricular function and filling. While TOE has not rendered the Swan–Ganz catheter obsolete, it provides similar information with fewer complications. This case is a dramatic illustration of the usefulness of TOE during cardiac surgery, but less dramatic examples occur much more frequently. The Department of Health and Ageing decision not to support TOE (except in valve repair or replacement) seems shortsighted. While we support the Department’s evidence-based approach, it would be interesting to know how many procedures listed in the Medicare Benefits Schedule would withstand the same scrutiny. Randomised trials are difficult to perform, but, at the very least, TOE has excellent peer consensus, strong anecdotal evidence and large series reviews2,3 supporting its routine use in cardiac surgery. Atrial thrombus in left atrium detected by transoesophageal echocardiography during cardiac surgery (a) Echocardiogram showing the mass. (b) The clot that was removed.

Chris J Cokis · John Faris

Cardiovascular malformations occur in up to 47% of women with Turner syndrome. Aortic dissection, a devastating and often fatal condition, occurs more frequently in women with Turner syndrome than in the general population (0.8% v 0.00001%), particularly in women with 45XO monosomy. There have been many reported cases of Stanford type A aortic dissection (involving the ascending aorta or aortic arch, with variable distal extension) in women with Turner syndrome, but type B dissections (involving only the aorta distal to the arch) are relatively uncommon. We recently successfully treated a 38-year-old woman with Turner syndrome (45XO) who had a Stanford type B thoraco-abdominal aortic dissection. A computed tomography scan (Box) demonstrated contrast within the larger true lumen of the aorta and the smaller false lumen of the dissection, separated by intima. Clinicians treating a patient with Turner syndrome should be aware of their patient’s genotype and investigate for the presence of cardiovascular malformations to help stratify the risk. It is important to remain alert to the possibility of aortic dissection in patients with Turner syndrome who complain of chest pain, abdominal pain or dyspnoea, as early detection may save a life. Ao = aorta (true lumen). D = diaphragm. Ht = heart. IVC = inferior vena cava. Lg = lung. Lr = liver. Arrow indicates false lumen of aortic dissection.

Colin I Clement MB BS, PhD · John Brereton FRACS · Phillip Clifton-Bligh FRACP