Cardiovascular diseases

Robert Cutforth, a pioneer of cardiac services in Tasmania and an important contributor to the field of cardiology in Australia as a whole, died on 25 March 2008. Born in England on 19 August 1921, Robert graduated from St Thomas’ Hospital Medical School, London, in 1944 and became a House Physician at St Thomas’ before volunteering for the army and serving in India in 1945. In 1948, he resumed postgraduate training in cardiology at King’s College Hospital, London, where he became a medical tutor in 1954. Working with Dr Sam Oram, he published a highly quoted article on the electrocardiogram in pulmonary embolism.1 In 1960, Robert emigrated to Australia with his wife Grace to take a position as the Physician in North West Tasmania. Two years later, he was appointed Medical Director of the National Heart Foundation and Cardiologist at the Royal Hobart Hospital (RHH). For 30 years, he played a major role in crafting cardiac services in Tasmania. He was a pioneer in many ways — the first to perform cardiac catheterisation and angiography in Tasmania, and an innovator in cardiac rehabilitation. In the late 1960s and early 1970s, his unit at the RHH was highly sought after by aspiring physicians, and he was a tremendous mentor to young physicians going into medical research. In the mid 1970s, he established echocardiography services in Tasmania and worked at the RHH until 1979, when he opened a private practice and continued as a Visiting Medical Officer at the Hospital until he had a major heart attack in 1989. His experience as a cardiac patient led him to write a book for patients, Heart attack: what’s it really like?, which helped many patients recover from their own cardiac events. Robert was a superb clinician and a master of the stethoscope, a stickler for process and a great teacher, influencing the lives of many medical graduates from the University of Tasmania. He was a true Renaissance man, with wide interests in literature, politics, music and boat-building. Conversations on a broad range of topics often commenced around the daily ritual of morning tea in his office at the National Heart Foundation and continued during the hours spent researching or catheterising clinical patients. He had a great sense of humour and terrific communication skills with his patients, who benefited greatly from his expertise. One of Robert’s favourite sayings when you had got something correct was “Well done, that man!”. In terms of cardiology in Tasmania, we can only say “Well done, Robert Cutforth!”

Peter M Brooks · Michael G Loughhead

Percutaneous coronary intervention (PCI) is increasingly used in the management of acute coronary syndromes and refractory angina, and technical advances such as drug-eluting stents (DES) and potent antithrombotic therapies (such as clopidogrel and glycoprotein IIb/IIIa inhibitors) have been heralded as improving long-term outcomes. Offsetting these advances has been: considerable concern about the safety of DES in regard to late stent thrombosis and antithrombotic drug-induced bleeding; the rising use of PCI and DES in clinical situations where evidence of efficacy is lacking; preferential use of PCI in low-risk populations; and limited cost-effectiveness data comparing PCI with other treatments. There are few contemporary data in Australia on the efficacy, safety and costs of PCI — as used in everyday clinical practice — that matches clinical outcomes with baseline patient characteristics, indications for intervention, coronary anatomy, procedural technique, co-interventions and site of care. A national registry that prospectively collects standardised data on processes and outcomes of PCI is warranted. This would ensure safe and appropriate evidence-based use of limited resources in an era of expanding use of PCI in clinical circumstances not tested in randomised trials.

Ian A Scott FRACP, MHA, MEd

Stent thrombosis is an infrequent but severe complication after coronary stent implantation. Dual antiplatelet therapy has markedly reduced the occurrence of this potentially catastrophic event. The optimal duration of clopidogrel therapy in patients with drug-eluting stents is unknown. We describe a case of stent thrombosis 9 days after discontinuation of clopidogrel therapy, more than 3 years after placement of drug-eluting stents. (MJA 2008; 189: 229-230) Clinical record A 60-year-old man presented to his local community hospital with chest pain. He had had a percutaneous coronary intervention more than 3 years previously, when drug-eluting TAXUS stents (Boston Scientific Corporation, Natick, Mass, USA) were implanted in his left anterior descending coronary artery (LAD) and right coronary artery (RCA). Overlapping stents were placed in the LAD, measuring 2.5 × 16 mm and 2.5 × 8 mm, inflated to 1620.8 kPa. He had been taking aspirin and clopidogrel as dual antiplatelet therapy since that time. His past medical history included well controlled hypertension. At the time of presentation, he was haemodynamically stable, with normal resting electrocardiograms and normal troponin levels. As intermittent chest pain persisted despite medical management, he was transferred to an interventional centre for further investigations. Coronary angiography showed mild irregularities of his LAD with widely patent stents in both the LAD (Figure, A) and RCA, with normal left ventricular function. There was no evidence of in-stent restenosis or disease adjacent to the stents. The next day, the patient developed abdominal pain associated with liver function test abnormalities indicative of cholestasis. Ultrasound of his abdomen showed multiple gall stones. It was thought likely that his chest pain was the result of his subdiaphragmatic disease. His clopidogrel therapy was stopped in anticipation of surgery, and he underwent a successful laparoscopic cholecystectomy. Five days later, he was discharged and clopidogrel therapy was not reinitiated. The patient re-presented to his local hospital 4 days after discharge, with central chest pain. His electrocardiogram showed ST-segment elevation in the anterior leads, and reciprocal ST-segment depression in the inferior leads. In view of his recent surgery, he was not deemed a candidate for thrombolytic therapy, and was urgently transferred to our hospital. An angiogram showed thrombus within the stent in his LAD (1190 days after it was implanted), with slow antegrade filling of the distal vessel (thrombolysis in myocardial infarction [TIMI] grade 1 flow; Figure, B). His right coronary and circumflex arteries were normal, and a left ventriculogram showed severe hypokinesis of his apical wall. The clot was partially removed using a 6-French Export Aspiration Catheter (Medtronic Inc, Minneapolis, Minn, USA), and the artery was further dilated within the stent. No further stents were implanted. A small residual filling defect was noted after balloon angioplasty (Figure, C). Intravenous therapy with the glycoprotein IIb/IIIa inhibitor abciximab was initiated, and a loading dose of clopidogrel given. The period after percutaneous transluminal coronary angioplasty was uneventful, and the patient was subsequently discharged in a stable condition. A: Arrow indicates patent stents in the left anterior descending coronary artery. B: Arrow indicates thrombus within the stent in the left anterior descending coronary artery. C: Arrow points to a small residual filling defect after balloon angioplasty. DiscussionDrug-eluting stents (DES) have been shown to be more effective than bare-metal stents (BMS) in reducing angiographic restenosis, by limiting intimal hyperplasia. This reduces the need for subsequent revascularisation procedures.1-3 However, there is growing concern that delayed endothelisation and incomplete neointimal healing might lead to adverse cardiac outcomes and death as a result of late or very late stent thrombosis.4,5 Mortality rates have ranged from 16% in a recent published registry from Spain documenting definite angiographic thrombus6 to as high as 45% in another series including both definite and probable thrombosis.7 Stent thrombosis is an uncommon but life-threatening complication of stent implantation.7,8 Stent thrombosis may be classified according to the time since implantation:9 acute stent thrombosis occurs within 24 hours of the procedure; subacute stent thrombosis between 1 and 30 days after implantation; late stent thrombosis between 1 month and 1 year after implantation; and very late stent thrombosis more than 1 year after the procedure. The cumulative incidence of stent thrombosis with DES at 9–12 months has ranged from 0.5% to 1.5%, which is comparable to stent thrombosis with BMS,10,11 with an incidence as high as 0.6% per year thereafter.12 Recent clinical trials and registries have raised concern over increased rates of very late stent thrombosis with DES.10,13,14 The cessation of dual antiplatelet therapy has been implicated as a pathophysiological factor in late and very late stent thrombosis.7,11,15 Incomplete endothelisation of the metal struts because of the antiproliferative properties of the drug has also been implicated.7,12,15 Mechanical factors involved in stent thrombosis have included malapposition of the stent to the vessel wall when originally implanted, and late malapposition because of retraction of the vessel wall during vessel remodelling.11,12 Whether this is related to the drug, polymer, or stent platform itself is unknown.12 The optimal duration of dual antiplatelet therapy after DES placement is still unknown. Current guidelines recommend clopidogrel therapy for at least a month and ideally up to a year with BMS, and for at least a year for patients treated with DES after hospitalisation for an acute coronary syndrome.16 However, reports of very late cardiac events among patients with DES, particularly in relation to stent thrombosis and cessation of clopidogrel therapy, have cast doubt on these recommendations.10,17,18 A recent observational study comparing DES with BMS suggested that clinical events related to late stent thrombosis in patients with DES after the discontinuation of clopidogrel therapy might limit the benefit of DES.10 Though there have been similar case reports,17,18 ours is a unique example of an angiographically proven very late stent thrombosis, 3 years after placement of DES. During angiography 9 days prior to the event, no abnormality was noted within the previously implanted DES, nor at the stent edges before the cessation of clopidogrel therapy. Nine days after stopping therapy with this drug, filling defects were seen (Figure, B). This case highlights the concerns about the duration of clopidogrel therapy following implantation of DES. It also raises the question of whether life-long clopidogrel therapy may be warranted in some patients.

Rohit Barthwal MB BS, FRACP · Brian A Herman MD, PhD, FACC

Objective: To determine the incidence of venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), in a well defined urban community broadly representative of the Australian population in terms of age, sex and ethnic distribution.Design, setting and participants: A prospective, community-based study conducted over a 13-month period from 1 October 2003 to 31 October 2004. People in a population of 151 923 permanent residents of north-eastern metropolitan Perth, Western Australia, who developed VTE during the study period were identified prospectively and retrospectively through multiple overlapping sources.Main outcome measure: Number of cases of symptomatic, objectively verified DVT and PE.Results: 137 patients had 140 VTE events (87 DVT and 53 PE). The crude annual incidence per 1000 residents was 0.83 (95% CI, 0.69–0.97) for VTE, 0.52 (95% CI, 0.41–0.63) for DVT, and 0.31 (95% CI, 0.22–0.40) for PE. The annual incidence per 1000 residents after age adjustment to the World Health Organization World Standard Population was 0.57 (95% CI, 0.47–0.67) for VTE, 0.35 (95% CI, 0.26–0.44) for DVT, and 0.21 (95% CI, 0.14–0.28) for PE.Conclusion: If the crude annual incidence of VTE in this area of metropolitan Perth is externally valid, then VTE affects about 17 000 Australians annually. Future studies of trends in VTE incidence will be needed to measure the effectiveness of VTE prevention strategies.

Wai Khoon Ho FRACP, FRCPA · Graeme J Hankey MD, FRACP · John W Eikelboom FRACP, FRCPA

To the Editor: We report significant sinus bradycardia in a patient presenting with an acute coronary syndrome shortly after beginning bupropion therapy to assist with smoking cessation. A 53-year-old man was attended by paramedics for typical ischaemic chest pain. He had sinus bradycardia (45 beats/min) and hypotension (blood pressure, 85/60 mmHg), and was found to have a serum troponin I concentration of 1.2 μg/L, but no diagnostic electrocardiographic changes. He was admitted to our hospital with an acute coronary syndrome. He reported his medications at the time of admission as including metoprolol 50 mg twice daily (for hypertension) and paroxetine 20 mg daily (for depression). The patient was given multiple doses of intravenous atropine (total, 1.2 mg) and adrenalin (total, 2 mg). After an adrenalin infusion was begun, he developed ventricular tachycardia (170 beats/min), but his cardiac rhythm spontaneously returned to sinus bradycardia. Two days after admission, two coronary stents were successfully deployed in a critically stenosed right coronary artery. Bradycardia (45–50 beats/min) persisted. The following day, it was discovered that 3 weeks previously, the patient’s general practitioner had prescribed bupropion 150 mg twice daily to assist with smoking cessation, which he had been taking up until the day of admission. Bradycardia continued until hospital discharge. One month after discharge, he was in sinus rhythm (60 beats/min) and was clinically well. Bupropion is a selective noradrenalin, dopamine and serotonin reuptake inhibitor. The mechanism by which it enhances the ability of patients to abstain from smoking is unknown.1 Bupropion inhibits the activity of the cytochrome P450 2D6 isoenzyme, which metabolises metoprolol.2 Concurrent use of bupropion and metoprolol can increase serum metoprolol levels, and clinically significant bradycardia has been reported.3 Further, paroxetine, a selective serotonin reuptake inhibitor (SSRI), is a potent cytochrome P450 2D6 inhibitor, which would have further increased serum metoprolol levels. Bradycardia associated with metoprolol and paroxetine dual therapy has been described.5 Additionally, there is the potential for serotonin syndrome to develop in a patient administered multiple SSRIs. In our patient, the administration of bupropion and paroxetine could have potentially led to serotonin syndrome.6 Our patient’s pharmacological profile was complex, with potential adverse pharmacodynamic effects. The most likely precipitant of the patient’s bradycardia was his acute coronary syndrome, although bupropion may have contributed. The case highlights the potential for significant drug interactions when new drug therapies are initiated. Bupropion and metoprolol (and other drugs metabolised by the cytochrome P450 2D6 isoenzyme pathway) should be co-administered with caution. The importance of common pathways of drug metabolism should be recognised to avoid potential adverse events, particularly when multiple medications are used.

Jacqueline Landau · Andrew E Ajani

Aim: To determine the feasibility of performing a large clinical trial of the use of aspirin for the primary prevention of cardiovascular disease in older participants — the ASPirin in Reducing Events in the Elderly (ASPREE) trial.Design and participants: A randomised double-blind placebo-controlled pilot trial of 100 mg of enteric-coated aspirin tablets daily, in men and women aged 70 years and over who did not have overt cardiovascular disease, and who were followed for 12 months. Participants were identified from the computer databases of general practitioners who were co-investigators in a previous trial.Setting: The Melbourne metropolitan area between March 2003 and June 2005.Main outcome measures: The level of response to participation by GPs; the level of response from potential trial participants; the screening-to-randomisation rate to ensure the recruitment target could be achieved; and the retention of participants in the trial after 12 months.Results: Forty-two GPs (23% of 180 mailed) expressed interest in participating in the pilot trial. Nineteen became co-investigators, of whom six were not required to meet recruitment targets. Letters were sent to 2614 patients, of whom 243 were screened and 209 (86%) were randomly allocated to receive aspirin or placebo. At 12 months,192 (92%) returned for follow-up, and 153 of these (80%) were still taking trial medication. There was a significant reduction in mean haemoglobin level in those taking aspirin.Conclusions: The recruitment strategy for ASPREE, based on methods developed for the conduct of a previous large-scale trial conducted in general practice, was successfully redeployed in this pilot study, with improved efficiency resulting from computerised database searching, telephone pre-screening, a simpler run-in phase and participant familiarity with the trial drug. We conclude that conducting ASPREE in Australian general practice with 18 000 participants is feasible.Trial registration: International Standard Randomised Controlled Trial Number Register ISRCTN83772183.

Mark R Nelson FRACGP, PhD, FAFPHM · Christopher M Reid BA, MSc, PhD · David Ames MD, FRCPsych, FRANZCP · Lawrence J Beilin MD, FRACP, FRCP · Geoffrey A Donnan MD, FRACP · Peter Gibbs MB BS, FRACP · Colin I Johnston MB BS, FRACP · Henry Krum FRACP, PhD · Elsdon Storey DPhil, FRACP · Andrew Tonkin MB BS, FRACP · Rory Wolfe BSc, PhD · Robyn Woods BSc(Hons), PhD · John J McNeil PhD, FRACP

To the Editor: We believe that Tang and Nordin1 misunderstood the findings of our recent study of calcium supplementation.2 We disagree with their claim that the increase in the number of women with self- or family-reported myocardial infarction, stroke or sudden death became non-significant after adjustment for covariables. They correctly noted that the increased number of women experiencing the composite endpoint of cardiovascular events (after adjudication of events and inclusion of unreported events from hospital records) was not statistically significant. However, the increased event rate for this composite endpoint with calcium was statistically significant (rate ratio, 1.43; 95% CI, 1.01–2.04; P = 0.043). Thus, in our study, the number of women needed to treat with calcium for 5 years to cause one cardiovascular event was 29, and the corresponding number to prevent one fracture was 50.2 Tang and Nordin then meta-analysed data from five studies of calcium and vitamin D supplementation to conclude that calcium supplementation does not increase mortality.1 We disagree. For one of the studies, they classified a subgroup of participants who received annual vitamin D but no calcium supplements as having received “calcium supplementation”.3 Further, for the RECORD (Randomised Evaluation of Calcium Or vitamin D) study, they compared the number of deaths between people receiving and not receiving vitamin D (16.5% v 17.4%) rather than between those receiving and not receiving calcium (17.7% v 16.2%).4 The trend for increased deaths with calcium supplementation in RECORD was greater when analysis was restricted to those treated with calcium monotherapy (18.5%) and placebo (16.3%). As our study was of calcium monotherapy, the results of Tang and Nordin’s meta-analysis are of questionable relevance to our findings. In addition, ours was a 5-year study, and the differences in vascular events between the groups only emerged after 2 years.2 Only one study in Tang and Nordin’s meta-analysis had an average follow-up duration of more than 25 months.4 Further, there is evidence from other studies of trends towards vascular events occurring more frequently in people who take calcium monotherapy.2,5,6 In three out of four studies that reported mortality, there were trends towards increased death rates in people receiving calcium.2,4-6 As we concluded,2 these data are not definitive, but flag cardiac health as an area of concern in relation to calcium use. Finally, we did not suggest that calcium supplementation should not be given to older women. However, in view of the evidence that any fracture risk reduction with calcium is small (< 10%),7,8 and the suggestions that calcium supplementation might increase the risk of hip fractures9-11 and vascular events, it seems reasonable and timely to reassess the role of calcium supplementation.

Mark J Bolland · Andrew B Grey · Ian R Reid

In reply: In Table 5 of Bolland and colleagues’ study, the P value after allowing for covariables was 0.08,1 which is not significant. This was without including smoking, which would undoubtedly have reduced the significance further as there were more smokers in the calcium group. Based on Bolland and colleagues’ suggestion, we reanalysed the data by removing the group receiving vitamin D but no calcium supplements in the NoNOF (Nottingham Neck of Femur) study,2 and using data for those treated with calcium monotherapy (18.5%) compared to placebo (16.3%) in the RECORD (Randomised Evaluation of Calcium Or vitamin D) study.3 The reanalysis still failed to show any evidence of an increase in mortality (relative risk, 1.05; 95% CI, 0.88–1.26; P = 0.56).

Benjamin M P Tang · B E Christopher Nordin

To decrease overall mortality, we need to focus on maximising appropriate medical therapies Increasing attention is being given to assessing and improving the quality of care of patients presenting with acute coronary syndromes (ACS).1,2 In this issue of the Journal, Chew and colleagues report on the use and survival impact of early invasive management (coronary angiography and revascularisation) in 3393 patients with ACS enrolled in the Australian prospective ACACIA (Acute Coronary Syndrome Prospective Audit) registry.3 They used propensity-adjusted regression modelling to quantify effects of invasive care independently of other confounders such as patient characteristics, contraindications to invasive care and use of pharmacological treatments. While rates of invasive care appeared near to optimal (90%) in patients with ST-segment-elevation myocardial infarction (STEMI), rates were purported to be less optimal in those with non-STEMI (71%) and unstable angina (45%). The study is unique in showing a 47% reduction in all-cause death at 1 year as a result of early invasive care, a finding used to argue for a greater use of this approach across the spectrum of ACS. The magnitude of this treatment effect is at odds with systematic reviews of randomised trials which report that survival benefits are restricted to patients with STEMI undergoing primary angioplasty, with relative risk reduction of death (compared with thrombolysis) no more than 32%.4 Such patients represented just over a fifth of the patients evaluated in ACACIA. In contrast, contemporary trials of routine invasive care versus medical therapy in patients with non-ST-segment elevation ACS (NSTEACS), who comprised three-quarters of the cohort, show no conclusive mortality benefit, although reinfarction and anginal burden are significantly reduced.5 Separate analyses for patients with STEMI versus those with NSTEACS were not reported, which brings into question the validity of implying that greater use of an invasive strategy among all patients with ACS would translate into proportionately more survival benefit. The authors argue that their cohort included many high-risk patients who tend to be excluded from trials, and among whom they infer a survival benefit was achieved. Several issues warrant consideration. Can observational studies validly show treatment benefits not seen in randomised trials? How replicable are these effects? If such an effect is real, would the number of lives saved from optimising invasive care exceed that achieved from optimising other forms of care, thus serving as a quality improvement priority? If so, what might be the most effective optimisation strategies? Even the best observational design can be biased by prognostically important baseline differences among patients, often because of unobserved or unreported treatment selection biases. Chew et al did their best to minimise such bias by estimating the likelihood (or propensity) of patients to receive invasive care on the basis of patient characteristics ascertained before such treatment was given. The association between invasive care and 12-month mortality was then assessed with regression modelling that adjusted for variables known or thought highly likely to influence mortality, including medical therapies such as statins and angiotensin-converting enzyme (ACE) inhibitors — although antiplatelet agents and β-blockers were notably absent. This association was then further adjusted after inserting the propensity score as a continuous variable. Unfortunately, methodological concerns persist for several reasons. First, the literature is replete with high-profile examples of well performed observational studies (eg, hormone replacement therapy and cardiovascular mortality, β-carotene and cancer prevention) suggesting favourable treatment effects that were later dismissed or reversed in large, pragmatic randomised trials. Second, different observational studies, which have included analytical methods other than propensity scoring, give very different results. An American study showed that early coronary angiography for acute myocardial infarction (AMI) was associated with a 50% reduction in mortality at 7 years using propensity analysis (designed to control for overt bias), but this fell to a 16% decrease when instrumental variable analysis was used (designed to control for hidden bias as well).6 A propensity-adjusted analysis of French patients with STEMI presenting to interventional versus non-interventional hospitals (the former highly correlated with higher rates of invasive care) revealed only a 24% decrease in mortality at 1 year.7 Third, the most appropriate design for observational studies remains unclear, with some arguing propensity scoring is no better than traditional multivariate regression adjustment.8 Fourth, as propensity analysis cannot adjust for unmeasured characteristics, sensitivity analyses are recommended to gauge effects of potential confounders which, for invasive care in ACS, may include patients’ socioeconomic status.9 Finally, trials of invasive care may actually overestimate treatment effects achievable in routine practice given the expertise, logistical support and rapid institution required for the optimal results available in high-volume research centres. With regard to prioritising efforts at improving quality of care, the use of early invasive care in patients with STEMI in the study by Chew et al was in accordance with trials and guidelines. In contrast, within the total cohort, there was considerable underuse of key drugs at discharge and at 12 months, respectively: β-blockers, 68% and 57%; aspirin, 87% and 74%; statins, 82% and 72%; ACE inhibitors or angiotensin receptor antagonists, 67% and 64%. This underuse was most pronounced in patients not receiving invasive care and, by association, not admitted to a metropolitan centre. Of all AMI-related deaths that are prevented by therapeutic interventions, both acutely and as secondary prevention, medical treatments account for 80% of these (35% acutely, 45% secondarily) compared with only 6% for early invasive management.10 If all indicated drugs are prescribed to eligible patients, risk-adjusted mortality at 6 months is reduced by 90% compared with patients who receive none of these drugs.11 Routine use of more costly invasive care is not associated with population survival benefit beyond that seen with optimal medical management.12 Thus, if decreasing overall mortality is the aim, a focus on maximising administration of appropriate medical therapies across all hospitals should take precedence over extending invasive care to all or most patients with ACS, especially as there are low-cost interventions that can increase rates of prescribing at discharge up to 90%.13 This is not to say the delivery of timely invasive intervention, particularly to patients presenting to non-interventional hospitals, is unimportant given its mortality benefit in STEMI4 and morbidity reduction in high-risk NSTEACS.5 There are actionable strategies for improving region-wide access to intervention14 and reducing door-to-balloon times15 for patients with acute STEMI, and these deserve consideration in Australian settings. Risk stratification methods for identifying patients with NSTEACS who are most in need of referral to interventional centres16 require universal implementation. More globally, quality improvement strategies — comprising use of opinion leaders and educational outreach, guideline-based decision support tools, regular audit and feedback, and clinical process redesign — have been validated in the management of patients with ACS,17 and innovative, multidisciplinary programs that integrate multiple strategies need to be maintained. What is critical is the continuance of well designed prospective registries like ACACIA, which provide standardised and representative data that allow us to monitor the quality of care and the effects of whatever actions we may take towards improving it.

Ian A Scott FRACP, MHA, MEd

Long (or short) QT syndrome is life-threatening, not as rare as once thought, and treatable if diagnosed “The fault dear Brutus is not in our stars, but in ourselves”. Through the lens of molecular medicine we are now beginning to see those faults more clearly. We can now increasingly understand why some apparently healthy children and young adults die without warning. The long-QT syndrome is foremost among responsible causes, and is known to be the consequence of mutations in genes encoding ion channel function.1 Originally an esoteric condition of great rarity, its prevalence is now estimated as one in 2000.2 Life depends on the continuous sequence of depolarisation and repolarisation in our heart cells. The QT interval is the time from the onset of depolarisation (the q wave) to the end of repolarisation (completion of the T wave) and is best measured over several R-R intervals in leads II or V5. It is not a value physicians ordinarily pay much attention to when they read an electrocardiogram (ECG; Box). Nor is it always easy to measure. Exactly where the T wave merges with the isoelectric baseline is subject to individual interpretation and hence error.3 It also varies with heart rate, requiring normalisation for comparison, and is longer in women than men. But it is important. The long-QT syndrome is essentially an autosomal dominant condition in which sudden death is commonly linked to situations of increased adrenergic activity, such as exercise and emotion, but also occurs at rest and during sleep.4 Seizures are common and easily lead to misdiagnosis. Although mutations in at least 10 genes have been found, long-QT syndromes 1 (LQT1), 2 (LQT2) and 3 (LQT3) constitute 95% of genotyped cases. LQT1 and LQT2 involve decreased function and hence diminished current flow in the slow and fast repolarising potassium currents, IKs and IKr, respectively, while LQT3 involves an increase in slow sodium current during the plateau phase of the action potential. The net effect is prolongation of the action potential and, most importantly, an increased dispersion of recovery times in different myocardial cells. This increased dispersion allows re-entry to occur with potentially fatal ventricular tachycardia and fibrillation, which manifests clinically as fainting and sudden death. LQT1 is the most common type, and events are typically triggered by exercise, including swimming, and emotion.5 The child found unconscious at the bottom of the swimming pool may well have LQT1.6 Events may occur with exercise or at rest in LQT2 and also, characteristically, with loud noises such as being awakened by a telephone call.7 LQT3 has been linked to death during sleep or inactivity, with a lower likelihood of events, but increased mortality. What are the implications for physicans and general practitioners? Fainting is common, most often vasovagally mediated, and benign. How do we decide otherwise? The key is to be mindful of possible long-QT syndrome when checking the history; fainting or a seizure during exercise, or when upset or angry, and premature death (including drownings or accidents) in family members should ring alarm bells and trigger detailed exploration of the family history, close scrutiny of ECGs and appropriate referral. In such settings, a corrected QT (QTc) interval > 0.45 seconds in males and > 0.47 seconds in females makes the diagnosis virtually certain. With diagnosis comes the dual responsibility of triaging individual patient risk and screening the wider family. The most important factor determining individual risk is the length of the QT interval — long intervals (QTc ≥ 0.5 seconds) equal high risk.8 Knowledge of the genotype is also predictive. β-Blockers are generally first-line treatment, although in genotyped individuals, evidence is lacking for a protective action in LQT3. Modifying risk by avoidance of competitive sport and QT-prolonging drugs (see http://www.qtdrugs.org) is important. Implantable defibrillators are appropriate in high-risk patients, but decisions about prophylactic implantation in intermediate-risk patients must balance the reduction in probability of sudden death against the not inconsiderable morbidity of life-long device therapy in young people. As well as personal history and ECG, family screening should include genetic testing if it is available. When a functionally important mutation is uncovered, testing of family members will disclose up to a third of individuals whose QT intervals are normal, and yet who carry the mutation.9 However, a genotypic diagnosis is possible in only two-thirds of clinically certain cases. Continuing research may diminish this gap. The establishment of registries, such as presently exist in New Zealand (http://www.cidg.org), facilitates surveillance of widely dispersed families and aids ongoing research. While the risks of QT prolongation are now well established, attention has recently been drawn to excessively short QT intervals. In a small number of families identified to date, a QTc interval of < 340 milliseconds has been also associated with a family history of sudden death.10 The first two syndromes described (short-QT syndromes 1 and 2), show a gain of channel function for IKr and IKs, the mirror opposite of the corresponding LQT2 and LQT1 with loss of function in those same channels. Although five short-QT syndromes have been recognised already, it nonetheless seems unlikely that they will rival the long-QT syndrome in prevalence. In conclusion, cardiac repolarisation is a complex interplay of ionic currents precariously maintaining stability. Dramatic progress has been made over the past 50 years in recognising, deciphering and predicting the clinical risk of the long-QT syndrome. Yet this knowledge counts for little if we fail to identify and protect at-risk individuals. Perhaps you will take a closer look at the QT interval in your next patient presenting with “just” another fainting attack. Electrocardiogram showing a markedly prolonged QT interval. The long ST segment is suggestive of long-QT syndrome 3.

Warren M Smith MB BS, FRACP

Objective: To describe the impact of invasive management on 12-month survival among patients with suspected acute coronary syndrome (ACS) in Australia.Design and setting: Prospective nationwide multicentre registry.Patients: Patients presenting to 24 metropolitan and 15 non-metropolitan hospitals with ST-segment-elevation myocardial infarction (STEMI), and high-risk and intermediate-risk non-ST-segment-elevation ACS (NSTEACS) between 1 November 2005 and 31 July 2007.Main outcome measures: Death, myocardial infarction (MI) or recurrent MI, revascularisation and stroke at 12 months.Results: Among 3402 patients originally enrolled, vital status at 12 months was available for 3393 (99.7%). Patients from non-metropolitan areas (810) constituted 23.9% of patients. Early invasive management was more commonly undertaken among patients with STEMI (STEMI, 89.7% v non-STEMI, 70.8% v unstable angina, 44.8% v stable angina, 35.8%; P < 0.001). Factors most associated with receiving invasive management included admission with suspected STEMI or high-risk NSTEACS, being male and the hospital having an onsite cardiac surgical service. Overall mortality by 12 months among patients with STEMI, non-STEMI, unstable angina and stable angina was 8.0%, 10.5%, 3.3%, and 3.7% (P < 0.001), respectively. After adjusting for a propensity model predicting early invasive management and other known confounders, early invasive management was associated with a 12-month mortality hazard ratio of 0.53 (95% CI, 0.34–0.84, P = 0.007).Conclusions: A substantial burden of late morbidity and mortality persists among patients with ACS within contemporary Australian clinical practice. Under-use of invasive management may be associated with an excess in 12-month mortality, suggesting the need for more use of invasive management among these patients.

on behalf of the ACACIA investigators

Objective: To determine the causes of death in Australians with type 1 diabetes mellitus who died aged 40 years or younger.Design and setting: Retrospective review of autopsy reports at the Department of Forensic Medicine, Sydney, New South Wales, 1 January 1994 – 31 December 2006.Main outcome measure: Causes of mortality in people with type 1 diabetes aged ≤ 40 years.Results: Of the 26 682 autopsy reports, 1914 were for individuals with diabetes (type 1, 400; type 2, 1514). Cardiovascular disease accounted for 51% of deaths (169/333) in people with type 1 diabetes aged > 40 years, versus 13% among those aged ≤ 40 years (9/67; P = 0.001). Acute complications of diabetes (27%; 18/67), unnatural deaths (28%; 19/67), and sudden unexpected deaths (22%; 15/67) were the predominant causes of death in young individuals with diabetes. Sudden unexpected death was more common in those with type 1 diabetes compared with a sex-matched control population in the same age range (22% v 5%; χ2 P < 0.001). Of the sudden unexpected deaths, 10 people were found dead in an undisturbed bed with no cause of death found at autopsy (“dead-in-bed” syndrome; mean age [SD], 30.2 [9.4] years; males : females = 4 :1).Conclusions: In deceased young people with type 1 diabetes examined by the Coroner, acute diabetic complications, unnatural causes, and sudden unexpected deaths were the predominant causes of death. The relatively high frequency of sudden unexpected deaths, such as dead-in-bed syndrome, requires further investigation.

Emily Tu BSc · Stephen M Twigg PhD, FRACP · Johan Duflou FRCPA · Christopher Semsarian PhD, FRACP

Objective: To investigate rates and predictors of cardiac rehabilitation (CR) attendance after coronary artery bypass graft surgery (CABGS) at Royal Melbourne Hospital (RMH), Victoria, where current best practice referral and recruitment strategies have been adopted.Design, setting and participants: Prospective cohort study of 184 patients who underwent CABGS at RMH between July 2001 and April 2004. Patients completed questionnaires pre-operatively, and 170 patients (92%) had their CR attendance tracked after referral to CR either at RMH or elsewhere.Main outcome measures: Rates of CR attendance among RMH patients referred to CR either at RMH or elsewhere; sociodemographic, medical, cognitive, psychosocial and geographical predictors of CR non-attendance.Results: The CR attendance rate was 72%. Patients referred to CR at RMH were more than four times more likely to attend than patients referred elsewhere (odds ratio [OR], 4.36; P = 0.024). Travel time significantly predicted CR attendance (OR, 0.86; P = 0.039).Conclusions: CR attendance rates were found to be higher than previously reported for CABGS patients, suggesting that best practice referral and recruitment procedures minimise common barriers to CR attendance.

Rosemary O Higgins GradDipBehavHealthCare, BBSc · Barbara M Murphy PhD · Alan J Goble MD, FRCP, FRACP · Michael R Le Grande BSc(Hons), MPH · Peter C Elliott PhD · Marian U C Worcester PhD

Objective: To identify the health and mental health information needs of people with coronary heart disease (CHD), with and without comorbid depression.Design and setting: A qualitative study conducted in Melbourne in 2006, using thematic analysis of semi-structured interviews on the types of health information that patients with CHD considered useful to assist with the management of their illness. Structured clinical interviews were used to assess current and prior depressive episodes in these patients.Participants: 14 general practice patients (eight with current or prior history of major depression) who had experienced myocardial infarction, coronary artery bypass graft surgery, angioplasty or angina (confirmed via testing).Results: Four themes relating to information on how patients could manage their cardiovascular health and improve their psychosocial wellbeing emerged: psychosocial; physical activity; medical; and information for family. The most prominent information needs included identification and management of risk-related physical symptoms, and psychosocial information, most notably to enhance patients’ social support. Patients considered this information important for alleviating health anxiety and negative affect.Conclusion: This small patient sample endorsed the need for health and mental health information on a range of psychosocial and physical health topics. Participants desired specific types of information to assist with the self-management of their health and to assuage their health concerns.

Ciaran Pier PhD, BA(Hons)(Psych) · Kerrie A Shandley MPsych(Health), GradDip(Psych), BSc · Julie L Fisher PhD, MBusInfoSys, GradDipComputersInEducation · Frada Burstein MSc(ApplMath), PhD · Mark R Nelson PhD, FRACGP · Leon Piterman MMed, MEdSt, FRACGP

Takotsubo cardiomyopathy is an increasingly recognised syndrome characterised by transient apical left ventricular dysfunction in the absence of significant coronary artery disease. We describe a case of Takotsubo cardiomyopathy complicated by Dressler’s syndrome. To our knowledge, these two conditions have not previously been reported in combination. Clinical recordA 75-year-old woman presented with acute onset of discomfort in the chest, left scapula, neck and arm after being informed of the unexpected death of her son, and 2 days after undergoing an uncomplicated laparoscopic cholecystectomy. Her medical history included Graves’ disease and a hysterectomy. She had no modifiable risk factors for coronary artery disease. Examination revealed a heart rate of 90 beats per minute and a blood pressure of 120/80 mmHg, with no evidence of acute pulmonary oedema. At presentation, an electrocardiogram demonstrated 1–2 mm ST elevation in leads V1–V6, I and aVL (Box 1). The patient was immediately transferred to the cardiac catheter laboratory, where angiography revealed angiographically normal coronary arteries but extensive anteroapical and inferoapical ballooning consistent with Takotsubo cardiomyopathy.1-9 Peak creatinine kinase and troponin I levels were 245 μg/L (reference range [RR], < 200 μg/L) and 6.62 μg/L (RR, < 0.1 μg/L), respectively. The patient’s in-hospital course was complicated by heart failure, necessitating treatment with intravenous diuretics. The patient also developed pleuritic-type chest pain, but computed tomographic pulmonary angiography (CTPA) excluded pulmonary embolism. The patient was discharged 3 days after admission on a medication schedule of metoprolol 25 mg twice a day, and perindopril 2.5 mg, frusemide 40 mg and aspirin 150 mg once a day. A follow-up echocardiogram 6 weeks later showed normal left ventricular function and size, with a calculated ejection fraction of 72%. A trivial pericardial effusion measuring less than 0.2 cm was noted. All cardiac medications were ceased at that point. About a week after the follow-up echocardiogram, the patient presented again with severe pleuritic chest pain that was relieved by sitting forward. The pain was associated with low-grade fever, shortness of breath and a dry cough. She did not report any other symptoms suggestive of an upper respiratory tract infection. Examination revealed signs of a pericardial friction rub and bilateral pleural effusions but no evidence of cardiac tamponade. In view of the recent cholecystectomy, the patient underwent repeat CTPA, which excluded a pulmonary embolus but revealed a moderate pericardial effusion measuring up to 2.1 cm laterally and small bilateral pleural effusions (Box 2). An echocardiogram confirmed the pericardial effusion but showed no evidence of cardiac tamponade. Inflammatory markers were markedly elevated, with a C-reactive protein level of 290 mg/L (RR, < 12 mg/L) and an erythrocyte sedimentation rate of 103 mm/h (RR, < 21 mm/h). The patient had low-grade anaemia (haemoglobin level, 96 g/L; RR, 115–165 g/L), but this improved to 116 g/L without treatment. Her white cell count was elevated at 16 × 109/L (RR, 4–11 × 109/L), with predominant neutrophilia, and her platelet count was significantly elevated at 800 × 109/L (RR, 150–400 × 109/L). Renal function, urinalysis, autoimmune markers and a repeat troponin I measurement were normal. These findings were consistent with a diagnosis of Dressler’s syndrome. Treatment with ibuprofen 400 mg three times daily resulted in a rapid reduction in pain and levels of inflammatory markers. Inflammatory marker levels normalised within 3 months. DiscussionTakotsubo cardiomyopathy was first described in Japan in 1991. It is characterised by transient apical left ventricular ballooning in the absence of significant coronary artery disease.1 Our patient’s initial presentation was consistent with a diagnosis of Takotsubo cardiomyopathy. The pathogenesis of this condition is not well understood but is postulated to be caused by coronary artery vasospasm in association with intense emotional or physical stress, leading to apical myocardial stunning.2-4 As a result there is often minimal myocardial necrosis, as reflected by the minor cardiac enzyme rise in this case.5 Left ventricular function usually returns to normal within 1–4 weeks, as seen in our patient.6-8 The role of catecholamines in the pathogenesis of Takotsubo cardiomyopathy has been documented in numerous studies.9-12 Dressler’s syndrome was first described by Dressler in 1956.13 It is characterised by a late-presentation pericarditis, presenting weeks to months after a myocardial infarction. Six weeks after the diagnosis of Takotsubo cardiomyopathy, our patient displayed typical features of Dressler’s syndrome: pleuritic chest pain, pericardial friction rub with associated effusion, fever, leukocytosis, pleural effusions and elevated levels of inflammatory markers.13 The pathogenesis of Dressler’s syndrome is thought to be immune-mediated, as evidenced by late onset of the syndrome. The putative pathogenetic sequence begins with myocardial injury that releases cardiac antigens and stimulates antibody formation. The immune complexes that are generated then deposit onto the pericardium, pleura and lungs, eliciting an inflammatory response.14-16 Earlier studies quoted the incidence of Dressler’s syndrome to be as high as 3.3%–4.8% after myocardial infarction,17-18 but more recent estimates have been significantly lower, possibly as a result of reperfusion strategies that limit the size of the infarct and the release of cardiac antigens that stimulate an immune response.19 Our patient presented with Takotsubo cardiomyopathy and developed Dressler’s syndrome 6 weeks later. To our knowledge, Dressler’s syndrome following Takotsubo cardiomyopathy has not been previously described in the literature. This may be because the extent of biochemical myocardial damage demonstrated is often small in Takotsubo cardiomyopathy, whereas Dressler’s syndrome is often associated with significant myocardial necrosis. For this reason, the diagnosis of Dressler’s syndrome in our patient was unexpected and the mechanism is unclear. 1 Electrocardiogram showing 1–2 mm ST elevation in leads V1–V6, I and aVL ST elevation was noted anterolaterally, with reciprocal changes inferiorly. 2 Pericardial effusion seen on computed tomographic pulmonary angiography The pericardial effusion (white arrow) measured up to 2.1 cm laterally. A small pleural effusion (black arrow) is also visible.

Edmund J Lee MB BS(Hons) · Randall Hendriks MB BS, FRACP, FCSANZ · Alan P Whelan MB BS, MRCP, FRACP

The burden of atherosclerosis has triggered intense interest in the study of “vulnerable” plaques at high risk of rupture. Optical coherence tomography (OCT) has recently contributed to the in-vivo visualisation of plaque, providing unique insights into the atherosclerotic process, previously only attainable through postmortem examination. This technique uses near infrared light and an optical imaging wire attached to a patient interface unit with a pullback speed of up to 3.0 mm/s. In this patient, a 62-year-old man with treatment-resistant dyslipidaemia and stable angina, coronary angiography revealed possible non-flow-limiting plaque in the proximal left anterior descending coronary artery (arrow; Figure, A). OCT images confirmed extensive non-flow-limiting plaque (Figure, B–D), consisting of lipid (L)-rich areas with characteristic low reflectivity and homogenous appearance (Figure, B and C), and a fibrous (F) plaque with a high reflective and homogenous appearance (Figure, B). The images revealed almost circumferential thin cap fibroatheroma (TCFA; Figure, D), a marker of plaque vulnerability, as well as the plaque’s necrotic core (NC; Figure D). This case demonstrates the potential of OCT to visualise plaque and detect TCFA. This is particularly useful in stable patients in whom aggressive management of risk factors might prevent future adverse events.

Peter Barlis · Giuseppe Ferrante · Francesca Del Furia · Carlo Di Mario

Hypertension. A companion to Braunwald’s Heart Disease. Henry R Black and William J Elliott. Philadelphia: Elsevier Saunders, 2007 (xxii + 615 pp). ISBN 978 1 4160 3053 9. At the clinical interface little seems to be new in the area of hypertension. Non-pharmacological strategies have been unchanged for decades and there have been no new drug therapies since the advent of the angiotensin receptor blocker class in the mid to late 1990s. However, much has changed in the past few years with regard to our understanding of the genetics of hypertension, the underlying pathophysiology of the condition and recognition of hypertension as the main risk factor driving cardiovascular morbidity globally. Furthermore, a number of new classes of agents are being developed and indeed (the renin inhibitor class) have been approved in a number of countries outside Australia. For all of these reasons a comprehensive update on new developments in hypertension, anchored by sections on the fundamentals of knowledge regarding this condition, is clearly warranted. Is Black and Elliott’s Hypertension: a companion to Braunwald’s Heart Disease the definitive textbook in this regard? It is certainly a handsome volume with an easy-on-the-eye layout accompanied by appropriate figures, tables and drawings. Its chapters fall along classical lines comprising epidemiology, pathophysiology, diagnosis, risk stratification, treatment, concomitant diseases and management in special populations. Thus, it appears to provide a comprehensive overview of this condition. To test whether this is in fact the case I consulted a similar publication, Hypertension: a companion to Brenner and Rector’s The Kidney by Oparil and Weber (interestingly, put out by the same publishers, Elsevier Saunders). I would have to say that the Black and Elliott text suffers by comparison. One is struck by the much more comprehensive approach by Oparil and Weber in outlining the pathophysiology of the condition. As well, there is much greater attention to diet and nutrition, with six separate chapters on non-pharmacological management of the condition. There are also extremely thorough assessments of individual drug trials contributing to the evidence base of hypertension management. Drilling down into my own area of interest (the interface between hypertension and heart failure), again the Black and Elliott book came across as somewhat superficial with little discussion on left ventricular hypertrophy (an important disease entity in its own right) and essentially a restating of management strategies for heart failure per se, rather than as it specifically pertains to hypertension patients. Despite these reservations, there are particular areas of strength in Black and Elliott’s text. There are extremely important and sorely needed chapters on hypertension in special populations and across Third World geographic areas, which underscores the global epidemic we face (expected to reach almost 50% of the adult population by 2025). Furthermore, chapters on the drug development process in hypertension and a focus on guidelines and their differences across regions also give the text a comprehensive feel. Clearly, with sections and chapters of this type, this textbook will not be for everyone. For the busy general practitioner requiring guidance as to how best to manage the individual hypertension patient, this is not the book. For others requiring an in-depth review of the fundamentals of hypertension, pathophysiology, diagnosis and management, Black and Elliott is a worthy addition to one’s library (or that of one’s institution). Oparil and Weber may, however, be an even worthier addition!

Henry Krum

When I first learned about the Dr Ross Ingram Memorial Essay Competition through the Healthy Vibe section of Deadly Vibe magazine, I realised it was an opportunity to publicly discuss an issue of significance to all Australians, Indigenous and non-Indigenous alike. Specifically, the issue is about cardiovascular health, rehabilitation and, more to the point, the levels of participation and non-compliance with treatment of people affected by cardiovascular disease. Like Ross Ingram, the Koori GP after whom the essay competition is named, I have been directly affected by heart disease. As I read about Dr Ingram and how heart disease cut short a dedicated young Indigenous leader’s life, I decided to do something to sound a warning and be a positive influence on others. I tell my story to raise awareness of cardiovascular disease, which is claiming the lives of our brothers, sisters, uncles, aunties and grandparents. I would also like to discuss what actions we can take to help our people, the Indigenous community and ourselves. First I will give some background information about myself. I am 41 years young, of Aboriginal and Australian South Sea Islander descent. At 39 years of age, I experienced an acute myocardial infarction (commonly referred to as a heart attack). I mistook the severe chest pain for heartburn or indigestion, and did not present to a GP until the following morning. On examination it was clear that I was experiencing acute coronary syndrome. Within less than an hour, I was an inpatient in a hospital coronary care unit receiving all the necessary acute care available. Eventually I was diagnosed with cardiovascular disease (ischaemic heart disease). I was told I had a 99% blockage of the left anterior descending coronary artery and that 10% of my heart was damaged irreparably. Surgery was ruled out, as the affected area was “dead” because I had not recognised the symptoms of a heart attack at the time. Had I sought medical assistance earlier, I might have received thrombolytic medication designed to dissolve the blockage. I did not know any of this information — knowledge is power. I was in total shock and denial when told by the attending GP what was happening inside my body. I thought, “This doesn’t happen to youngish people like me — only to older people in their 60s and 70s!” However, on reflection, all the signs were there: I smoked 30–40 cigarettes per day; I used and abused alcohol habitually and heavily; My diet included anything, any time I wanted, regardless of nutritional value; I had not exercised regularly for over 10 years; and Both my parents had experienced cardiovascular health conditions. On reflection, my behaviour seemed as if I was determined to self-destruct. After adjusting to the new reality that I had experienced a heart attack and survived, I realised it was time to make some deadly serious lifestyle improvements as soon as possible. The changes I made included decisions to attend and complete cardiac rehabilitation, to seriously consider therapeutic lifestyle changes and to comply with all prescribed medications and subsequent follow-up appointments. After I was discharged from hospital, I quit smoking immediately (and have not looked back); completed a hospital-based cardiac rehabilitation program; began to exercise regularly (resulting in gradual loss of 20 kg of excess weight); stopped all use of alcohol; and adopted a low-sugar, low-salt and low-fat diet, including avoidance of red meat and experimentation with low-fat, low-calorie, vegetarian alternatives. From my perspective, I have been given a second chance. I tell people (anyone who will listen) that surviving a cardiac event can present opportunities to make quality-of-life improvements. A heart attack need not be a death sentence. My health and fitness levels have improved dramatically. I have 10–15 kg more to lose, but I know it’s possible now. I have also experienced a spiritual awakening that, in turn, has led me to renew my faith and commit to a purpose-driven life. Despite all this, it took a surprising amount of time to regain my confidence and a healthy level of self-assurance. When this finally happened it was, I think, an outcome of participating in rehabilitation and self-management measures, like taking greater responsibility for my future health. A major factor in my recovery was support from family and friends. It was the existence of these interdependent relationships that was very important in helping me to find my equilibrium again. Cardiac rehabilitation and Indigenous health management in the broader context of cardiovascular health have become important matters for me since my recovery. Even though I have plenty of fight in me, I am always conscious of the need to not overcommit myself. All the while, there is a sense of impending urgency to give back to others in the Indigenous community who also need assistance. I think of others who don’t know or understand what is happening to their bodies. They may not know how to cope with surviving a cardiac event or heart surgery, and may not be aware of what they can do to reduce the risk of future cardiovascular damage. The journey from cardiac patient to cardiovascular health advocateThere were many uncomfortable changes after my heart attack. I was left without a job, as my previous employer decided I was an unacceptable risk as a fly-in-fly-out plant operator on Cape York Peninsula. My personal and social life disintegrated due to psychological aspects such as unanswered questions, post-traumatic stress, self-imposed social isolation, depression and anxiety. Eventually it was family and true friends that made the difference by being there when it really mattered. Prior to operating machinery for mining companies, I had been an Indigenous community development worker, so I decided it was time to do a refresher course at TAFE* to update skills I hadn’t used for over 10 years. With updated community services knowledge and abilities, I approached the Cardiac Rehabilitation Coordinator at Cairns Base Hospital and the Wuchopperen Health Service, offering to serve as a volunteer in some capacity. Their eager response was surprising and welcome. They were keen to try something different to improve Aboriginal and Torres Strait Islander (ATSI) cardiovascular health. We discussed employment in a mentoring/coordinating role in an Aboriginal Medical Service-based outpatient cardiac rehabilitation program. * A Technical and Further Education college. We had several discussions by phone and email about matters that concerned me. I noticed that many of the Indigenous people admitted to the coronary care ward did not go on to attend rehabilitation sessions. I noted the age differences between Indigenous and non-Indigenous people affected with cardiovascular disease, and thought about the reasons why I had not enjoyed the hospital-based cardiac rehabilitation sessions. I was very curious about what was happening to all those Murri and Islander people once they were released from hospital. Indigenous cardiovascular health began to affect me again personally only a few months later, with my older brother (aged 45) experiencing heart problems resulting in several unstable angina events, arrhythmias leading to unconsciousness, and several minor heart attacks. He required triple coronary artery bypass graft surgery and a permanent pacemaker, and has to take medication for the rest of his life. My brother refused to attend rehabilitation and is non-compliant with his medication. He stubbornly believes the heart surgery and the insertion of a permanent pacemaker were a cure-all for his heart problems. He is living on borrowed time as it is, yet he casually spouts that his days are numbered, like everyone else’s, surgery or not. This difficult reality has driven me to become more involved in Indigenous health. Today I am employed with Wuchopperen Health Service, based in Cairns, as a health worker in the chronic disease management program area. I work with the Continuous Improvement Program team as program coordinator for the Healthy Hearts Cardiac Rehabilitation Program. This is a community-based outpatient cardiac rehabilitation (OCR) program operating from an Aboriginal-controlled community health organisation (ACCHO), working in partnership with the Cairns Base Hospital’s Cardiac Rehabilitation Unit to provide a culturally appropriate and relevant program focused on ATSI people. The availability of this support through an Aboriginal health service, as opposed to a hospital, is a major positive point for ATSI people attending the Healthy Hearts program. To date, there have been over 30 people attending regular exercise sessions and education days held at Wuchopperen Health Service since the program began in August 2006. I have been able to assist the cardiac rehabilitation coordinator with a Cardiac Rehabilitation for Indigenous Communities project that is jointly funded by the Australian Government Department of Health and Ageing and Queensland Health. This project is about training staff like me at Wuchopperen and also at the pilot sites of Yarrabah, Coen and Thursday Island. The overall aim of the cardiac rehabilitation project is to enable the delivery of flexible OCR models to these Indigenous communities. I assist the project when and how I can as a cultural adviser, contributing to or participating in cardiac rehabilitation training. Our program provides an Indigenous OCR program role model for similar emerging programs. We have been contacted by over a dozen services seeking advice and information about setting up ATSI OCRs. I have since become the Indigenous representative for the Queensland Cardiac Rehabilitation Association (QCRA), allowing me to raise matters from an Indigenous perspective in a state forum, attend a Queensland Cardiac Rehabilitation Collaborative forum as a guest speaker and contribute Indigenous-related articles to the national newsletter of the Australian Cardiovascular Health and Rehabilitation Association. I enjoy my role and believe that my story also demonstrates the level of interest and support in northern Queensland for workable solutions to very difficult health issues. Recently, I have been seeking to promote the Wuchopperen Health Service Healthy Hearts program through interviews with media groups such as the Brisbane Indigenous Media Association, the local Bumma Bippera Media broadcast service and the national Indigenous newspaper Koori Mail. I think it’s really important to advertise positive things happening in the Indigenous community. In closingIn the past few months, two young men I knew (seemingly fit and healthy) have died from coronary arrest in their mid to late 30s. It is a very sad thing when young Indigenous men leave their wives, children and extended families at such an early age. I am certain that, throughout Australia, many Indigenous families can tell similar stories — but this does not have to continue. It serves as a reminder of why I got involved in this quite serious business, and why people like my two young friends and my non-compliant brother need help. Health crisisEvery article written on Indigenous cardiovascular health problems inevitably calls for an urgent long-term solution. As an inpatient and now as an allied health worker, I can understand both sides of the coin. I deal with people associated with a health system in which the following issues are a daily reality: Tyranny of distance issues; Chronic comorbidities that result in surgery being contraindicated for ATSI people; Non-compliance with medication and follow-up appointments; Mistrust of hospitals by Indigenous people; A high proportion of Indigenous people refusing to undergo cardiac investigations; An unacceptably high rate of people refusing cardiac surgery; Long waiting times for life-saving surgery; Low uptake and follow-through of lifestyle changes and behaviour modification; Unwillingness to attend traditional hospital-based and ACCHO-based cardiac rehabilitation; and Primary, secondary and tertiary prevention measures missing their mark. These are only some of the issues I have become aware of in my work as an Indigenous health worker. I am sure there are far more qualified, knowledgeable people in the health field who can discuss the issues and solutions in more detail than I can. These people need to stand up and speak out too. Regardless, the issues raised represent serious unmet needs that require an urgent solution. Without a concerted effort, I predict the consequences will be dire for the Indigenous community throughout Australia. Governments, health departments, ACCHOs and the Indigenous community must demonstrate they are absolutely serious about improving the future health of Indigenous Australians. All groups mentioned have a role, particularly governments and Indigenous people. What’s needed is strong leadership from both sides and a coordinated effort, including, for example, examining funded regionalised agreements between ACCHOs and government health service providers and non-government organisations as a possible way forward. These kinds of partnerships and other creative solutions ought to be given due consideration before being dismissed. The issue of Indigenous health has always been controversial, certainly in my lifetime, and no doubt will continue to be so until the powers that be, namely federal and state health departments, decide to stop the blame-shifting and buck-passing and work together for the greater interest to create policy-driven outcomes, accordingly matched by funding and providing the right people and the necessary resources. Any review of past and current data relating to Indigenous cardiovascular health makes it clear that it’s time for all of our leaders to show some heart and exercise the political will needed to engage cardiac service/support providers and consumers in a long-term, committed, national response.

Barry N Fewquandie

The medical community lost one of its most passionate, innovative and hardworking members with the recent death of Ralph Reader. He changed the way Australians thought about cardiovascular disease, raising awareness of risk factors and promoting policies to counter the disease. He also championed cardiovascular research, being one of the key drivers of National Health and Medical Research Council (NHMRC) policies and decisions during the 1960s and 1970s. Ralph was born in Brisbane in 1918, but grew up in Sydney, where he attended Fort Street Boys’ High School and the University of Sydney. After graduating in medicine in 1940, he became a Resident Medical Officer at Royal Prince Alfred Hospital (RPAH) before joining the navy and serving as a surgeon until the end of World War II. In 1941, he married Hazel Scanlon, to whom he remained married until her death in 1994. After the War, Ralph conducted research into renal disease at the University of Sydney. In 1948, the grant of a Nuffield Medical Fellowship took him to Oxford, UK, where he completed a PhD. On his return to Australia, he set up a private practice, worked as an Honorary Medical Officer at RPAH and lectured at the University of Sydney. His research led to kidney transplants at RPAH, where he established the first nephrology unit. In 1961, Ralph was appointed inaugural Medical Director of the National Heart Foundation (NHF), and was its Director and Chief Executive until 1980. It was during this period that he played a key role in the establishment of the triple-0 emergency telephone line. Over two decades, Ralph became the face of the NHF, devoting his time and energy to public education and professional practice, as well as developing the Foundation’s research program. He was also very active in the NHMRC. Between 1966 and 1975, he was a member of several of its committees and subcommittees, including the Medical Research Advisory Committee, the Standing Postgraduate Scholarship Committee and the Medical Statistics (Standing) Committee. In 1968, Ralph was the first to report a plateau then a fall in the number of deaths related to heart attacks, heart failure and stroke. Australia was the first country to reverse the upward trend. (At its peak, cardiovascular disease was the cause of two in three Australian deaths.) He also helped to develop policies for reducing cholesterol levels and oversaw the establishment of coronary care units in hospitals across Australia. He discovered the effectiveness of prescribing antihypertensive drugs for patients with mild hypertension and conducted the groundbreaking Australian National Blood Pressure Study. Ralph was made a Companion of the Order of St Michael and St George in 1976 and was awarded an honorary doctorate by the University of Sydney in 2006. Ralph died in Canberra on 13 January 2008. He is survived by his children Brian, Carolyn and Jeremy.

Warwick P Anderson · John S Horvath · Phil Mayne

A 25-year-old woman presented with progressively worsening shortness of breath, which was attributed to cardiac tamponade caused by pericardial effusion. Urgent pericardiocentesis revealed haemorrhagic fluid, which continued to accumulate after the procedure. A repeat echocardiogram after pericardiocentesis showed dilatation of the right ventricle and severe pulmonary hypertension. Subsequent computed tomography revealed a massive pulmonary embolism in the right lung (Figure) and multiple small emboli in the left lung, while cytological examination of pericardial and pleural fluid showed adenocarcinomatous cells from a primary lung cancer. Pericardial effusion and pulmonary embolism usually present in isolation. Their coexistence in this patient — presumably related to the underlying neoplasm — may paradoxically have saved her life, as the raised right ventricular pressure created by the pulmonary emboli delayed the onset of cardiac tamponade.1 Her condition improved initially with chemotherapy and anticoagulation, but she died a year later due to progression of the lung cancer. PE = pulmonary embolism. PCE = pericardial effusion. PLE = pleural effusion.

Namal Wijesinghe · Cherian Sebastian · Hugh McAlister

The benefits are greater efficacy and faster onset of action; the price is increased risk of bleeding . . . The mainstay of antiplatelet therapy for patients with acute coronary syndromes (ACS), including those undergoing early percutaneous coronary intervention (PCI), is the combination of aspirin and clopidogrel.1-3 Aspirin inhibits platelet thromboxane A2 production and platelet activation, and reduces the relative risk of recurrent ischaemic events in patients at high risk of vascular events by about 22% (absolute risk reduction [ARR], about 2%) at the expense of an increase in the odds of major bleeding events by about 60% (absolute risk increase [ARI], about 0.5%).1 Clopidogrel inhibits ADP-induced platelet activation by blocking the platelet P2Y12 receptor. When added to aspirin therapy in patients with ACS, it reduces the risk of recurrent ischaemic events by a further 20% (ARR, about 2.1%) at the expense of an increase in major bleeding events by approximately 38% (ARI, about 1%).2,3 Clopidogrel has several potential limitations, however. First, the onset of action is delayed, with a “therapeutic” level of 50% inhibition of ADP-induced platelet aggregation, as measured by light transmission aggregometry (LTA), not being reached until 4–6 hours after a 300 mg loading dose, and 2 hours after a 600 mg dose. Second, there is a “ceiling” effect — even a 900 mg dose achieves only around 60% inhibition of ADP-induced platelet aggregation. Third, laboratory testing suggests that “therapeutic” platelet inhibition is not achieved in a substantial proportion of patients because of individual variability in platelet inhibition by clopidogrel.4 Finally, there is uncertainty about the clinical benefit with higher loading doses of clopidogrel of 600 mg or 900 mg compared with 300 mg.5,6 Prasugrel is a novel thienopyridine prodrug whose rate, magnitude and consistency of platelet ADP inhibition is greater than for clopidogrel. It achieves more than 50% inhibition of platelet aggregation (measured by LTA) within 1 hour of a 60 mg loading dose.7,8 The safety and effectiveness of prasugrel have been compared with standard-dose clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel — Thrombolysis in Myocardial Infarction (TRITON–TIMI 38).9 A total of 13 608 patients with moderate-to-high-risk ACS scheduled for PCI were randomly assigned to receive prasugrel (60 mg loading and 10 mg daily maintenance dose) or clopidogrel (300 mg loading and 75 mg daily maintenance dose) for 6 to 15 months. Aspirin 75–162 mg daily was recommended for all patients. After a median duration of 14.5 months, the primary efficacy outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke occurred in 12.1% of patients taking clopidogrel and 9.9% of those taking prasugrel (hazard ratio [HR], 0.81; 95% CI, 0.73–0.90). Stent thrombosis was also reduced (2.4% clopidogrel v 1.1% prasugrel; HR, 0.48; 95% CI, 0.36–0.64). However, the key safety endpoint of major bleeding not related to coronary artery bypass graft (CABG) was increased (1.8% clopidogrel v 2.4% prasugrel; HR, 1.32; 95% CI, 1.03–1.68). All major bleeding (including CABG-related) was increased (1.7% v 2.5%; HR, 1.31; 95% CI, 1.16–1.50), as was fatal bleeding (0.1% v 0.4%; HR, 4.19; 95% CI, 1.6–11.1). Overall mortality did not differ significantly between treatment groups. A post-hoc subgroup analysis identified less clinical efficacy and greater bleeding among patients with a history of stroke or transient ischaemic attack, older people (age > 75 years), and those with bodyweight less than 60 kg. It is likely that these results are externally valid. However, by design, the study drug was only given after the coronary anatomy had been defined by angiography. This does not reflect usual clinical practice where clopidogrel is given at the time of presentation with ACS. Because there is a delay in the onset of action of clopidogrel, the design was biased in favour of prasugrel. Also, the prescribed standard 300 mg loading dose of clopidogrel was lower than that now adopted by many clinicians following reports of an improved inhibition of platelet aggregation with higher loading doses of clopidogrel such as 600–900 mg in patients with PCI.6 These caveats aside, the data suggest that treating 1000 patients with ACS at moderate-to-high risk of vascular events with prasugrel (compared with clopidogrel at the standard approved dose) for a median duration of 14.5 months would prevent about 22 major vascular events and cause eight major haemorrhages, including three fatal bleeds. The implications for clinicians, should prasugrel gain regulatory approval, are that it may allow cardiologists to delay their decision to administer a P2Y12 inhibitor until after coronary angiography (thus avoiding the bleeding risk of clopidogrel in patients who need urgent CABG), and to use prasugrel instead of clopidogrel in the acute phase of ACS, possibly using clopidogrel for long-term maintenance therapy. The implications of these results for researchers are that it is important to determine whether the risk of long-term bleeding with prasugrel may be reduced, without compromising efficacy, by using lower doses and by avoiding its use in those with previous stroke or low bodyweight, and older people. A lower dose of prasugrel is presently being compared with clopidogrel in the TRILOGY study, involving 10 000 patients with ACS who are treated medically. Research is also needed to evaluate the potential for individualised antiplatelet therapy based on the results of point-of-care testing of platelet function and genetic polymorphisms. Meanwhile, large randomised trials are presently comparing: the efficacy and safety of a high loading dose and maintenance dose of clopidogrel (versus a low loading dose and maintenance dose); the oral reversible non-thienopyridine ADP receptor antagonist, AZD6140, with clopidogrel; and the parenteral reversible non-thienopyridine ADP receptor antagonist, cangrelor, with clopidogrel, all in patients with ACS treated with an early invasive strategy.

Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MB BS, FRACP, FRCPA · Paul E Langton MB BS, FRACP

A 14-year-old boy was admitted with a 2-week history of increasing breathlessness and fatigue. He had a pulse rate of 130 beats/min and blood pressure of 100/66 mmHg with 16 mm paradox. Jugular venous pressure was raised 10 cm above the sternal angle, and heart sounds were faint. He had been diagnosed with refractory iron-deficiency anaemia in early childhood, for which he had been receiving blood transfusions. He denied any history of epistaxis, haemoptysis, malaena, haematuria or overt bleeding from any other site. On examination, the patient had multiple, blue-black, papular and nodular, compressible, non-pulsatile, vascular skin lesions, ranging in size from a few millimetres to 1–2 cm, distributed over the trunk and limbs, including the soles of the feet, perineal region (Figure A) and lips. A chest x-ray showed an enlarged cardiac silhouette suggestive of pericardial effusion (Figure B). This was confirmed by transthoracic echocardiography. Therapeutic pericardiocentesis showed haemopericardium. Blue rubber bleb naevus syndrome (Bean syndrome) is diagnosed in the presence of distinctive venous malformations on the skin, in the gastrointestinal tract and, less often, in other organs, leading to occult or overt gastrointestinal bleeding and chronic anaemia.1-3

Pankaj Malhotra · Madhav C Menon · Subramaniyan S Anand · Arshjyot Narula · Subhash Varma

Heart failure and palliative care: a team approach. Miriam Johnson, Richard Lehman, editors. Oxford: Radcliffe Publishing, 2006 (x + 150 pp). ISBN 978 1 85775 643 2. At first glance, this appeared to be another of the “palliative care for another subspecialty” works that have been appearing over the past few years. The amount of new and truly specialty-specific material in these can be limited, and one can only suppose that they are sometimes driven as much by publisher catalogue agendas as by real need. This is not the case with this short and well written book from the United Kingdom. The editors are a palliative care physician and a general practitioner who have developed an interest in this subpopulation of patients, for whom palliative and supportive care needs have hitherto tended to be largely ignored. They are modest about their aims, and write clearly with what appears to be comprehensive referencing to the small but growing literature on caring for patients who have end-stage heart failure. The syndrome of advanced heart failure is explained, with very readable accounts of epidemiology, pathophysiology and treatment. There is much reference to the work of one of the contributors, Scott Murray, and his coworkers in primary care at the University of Edinburgh, who have published on comparative needs of patients with heart failure and lung cancer. They highlight the fact that decision making and prognostication are, in general, harder in heart failure, which tends to run a more protracted and unpredictable course than many cancers. Murray has proposed a simple but radical alternative to attempts at precise prognosis as a guide to care planning, by asking: “Would I be surprised if my patient were to die within the next 12 months?” If the answer is “no”, then it is time to start thinking about the deployment of supportive and palliative care.1 The work is certainly UK-centric, however, for Australian readers this is still a good summary of the issues and the literature, together with some useful experience of setting up services in selected UK centres. The heart content would be of no interest to a cardiologist, just as most of the palliative care content would not be news to specialists in that discipline, but each discipline can learn about the other, and generalists will probably find some benefit in both.

Michael A Ashby

Should we be devoting energy and resources to reversing obstructive sleep apnoea in patients without symptoms? Over the past four decades, obstructive sleep apnoea (OSA) has emerged as a prevalent, clinically important disorder. Snoring, which is often a hallmark of OSA, is seemingly ubiquitous in middle-aged men. Over 80% of Australian middle-aged men snore for more than 10% of the night.1 Snoring is also common in women. Although it is undoubtedly an important social nuisance, it remains unclear whether snoring alone (in the absence of sleep apnoea) carries with it any serious health risk. Twenty-five per cent of middle-aged men and 10% of women have OSA, defined as > 5 obstructed breathing events per hour of sleep.2 The prevalence in women rises sharply after menopause. Other risk factors are obesity, older age and a family history of OSA. Population-based studies in China and India indicate that its prevalence is at least as high as that reported in Western countries. A complex interplay between regulation of breathing during sleep, facial anatomy and obesity predicts the development of OSA.2 In contrast to the uncertainty of the effects of simple snoring, OSA clearly has significant health consequences. Many patients with OSA experience excessive daytime sleepiness and impaired cognitive function, increasing the potential for traffic crashes, work accidents and reduced productivity at work.3 Over 50% of Australian truck drivers have mild OSA or worse.4 Moreover, Access Economics has estimated that the cost of sleep disorders to the Australian community is over $7 billion, and much of this cost relates to OSA.5 Increasing awareness of OSA has been followed by an appropriate increase in clinical investigations of sleepy patients with suspected OSA. This is further driven by the availability of cost-effective treatments, notably continuous positive airway pressure (CPAP) and mandibular advancement splints. Recent studies have suggested that OSA is associated with an increased risk of cardiovascular disease.6 Publicity about this research has led to an increasing tendency for people who are not sleepy or who have minimal symptoms to be referred for assessment and treatment of OSA. However, in contrast to the sleepy patient, for whom CPAP usage is reinforced by reduction in sleepiness, asymptomatic patients have more variable compliance.7 Should we be devoting substantial clinical energy and resources to reversing OSA in such patients to prevent cardiovascular disease and death? Certainly, data from cross-sectional and prospective population studies and sleep clinic studies indicate that OSA is associated with a higher prevalence of cardiovascular and cerebrovascular disease and insulin resistance.6 Untreated male patients with severe OSA have significantly greater risks of fatal and non-fatal cardiovascular events than healthy controls (odds ratios, 2.87 and 3.17, respectively).8 However, cross-sectional and observational studies have unmeasured confounders, such as visceral obesity.6 In addition, observational studies can be affected by treatment bias. Patients who refuse to use CPAP and seemingly have higher cardiovascular risk than those who comply with CPAP treatment8 may be the same people who refuse to stop smoking or take lipid-lowering or blood pressure-lowering medication. In contrast, there is good evidence from randomised controlled trials that CPAP lowers blood pressure (mean decrease in systolic and diastolic blood pressure of 2.46 and 1.83 mmHg, respectively), but most studies are relatively short (less than 8 weeks), and treatment effects are hard to demonstrate in patients who are not sleepy.9 The remaining short-term CPAP trials that have focused on other intermediate markers of cardiovascular disease (lipids, glucose control, high-sensitivity C-reactive protein) have been inconclusive. For example, a recent short-term randomised trial failed to show any improvement in insulin sensitivity in patients with type 2 diabetes and OSA.10 No data are available from long-term, well powered, randomised controlled trials assessing the effect of CPAP on hard cardiovascular endpoints, such as myocardial infarction and stroke, in patients with OSA. Medical research is well populated by “positive” results from cross-sectional, observational or short-term intervention studies, but their results have not been reproduced in rigorous, long-term, large-scale clinical trials. To remedy this lack of information, several long-term trials of CPAP treatment in OSA are being planned or have commenced, including one initiated by Australian investigators (Sleep Apnea CardioVascular Endpoints Study [http://www.savetrial.org]). These trials will determine whether treatment of OSA decreases the incidence of new cardiovascular events. In the interim, how should we manage patients with a diagnosis of repetitive OSA who present with complaints of snoring but have minimal or no daytime sleepiness? First, it is important to establish whether such patients are genuinely asymptomatic or simply underreport symptoms that are obvious to their families or work colleagues.11 Second, the disorders of these patients typically are characterised by higher rates of central adiposity, glucose intolerance and other vascular risk factors.6 Given that middle-aged men often neglect to monitor such risk factors, referral for snoring may provide an excellent opportunity for a general health assessment and to institute an intervention, such as advice to exercise and lose weight. Moreover, it would be reasonable to prescribe a trial of CPAP for a patient with asymptomatic OSA and hypertension refractory to maximal medical therapy and to monitor the blood pressure response over 24 hours. Finally, it would be reasonable also to inform asymptomatic patients with severe OSA and coexisting cardiovascular disease of the possible association between OSA and a risk of future vascular events. However, it would be inappropriate to coerce these patients into accepting a treatment that might falsely make them feel secure about future risk and might result in neglect of proven risk factors. Future research, ideally, will enable clinicians to get to the “heart of the matter” when discussing cardiovascular risk management and sleep apnoea with these patients.

Ronald R Grunstein MD, PhD, FRACP · Craig L Phillips BSc

To the Editor: Abdulla and Ward’s excellent article on tako-tsubo cardiomyopathy (TTC)1 raises two important issues. The first issue is the diagnostic dilemma faced by emergency physicians and cardiologists in differentiating TTC from ST-elevation myocardial infarction (STEMI) in centres that lack coronary angiogram capabilities. In patients presenting with chest pain and ST elevation on electrocardiography, the diagnosis of TTC might be suspected on recognition of risk factors and the common psychological, physical and emotional stressors that precipitate TTC.1 Supporting evidence can be obtained by demonstration of basal hyperkinesis and apical or midventricular hypokinesis on transthoracic echocardiography. This modality is now available in many centres without coronary angiography. However, if the diagnosis is incorrectly made as STEMI rather than TTC, the patient runs the risk of unnecessary thrombolysis. Alternatively, after risk–benefit analysis, the clinicians may transfer the patient to a facility with coronary angiography to confirm TTC. The second issue is the therapeutic dilemma facing intensivists treating TTC-related shock with adrenergic inotropes. Although cardiogenic shock in TTC is uncommon, it can still occur (4.2%).2 As increased endogenous catecholamines are thought to be central to the pathophysiology of TTC,3 treating shock with inotropes puts the clinician in a quandary. Agents such as adrenaline, dobutamine, dopamine, milrinone and noradrenaline increase cyclic AMP within the myocardial cell, and are commonly used to restore blood pressure and cardiac output. However, in TTC, inotropes may theoretically delay resolution of the apical ballooning. A recent echocardiographic study showed no improvement in apical and midventricular akinesis with the use of low-dose dobutamine.4 Levosimendan is a calcium sensitiser that has been used successfully to stabilise shock secondary to TTC (with and without use of an intra-aortic balloon pump).5 Levosimendan is non-adrenergic and allows earlier introduction of β-blockers than would be possible with adrenergic inotropes. I agree that prospective trials are needed to guide management in this intriguing condition.

Laven Padayachee