Cardiovascular diseases

Clinical Update Out-of-hospital cardiac arrest Out-of-hospital cardiac arrest (OHCA), with its high fatality rate, is a significant public health issue. The aetiology of OHCA is reviewed, and management strategies are discussed, including the "chain of survival", the Utstein method of data collection, and recent developments in advanced cardiac life support emphasising defibrillation. Alastair D McR Meyer, Peter A Cameron, Karen L Smith and John J McNeil MJA 2000; 172: 73-76 Background - Recent advances in management of OHCA - Improving survival rates after OHCA in Australia - References - Authors' details - - More articles on Emergency medicine Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in First World countries. The estimated incidence in the United States is about 1/1000 population per year (15%-20% of all deaths).1 Current Australian data based on ambulance attendances in metropolitan Melbourne suggest that about 2000 lives are lost from OHCA per year.2OHCA is often the first presentation of ischaemic heart disease. If victims of OHCA can receive immediate and appropriate treatment, they have a 30%-70% chance of survival.3 There is a paucity of data on survival from OHCA in Australia (Box 1). The Melbourne report of cardiac arrest victims mentioned above, which included all patients with arrhythmia of presumed cardiac cause, suggests that the survival rate may be as low as 3%.2 The management of OHCA is presently the only area of pre-hospital emergency care where there is clear evidence that appropriate intervention leads to improved survival.10 We present a clinical update on the management of OHCA. Background The usual cause of sudden cardiac death is coronary artery disease, which accounts for up to 90% of all victims;11 most have major pathological changes in two or more coronary arteries.11An arrhythmia is the most common cause of cardiac arrest, with ventricular fibrillation (VF) being more common12,13 than asystole, pulseless ventricular tachycardia (VT) and other arrhythmias. VF generally has a better prognosis than the other arrhythmias.12,13 Ischaemia, electrolyte imbalance, stress, and neurochemical transmitters (eg, adrenaline, noradrenaline), as well as clotting disorders (eg, massive pulmonary emboli), may trigger arrhythmia.12 VF rarely reverts spontaneously, and the definitive treatment is defibrillation.10 Hypoxic brain injury occurs at four minutes, and death will occur within 12 minutes if no therapy is offered.3,10 It has been predicted that with ideal pre-hospital care, survival rates would be of the order of 70%.3 Recent advances in management of OHCA The "chain of survival" Successful resuscitation of victims of OHCA depends on each individual's unique features (eg, prior medical condition, cardiac rhythm associated with the collapse, collapse witnessed or not witnessed), and the system in the community to deal with such problems. The system must provide a "chain of survival". This concept, initially described by Cummins et al in 1991, and adopted by the American Heart Association, focuses attention on four critical links in the resuscitation process of a victim of OHCA:14 Early recognition and access to emergency medical services Early cardiopulmonary resuscitation Early defibrillation Early advanced cardiac life support. Communities with integrated links along this chain have higher survival rates after OHCA than those with deficiencies in these links.15 Analysing emergency medical services (EMS) in different countries has been difficult, but, in 1990, an international Consensus Conference established uniform terms and definitions for out-of-hospital resuscitation.15 The Consensus Conference recommended that a template approach, the Utstein template, be used for reporting data from out-of-hospital resuscitations.16 This allows comparison and benchmarking between EMS in different countries (Box 2). Early access Recognition of cardiac arrest is often difficult, as it may be confused with fitting or fainting. Cardiac arrest is assumed in an unconscious patient who has no palpable pulse. Spontaneous breathing and pupil size are irrelevant to the diagnosis. Early access to EMS in Australia needs improvement. Two studies of OHCA found that bystanders do not know who to call and have trouble describing the victim.2,5 Education and training programs have been used to raise community awareness and response to OHCA. The "Phone first" campaign in rural Iowa (USA) decreased access times by over a minute. This simple campaign emphasised the need for citizens witnessing a collapse to call the EMS without delay.17 Early cardiopulmonary resuscitation (CPR) The available evidence shows that the earlier patients receive CPR, the greater their chance of survival.18-20For resuscitative efforts to be effective, the patient must be supine, and on a flat, firm surface. Chest compressions are performed in the lower part of the sternum, 4-6 cm in depth and at a rate of 80-100 compressions per minute. During cardiac arrest, properly performed chest compressions can produce systolic blood pressure peaks of 60-80 mmHg. Cardiac output is only 25%-30% of normal.21 Bystander CPR is seldom practised in Australia. Despite there being witnesses to 54% of OHCAs presenting as VF in the Melbourne report, only 22% received bystander CPR and it was often of questionable quality.2 Family members who witness their own relative's OHCA are less likely to perform CPR than a stranger who happens by a victim of OHCA in the street.22,23 Early defibrillation Defibrillation is the definitive treatment for VF.24 The chance of success deteriorates with each minute.3 Such is the importance of defibrillation that Wei and Tang have suggested the appropriate sequence to follow in resuscitation from cardiac arrest is D (defibrillation), C (circulation), B (breathing) and A (airway), rather than the more familiar ABC.25New technology has allowed defibrillators to become more user friendly. Automated external defibrillators (AEDs) can analyse patients' electrical rhythm and can proceed to deliver pre-programmed shocks without further decisions by the rescuer. These machines are simple to operate and are ideal for use by unskilled first responders. This technology is suitable for health clinics and general practitioners' surgeries.26 Members of the public may soon have access to such devices. In the United States, they have been deployed in public buildings, sporting venues and are carried by police. They have also been successfully used by family members of patients known to be at high risk of OHCA.26 New developments in the defibrillating shock may increase the efficacy and safety of defibrillation.26,27 Kerber et al have described a dual-pulse defibrillating shock.27 Different energy waveforms during defibrillation have been described by Bardy et al.28 A damped sinusoidal pattern is most often used for traditional transthoracic defibrillation. These authors have shown that during transthoracic defibrillation, a biphasic shock at 130 J is as effective as a (traditional) monophasic shock at 200 J. The shock also produces less myocardial injury and is potentially safer for bystander use.28 Current-based defibrillation is another promising alternative to traditional energy-based defibrillation. Current-based defibrillation requires the operator to select the electrical dose (amperes) rather than the energy (joules). In this way, delivery of low energy in the face of high transthoracic impedance is avoided. The defibrillator measures the transthoracic impedance, then delivers the exact current requested.26 Early advanced cardiac life support (ACLS) ACLS has traditionally been described as having three interventions: defibrillation, endotracheal intubation and intravenous medications. Defibrillation now stands alone as the single most vital intervention of resuscitation from OHCA, and must be delivered as early as possible. Consequently, it is now rightly the responsibility of primary responders. Endotracheal intubation Endotracheal intubation isolates the airway, keeps it patent, permits tracheal toileting, ensures delivery of a high concentration of oxygen and provides a route for administration of certain drugs. However, no randomised controlled studies have yet been published that demonstrate a significant survival difference with this intervention when compared with basic airway management.18 Intravenous medications Intravenous medications can be administered by a variety of routes (eg, central vein, peripheral vein). The ideal route for administering drugs to a patient in cardiac arrest is one which delivers the drug to the target organ, is simple and rapid to perform with minimal expertise, and has minimal complications. At present, no single route has all of these features.29 A large antecubital fossa vein is recommended for the initial intravenous access. Intravenous medications are discussed in Box 3. Improving survival rates after OHCA in Australia To improve the chance of surviving an OHCA in Australia, data must be collected according to the Utstein template. From this, all aspects of the "chain of survival" can be clearly studied and benchmarked, and developments such as public education programs and public access defibrillators can then be implemented and accurately evaluated (Box 4). Future modification of ACLS management protocols should only be made on the basis of controlled studies. References Becker LB, Smith DW, Rhodes KV. Incidence of cardiac arrest: a neglected factor in evaluating survival rates. Ann Emerg Med 1993; 22: 86-91. Bernard S. Outcome from prehospital cardiac arrest in Melbourne, Australia. Emerg Med 1998; 10: 25-29. Larson MP, Eisenberg MS, Cummins RO, et al. Predicting survival from out-of-hospital cardiac arrest. Ann Emerg Med 1993; 22: 1652-1658. Bett JHN. Experience with a mobile coronary care unit in Brisbane. Ann Emerg Med 1989; 18: 969-974. Jacobs IG, Oxer HF. A review of pre-hospital defibrillation by ambulance officers in Perth, Western Australia. Med J Aust 1990; 153: 662-664. Scott IA, Fitzgerald GJ. Early defibrillation in out-of-hospital sudden cardiac death: an Australian experience. Arch Emerg Med 1992; 10: 1-7. Brennan RJ, Luke C. Failed hospital resuscitation following out-of-hospital cardiac arrest: are further efforts in the emergency department warranted? Emerg Med 1995; 7: 131-138. Jackson T, Cameron PA. Prehospital defibrillation in Geelong. Emerg Med 1993; 5: 184-187. Sammel NL, Taylor K, Selig M, O'Rourke M. New South Wales intensive care ambulance system: outcome of patients with ventricular fibrillation. Med J Aust 1981; 2: 546-550. American Heart Association. Emergency Cardiac Care Committee and Subcommittees. Guidelines for cardiopulmonary resuscitation and emergency care. JAMA 1992; 268: 2171. Reichenbach DD, Moss NS, Meyer E. Pathology of the heart in sudden cardiac death. Am J Cardiol 1977; 39: 865. Eisenberg MS, Horwood BT, Cummins RO, et al. Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990; 19: 179-186. Eisenberg MS. Prehospital care. In: Skinner D, Swain A, Peyton R, Robertson C, editors. Cambridge textbook of accident and emergency medicine. Cambridge: Cambridge University Press, 1997: 288-298. Cummins RO, Ornato JP, Theis W, et al. Improving survival from cardiac arrest: the chain of survival concept. Circulation 1991; 83: 1832-1847. Cummins RO and Graves. Prehospital care II: European and American perspectives. In: Skinner D, Swain A, Peyton R, Robertson C, editors. Cambridge textbook of accident and emergency medicine. Cambridge University Press, 1977: 298-303. AHA Medical/Scientific Statement. Recommended Guidelines for Uniform Reporting of Data from Out-of-Hospital Cardiac Arrest: The Utstein Style. Circulation 1991; 84: 960-975. Montgomery WH, Brown DD, Hazinski MF, et al. Citizen response to cardiopulmonary emergencies. Ann Emerg Med 1993; 22: 428-434. Maguire JE. Advances in cardiac life support: sorting the science from the dogma. Emerg Med 1997; 9 Suppl: 1-8. Callahan M, Madsen CD. Relationship of timeliness of paramedic Advanced Life Support interventions to outcome in out-of hospital cardiac arrest treated by first responders with defibrillators. Ann Emerg Med 1996; 27: 638-648. Weaver WD, Cobb LA, Hallstrom AP, et al. Considerations for improving survival from out-of-hospital cardiac arrest. Ann Emerg Med 1986; 10: 1181-1186. Varon J, Marik PE, Fromm RE Jr. Cardiopulmonary resuscitation: a review for clinicians. Resuscitation 1998; 36: 133-145. De Vreede-Swagamakers JJ, Gorgels AP, Dubois-Arbouw WI, et al. Out of hospital cardiac arrest in the 1990s: a population-based study in the Maastricht area on incidence, characteristics and survival. J Am Coll Cardiol 1997; 30: 1500-1505. Jackson RE, Swor RA. Who gets bystander cardiopulmonary resuscitation in a witnessed arrest? Acad Emerg Med 1997; 4: 540-544. Pantridge JF, Geddes JS. A mobile intensive care unit in the management of myocardial infarction. Lancet 1967; 2: 271-273. Wei MH, Tang W. Science challenges the dogma of ACLS [editorial]. Chest 1996; 109: 597-598. Robertson CE, Nichol NM. Recent advances in defibrillation therapy. Curr Opin Crit Care 1997; 3: 214-217. Kerber RE, Spencer KT, Kallok MJ, et al. Overlapping sequential pulses: a new wave form for transthoracic defibrillation. Circulation 1994; 89: 2369-2379. Bardy GH, Marchlinski FE, Sharma AD, et al. Multicentre comparison of truncated biphasic shocks and standard damped sinewave monophasic shocks for transthoracic ventricular defibrillation. Circulation 1996; 94: 2508-2514. ALS Working Party of the ERC. Guidelines for advanced life support. Resuscitation 1992; 22: 191-195. Hapnes SA, Robertson CE. CPR-drug delivery routes and systems. Resuscitation 1992; 24: 137-142. Linder KH, Koster R. Vasopressor drugs during cardiopulmonary resuscitation. Resuscitation 1992; 24: 147-154. Stiell IG, Herbert PC, Weitzman BN, et al. High grade epinephrine in adult cardiac arrest. N Engl J Med 1992; 327: 1045-1049. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard dose and high dose epinephrine in cardiac arrest outside hospital. N Engl J Med 1992; 327: 1051-1055. Callahan M, Madsen CD, Barton CW, et al. A randomised clinical trial of high dose epinephrine and norepinephrine and standard dose epinephrine in prehospital cardiac arrest. JAMA 1992; 268: 2667-2672. Woodhouse SP, Case C, Cox S, et al. Trial of large dose adrenaline vs placebo in cardiac arrest [abstract]. Resuscitation 1993; 25: 89. Woodhouse SP, Cox S, Boyd P, et al. High dose and standard dose adrenaline do not alter survival compared with placebo in cardiac arrest. Resuscitation 1995; 30: 243-249. Linder KH, Dirks B, Strohmenger HU, et al. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997; 349: 535-537. Stahmer SA, Varon J, Fromm RE. Controversies in cardiopulmonary resuscitation pharmacotherapy. Hosp Physician 1994; 30: 23-30. Steedman DJ, Robertson CE. Acid-base changes in arterial and central venous blood during cardiopulmonary resuscitation. Arch Emerg Med 1990; 9: 169-176. Steuven HA, Thomson BM, Aprahamian C, et al. Calcium chloride: reassessment of use in asystole. Ann Emerg Med 1984; 13: 820-822. Authors' details Emergency Department, Royal Melbourne Hospital, Melbourne, VIC. Alastair D McR Meyer, BSc(Hons), MB BS, FACEM, Research Fellow in Emergency Medicine; and PhD Scholar, Department of Epidemiology and Preventive Medicine, Monash University. Peter A Cameron, MD, FACEM, Director of Emergency Medicine. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC. Karen L Smith, BSc(Hons), GradDipEpiBiostats, PhD Scholar. John J McNeil, PhD, FRACP, Professor; and Head of Department. Reprints will not be available from the authors. Correspondence: Dr A D McR Meyer, Research Fellow in Emergency Medicine, Emergency Department, Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050. Make a comment 1: Survival from out-of-hospital cardiac arrest - Australian studies StudyPatients/presenting rhythmSurvival (%) to dischargeBett (1989)4 Ventricular fibrillation110 (9%)Jacobs and Oxer (1990)5Ventricular fibrillation231 (22%)*Scott and Fitzgerald (1992)6All patients with OHCA103 (17%)Brennan and Luke (1995)7All patients with presumed cardiac arrest, arriving at hospital274 (5%)Bernard (1998)2All OHCA victims, presumed cardiac cause, all rhythms 361 (3%)Jackson and Cameron (1993)8Ventricular fibrillation/pulseless ventricular tachycardia79 (18%)Sammel et al (1981)9Ventricular fibrillation/pulseless ventricular tachycardia434 (21%)*28 days after discharge. OHCA=Out-of-hospital cardiac arrest. Back to text 2: The Utstein Consensus Conference Two meetings in 1990 with representatives from the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council: Established uniform terms and definitions for out-of-hospital resuscitation; Established a reporting template for resuscitation studies to ensure comparability; Defined time points and time intervals relating to cardiac resuscitation; Defined clinical items and outcomes that the emergency medical service should gather; and Developed guidelines for describing resuscitation systems. Back to text 3: Intravenous medications in early advanced cardiac life support Adrenaline Catecholamines, such as adrenaline and noradrenaline, are vasopressors and have long been used as adjuncts to improve the success rate in CPR. These catecholamines increase aortic diastolic pressure by producing arteriolar vasoconstriction and improve blood delivery to the central circulation. If exogenous catecholamines are administered, improved myocardial and cerebral perfusion occurs. The optimal dose range for humans in both the prehospital and hospital stage remains unclear.30 Three large North American multicentre trials have failed to show any benefit from the administration of high-dose adrenaline or noradrenaline in the prehospital or inhospital setting.31-33 The recommended dose is 1mg intravenously repeated at 2-3-minute intervals.34 There is evidence, however, that the use of adrenaline may make absolutely no difference to the outcome of VF cardiac arrest.35,36 Vasopressin There are encouraging results with the use of vasopressin in OHCA.37 In cardiac arrest of long duration, vasopressin seems to have greater efficacy in restoring spontaneous cardiovascular function compared with adrenaline alone.37 More evidence is required before this drug can be recommended. Antiarrhythmics There are many agents which have antiarrhythmic properties in patients with a cardiac output. However, the overwhelming evidence is that antiarrhythmic drug therapy has very little, if any, role to play in the treatment of OHCA.38 Acidaemia When cardiac arrest occurs, anaerobic metabolism occurs in tissues and this results in the production of large amounts of lactic and other organic acids. Good quality CPR and adequate alveolar ventilation limits the development of acidaemia.39 Significant falls in arterial pH do not occur for the first 20 minutes after cardiac arrest. Correction of the acidosis through measures other than ventilation and restoration of circulation has not been shown to improve outcome.38 Calcium Calcium ions play a role in myocardial contractility. A deficiency of calcium is associated with cardiac arrest. However, there is no benefit for the use of calcium in patients with asystole or VF.40 There may be some use for this agent in specific situations of pulseless electrical activity secondary to hyperkalaemia, calcium channel blocker overdose, or hypocalcaemia.40 Back to text 4: Strategies to improve survival from out-of-hospital cardiac arrest in Australia Improved education of the public and healthcare providers in recognising cardiac arrest and accessing emergency medical services (EMS) Improved training of laypersons in cardiopulmonary resuscitation Increased deployment of automatic external defibrillators Public access defibrillation Improved ambulance response times Improved data collection by the EMS throughout Australia Improved communication between units researching pre-hospital resuscitation An evidence-based approach to allocating resources for pre-hospital early advanced cardiac life support protocols Back to text

Peter A Cameron · Karen L Smith · John J McNeil

The Weight Debate The sources of risk factor information for general practitioners: is physical activity under-recognised? Fiona Dupen, Adrian E Bauman and Rose Lin MJA 1999; 171: 601-603 For editorial comment, see Caterson Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - - More articles on General practice and primary care

Fiona Dupen · Adrian E Bauman · Rose Lin

Editorial Erectile dysfunction in the Australian community This problem is both increasingly recognised and increasing in prevalence with the ageing of our population MJA 1999; 171: 342-343 Erectile dysfunction (ED) is the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual activity.1 Worldwide, 100 million men are estimated to have some degree of ED, with around 30 million men in the United States1 and around one million men in Australia affected. With our ageing, but relatively fit, population the incidence of ED is certain to escalate. The first major community-based study on ED was the Massachusetts Male Aging Study (MMAS),2 an observational study (conducted from 1987 to 1989) of a random sample of men aged between 40-70 years living in and around Boston, Massachusetts. This study yielded, for the first time, an understandable concept of ED; comparable studies in Australia have been singularly lacking. The first report on the prevalence of ED in our community was a study by Chew et al from the Keogh Institute for Medical Research in Perth3 (formerly the Reproductive Medicine Research Institute). The generalisability of this 1996 study was limited as it only included men who presented to general practices in Perth. The South Australian community study by Pinnock and colleagues in this issue of the Journal,4 which recruited men from the general community through a 1997 household survey, provides data that are, firstly, drawn from a more general community sample than the one in the Perth study, and secondly, more suited to our own demographic situation than data from overseas surveys. The South Australian study confirms that age is the strongest contributing demographic factor to ED, with 60 years of age being the turning point where desire exceeds potency and sexual frequency diminishes.4 The MMAS found that 52% of men aged between 40 and 70 years had some form of ED, with almost 60% of 60-year-old men having this complaint.2 Both studies found that sexual function was also affected by risk factors such as smoking, hypertension, obesity and a high total cholesterol level with a low concentration of high density lipoprotein. Vigorous exercise was found to be protective. The Perth study also found diabetes mellitus (types 1 and 2) to be significant contributors to ED. It should be noted that Pinnock et al used a questionnaire based on the UCLA Prostate Cancer Index that covered sexual function parameters including desire and orgasm, frequency of intercourse, prostate surgery and erectile function. As this index has not been validated in patients who do not have prostate cancer, its use in a randomly based population study represents a methodological flaw. A more appropriate questionnaire for this study would have been the better-known International Index of Erectile Function (IIEF),5 a 15-question survey that includes similar parameters, assesses intercourse and overall satisfaction, but excludes questions related to prostate cancer. The higher incidence of ED reported in the South Australian study4 compared with the MMAS2 probably reflects improvements in public awareness and keenness to discuss and report ED over the past 10 years. The study by Pinnock et al4 clearly shows that cardiovascular disease and ED have similar risk factors and present in a similar age group. Thus, it seems possible that, by improving their risk factor profile, men may benefit both their cardiovascular health and their sexual function. Pinnock et al also suggest non-cancer prostate surgery appears a more important contributor to ED than previously recognised. Erectile dysfunction is clearly an established and recognised male health problem -- one that is decreasingly being regarded as an inevitable consequence of ageing. The estimated 10% of men currently seeking help will increase, as more men will seek help in the future. Doctors will need to improve their skills in obtaining patients' sexual histories as more men request help. A full assessment of men, with emphasis on cardiovascular risk factors, will help direct the consultation to discussion of sexual matters -- it makes good sense to combine cardiac and sexual issues. Sildenafil is the first effective oral medication for ED, and its arrival on the market was well timed with the increasing interest in ED and the increasing numbers of men wanting a simpler treatment. Initial media interest over coital deaths associated with sildenafil has abated, and the drug is now accepted as a safe treatment when prescribed within the recommended guidelines. These guidelines advise caution when prescribing sildenafil to male cardiac patients who may not be fit enough to engage in sexual activity. Sildenafil is also absolutely contraindicated in men receiving nitrate therapy and those who use amyl nitrite "poppers". When sildenafil is contraindicated or fails to achieve the desired result, the use of injectable vasoactive agents is appropriate. Penile injection therapy is still considered the "gold standard", having been used for over 10 years. Alprostadil is the only approved injectable prostaglandin medication available on the Pharmaceutical Benefits Scheme. Alprostadil is also available as an intra-urethral pellet. Vacuum erection devices have been available for over 20 years and are still an acceptable choice for some men. Penile prostheses may be used in more difficult cases. The Australian community-based studies on male sexual function show a pattern similar to that in overseas studies, and highlights two important points in this era of increasing demand for treatment for ED: Doctors need to understand "normal" sexual function for men at different age groups, as knowing the effects of ageing on sexuality is important when counselling patients and advising on treatment; and Knowing that an apparently healthy patient presenting with ED may have underlying cardiovascular disease can advantage the patient's health outcome, and conversely, reducing a patient's cardiovascular risk factors may benefit both cardiovascular health and sexual function; the implications for sexual function may add weight to the arguments against obesity, smoking and excessive alcohol intake. Michael P Lowy Sexual Health Physician Australian Centre for Sexual Health St Luke's Hospital Complex, Sydney, NSW NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-88. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54-61. Chew KK, Earle CM, Stuckey BGA, et al. Erectile dysfunction in general medical practice. A study in Perth, Australia. Int J Impotence Res 1997; 9 (Suppl 1): A17. Pinnock CB, Stapleton AMF, Marshall VR. Erectile dysfunction in the community: a prevalence study. Med J Aust 1999; 171: 353-357. Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. J Urol 1997; 49: 822-830.

Michael P Lowy

Research Erectile dysfunction in the community: a prevalence study Carole B Pinnock, Alan M F Stapleton and Villis R Marshall MJA 1999; 171: 353-357 For editorial comment see Lowy Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Urology Abstract Objective: To investigate the prevalence of erectile dysfunction (ED) in the South Australian community, and the influence of demographic and other risk factors. Design: Survey by mailed questionnaire (based on the University of California, Los Angeles prostate cancer index) of a subset (men who agreed to participate) of a probability sample of the South Australian community who completed a multiuser interview survey. Participants and setting: Men over the age of 40 in South Australia. Main outcome measures: Sexual desire, orgasm, ability to have an erection, adequacy (firmness) of erections for intercourse, frequency of erections when wanted, frequency of intercourse, nocturnal or morning erections, and history of prostate surgery; total sexual function score based on these. Results: 612 men (86.7%) agreed to answer the sexual function survey; 427 (69.8%) returned questionnaires. ED was strongly correlated with age in all seven domains of sexual function. Erections inadequate for intercourse affected 3% of 40-49-year-olds, increasing to 64% of 70-79-year-olds. The frequency of intercourse considered normal for age by men 50-69 years was 1-6 times weekly; the disparity between this and reported frequency increased in men over 60 years, as did the difference between sexual desire and potency. A history of vigorous exercise was protective across all ages. High triglyceride levels, blood pressure medication and non-cancer surgery for prostate disease were independent predictors of poor sexual function at older ages. High cholesterol level was an independent predictor of impotence. Conclusions: We found similar or higher levels of ED than in comparable overseas studies. Disparity between potency and desire was greatest, and hence the age group in whom demand for treatment may be highest, in those 60 years and older. Cardiovascular risk factors were predictors of ED in these older men, suggesting that prevention may benefit sexual function. Non-cancer prostate surgery may be a greater contributor to ED than previously realised. Introduction Establishing the prevalence of erectile dysfunction (ED) in the community is difficult,1 but important for understanding the need for services, establishing functional expectations of men as they age and for determining the influence of demographic and preventable risk factors. An understanding of community prevalence of ED is useful when evaluating treatments for prostate disease which carry high risks of ED. Community prevalence has been examined in international, but not Australian, studies.1-4 One Australian study of ED prevalence in a Perth general practice population has been reported in conference proceedings.5 We undertook this study to establish the prevalence of erectile dysfunction among Australian men, and to investigate the influence of risk factors. Methods Questions were included in the spring 1997 Omnibus survey, a multiple-user household interview survey which provides a representative sample of the South Australian population. We have reported the methods of and results from this annual survey previously.6-8 The Omnibus survey included questions about age, educational attainment, marital status, household income, area of residence, blood pressure group (low, normal, borderline, high), cholesterol group (low, normal, high), alcohol intake by frequency (days per week) and volume (standard drinks per day when drinking), doctor's report of high triglyceride levels, body mass index (BMI), whether vigorous exercise was undertaken in the past two weeks, current and previous smoking status, and number of cigarettes per day usually smoked. Also included were questions about the presence of lower urinary tract symptoms (LUTS) such as nocturia, frequency, urgency, and a visit to a doctor for LUTS, as reported previously.6 In addition, men aged 40 years and over were asked if they would be prepared to answer a further, mailed questionnaire on urological issues. This comprised an introductory letter explaining the purpose of the survey,7 questions on sexual function and one on history of prostate surgery. To provide an indication of men's expectations of intercourse frequency across age groups, the first question asked what frequency of intercourse the respondent considered normal for a man of his age. Respondents were then offered the opportunity to return the questionnaire without answering further questions if they considered these too intrusive. Sexual function questions were derived from the UCLA (University of California, Los Angeles) prostate cancer index developed by Litwin et al.9,10 These applied to the previous three months and covered seven domains: (i) sexual desire, (ii) orgasm, (iii) ability to have an erection, (iv) frequency of erections when wanted, (v) frequency of intercourse, (vi) frequency of morning or nocturnal erections, and (vii) firmness of erections. The first six of these had five response options ("nil", "poor", "fair", "good", "very good" for domains i-iii; "never had an erection when I wanted one", "less than half the time when I wanted one", "about half the time I wanted one", "whenever I wanted one" for domain iv; "once or more daily", "1-6 times weekly", "1-3 times monthly", "less than once a month", "not at all" for domain v; "never", "seldom [less than a quarter of the time]", "not often [less than half the time]", "often [more than half the time]", "very often [more than 75% of the time]" for domain vi), while the seventh had four ("no erections at all", "not firm enough for any sexual activity", "firm enough for masturbation and foreplay only", "firm enough for intercourse"). Additional questions involved history of prostate surgery (for cancer and for non-cancerous conditions). Ethical consideration for the study was by Repatriation General Hospital's Research Ethics Committee. Analysis We defined sexual dysfunction as a response of one of the two lowest response categories (eg, "nil" or "poor") in each of the first six domains. Confidence intervals were adjusted for a design effect of 1.1 to allow for clustering.11 Dysfunction in the seventh domain (firmness of erections) was termed "impotence", defined as "usual quality of erections during the past three months not firm enough for intercourse" (corresponds with National Institutes of Health definition)12 -- one of the three lowest response options for this domain. A total erectile function score was derived by adding scores for each of the seven domains. The resulting score out of a possible 34 was expressed as a percentage; a score of 0 indicated worst possible function and 100% indicated best possible function in all domains. The reliability coefficient (Cronbach's alpha) of this seven-item score was 0.940. The association of demographic and cardiovascular risk factors with total sexual function (expressed as a continuous variable) and with impotence (a dichotomous variable) was examined after allowing for the effects of age by means of analysis of variance and logistic regression. For analysis, data were weighted by household size, age, sex and geographic region to benchmarks derived from the resident South Australian population in August 1996. We used SPSS for Windows13 for statistical analysis. Results The numbers and age breakdown of respondents are shown in Box 1. The mean age of respondents was 57.5 years (standard error, 0.58). Of the 745 men aged 40 years and over who responded to the Omnibus survey (representing a response rate of 70.8%), 612 (82.1%) agreed to complete a further, mailed questionnaire on urological issues. These questionnaires were returned by 427 respondents (69.8%), 371 (86.9%) of whom agreed to answer the full questionnaire. Box 1 shows that the age distribution was the same in all of these groups. We weighted further analyses to reflect the age distribution in the South Australian community; marginal totals thus do not correspond to the totals in Box 1. A comparison of respondents who agreed to answer the sexual function questions with those who did not agree to a further survey, did not respond to the mailed form or did not agree to answer the sexual function questions showed no significant differences in age, marital status, blood pressure, cholesterol and triglyceride levels, blood pressure medication or visit to a doctor for LUTS. Men who answered the sexual function questions were more likely to report vigorous exercise in the past two weeks (25.0% v 15.4%; P = 0.001), and more likely to drink alcohol five or more times per week (34.2% v 25.3%; P = 0.026) than those who did not answer these questions. Frequency of intercourse The frequency of intercourse considered by respondents as normal for their age, shown in Box 2(a), and actual reported frequency of intercourse were strongly correlated (Spearman's correlation coefficient, 0.62; P < 0.0001). Most 40-60-year-olds considered that intercourse 1-6 times per week was normal for their age and most reported this frequency of intercourse. In older men, however, a discrepancy emerged: most 70-79-year-olds considered 1-3 times per month to be normal for their age, but most reported an actual frequency of less than once per month. Box 2(b) illustrates this more clearly. In younger age groups, the reported frequency approximated that considered normal for age, but in older age groups it was substantially lower. Similarly, Box 2(c) shows that, while potency exceeds desire in men aged 40-59 years, after age 60 years desire exceeds potency. Prevalence of erectile dysfunction Erectile dysfunction was strongly correlated with age across all seven domains (Box 3). The prevalence of impotence (defined above) increased sharply from 3% in 40-49-year-olds to 42% in 60-69-year-olds and 64% in 70-79-year-olds. Other domains of sexual function, including morning or nocturnal erections, followed this pattern of steep decline in the fifth and sixth decades. Total sexual function scores ranged from 17% to 97%, with a mean of 68.1% (standard error, 1.1); 21% of respondents had a score of 50% or less. The sexual function score was also strongly correlated with age (Pearson's correlation coefficient, 0.63; P < 0.0001). Demographic risk factors Age, income, education, marital status, area of residence, occupation and country of birth were examined for their association with total sexual function and impotence. By far the strongest contributor to total sexual function score was age, and so the contribution of other factors was examined singly after first accounting for the effects of age in analysis of variance models, including first-order interactions (sexual function) and logistic regression (impotence). Where factors or their first-order interactions were significant, a combined model was examined. A summary of these analyses is given in Box 4. Men with lower socioeconomic status (income, education, occupation) tended to have lower sexual function, and this association was seen particularly in older men. In the 70-79 years age group, the total sexual function score varied from 47.1 in the lowest education category to 61.7 in the highest. Sexual function tended to be lower in Australian-born than overseas-born respondents. When tested in a model containing cardiovascular risk factors, this association remained. No demographic factors, apart from age, were significant contributors to impotence. Cardiovascular and other risk factors The cardiovascular risk factors shown in Box 4, as well as presence of LUTS, doctor visit for LUTS and surgery for prostate disease (cancer or non-cancer), were examined for their effects on total sexual function and impotence, as described for demographic factors. A number of factors were significantly (P < 0.05) associated with decreased sexual function after controlling for the effects of age. For total sexual function, these were ever having smoked, taking blood pressure medication and having had surgery for non-cancer prostate disease. A history of vigorous exercise was protective. Risk factors for impotence were high body mass index, high levels of triglycerides and cholesterol, and surgery for non-cancer prostate disease. Again, a history of vigorous exercise was protective. When combined models were constructed with these factors, the number that remained independently significant was reduced (Box 4). For total sexual function, these were vigorous exercise, high triglyceride levels, blood pressure medication, and surgery for non-cancer prostate disease. The combined model for total sexual function explained 55% of the variance. The observed power was low for all non-significant factors. The effects of cardiovascular risk factors were stronger in older age groups. For example, men in their 60s with high triglyceride levels had a total sexual function score of 41% (95% CI, 31%-52%), compared with 64% (95% CI, 59%-70%) for men of the same age who did not have this risk factor. Discussion Few international or Australian studies of the prevalence of sexual dysfunction have surveyed the general community.1 Our study was based on a representative sample of the South Australian community, and employed rigorous methods which have been previously used in other prevalence studies.1,8 The study was undertaken before the recent introduction of the drug oral sildenafil for erectile dysfunction. The subsample who answered questions on sexual function were similar in terms of most demographic and risk factor variables tested, but did report undertaking more vigorous exercise, and more frequent alcohol consumption. They may therefore reflect a more physically active subgroup, and our estimates of erectile dysfunction are likely to be conservative. Relative to other studies with comparable methods and measures of sexual dysfunction, the prevalences we found were similar or higher. For example, a study of frequency of sexual activity reported that 34.7% of married 60-65-year-old people did not have sexual intercourse within the preceding month,14 while we found that 34.3% of 60-69-year-old men reported having intercourse "less than once a month". A survey of 1240 men attending general practices in Perth found a 45% prevalence of "complete ED [erectile dysfunction]" in 70-79-year-old men,5 compared with our finding of impotence in 64.2%, and 64.3% in a study by Diokno et al.15 The frequently quoted Massachusetts Male Aging Study reports a prevalence of complete impotence of 9.6% for a 40-70-year-old population;2 the corresponding figure in our study was 16%. As expected, frequency of intercourse considered normal for age was strongly correlated with the frequency of intercourse reported (Figure 2). Solstad and Hertoft found that, while 40% of interviewed Danish men reported some kind of sexual dysfunction, only 7% considered their problems abnormal for their age,16 implying that men tend to see their own functional level as normal. Nevertheless, in our study, the discrepancy between reported frequency of intercourse and that considered normal for age increased with age. It was greatest in men 70 years and older, suggesting that it is older men who may be most concerned about their sexual function. Consistent with this, potency exceeded desire in younger age groups, but the relationship was reversed in men aged 60 years and over. About one in five men over the age of 50 experience good to very good sexual desire, but nil to poor erectile function; these men may be more likely to seek treatment. If the goal of treatment is to achieve perceived "normal function for this age", this may be a frequency of intercourse of 1-3 times monthly for 70-79-year-olds and weekly in the case of 40-69-year-olds. The effects of demographic risk factors such as income and education were more apparent in older age groups and were consistent with lower sexual function in lower socioeconomic groups. No reason is immediately apparent for the lower sexual function of Australian-born men compared with their overseas-born counterparts. Cardiovascular and medical risk factors reflected a conventional pattern.1,17 Predictors of low total sexual function scores after controlling for age only were smoking, blood pressure medication, high triglyceride levels and non-cancer prostate surgery, while a history of vigorous exercise provided a protective effect. In a combined model, smoking was no longer significant. Predictors of impotence after controlling for age only were high body mass index, high triglyceride levels, high cholesterol level, surgery for non-cancer prostate disease, while vigorous exercise was again protective. In a combined model, only high cholesterol remained significant. However, it is likely that small numbers of respondents limited the power of our study to investigate all these factors simultaneously. Our findings suggest that men experience poor sexual function as a deficit in the same age ranges in which cardiovascular risk factors are major determinants of that function, raising the possibility of prevention. It would be interesting to know whether, for men 60 years and over, improving cardiovascular risk factor profile would also reduce the prevalence of sexual dysfunction. Also of interest is the consistent and independent effect of non-cancer prostate surgery on sexual function. While its effects are small relative to age, it may point to a higher impotence rate than is commonly believed to result from this type of surgery,18 and this warrants further investigation. Acknowledgements We thank Living Health and Quitline for generously sharing their data on cardiovascular risk factors, and the AntiCancer Foundation for funding the prostate cancer questions. We would also like to thank the Behavioural Epidemiology Unit, South Australian Department of Human Services, and Lynne Giles, Flinders University, for assistance with aspects of the statistical analyses. References Bortolotti A, Parazzini F, Colli E, Landoni M. The epidemiology of erectile dysfunction and its risk factors. Int J Androl 1997; 20: 323-334. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54-61. Helgason AR, Adolfsson J, Dickman P, et al. Factors associated with waning sexual function among elderly men and prostate cancer patients. J Urol 1997; 158: 155-159. Jonler M, Moon T, Brannan W, et al. The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol 1995; 75: 651-655. Chew K, Burio C, Stuckey B, Jamrozik K. Erectile dysfunction in general medical practice. A study in Perth, Australia. Int J Impotence Res 1997; 9 (Suppl 1): S36. Pinnock C, Marshall V. Troublesome urinary symptoms in the community: a prevalence study. Med J Aust 1997; 167: 72-75. Weller D, Pinnock C, Silagy C, et al. Prostate cancer testing in South Australian men: influence of sociodemographic factors, health beliefs and lower urinary tract symptoms. Aust N Z J Public Health 1998; 22: 400-402. Pinnock C, Weller D, Marshall V. Self-reported prevalence of prostate specific antigen (PSA) testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Litwin MS, Hays RD, Fink A, et al. Quality-of-life outcomes in men treated for localized prostate cancer. JAMA 1995; 273(2): 129-35. [See comments.] Litwin MS, Nied RJ, Dhanani N. Health-related quality of life in men with erectile dysfunction. J General Intern Med 1998; 13: 159-166. Kish L. Estimates of unit variance: design effect. Survey sampling. New York: John Wiley and Sons, 1965: 257-263. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-88. SPSS for Windows [computer program], version 6.1. Chicago, Ill: SPSS Inc, 1996. Marsiglio W, Donnelly D. Sexual relations in later life: a national study of married persons. J Gerontol 1991; 46(6): S338-S344. Diokno AC, Brown MB, Herzog AR. Sexual function in the elderly. Arch Intern Med 1990; 150: 197-200. Solstad K, Hertoft P. Frequency of sexual problems and sexual dysfunction in middle-aged Danish men. Arch Sexual Behavior 1993; 22: 51-58. Helgason AR, Adolfsson J, Dickman P, et al. Waning sexual function -- the most important disease-specific distress for patients with prostate cancer. Br J Cancer 1996; 73: 1417-1421. Clinical practice guidelines for the management of uncomplicated lower urinary tract symptoms in men. Canberra: National Health and Medical Research Council, 1997. (Received 30 Nov 1998, accepted 28 Jun 1999) Authors' details Repatriation General Hospital, Daw Park, Adelaide, SA. Carole B Pinnock, PhD, Principal Research Scientist, Division of Surgery; Alan M F Stapleton, PhD, FRACS, Director, Urology Unit; Villis R Marshall, MD, FRACS, Head, Division of Surgery, and Head, Department of Surgery, Flinders Medical Centre. Reprints will not be available from the authors. Correspondence: Dr C B Pinnock, Division of Surgery, Repatriation General Hospital, Daws Road, Daw Park, SA 5041. carole.pinnockAThealth.sa.gov.au Back to text Back to text Back to text Back to text

Carole B Pinnock · Villis R Marshall

Research Impact of written information on knowledge and preferences for cardiopulmonary resuscitation Ian H Kerridge, Sallie-Anne Pearson, Isobel E Rolfe, Michael Lowe and John R McPhee MJA 1999; 171: 239-242 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Ethics Abstract Aim: To investigate knowledge about and attitudes to cardiopulmonary resuscitation (CPR), and to determine whether written information about CPR alters knowledge and choices made. Design: Questionnaire-based survey before and immediately after provision of written information describing CPR and its risks and benefits. Subjects and setting: All health professionals (803) and competent inpatients (260) in a tertiary care hospital (John Hunter Hospital, Newcastle, New South Wales, Australia) in June 1994. Main outcome measures: CPR knowledge scores and choice scores (number of hypothetical clinical scenarios in which CPR would be chosen) before and after provision of information about CPR. Results: Response rates were 64% (health professionals) and 58% (patients). Patients had limited awareness of procedures involved in CPR, while both patients and health professionals overestimated its success rates. Mean knowledge scores increased after provision of information: for patients, from 6.4 out of 18 (95% confidence interval [CI], 6.0-6.9) to 10.4 (95% CI, 9.9-11.1); and for health professionals, from 11.9 (95% CI, 11.7-12.1) to 13.9 (95% CI, 13.7-14.2). In contrast, mean choice scores decreased after provision of information: for patients, from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8); and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). Conclusion: Our results imply that people understand and use prognostic information to make decisions about CPR. To make autonomous judgements, patients and health professionals need better education on CPR outcomes. Introduction While cardiopulmonary resuscitation (CPR) can be lifesaving, success rates (survival to discharge) are less than 5% in some types of patients, particularly those with chronic illness or multiple comorbidities.1 Among those who survive, quality of life is often poor and life expectancy often short.2 In the mid-1970s, growing concern about inappropriate application of CPR and increased awareness of patient rights led to the development of "do-not-resuscitate" (DNR) orders.3 Health professionals are now increasingly encouraged to discuss DNR decisions with patients and their families.4 However, for decision-making about CPR to be appropriate, patients and their surrogates must have some understanding of the likelihood of surviving CPR and the possible adverse effects. Previous research has found that 50%-80% of patients claimed awareness of CPR, but their knowledge was very limited and derived mainly from television dramas. Most patients believed erroneously that CPR is generally successful,5,6 and both patients and health professionals were found to overestimate its success by up to 300%.7 We aimed to investigate knowledge of and attitudes to CPR among hospital inpatients and health professionals and to determine whether written information about CPR alters knowledge and preference for CPR. We have previously reported the opinions of patients and health professionals on the process of decision-making about CPR.8 Methods Subjects and setting The study was conducted at the John Hunter Hospital, Newcastle, New South Wales (a 530-bed tertiary care hospital), over a four-day period in June 1994. Subjects comprised all health professionals working in the hospital (doctors, nurses and allied health professionals) and all eligible (competent) inpatients, as described previously.8 Informed consent was obtained by trained interviewers, and a Mini Mental State Examination (MMSE) performed on patients. Those with MMSE scores < 24 were excluded. A questionnaire for self-completion was administered before and immediately after provision of written information about CPR. Questionnaire The questionnaire asked about: sociodemographic characteristics; sources of information on CPR (respondents could nominate as many as applied from a list of 11); whether each of 10 procedures is part of CPR (possible answers: yes, no or don't know); how successful CPR is in eight clinical scenarios, using a five-point scale: rarely (< 5%), seldom (5%-30%), sometimes (31%-60%), mostly (61%-90%) or almost always (> 91%); and whether respondents would like CPR performed on themselves in 12 specific clinical scenarios (possible answers: yes or no). On completing the questionnaire, respondents were given a one-page information sheet that explained various aspects of CPR, including its definition, procedures that may or may not be considered part of CPR, risks and benefits, success rates, and prognostic indicators (good prognosis: after acute myocardial infarction; poor prognosis: cancer, severe infection, organ failure). Respondents were then asked to repeat the questions on knowledge and choices. Statistical analyses Data were analysed with SPSS version 6.0 for Windows.9 Sociodemographic characteristics of patients and health professionals were compared using continuity-corrected χ2 analyses. All other analyses were performed for patients and health professionals separately. Knowledge of CPR was scored by allocating a point for each correct response. We assessed the relationship between this score and sociodemographic characteristics by standard multiple linear regression, with knowledge score as the dependent variable. For this analysis, we converted the discrete sociodemographic variable (health professional background) into a set of dichotomous independent variables using dummy variable coding (ie, doctors versus all other health professionals, and nurses versus all other health professionals). Significance of change in knowledge scores after provision of information was examined by one-way repeated-measures analysis-of-variance (ANOVA). As answers to some of the knowledge questions may be contentious (whether CPR involves intravenous drugs, intubation and defibrillation), analyses were repeated using scores with these questions omitted. Composite "choice scores" about CPR were calculated by allocating a point for each condition in which the subject would choose to have CPR. The relationship between choice score, sociodemographic characteristics and knowledge score after provision of information was assessed by standard multiple linear regression, with choice score as the dependent variable and knowledge score and sociodemographic factors as independent variables. Significance of change in choice scores after provision of information was examined by ANOVA. Ethical approval The study was approved by the Hunter Area Health Service Research Ethics Committee and the University of Newcastle Human Research Ethics Committee. Results Subjects Of the 803 questionnaires delivered to health professionals, 511 (64%) were returned (148 from doctors, 312 from nurses and 51 from allied health professionals). Of the 443 adult patients in the hospital during the study, 183 were excluded (because of dementia, neurological impairment or delirium [110], incompetence as assessed by MMSE [35], visual or language problems [24], psychiatric illness [9], or as they were undergoing procedures [5]); 153 (58%) of the remaining 260 completed the questionnaire. Sociodemographic characteristics of respondents are shown in Box 1. Knowledge about CPR Sources of information about CPR most commonly identified by health professionals were first aid or in-service courses (33% of responses); school, college or university (27%); and other health professionals (17%). Sources most commonly identified by patients were television (28% of responses), books or magazines (15%), first aid classes (15%), and school (10%). Knowledge before provision of information is shown in Box 2. Patients' knowledge scores were low (mean, 6.4 out of 18; 95% confidence interval [CI], 6.0-6.9), mainly because of lack of awareness of success rates of CPR, with 90% overestimating success for the "all patients" category. Health professionals' knowledge scores were higher than patients' (mean, 11.9; 95% CI, 11.7-12.1), but health professionals also overestimated success of CPR, with 65% overestimating success for "all patients". ANOVA showed that knowledge scores improved significantly after provision of written information for both patients and health professionals (patients: mean, 10.4; 95% CI, 9.9-11.1; health professionals: mean, 13.9; 95% CI, 13.7-14.2). The only sociodemographic characteristics that significantly predicted knowledge scores before provision of information were age (for patients) and professional background (for health professionals): younger patients achieved higher scores than older patients, while doctors and nurses achieved higher scores than allied health professionals. Repeat analysis of the data after omission of contentious questions did not affect the relationship between sociodemographic variables and knowledge scores or the change in knowledge scores after provision of information. Choices about CPR Percentages of patients and health professionals who chose CPR are shown in Box 3. Percentages varied between clinical scenarios, but decreased after provision of information for almost all. ANOVA showed that choice scores also decreased significantly for both patients and health professionals. Mean choice scores decreased for patients from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8), and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). CPR was chosen for more scenarios by patients who were younger or had lower knowledge scores and by health professionals who were younger, male, tertiary educated or had better self-reported health status. Discussion We found that patients in an Australian teaching hospital had poor knowledge of CPR, and that both they and, to a lesser extent, hospital staff had unrealistic expectations about its success rates. We also found that provision of written information about CPR risks, benefits and success rates had a clear impact on whether patients and health professionals reported wanting CPR performed on themselves in hypothetical clinical scenarios, decreasing their preference for CPR. Other studies have also found that patients are unaware of the procedures involved in CPR and, along with their relatives, generally overestimate success rates.10 This is not surprising, as television, books and magazines are often their most common sources of information. In addition, community education tends to be positive about CPR, often failing to describe its real success rates. Several previous studies have investigated the relationship between choices about CPR and estimated probability of survival.5,11 They found, similarly to us, that many patients change their minds about wanting CPR when they learn the true probability of survival. Furthermore, formal processes of information disclosure, including discussion of the likely outcome of resuscitation in specific clinical situations, has been shown to modify preferences for CPR.12 In our study, the change in preference followed provision of a one-page information sheet. It is possible that a more optimal form of education (eg, repeated explanations tailored to the individual, with time for reflection and questions) would have produced a greater change in preferences. Perceived morbidity after CPR also strongly influences many people's choices. A survey of 200 medical inpatients found that choice of CPR or DNR status was strongly influenced by anticipated outcome; 90% of patients desired CPR if they were to be restored to their normal health, 30% if the likely outcome after recovery was dependence, 15% if it was perceived as "hopeless", and 6% if it was coma.13 Other studies from the United States14 and United Kingdom15 have found that senile dementia, more than any other condition, is associated with a preference for DNR status. We found similarly that patients and health professionals would be unlikely to opt for CPR in the presence of brain injury or severe dementia. Nevertheless, as found by others,6,10 some patients continued to opt for CPR even if they were likely to have a serious disability, such as coma or terminal illness. We also found, in common with others overseas, that health professionals vastly overestimate the success rates of CPR. These rates (3%-30% in general hospitals) have not changed significantly in the past 30 years.1,16 However, they are well below the rates perceived by physicians and nurses, who are responsible for making decisions about resuscitation status and informing patients and their surrogates.17,18 There are several limitations to our study. Subjects included hospitalised patients with acute illness, and the findings may not be generalisable to other patient populations. The study instrument was a self-report questionnaire using hypothetical clinical scenarios; answers may not accurately reflect what individuals would choose in reality. However, the study has strengths; it assessed both knowledge of and attitudes to CPR in variable clinical contexts and included a formal assessment of competence (the MMSE). The study also used trained interviewers rather than clinicians to distribute questionnaires and so was less likely to introduce bias and perhaps more likely to elicit patients' true preferences. As factors such as likelihood of survival and functional status after resuscitation may contribute to patients' wishes for CPR, it is ethically and clinically desirable that patients be provided with this information. Furthermore, the High Court of Australia has reaffirmed that patients must be given adequate information when making decisions concerning their healthcare.19,20 It is also essential that health professionals who advise patients are aware of the real success rates of CPR. Otherwise, they have failed to meet the standards required both for ethical medical care and by law.21 Respect for autonomy demands that the views of patients or their surrogates should be sought in decision-making about CPR. Our study implies that patients understand and use prognostic information in their decision-making. For truly autonomous judgements, patients and health professionals clearly need better education on risks and benefits of CPR. Acknowledgements We would like to thank the interviewers and patients and staff of the John Hunter Hospital for their generous participation in this study. References Robinson GR, Hess D. Post-discharge survival and functional status following in-hospital cardiopulmonary resuscitation. Chest 1994; 105: 991-994. Landry FJ, Parker JM, Phillips YY. Outcome of cardiopulmonary resuscitation in the intensive care setting. Arch Intern Med 1992; 152: 2305-2308. Rabkin MT, Gillerman JD, Rice NR. Orders not to resuscitate. N Engl J Med 1976; 295: 364-366. Decisions relating to cardiopulmonary resuscitation. A statement from the British Medical Association and the Royal College of Nursing in association with the Resuscitation Council (UK). London: BMA, 1993. Miller DL, Jahnigen DW, Gorbien MJ, Simbarti L. Cardiopulmonary resuscitation: how useful? Attitudes and knowledge of an elderly population. Arch Intern Med 1992; 152: 578-582. Schonwefter RS, Walker RM, Kramer DR, Robinson BE. Resuscitation decision-making in the elderly: the value of outcome data. J Gen Intern Med 1993; 8: 295-300. Potter JM, Stewart D, Duncan G. Living wills: would sick people change their minds? Postgrad Med J 1994; 70: 818-820. Kerridge IH, Pearson SA, Rolfe IE, Lowe M. Decision making in CPR: attitudes of hospital patients and health care professionals. Med J Aust 1998; 169: 128-131. SPSS. Statistical package for the social sciences. Version 6.0 for Windows. Chicago, Ill: SPSS Inc, 1990. Schmerling RH, Bedell SE, Lilienfeld A, Delbanco TL. Discussing cardiopulmonary resuscitation: a study of elderly outpatients. J Gen lntern Med 1988; 3: 317-321. Murphy DJ, Burrows MD, Santilli S, et al. The influence of the probability of survival on patients' preferences regarding cardiopulmonary resuscitation. N Engl J Med 1994; 330: 545-549. Schonwetter RS, Teasdale TA, Taffet G, et al. Educating the elderly: cardiopulmonary resuscitation decisions before and after intervention. J Am Geriatr Soc 1991; 39: 372-377. Frankl D, Oye RK, Bellamy PE. Attitudes of hospitalised patients toward life support: a survey of 200 medical inpatients. Am J Med 1989; 6: 645-648. Ebell MH, Doukas DJ, Smith MA. The do-not-resuscitate order: a comparison of physician and patient preferences and decision-making. Am J Med 1991; 91: 255-260. Robertson GS. Resuscitation and senility: a study of patients' opinions. J Med Ethics 1993; 19: 104-107. Bedell SE, Delbanco TL, Cook EF, Epstein FH. Survival after cardiopulmonary resuscitation. Crit Care Med 1983; 309: 569-576. Miller DL, Gorbien MJ, Simbarti LA, Jahnigen DW. Factors influencing physicians in recommending in-hospital cardiopulmonary resuscitation. Arch Intern Med 1993; 153: 1999-2003. Wagg A, Kinirons M, Stewart K. Cardiopulmonary resuscitation: doctors and nurses expect too much. J R Coll Physicians Lond 1995; 29: 20-24. Rogers v Whitaker (1992) 175 CLR 479. Chappel v Hart [1998] HCA 55. Wyong Shire Council v Shirf (1980) 146 CLR 40. (Received 13 Jan, accepted 7 Jul, 1999) Authors' details Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, NSW. Ian H Kerridge, MPhil, Lecturer in Clinical Ethics; Sallie-Anne Pearson, PhD, Research Academic; Isobel E Rolfe, MMedEd, Senior Lecturer in Medical Education; Michael Lowe, FRACP, Tutor in Clinical Ethics; John R McPhee, BCom(Hons) (Legal Studies), Consultant in Health Law. Reprints will not be available from the authors. Correspondence: Dr I H Kerridge, Clinical Unit in Ethics and Health Law, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310. Email: ikerridgATmail.newcastle.edu.au 1: Sociodemographic characteristics of patients and health professionals surveyed about cardiopulmonary resuscitationPatients (n =153)Healthcare professionals (n =511)PAge > 35 years*90 (59%)235 (46%) 0.007Female98 (65%)373 (73%)< 0.001Marital status† Married/de facto97 (64%)328 (64%) Single/divorced/widowed55 (36%)183 (36%) 0.99Education† Secondary or less117 (77%)72 (14%) Tertiary35 (23%)438 (86%) < 0.001Religion† Religious‡127 (84%)401 (79%) Not religious25 (16%)109 (21%) 0.18Ethnic background† Australian/British144 (95%)463 (91%) Other7 (5%)45 (9%) 0.09Self-reported health status Good68 (45%)493 (97%) Fair/poor/very poor84 (55%)17 (3%)< 0.001CI = confidence interval. * Median split. †Data were missing for some respondents. ‡Any belief system: Christian, Jewish, Islamic, Hindu or Buddhist. Back to text 2: Percentages of 153 patients and 511 health professionals who replied correctly to questions about cardiopulmonary resuscitation (CPR) before provision of written information% Correct (95% confidence interval)QuestionCorrect responsePatientsHealthcare professionalsWhat is involved in CPR?Chest compression (external cardiac massage)Yes*84% (77%-90%)100%Kidney machine (dialysis)No62% (54%-70%)99% (98%-100%)Intravenous drugsYes*25% (18%-33%)84% (80%-87%)Mouth-to-mouth (artificial respiration) Yes86% (80%-91%)99% (98%-100%)Feeding tube into the nose (nasogastric tube)No48% (40%-56%)96% (94%-98%)AntibioticsNo56% (48%-64%)98% (93%-97%)Tube into the throat to assist breathing (intubation)Yes*35% (27%-43%)85% (82%-88%)External electric shock to the heart (defibrillation)Yes*60% (51%-68%)91% (88%-93%)SurgeryNo48% (40%-56%)98% (96%-99%)Breathing machine (ventilator)No27% (20%-35%)57% (53%-61%)How successful is CPR?All patients5%-30%1% (0-4%)26% (22%-30%)Nursing home patients< 5%8% (4%-13%)62% (58%-66%)Patients who have had recent heart attack31%-60%40% (32%-48%)40% (36%-44%)Patients with widespread cancer< 5%42% (34%-50%)61% (57%-65%)Patients with severe infections (eg, pneumonia)< 5%17% (11%-24%)28% (24%-32%)Patients with kidney failure< 5%25% (18%-33%) 39% (35%-43%)Patients under 60 years5%-30%5% (2%-10%)22% (18%-26%)Patients over 70 years5%-30%15% (10%-22%)34% (30%-38%)* As these answers are contentious, analyses were performed using both responses. 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Ian H Kerridge · Sallie-Anne Pearson · Isobel E Rolfe · Michael Lowe · John R McPhee

Editorial Primary stenting in acute myocardial infarction: paving the way to arterial patency No matter how enticing the data may be, all the answers are not in MJA 1999; 170: 518-519 Acute myocardial infarction (AMI) remains a major cause of morbidity and the single most common cause of mortality among adult Australians.1 It has been estimated that there is one AMI every half hour and one fatal event every hour among men and women under 70 years of age.1 Despite a decade of remarkable insights into the pathobiology of AMI and innumerable randomised clinical trials evaluating therapeutic approaches, the optimal acute management strategy still remains unclear. It is widely accepted that the primary objective in AMI is early reperfusion,2 which, by preserving myocardial cell viability and contractility, results in improved survival.3-6 However, the main mechanism of achieving coronary artery reperfusion -- intravenous thrombolytic therapy -- is not without its limitations: up to half the patients may be ineligible on clinical grounds, and it is only moderately effective in reinstituting the level of coronary flow necessary for improved survival.7 Other problems include recurrent ischaemia, reinfarction and a small but significant chance of life-threatening haemorrhagic complications.8 Because of these drawbacks, interest in mechanical reperfusion by primary coronary balloon angioplasty (without prior thrombolysis) has steadily increased. Despite its 17-year history, balloon angioplasty is not as widely available or as frequently used9 as perhaps it should be (for reasons beyond the scope of this editorial). However, current evidence for its use in primary treatment of AMI is quite encouraging. A review of 10 randomised clinical trials comparing primary coronary balloon angioplasty with thrombolytic therapy in 2606 patients with AMI found those treated with balloon angioplasty had a 34% lower mortality rate, a lower rate of death and/or non-fatal reinfarction and a significantly lower rate of total and haemorrhagic stroke.10 Other randomised trials have indicated that, by reducing early and late recurrent ischaemia, primary balloon angioplasty may expedite early discharge and thus reduce costs.11,12 Promising as these data might be, they are far from conclusive, in part because of the size of the dataset and the unblinded nature of the clinical trials. Almost 13 000 patients would need to be enrolled in a trial to detect a 20% advantage in 30-day mortality rates of primary coronary balloon angioplasty over thrombolytic therapy (assuming a 7% mortality rate in the thrombolytic therapy group).13 Equally concerning are the incidence of no reflow due to distal thrombus embolisation at the time of balloon dilatation; early recurrent ischaemia and/or reinfarction (5%-10% of patients14) due to elastic vascular recoil and/or platelet and thrombus deposition at the site of balloon-induced intimal disruption (dissection); and late restenosis (30%-50% of patients14) due to a varying mix of neointimal proliferation, unopposed recoil and vascular remodelling. While there have been substantial improvements in operator skills, procedural techniques, equipment design and adjunctive antiplatelet therapies, the issues mentioned above continue to frustrate the proponents of primary coronary balloon angioplasty. It is not surprising, therefore, that they should have become infected and intoxicated by the euphoria surrounding coronary stenting in elective angioplasty. Compared with simple balloon angioplasty, coronary stenting in elective (non-infarct-related) coronary angioplasty has been shown to reduce the rate of periprocedural complications and late restenosis, and to be beneficial in the management of saphenous vein graft lesions and restenotic lesions after balloon angioplasty. The thought of in-situ coronary thrombus and the likely consequences of deploying a metal stent into such an environment in a patient with AMI initially struck fear into the hearts of even the most ardent supporters of primary balloon angioplasty. However, the realisation that antiplatelet therapy could prevent stent-related thrombotic complications and the publication of a bold study of primary infarct stenting without conventional anticoagulation therapy15 strengthened the advocates' resolve. This first study, although small and non-randomised, paved the way for larger feasibility trials,16 and, more recently, randomised controlled trials of primary stenting in AMI.17,18 These studies demonstrate a substantially lower rate of recurrent ischaemia, reinfarction, angiographic restenosis and a reduced need for target-vessel revascularisation compared with good old balloon angioplasty. Unfortunately, neither of the randomised trials had sufficient power to assess effects on mortality. As is often the case with provocative new data, these observations on primary stenting in AMI provide many more questions than answers. Clearly, it is now important to establish in whom and by whom primary stenting should be done. What patient, vessel or lesion characteristics respond best to primary stenting? For example, should primary stenting be the treatment of choice in diabetic patients, who tend to have more diffuse atherosclerotic disease and a higher risk of restenosis? Should only experienced operators attempt primary stenting in AMI? Coronary stenting may add to the complexity and risks of the procedure rather than lessen them, and most of the recently published data16-18 emanate from centres with unparalleled resources and expertise. Furthermore, what if the lesion is not amenable to primary stenting, or, for that matter, even primary angioplasty? The question of a second-line strategy is often not addressed. In this issue of the Journal, Hansen and colleagues19 indeed address some of these important practical issues. In a pilot study, they assessed the feasibility, safety and short term clinical outcomes of a primary stenting strategy (embracing several critical contingency plans) in a consecutive group of patients with AMI and eligible for fibrinolysis. The authors observed that primary stenting was possible in 71% of their cohort, and, by adopting a strategy that included the "fall-back" options of simple balloon angioplasty, emergency or semiurgent coronary artery bypass grafting (CABG) and medical therapy, they achieved successful early revascularisation of the infarct-related artery in 95% of their patients, with a remarkably low rate of early, six-week and six-month cardiovascular events. The immediate questions that come to mind concern, firstly, the costs, and what well-timed thrombolytic therapy might have achieved in this cohort, and, secondly, whether these results can be extrapolated to centres where resources such as CABG might not be as readily available. The study by Hansen et al is limited by being non-randomised and observational and the experience of a single centre. Nonetheless, it provides important local insight into primary stenting in AMI and indicates that this strategy is safe and feasible and can be delivered in a timely fashion in an appropriately equipped Australian hospital. Whether this holds true for patients at remote centres is unknown, and it is not clear whether patients should be denied early lytic therapy at one institution so they may be transferred to another to obtain primary coronary balloon angioplasty/primary stenting. Thrombolytic therapy has an inherent time delay of approximately 45-60 minutes. A modest delay in obtaining primary angioplasty/primary stenting may therefore be acceptable, but has not been formally tested. In summary, there is a growing body of evidence which suggests that primary stenting in AMI may be preferable to primary coronary balloon angioplasty and possibly more efficacious than conventional thrombolytic therapies. However, no matter how enticing the data may be, all the answers are not in. Does it save lives? Is it cost effective? Is it widely applicable? Does it improve myocardial salvage? Are all stents equal or are some more equal than others? Is it better than primary coronary balloon angioplasty with adjunctive glycoprotein IIb/IIIa platelet receptor blockade? These are but a few of the questions that need addressing, and until these issues are resolved primary stenting must be viewed as a procedure undertaken with the best of intentions. And need I mention where the road paved with good intentions might lead? Ian T Meredith Associate Professor; and Director, Cardiac Catheterisation and Interventional Cardiology, Centre for Heart and Chest Research Monash Medical Centre, Melbourne, VIC Email: ian.meredithATmed.monash.edu.au National Heart Foundation of Australia. Heart and stroke facts. Canberra: NHF, 1996: 1. Lange RA, Hillis LD. Thrombolysis -- the preferred treatment. N Engl J Med 1996; 335: 1311-1312. White HD, Norris RM, Brown MA, et al. Effects of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987; 317: 850-855. O'Rourke M, Baron D, Keogh A, et al. Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator. Circulation 1988; 77: 1311-1315. Gruppo Italiano per lo Studio della Streptochinasi nell' Infarto Miocardico, GISSI. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-401. ISIS-2 Collaborative Group. A randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase or both on coronary artery patency, ventricular function and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-1622. Grines CL. Primary angioplasty -- the strategy of choice. N Engl J Med 1996; 335: 1313-1315. Coronary angioplasty in Australia 1995. Canberra: Australian Institute of Health and Welfare, 1995. (Cardiovascular Disease Series No. 8.) Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction. A quantitative review. JAMA 1997; 278: 2093-2098. Stone GW, Grines CL, Rothbaum D, et al. Analysis of the relative costs and effectiveness of primary angioplasty versus tissue-type plasminogen activator: The Primary Angioplasty Myocardial Infarction (PAMI) Trial. J Am Coll Cardiol 1997; 29: 901-907. De Boer MJ, van Hout BA, Liem AL, et al. A cost-effective analysis of primary coronary angioplasty versus thrombolysis for acute myocardial infarction. Am J Cardiol 1995; 76: 830-833. Yusuf S, Pogue J. Primary angioplasty compared with thrombolytic therapy for acute myocardial infarction. JAMA 1997; 278: 2110-2111. Stone GW, Grines CL, Topol EJ. Update on percutaneous transluminal coronary angioplasty for acute myocardial infarction. In: Topol E, Serruys P, editors. Current review of interventional cardiology. 2nd edition. Philadelphia, Pa: Churchill Livingstone, 1995: 1-56. Saito S, Hosokawa G, Kim K, et al. Primary stent implantation without coumadin in acute myocardial infarction. J Am Coll Cardiol 1996; 28: 74-81. Stone GW, Brodie BR, Griffin JL, et al. Clinical and angiographic follow-up after primary stenting in acute myocardial infarction. The primary angioplasty in myocardial infarction (PAMI) Stent Pilot Trial. Circulation 1999; 99: 1548-1554. Suryapranata H, van't Hof AWJ, Hoorntje JCA, et al. Randomised comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation 1998; 27: 2502-2505. Antonucci D, Santoro GM, Bolognese L, et al. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction. Results from the Florence randomized elective stenting in acute coronary occlusions (FRESCO) trial. J Am Coll Cardiol 1998; 31: 1234-1239. Hansen PS, Rasmussen HH, Vinen J, Nelson GIC. A primary stenting strategy as an alternative to fibrinolytic therapy in acute myocardial infarction. An analysis of results in hospital and at 6 weeks and 6 months. Med J Aust 1999; 170: 537-540. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Ian T Meredith

Healthcare A primary stenting strategy as an alternative to fibrinolytic therapy in acute myocardial infarction An analysis of results in hospital and at 6 weeks and 6 months Peter S Hansen, Helge H Rasmussen, John Vinen and Gregory I C Nelson MJA 1999; 170: 537-540 For editorial comment, see Meredith Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Cardiology and cardiac surgery Abstract Objective: To report the feasibility and results to 6 months of a primary stenting strategy in patients with acute myocardial infarction (AMI). Design: Prospective, single-centre, observational study. Setting: A tertiary referral teaching hospital (Royal North Shore Hospital, Sydney), July 1997 to November 1998. Subjects: 102 (of 194) consecutive patients presenting to the emergency department with AMI who were eligible for fibrinolytic therapy, and for a primary stenting strategy. The first 50 patients were under 70 years of age, and had not had previous coronary artery bypass grafting (CABG). The following 52 patients included patients up to 80 years and with previous CABG. Outcome measures: Major adverse cardiac and cerebrovascular events: death, reinfarction, cerebrovascular accident (CVA) and repeat target lesion revascularisation, in hospital, and at 6 weeks and 6 months. Minor inhospital adverse events: bleeding requiring blood transfusion, vascular complications and new-onset heart failure. Time delays to treatment, and duration of hospital stay. Results: Normal flow was established in the infarct-related artery in 97/102 patients (95%). Stenting, percutaneous transluminal coronary angioplasty (PTCA), CABG or medical therapy was performed in 74, 11, 9 and 8 patients, respectively. Minor inhospital events, time delays and hospital stay were similar to those reported previously. At 6 weeks, major adverse cardiac and cerebrovascular events had occurred in 5% of patients (four repeat target lesion revascularisation and one reinfarction). By 6 months, repeat target lesion revascularisation had been performed in an additional 10% of patients. No deaths had occurred. Conclusions: A primary stenting strategy can be performed safely, without significant delays and with excellent short and intermediate term outcomes. Introduction Early patency of the infarct-related artery after acute myocardial infarction (AMI) (defined as patency 90 minutes after the start of fibrinolytic therapy) improves early and late survival.1-3 With fibrinolytic therapy, the key treatment of AMI for the past 12 years,4,5 at best only about half the patients treated achieve early patency, the proportion varying with the fibrinolytic agent used (29% with streptokinase and 54% with tissue plasminogen activator [t-PA]).1 Moreover, in up to 30% of patients the artery reoccludes within 3 months.6 Prospective randomised trials of primary percutaneous transluminal coronary angioplasty (PTCA) have shown improved early patency and short-term clinical outcomes in comparison with fibrinolytic therapy.7-10 However, the benefits of primary PTCA are attenuated, as reocclusion occurs in 5%-10% of patients, reinfarction in 3%-5%, angiographic restenosis in 35%-45%, and recurrent ischaemia requiring repeat target lesion revascularisation in about 20% of patients.7-13Primary stenting in selected patients with AMI appears to be more effective than PTCA or fibrinolytic therapy,2,3,6-18 but not all infarct-related arteries are suitable for stenting. A primary stenting strategy incorporating primary stenting, PTCA, coronary artery bypass grafting (CABG) or medical treatment (except fibrinolytic therapy) is expected to cater for all patients. We examined prospectively the feasibility and clinical outcomes to 6 months of a primary stenting strategy in patients with AMI who were eligible for fibrinolysis. Methods During the period July 1997 to November 1998, we studied prospectively 194 consecutive patients who presented with AMI to the emergency department at Royal North Shore Hospital. Patients with contraindications to heparin, aspirin, ticlopidine or fibrinolytic therapy, and those with established cardiogenic shock, were not eligible for the study. Patient selection Patients included: 102 patients fulfilled GUSTO criteria for AMI,5 and were eligible for fibrinolysis. A lower age limit was imposed during the first half of the study (during the learning curve for the stenting team), and patients with previous CABG were excluded because stenting was initially thought to be less effective in vein-graft occlusion. Accordingly, the first 50 patients were under 70 years and had not had CABG. The following 52 patients, two of whom had had CABG, were under 80 years. Patients excluded: Reasons for non-entry to the study in 92 patients were age limit exceeded (over 70 years, 47 patients; over 80 years, 23 patients); transfer from other hospitals for primary intervention (5 patients); not eligible for fibrinolysis, including two with cardiogenic shock (8 patients); no vascular access (2 patients); prior CABG (2 patients); cardiogenic shock (1 patient); eligible but refused (2 patients); and eligible but interventional cardiologist unavailable (2 patients). Ethical approval The protocol was approved by the hospital's Human Research and Ethics Committee. All patients gave informed consent. Study protocol Patients were given aspirin (300 mg), ticlopidine (500 mg) and an intravenous heparin bolus (150 U/kg), and transferred immediately to the catheterisation laboratory, or, out of working hours, as soon as the interventional team arrived. Low-osmolar ionic contrast medium (sodium ioxaglate) was used to minimise thromboembolic complications.19 Blood flow was re-established in the occluded infarct-related arteries with Magnum (Schneider, Bulach, Switzerland) 0.014 inch wire through a 6 French (2 mm diameter) guide. Placement of a stainless steel stent (the majority were GFX (Arterial Vascular Engineering, Santa Rosa, Calif, USA) by high pressure balloon inflation (> 10 atmospheres) was attempted in vessels with a reference segment diameter of more than 2.5 mm and a lesion length of less than 32 mm. Thrombus was not considered a contraindication to stenting. Fibrinolytic therapy was not given. Medical treatment only was given (aspirin, heparin, β-blockers) if, after cardiac catheterisation, the infarct-related artery was patent with normal brisk flow (ie, grade 3 flow as defined by the Thrombolysis in Myocardial Infarction [TIMI] trial20), and had residual stenosis of less than 50% of vessel diameter. Emergency (immediate) or inhospital CABG was performed for left main coronary artery and/or severe triple-vessel disease, and PTCA was performed when the diameter of the infarct-related artery was less than 2.5 mm. A glycoprotein IIb/IIIa receptor antagonist (abciximab) was given to 23 of the 102 patients: 11 patients having primary PTCA, 3 patients in whom reflow did not occur, and 9 patients with persistent filling defects or a long stented segment (> 18 mm). Further heparin was given if activated clotting time (for monitoring high dose heparin) was under 300 seconds. No further heparin was given after the procedure and patients were mobilised 12 hours after femoral sheath removal. Ticlopidine (250 mg daily) was administered for 4 weeks and patients were monitored for side effects (neutropenia, thrombocytopenia). All patients were followed up by their general practitioner and specialist physician. Follow-up for the trial was at 6 weeks and 6 months; patients completed questionnaires or, if necessary, were interviewed by phone. Outcome measures Study outcome measures were major adverse cardiac and cerebrovascular events: death, reinfarction, cerebrovascular accident (CVA) and repeat target lesion revascularisation, in hospital, and at 6 weeks and 6 months. Reinfarction was defined as recurrent ischaemic symptoms with changes noted on the electrocardiogram (ECG) (ST-segment elevation or new Q waves) and elevation in the level of creatine kinase (MB fraction) to more than twice the upper limit (normal range, 0-7 µg/L) or any rise above a previously elevated level. CVA was defined as new persistent (> 24 hours) neurological deficit consistent with a stroke, confirmed by a physician or by computed tomography scan of the brain. Patency of the infarct-related artery was determined by TIMI classification.20 Minor inhospital adverse events included bleeding requiring blood transfusion, vascular complications and new-onset heart failure. Successful procedural outcome was a patent infarct-related artery with residual stenosis of less than 30% of vessel diameter (without major adverse cardiac and cerebrovascular events in hospital), or uncomplicated CABG. Results The baseline clinical characteristics of the 102 consecutive eligible patients with AMI are shown in Box 1, and their treatment and outcome in hospital are shown in the Figure. Overall, TIMI 3 flow in the infarct-related artery was restored in 97/102 (95%) patients within a mean of 64 minutes (range, 30-130 minutes) of notifying the interventional team. There were no inhospital deaths, reinfarctions or CVAs. Four patients (4%) required repeat target lesion revascularisation (three had been treated initially with PTCA and one with stenting). Unscheduled recatheterisation was performed in another four patients with chest pain, without ECG changes. All showed a widely patent stent. No patient developed recurrent chest pain with ECG changes while in hospital. Minor inhospital events included blood transfusion, all after CABG (7/102; 7%), new-onset heart failure (2/102; 2%), and femoral artery pseudoaneurysm requiring surgical repair (2/102; 2%). For more information see flow chart Six-week and 6-month follow-up Follow-up was completed for all patients due for follow-up at 6 weeks (n = 102) and at 6 months (n = 58). At 6 weeks no deaths or CVAs had occurred. One patient had had a reinfarction after a subacute stent thrombosis on Day 10. He underwent successful repeat PTCA (reperfusion at sites other than the target lesion was not performed). Major adverse cardiac or cerebrovascular events had occurred in 5/102 patients: one had a reinfarction after discharge and four required repeat target lesion reperfusion. At 6 months, still no deaths had occurred, and there had been no further reinfarctions or CVAs. Clinical restenosis requiring repeat target lesion revascularisation occurred in an additional 6/58 patients (10%). Revascularisation at a new site of stenosis was performed in 1/58 patients (2%). No deaths, reinfarctions or CVAs had occurred since discharge, and at 6 months there had not been any requirement for revascularisation in 51/58 patients (88%). Hospital stay Mean hospital stay was 5.0 days (95% confidence interval (CI), 4.5-5.5 days). Mean coronary care, intensive care and general ward stays were 1.5 (95% CI, 1.4-1.6), 0.5 (95% CI, 0.3-0.7) and 3.0 days (95% CI, 2.7-3.3), respectively. Median hospital stay was 3 days. Time delays Time delays between the onset of chest pain and re-establishment of TIMI 3 flow of the infarct-related artery are shown in Box 2. Although 58% of patients presented out of working hours, only 10% of "call-backs" for the intervention team took place between 23:00 and 04:00. Discussion We examined the feasibility and clinical outcomes to 6 months of a primary stenting strategy. Expected advantages of such an approach, compared with fibrinolytic therapy, are greater patency of the infarct-related artery with improved outcome, early recognition of high risk patients for surgical revascularisation and low risk patients for early discharge, reduced rate of CVA, and lower acute complication rate and need for reperfusion of the target lesion compared with primary PTCA.14 Our results support these expectations. Coronary artery patency with the primary stenting strategy was achieved in 95% of patients, similar to reports for primary stenting in selected patients,14-18 but higher than reported for primary PTCA (73%-87%) and fibrinolysis with t-PA (54%).1,3,7-9 Interestingly, 25% of patients in our study had TIMI 3 flow at cardiac catheterisation, a rate higher than reported by some investigators (7%-11%)14 and similar to rates after fibrinolysis with streptokinase (29%-32%). We gave a 150 U/kg bolus dose of intravenous heparin, which may explain this difference.21 Our results compare favourably with those of other primary stenting studies.14-18 A 30-day rate of 3% for major adverse cardiac and cerebrovascular events has been reported for patients undergoing primary stenting.14,15 However, in one of these studies,14 up to 15% of patients screened were excluded, owing to unsuitable anatomy of the infarct-related artery (eg, diffuse disease), and events in such patients were not included. Several studies report outcomes of patients treated by primary PTCA separately to those treated by stenting,14-18 making it difficult to directly compare the results with those of trials of fibrinolytic therapy in which all patients are included. We included all patients eligible for fibrinolysis who fulfilled the inclusion criteria in our analysis. This allows a more realistic impression of the benefits of a primary stenting strategy, as our data can be compared with data from trials of fibrinolytic therapy (the alternative treatment offered to all patients at enrolment). Feasibility In order to test the feasibility of a primary stenting strategy (our main aim), our emergency department had to triage patients without delay and the interventional team had to respond swiftly at all hours. Time delays (mean and median) from arrival at the emergency department to notification of the interventional team (42 and 35 minutes), from notification of the team to TIMI 3 flow (64 and 60 minutes), and from arrival at the emergency department to TIMI 3 flow (106 and 95 minutes), compare well with time delays from trials of fibrinolysis and angioplasty. The GUSTO investigators reported a median interval of 64 minutes from randomisation to administration of fibrinolytic therapy,5 and the GUSTO IIb investigators reported a median interval of 114 minutes from emergency department arrival to first balloon inflation in the primary PTCA group.10 Patency rates are reported 90 minutes after starting fibrinolytic therapy.1 Assuming a mean delay of 42 minutes in the emergency department to administration of fibrinolytic therapy, the equivalent inhospital delay from emergency department arrival to TIMI 3 flow with fibrinolytic therapy would be a mean of 132 minutes (but TIMI 3 flow would actually be achieved in only 54% of patients). We achieved TIMI 3 flow in 95% of patients within a mean of 106 minutes of arrival at the emergency department. Limitations of the study This study was a non-randomised, single-centre study with a small sample size. For the first half of the study, enrolment was restricted to a relatively low risk group under 70 years of age without previous CABG. Interventions were performed by two experienced operators. Thus, comparison of our data with results from much larger trials of fibrinolytic therapy must be performed with caution. Conclusions A primary stenting strategy is feasible and safe, with an excellent clinical outcome to 6 months. We are now planning a larger, randomised phase of this study, with patients from the Northern Sydney Area Health Region (which includes four district hospitals) outside the Royal North Shore Hospital (RNSH) catchment area being allocated at random to either conventional treatment with fibrinolytic therapy at the district hospital or a primary stenting strategy at RNSH. We hypothesise that mechanical reperfusion therapy will prove the superior strategy because of its higher early patency rate3 and offset any disadvantages of the small time difference imposed by a longer ambulance journey. Acknowledgements This study was supported by the North Shore Heart Research Foundation (NSHRF). GFX (AVE) stents and Magnum (Schneider) guide wires were donated. Dr P S Hansen received a Cordis-Johnson & Johnson Interventional Fellowship (1997) and a NSHRF Fellowship (1998). The study would not have been possible without the unselfish support from radiographers, technicians and nursing staff of the Royal North Shore Hospital cardiac catheterisation laboratories as well as all staff involved from the Cardiology, Emergency and Cardiothoracic departments. References The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-1622. Califf RM, White H, Van de Werf F, et al. One-year results from the global utilization of streptokinase and TPA for occluded coronary arteries (GUSTO-I) trial. Circulation 1996; 94: 1233-1238. Ross AM, Coyne KS, Moreyra E, et al, for the GUSTO-I Angiographic Investigators. Extended mortality benefit of early postinfarction reperfusion. Circulation 1998; 97: 1549-1556. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trials of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360. The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673-682. Meijer A, Verheugt FWA, Werter CJPJ, et al. Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Circulation 1993; 87: 1524-1530. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993; 328: 673-679. Zijlstra F, de Boer JM, Hoorntje JC, et al. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993; 328: 680-684. Gibbons RJ, Holmes DR, Reeder GS, et al. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993; 328: 685-691. The GUSTO-IIb angioplasty substudy investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997; 336: 1621-1628. Stone GW, Grines CL, Browne KF, et al. Predictors of in-hospital and 6 month outcome after acute myocardial infarction in the reperfusion era: the Primary Angioplasty in Myocardial Infarction (PAMI) trial. J Am Coll Cardiol 1995; 25: 370-377. Ohman EM, Califf RM, Topol EJ, et al. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. Circulation 1990; 82: 781-791. Weaver WD, Simes J, Amadeo B, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction. A quantitative review. JAMA 1997; 278: 2093-2098. Stone GW, Brodie B, Griffin J, et al. Prospective, multicentre study of the safety and feasibility of primary stenting in acute myocardial infarction: In-hospital and 30-day results of the PAMI Stent Pilot Trial. J Am Coll Cardiol 1998; 31: 23-30. Suryapranata H, van't Hof AWJ, Hoorntje JCA, et al. Randomized comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation 1998; 97: 2502-2505. Antoniucci D, Santoro GM, Bolognese L, et al. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction. Results from the Florence Randomized Elective Stenting in Acute Coronary Occlusions (FRESCO) Trial. J Am Coll Cardiol 1998; 31: 1234-1239. Saito S, Hosokawa G. Primary Palmaz-Schatz stent implantation for acute myocardial infarction: the final results of Japanese PASTA (Primary Angioplasty vs Stent Implantation in AMI in Japan) trial [abstract]. Circulation 1997; 96: A3320. Serruys PW, Garcia-Fernandez E, Kiemeney F, et al. Stenting in acute MI: A pilot study as preamble to a randomized trial comparing balloon angioplasty and stenting [abstract]. Circulation 1997; 96: A1822. Grines CL, Schreiber TL, Savas V, et al. A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable angina undergoing percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1996; 27: 1381-1386. The TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) Trial: Phase 1 findings. N Engl J Med 1985; 312: 1073-1092. Verheugt FWA, Liem A, Zijlstra F, et al. High dose bolus heparin as initial therapy before primary angioplasty for acute myocardial infarction: results of the heparin in early patency (HEAP) pilot study. J Am Coll Cardiol 1998; 31: 289-293. (Received 3 Jul 1998, accepted 15 Feb 1999) Authors' details Department of Cardiology, Royal North Shore Hospital, Sydney, NSW. Peter S Hansen, FRACP, Interventional Fellow. Helge H Rasmussen, DMSc, FRACP, Professor of Cardiology. John Vinen, FACEM, Director, Emergency Department. Gregory I C Nelson, FRACP, Director, Cardiac Catheterisation Laboratory and Coronary Care Unit. Reprints: Dr G I C Nelson, Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW 2065. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> 1: Baseline clinical and angiographic characteristics of the study population (n = 102)Age in years, median (range) 60 (35-79)Women18 (18%)Hypertension (< 160/190 mmHg) 46 (45%)Diabetes mellitus13 (13%)Current cigarette smoking28 (27%)Hypercholesterolaemia (< 5.5 mmol/L)62 (61%)Family history of IHD47 (46%)Prior AMI14 (14%)Prior PTCA2 (2%)Prior CVA or transient ischaemic attack7 (7%)Infarct-related artery: Left anterior descending artery (40), diagonal branch of left anterior descending artery (1), left main coronary artery (1) 42 (41%) Right coronary artery40 (39%) Left circumflex artery (12), obtuse marginal artery (2)14 (14%) Saphenous vein graft2 (2%)No infarct-related artery identified (3), normal coronary arteries (1) 4 (4%)Multivessel disease48 (47%)Admission Killip class < I6 (6%)Killip class > I = the presence of either lung crepitations and a third heart sound gallop, frank pulmonary oedema or cardiogenic shock. PTCA = percutaneous transluminal coronary angioplasty. CVA = cerebrovascular accident. IHD = ischaemic heart disease. AMI = acute myocardial infarction. Back to textBack to textBack to text

Peter S Hansen · Helge H Rasmussen · John Vinen

For Debate The 100-year conflict: salt intake and cardiovascular disease MJA 1998; 169: 174-180 The health effects of dietary salt have long been debated. As early as the beginning of the 20th century, salt restriction was used as a therapeutic measure, first for oedema and then for hypertension, particularly in France.1 Later, in the United States, the benefits of low salt diets for patients with hypertension and renal disease were championed by Allen in the 1920s and 30s and by Kempner in the late 1930s and 40s.1 However, not all investigators were convinced of the value of these diets, and the hazards of overzealous and prolonged salt restriction were also appreciated.1 By the 1960s and 70s, studies linking an increase in blood pressure of indigenous populations with the introduction of salty Western diets persuaded government bodies to recommend reduced salt as part of healthy dietary guidelines. One of the eight Dietary Goals for Australia, announced in 1979 by the then Commonwealth Department of Health, was "Decrease consumption of salt".2 There are, however, many researchers who maintain that there is insufficient evidence of benefit to recommend universal salt restriction. A summary of this controversy, described as "a philosophical clash between the requirements of public health policy and the requirements of good science", appeared in Science last year.3 In the MJA the salt controversy is alive and well. A study by Beard et al published in 1997 showing a low level of conformity with the year 2000 dietary salt target for Australians (<100mmol/day)4 brought an immediate response from Kincaid-Smith, reminding readers of the possible dangers of low salt intake.5 Then, in March 1998, a study by Alderman et al in the Lancet, claiming to have found an inverse association between dietary salt intake and all-cause and cardiovascular disease mortality,6 revived the international controversy, to which the Lancet's letters columns attest.7-10 Here, we present our own salt debate, with three views of the value (or otherwise) of salt restriction as part of a healthy diet. Universal recommendations for sodium intake should be avoided Restriction of salt intake is needed too ameliorate the cardiovascular disease epidemic The salt dilemma: some answers, many questions Link to salt debate references Dr Derek Denton showed unequivocally that increased salt intake causes a substantial rise in blood pressure in chimpanzees.11 Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

At the end of the 20th century, the good news about rheumatic fever is that it has become so rare in most of Australia that many medical practitioners will never see a case. This is a dramatic change from the first half of the century; in Melbourne during the 1930s, more than 50% of paediatric hospital medical beds were occupied by children with acute rheumatic fever or acute poststreptococcal glomerulonephritis, with rheumatic fever patients outnumbering those with glomerulonephritis (Dr Howard E Williams, previously In-Patient Physician, Royal Children's Hospital, Melbourne, personal communication). The decline of rheumatic fever in affluent populations occurred largely as a result of economic development and improved living conditions, with perhaps a small contribution from antibiotics and the possibly altered virulence of circulating group A streptococcal strains.1 The bad news is that socially and economically disadvantaged populations worldwide, including some indigenous and minority populations living in affluent countries, continue to have high rates of rheumatic fever and rheumatic heart disease. The highest published incidence of acute rheumatic fever in the world is in Aboriginal people living in the "Top End" of the Northern Territory.2 In this population the annual incidence of acute rheumatic fever (1989-1993) is between two and seven cases for every 1000 children aged 5 to 14 years, while up to three per cent of all people in some of the remote Aboriginal communities have established rheumatic heart disease. In contrast, the prevalence of rheumatic heart disease in the non-Aboriginal population is 0.014 per cent, and no non-Aboriginal children had acute rheumatic fever over this five-year period.2 While rheumatic fever appears to occur in only a subset of any given population, there are no data to support any major predisposition based on ethnicity. Similar high rates were documented in non-Aboriginal people in Melbourne during the 1930s and 1940s.3 The current high rates of rheumatic fever in the Aboriginal population are not related to ethnicity, but are likely to reflect high levels of exposure to group A streptococci, which, in turn, are related to overcrowding and continuing poor living conditions.4,5 The World Health Organization has promoted the use of rheumatic fever registers in developing countries,6 with the major aims of coordinating individual patient management and improving adherence to secondary prophylaxis to prevent recurrent rheumatic fever and the associated cumul ative valve damage. Registers are useful not only for developing countries: a register-based program in New Zealand, with acute rheumatic fever as a notifiable disease, helped reduce from 22% to 6% the proportion of hospitalised cases of rheumatic fever which were recurrences.7 The Commonwealth Department of Health and Family Services, together with the Australian Institute of Health and Welfare, has taken the commendable step of funding a register-based control program in the Top End of the Northern Territory (Dr Vicki Krause, Director, Centre for Disease Control, Territory Health Services, Darwin, personal communication). This program will also involve new health promotion strategies in Aboriginal communities -- directed at both health and education staff and at people with rheumatic fever and rheumatic heart disease and their families. Videos, booklets and treatment charts have been developed by indigenous educators and researchers.8 The program will attempt to create a partnership for change, involving indigenous and non-indigenous health professionals and government and non-government health services. Secondary prophylaxis will reduce the number of people developing rheumatic heart disease or requiring intervention for worsening valvular damage, but it will not stop initial episodes of acute rheumatic fever. This is where rheumatic fever control becomes difficult. While efforts to address social and economic inequities, particularly living conditions and overcrowding in Aboriginal communities, cannot be overemphasised,4,5 in some remote communities substantial change in these areas has not been evident over the past two decades and, in the current economic climate, is unlikely, we believe, to occur for some time. Conventionally, primary prevention relies on the accurate diagnosis and timely treatment with penicillin of group A streptococcal pharyngitis. However, most developing countries do not have the finances, skilled staff or laboratory facilities to do this well. Furthermore, more than two-thirds of cases of acute rheumatic fever may not follow symptomatic pharyngitis,9 so concentrating only on sore throats probably will not prevent most cases of rheumatic fever. Important progress is being made towards the development of a group A streptococcal vaccine, including current Australian initiatives,10 but in the shorter term other approaches are needed. In one such approach, a program of regular throat swabbing and treatment of streptococcal carriers in one Aboriginal community appeared to coincide with fewer cases of rheumatic fever,11 although the program was not sustained over the long term.12 This program appears to be the sole published effort to improve primary prevention of acute rheumatic fever in an Aboriginal community. While an association between streptococcal skin sores and acute rheumatic fever remains speculative, clues to further primary prevention strategies may come from understanding the epidemiology of group A streptococcal diseases in Aboriginal communities -- where the prevalence of streptococcal pyoderma (skin sores) may be up to 70% in children, but throat carriage rates of group A streptococci are often low.13 The ongoing epidemic of scabies in Aboriginal communities must underlie much of the streptococcal skin disease. More research is needed to better understand the epidemiology and best management of sore throats, streptococcal pharyngitis and skin sores in Aboriginal communities, as well as the relationship between streptococcal throat and skin infections and rheumatic fever. In the meantime, primary prevention strategies should include measures to reduce the reservoir of circulating streptococci found in skin sores; coordinated programs to control skin sores and underlying scabies can be effective in Aboriginal communities.13 Successful primary prevention strategies developed in Australia could have global implications for rheumatic fever control. Rheumatic heart disease in Aboriginal communities can be controlled in the short term through the use of comprehensive strategies to improve adherence to secondary prophylaxis regimens and to reduce exposure to group A streptococci, and possibly, in the longer term, with a vaccine. However, the ultimate aim must be improved living conditions for Aboriginal people, including emphasis on water supply, taps and showers, the disposal of sewage and solid waste, and resources to support better hygiene.

Jonathan R Carapetis · Bart J Currie

Panic disorder and coronary artery spasm Whatever the causative mechanism, prolonged chest pain during panic attacks requires investigation MJA 1998; 168: 376-377 The three cases reported by Mansour et al1 in this issue of the Journal add to the evidence for increased risk of adverse cardiovascular events in people with severe anxiety. The existing evidence derives from both prospective epidemiological studies2,3 and controlled longitudinal clinical studies.4 In the latter, mortality was related to severity of emotional arousal; panic disorder patients were at greater risk of sudden cardiac death than patients with lesser forms of anxiety, such as generalised anxiety disorder. Two of the cases reported by Mansour et al (Patients 1 and 3) showed a close temporal association between panic attacks and ischaemic chest pain. In the absence of severe obstructive coronary disease, might the ischaemia be due to coronary artery spasm? Patient 1 presented with severe chest pain accompanying episodes of panic. An electrocardiogram (ECG) showed mild tachycardia and ST-segment depression, but no cardiac enzymes were released, and the coronary angiogram was normal. With subsequent panic attacks, the patient continued to experience anginal pain, which resolved completely after prescription of amlodipine (a potent dihydropyridine calcium antagonist known to prevent epicardial coronary spasm). Patient 3 had long-standing panic disorder and mild hypertension. He had acute ischaemic chest pain during a panic attack; cardiac enzyme levels were raised, and infarction was diagnosed. Angiography showed no underlying atherosclerosis. Angina-like chest pain occurred during subsequent panic attacks, but once again resolved completely after amlodipine therapy. The other patient (Patient 2) experienced an infarct associated with exercise rather than with an acute panic attack. Coronary angiography during the acute stage showed that the infarct-related artery was occluded, while the other coronary arteries were normal. The patient had a nine-year history of panic disorder, and previous panic attacks had been accompanied by chest pain. However, no chest pain occurred during post-infarction panic attacks, and there was no temporal relationship between panic attacks and the major ischaemic episode. Although coronary artery spasm is one of the plausible mechanisms for the cardiac ischaemia, none of these patients had convincing evidence of spasm during panic attacks. Spasm of an epicardial coronary artery usually results in ST-segment elevation, which accompanies transmural ischaemia. A definitive diagnosis of coronary spasm requires demonstration of ST-segment elevation, or spasm at angiography, during spontaneous angina or after provocation with ergonovine, acetylcholine or hyperventilation. In Patient 1, the ECG during chest pain showed ST-segment depression, while in Patient 3 no ECG changes were seen. While coronary spasm with ST-segment depression or even no ST changes has been reported, this is very uncommon. In Patient 1, the presence of tachycardia along with ST-segment depression raises the possibility of Syndrome X (angina-like chest pain with ST-segment depression, no demonstrable myocardial ischaemia and normal coronary arteries,5 which is not to be confused with the endocrinological Syndrome X, or insulin resistance metabolic syndrome6 ). Another possible explanation is the coronary "slow flow" phenomenon, which may be caused by microvascular spasm, although slow flow was not mentioned in the angiography report. Nevertheless, the complete resolution of angina in Patients 1 and 3 after treatment with amlodipine provides circumstantial evidence that spasm was involved. Radionuclide studies shed some light on a possible link between mental stress and coronary vasoconstriction. Subjects exposed to minor experimental stress have been shown to develop significantly reduced coronary perfusion and ischaemic abnormalities of left ventricular wall motion. These abnormalities are due to coronary vasoconstriction, but are limited to subjects with at least minor degrees of underlying coronary artery disease, and are more pronounced when this disease is more severe. Subjects with normal arteries do not show such changes.7 Similarly, coronary spasm in the setting of emotional problems was described in nine women with normal or near-normal arteries,8 but it was likely that most had at least minor atherosclerosis (ie, <25% narrowing). In two of the patients reported by Mansour et al, coronary vessels were normal (and possibly also in Patient 2 before occlusion), so induction of spasm or vasoconstriction with ischaemia seems inconsistent with the experimental studies. However, angiographically "normal" arteries may harbour minor atherosclerotic lesions that do not encroach on the lumen. In addition, the severe and overwhelming emotional stress and arousal typical of panic, which these patients doubtless experienced, contrasts with the relatively minor tasks with minimal emotional responses to which the experimental subjects were exposed. The coronary vascular responses to severe and minor stress may be quite different. For example, extreme rage induced myocardial infarction in dogs, although after a critical stenosis had been created in a coronary artery.9 Severe emotional arousal deserves further investigation. Wilkinson et al showed that patients with panic disorder have dramatic increases in epinephrine secretion and cardiac epinephrine spillover during panic, but that baseline levels and responses to mild experimental stress differ little from those of control subjects.10 Cardiac perfusion and functional studies during panic would be of interest, but would require panic attacks to be artificially induced in the laboratory. The absence of ECG changes in Patient 3, despite severe chest pain and significantly raised cardiac enzyme levels, raises an important issue about myocardial ischaemia. In the radionuclide studies mentioned above, significant decreases in perfusion or abnormalities in wall motion often occurred without ischaemic pain or ECG changes. Ischaemia can be electrocardiographically "silent", particularly in certain vascular distributions, such as that of the left circumflex coronary artery. Nevertheless, it must be unusual that ischaemia sufficient to produce necrosis should produce no ECG changes. These cases should raise clinician awareness of the potential association between severe anxiety and myocardial ischaemia, so that patients with chest discomfort and panic disorder are appropriately investigated. All patients with severe panic accompanied by prolonged chest pain should have cardiac enzyme levels measured, irrespective of ECG findings. While epicardial coronary artery spasm is a plausible explanation, further investigations are needed into the mechanisms of ischaemia in panic disorder. S Ben Freedman Professor, and Head, Department of Cardiology Concord Repatriation General Hospital, University of Sydney, NSW Christopher C Tennant Professor and Head, Department of Academic Psychiatry Royal North Shore Hospital, University of Sydney, Sydney, NSW Mansour VM, Dominic JC, Jennings GL, et al. Panic disorder: coronary spasm as a basis for cardiac risk? Med J Aust 1997; 168: 390-392. Kawachi I, Sparrow D, Vokonas PS, Weiss ST. Symptoms of anxiety and risk of coronary heart disease. Circulation 1994; 90: 2225-2229. Kawachi I, Colditz GA, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89: 1992-1997. Coryell W, Noyes R, Clancy J. Excess mortality in panic disorder. A comparison with primary unipolar depression. Arch Gen Psychiatry 1982; 39: 701-703. Cannon RO. Does coronary endothelial dysfunction cause myocardial ischemia in the absence of obstructive coronary artery disease? Circulation 1997; 96: 3251-3254. Alford FP. Syndrome X (insulin resistance metabolic syndrome): a deadly quartet or an awesome foursome? Med J Aust 1996; 164: 4-5. Tennant C. Experimental stress and cardiac function. J Psychosom Res 1996; 40: 569-583. Bashour T, Hakim O, Cheng TO. Coronary spastic angina in middle-aged women: a psychosomatic disorder? Am Heart J 1983; 106: 609-613. Verrier RL, Hagestad EL, Lown B. Delayed myocardial ischemia induced by anger. Circulation 1987; 75: 249-254. Wilkinson DJC, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorders at rest, under laboratory mental stress and during panic attacks. Arch Gen Psychiatry 1998. In press. Reprints: Professor S Ben Freedman, Department of Cardiology, Concord Repatriation General Hospital, Hospital Road, Concord, Sydney, 2137. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Christopher C Tennant

Panic disorder: coronary spasm as a basis for cardiac risk? Virginia M Mansour, Dominic J C Wilkinson, Garry L Jennings, Rosemary G Schwarz, Jane M Thompson and Murray D Esler For editorial comment see Freedman & Tennant Patients with panic disorder often complain of angina-like chest pain during panic attacks, but this is not usually considered life-threatening. We describe three patients with panic disorder and documented cardiac ischaemia during episodes of chest pain. In two, it progressed to myocardial infarction. As none had atherosclerosis evident at coronary angiography, the mechanism was presumed to be coronary artery spasm. These cases illustrate that pain typical of angina during panic attacks may have an organic cause. (MJA 1998: 168; 390-392) Introduction - Case records - Discussion - Acknowledgement - References - Authors' details - - ©MJA1998 Introduction Panic disorder is characterised by unpredictable and overwhelming feelings of fear accompanied by various symptoms of sympathetic nervous system arousal, such as sweating, palpitations, diarrhoea, and tremor.1 Often, angina-like chest pain is also present, but detailed cardiac "workup" in patients with panic disorder typically shows no abnormalities. Thus, although panic disorder is distressing and disabling, it has not been thought life-threatening. However, recent well conducted, prospective epidemiological studies show substantially increased risk of myocardial infarction and sudden death in patients with panic disorder (three- to six-fold increase).2,3 These patients sit at the crossroads of cardiology and neuropsychiatry, and provide a clinical model for investigation of the relationship between stress and heart disease. The mechanism by which cardiac risk is increased in panic disorder is not known, but has been thought to involve activation of the sympathetic nerves of the heart, predisposing to ventricular arrhythmias. We present three patients with panic disorder and chest pain whose cases suggest coronary artery spasm as a pos sible mechanism. Case records All three patients met the diagnostic criteria for panic disorder of the Diagnostic and statistical manual of mental disorders (4th edition),4 and all were non-smokers. Patient 1 A 34-year-old woman presented to a hospital casualty department in November 1996 with severe chest pain radiating to her left arm and shortness of breath after having taken cocaine. She also complained of palpitations, dizziness, tremor, and an overwhelming sense of doom and fear. She had taken cocaine occasionally over the previous two years without panic symptoms. An electrocardiogram (ECG) showed inferolateral ST-segment depression suggesting ischaemia. The pain eased with sublingual nitroglycerine and intramuscular morphine. A thallium exercise stress test two weeks later gave normal results. The patient presented again a month later with recurrent episodes of severe chest pain accompanying panic attack symptoms. She had stopped using cocaine after the first panic attack. An ECG taken during persisting pain again showed inferolateral ST-segment depression (Figure 1, below). Serum creatine kinase (CK) levels were normal. Coronary angiography during subsequent hospital admission (when the patient was free of pain) showed a normal coronary arterial tree (Figure 1). The patient was prescribed the selective serotonin reuptake inhibitor paroxetine (20 mg, increasing to 40 mg, daily), low dose aspirin (100 mg daily) and alprazolam (0.5 mg daily). Over two months' follow-up, panic attacks were less frequent, but chest pain recurred with each. After the addition of the slow calcium-channel blocker amlodipine (5 mg daily), her infrequent panic attacks were pain-free. Patient 2 A 42-year-old woman suffered anteroseptal infarction in November 1996 after exercise. Although she had no antecedent panic attack, she had a nine-year history of panic disorder, with panic attacks commonly associated with chest pain. She had been jogging as usual that morning without any symptoms, and presented later in the day with chest tightness and left-arm pain. A 12-lead ECG (Figure 2, below) showed anteroseptal ST-segment elevation consistent with acute myocardial infarction. Acute coronary angiography (Figure 2) showed total occlusion of the left anterior descending coronary artery in its mid portion. Treatment with balloon angioplasty and abciximab (an inhibitor of platelet aggregation) achieved complete recanalisation, and the pain resolved. No atherosclerosis was evident in the coronary arterial tree. Although a vasodilator was not given during angiography, the treating cardiologist described the angiogram as indicating development of fresh thrombus at a site of spasm in an otherwise normal coronary artery. Low dose aspirin and amlodipine (5 mg daily) were prescribed. The patient had further panic attacks (without chest pain) until paroxetine (20 mg daily) was also prescribed. Patient 3 A 46-year-old man presented to a casualty department in October 1996 with severe chest pain during a panic attack. He had long-standing panic disorder and a 15-year history of mild essential hypertension treated by propranolol (40 mg daily). His ECG was normal in the casualty department, and he was not admitted. The chest pain failed to resolve over the next 10 hours and he attended his family doctor, who found a raised serum CK level and arranged urgent hospital admission. His serum CK level rose progressively in hospital, peaking at 518 U/L (normal range [NR], 0-130 U/L), with CK MB isoenzyme level 66 U/L (NR, 0-10 U/L), leading to a diagnosis of myocardial infarction. Coronary angiography 14 days later, when the patient was free of pain, gave normal results, with no evidence of atherosclerosis. Over the ensuing eight months, the patient had increasingly frequent panic attacks accompanied by angina-like pain. He was prescribed paroxetine (20 mg, increasing to 40 mg, daily) and alprazolam (0.5 mg daily). Although the panic attacks became less frequent when the daily paroxetine dose was increased to 40 mg, chest pain persisted until amlodipine (5 mg daily) and aspirin (100 mg daily) were added to the regimen. Discussion These three patients with panic disorder had otherwise inexplicable episodes of cardiac ischaemia. In all three, the panic attacks were typically accompanied by chest pain. In two, the documented ischaemic events (angina with ST-segment depression in one and myocardial infarction in the other) occurred during a panic attack. In the third, while myocardial infarction was associated with exercise rather than a panic attack, there was a long prior history of panic attacks with chest pain. None of the three had atherosclerosis evident on coronary angiography, and two were women with no classical cardiac risk factors. Coronary artery spasm was thought to be the underlying mechanism of the ischaemia in all three cases. In some circumstances, patients with primary cardiac arrhythmias can be misdiagnosed as having panic disorder.5 Similarly, it might perhaps be argued that our patients had variant angina, with the anxiety disorder developing after a period of misdiagnosis of the cause of the chest pain, so that the myocardial ischaemia was a cause rather than a consequence of the panic disorder. However, in Patients 2 and 3 the diagnosis of panic disorder antedated the development of chest pain during panic attacks, while in Patient 1 angina-like pain was a feature of the first and of most subsequent panic attacks. The mechanism by which coronary spasm develops in panic disorder is not clear. Cigarette smoking can underlie coronary spasm, but our three patients were non-smokers. Hyperventilation, often a concomitant of a panic attack, can precipitate coronary spasm in the presence of atheroma6 and even in coronary arteries free of atherosclerosis.7 Patients who had spontaneous panic attacks in the research laboratory have shown a substantial increase in adrenaline secretion and sympathetic nervous system activity. 8 However, adrenaline typically increases, rather than decreases, coronary blood flow by means of b -adrenergic coronary vasodilatation.9 Similarly, sympathetic nervous system stimulation usually causes coronary vasodilatation and increases flow, partly through the attendant metabolic myocardial stimulation, but also through direct effects on the vasculature.9 In some circumstances, disorders of coronary vasomotion have been linked to dysfunction of the vascular endothelium. Endothelial function was not assessed in our patients, but such tests would be relevant for future prospective studies given that the mechanism of presumed spasm remains elusive. We suspect that coronary spasm is not uncommon during panic attacks, particularly in patients with typical angina-like pain, and that panic disorder may be an undetected cause of otherwise inexplicable coronary heart disease, especially in premenopausal women, who are otherwise at low cardiac risk. It may possibly overlap clinically with "Syndrome X", a poorly understood condition in which recurrent myocardial ischaemia occurs despite the presence of structurally normal coronary arteries. This condition, not to be confused with the endocrinological Syndrome X (insulin metabolic resistance syndrome),11 seems to result, not from coronary spasm, but from reduced myocardial flow reserve caused by a functional abnormality in the cardiac microcirculation.10 Formal testing involving measurements of coronary blood flow under conditions which increase it reflexly, such as exercise, would be needed to exclude this syndrome. An understanding of the mechanism of coronary spasm in panic disorder would facilitate therapeutic intervention. At present, we treat patients with panic disorder and clinical evidence of coronary spasm with drugs and other measures aimed at preventing or minimising their panic attacks,1 a slow calcium-channel blocker as a non-specific antispasm measure, and low dose aspirin as prophylaxis against coronary thrombosis during spasm. It is difficult to know how far to pursue cardiac testing in patients with panic disorder. As we believe their level of cardiac risk is low overall, we recommend selective investigation of those with typical angina-like pain during panic attacks. Capturing ECG evidence of myocardial ischaemia during a panic attack, either during clinic or emergency department attendance or on Holter monitoring, is of central clinical relevance. While it is important to exclude the presence of fixed coronary artery stenosis (which may coexist, particularly in older patients), standard provocative ischaemia testing is not entirely satisfactory; exercise or vasodilator pharmacological challenges are inappropriate for behaviourally induced ischaemia. Panic attacks can be induced in some patients by breathing a mixture of carbon dioxide (10%-15%) and oxygen.12 ECG or thallium stress testing using this stimulus as a challenge is worth future research evaluation. Panic disorder may provide a useful clinical model for studying the possible link between stress and heart disease. A direct relationship between mental stress and sudden death has been seen in special circumstances, such as inherited long-QT-interval syndromes, in which there is electrical instability of the heart muscle.13 In addition, rates of non-traumatic sudden death were markedly increased in people with underlying coronary disease during the 1994 Los Angeles earthquake.14 However, research on stress and heart disease has been hampered by disagreement over what constitutes stress and how to measure it. In panic disorder, the episodes of recurring, often inexplicable, anxiety can be regarded as repeated mental stress reactions. The study of cardiac risk during panic attacks may be a valid method for testing the general proposition that the clinical endpoints of ischaemic heart disease can be "triggered" by stressful events. Acknowledgement This work was supported by a Project Grant from the National Heart Foundation of Australia and an Institute Grant to the Baker Medical Research Institute from the National Health and Medical Research Council of Australia. The contributions of Dr David Prior and Sister Leonie Johnston in the research cardiac catheter laboratory are gratefully acknowledged. The authors also wish to thank Dr Emmanuel G Manolas for provision, through the Epworth Hospital, of clinical and angiographic findings on his patient. References Agras WS. The diagnosis and treatment of panic disorder. Annu Rev Med 1993; 44: 39-51. Kawachi I, Colditz GA, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89: 1992-1997. Kawachi I, Sparrow D, Vokonas PS, Weiss ST. Symptoms of anxiety and risk of coronary heart disease. Circulation 1994; 90: 2225-2229. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994: 394-403. Lessmeier TJ, Gamperling D, Johnson-Liddon V, et al. Unrecognized paroxysmal supraventricular tachycardia. Potential for misdiagnosis as panic disorder. Arch Intern Med 1997; 157: 537-543. Girotti LA, Crosatto JR, Messuti H, et al. The hyperventilation test as a method for developing successful therapy in Prinzmetal angina. Am J Cardiol 1982; 49: 834-841. Yasue H, Nagao M, Omote S, et al. Coronary arterial spasm and Prinzmetal's variant form of angina induced by hyperventilation and Tris-buffer infusion. Circulation 1978; 58: 56-62. Wilkinson DJC, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress and during panic attacks. Arch Gen Psychiatry 1998. In press. Hjemdahl P. Physiology of the autonomic nervous system as related to cardio vascular function: implications for stress research. In: Byrne DG, Rosenman RH, editors. Anxiety and the heart. New York: Hemisphere Publishing, 1990: 95-158. Fragasso G, Rossetti E, Dosio F, et al. High prevalence of the thallium-201 reverse redistribution phenomenon in patients with Syndrome X. Eur Heart J 1996; 17: 1482-1461. Alford FP. Syndrome X (insulin resistance metabolic syndrome): a deadly quartet or an awesome foursome? Med J Aust 1996; 164: 4-5. Battaglia M, Perna G. The 35% CO 2 challenge in panic disorder: optimization by receiver operating characteristics (ROC) analysis. J Psychiatr Res 1995; 29: 111-119. Zipes DP. The long QT interval syndrome. A rosetta stone for sympathetically mediated ventricular tachyarrhythmias. Circulation 1991; 84: 1414-1419. Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an earthquake. N Engl J Med 1996; 334: 413-419. (Received 28 Aug 1997, accepted 21 Jan 1998) Authors' details Baker Medical Research Institute, Melbourne, VIC. Virginia M Mansour, MB BS, Clinical Research Associate; Jane M Thompson, MB BS, Clinical Research Associate; Murray D Esler, PhD, FRACP, Associate Director. Melbourne University, Melbourne, VIC. Dominic J C Wilkinson, BMedSci, Medical Student. Alfred Hospital Heart Centre, Melbourne, VIC. Garry L Jennings, MD, FRACP, Director. Medical Advisory Committee, The Melbourne Clinic, Melbourne, VIC. Rosemary G Schwarz, FRANZCP, Chair. Reprints: Professor M D Esler, Human Neurotransmitter Research Laboratory, Baker Medical Research Institute, PO Box 348, Prahran, VIC 3181. E-mail: Esler AT Baker.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Virginia M Mansour · Garry L Jennings · Rosemary G Schwarz · Jane M Thompson · Murray D Esler

Apolipoprotein screening in Australian children: feasibility and the effect of age, sex, and ethnicity Judith F Lynch, Michelle D Marshall, Xing L Wang and David E L Wilcken MJA 1998; 168: 61-64 Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - ©MJA1998 Abstract Objectives: (i) To evaluate the feasibility of detecting adverse lipid profiles in schoolchildren by measuring capillary dried blood spot apolipoprotein levels, and (ii) to assess the effect of age, sex and ethnicity on apolipoprotein levels. Design: We measured capillary dried blood spot apolipoproteins B and A-I (apo B and apo A-I); assessed levels in relation to age, sex and ethnicity; and recalled children with elevated levels for a full lipid profile measurement. Participants and setting: 6992 children (3501 boys and 3491 girls), aged 5-13 years, from schools in eastern Sydney, 1991-1995. Main outcome measures: Capillary blood levels of apolipoproteins B and A-I, and serum total cholesterol level. Results: Of the 6951 children who provided an adequate fingerprick blood sample, we recalled 1465 children (21.1%) (640 boys [43.7%] and 825 girls [56.3%]) with elevated apo B levels and/or apo B : apo A-I ratios for further testing, either by us or by their family doctor (overall estimated compliance rate up to 70%). Among the 458 children who returned to us, there was a 90% positive predictive value for a total cholesterol level of over 4.5 mmol/L in those with both elevated apo B levels and high apo B : apo A-I ratios. Girls had higher apo B levels and apo B : apo A-I ratios than boys (P < 0.00001 for both), and in both sexes there was a trend downwards for apo B and upwards for apo B : apo A-I ratio over the age range tested, but levels were relatively stable between the ages of 6 and 10 years. Indian children (1.5% of the screened population) had the highest apo B levels, followed by white children (71.1%); Asian children (9.2%) had the lowest (P < 0.00001 compared with Indian and white children). Conclusions: The high positive predictive value of capillary blood apolipoprotein levels for an adverse lipid profile in children suggests that measuring apolipoprotein levels by this method is a useful initial approach to cardiovascular risk assessment. Introduction Despite a recent decline in cardiac deaths, coronary disease is still the largest single cause of premature death in Australia.1 It is known that atherogenesis, the underlying pathological process, may begin in childhood;2,3 that relevant risk factors may track from childhood to adulthood (particularly elevated levels of total and low-density lipoprotein [LDL] cholesterol and increased body weight); and that these factors tend to aggregate within families.4,5 With these considerations in mind, we explored the feasibility of screening for adverse lipid profiles in a target group of primary schoolchildren, with the aim of implementing family-based coronary prevention by secondarily identifying any parents at risk. We measured levels of apolipoprotein B (apo B), the carrier protein for the atherogenic LDL cholesterol, and apolipoprotein A-I (apo A-I), the principal carrier protein for the antiatherogenic high density lipoprotein (HDL) cholesterol, in capillary dried blood spots from 6992 primary schoolchildren aged 5-13 years. There is increasing evidence that high apo B and low apo A-I levels are as reflective of cardiovascular risk as are their respective lipoproteins.6 We describe here the positive predictive value of high apo B and/or apo B : apo A-I ratio for elevated total cholesterol levels and the effects of age, sex and eth nicity on lipid levels in Australian children. Methods School and population demographics We received permission from 70 schools in eastern Sydney (public primary schools, 45%; Catholic primary schools, 29%; and private fee-paying schools, 26%) to contact parents and offer them the option of their child participating in a "Heart Health Screening Program". Children were given consent forms to take home to their parents. On the forms, we asked for the country of origin of each family, and this information was confirmed by a family history questionnaire (sent to all parents within a week of the testing at school) asking each parent to identify their country of origin. Only 1% of the total declined to answer this question (the "unknown" group) (Table 1). Blood collection and apolipoprotein measurement Testing took place between 1991 and 1995. From each child we obtained a capillary blood sample by fingerprick, which was spotted directly onto filter paper (No. 903: Schleicher & Schuell Inc., Keene, NH, USA), allowed to air dry and stored at 2 70¡C until analysis. Concentrations of dried blood spot apo B, apo A-I and lipoprotein (a) (Lp(a)) were measured within two weeks by our previously described enzyme-linked immunosorbent assay methods,7-9 and from these results an apo B : apo A-I ratio was also calculated. These methods allowed us to carry out all three measurements on one small (minimum, 20 µL sample) capillary dried blood spot. We report here the results obtained for measurement of apo B and apo A-I only. Recall In the first school tested, we established the frequency distribution for apo B levels and apo B : apo A-I ratios and set the level for recall for each of these as at or above the 90th percentile. These cut-off points were adjusted from the apo lipoprotein results obtained from each of the next seven schools. However, a stable cut-off level was reached by the third school. We defined three categories of children for recall: those with an ele vated apo B level only (Criterion 1), those with a combination of elevated apo B level and apo B : apo A-I ratio (Criterion 2), and finally those with an elevated apo B : apo A-I ratio only (Criterion 3). We notified the parents of the children for recall by letter, explaining the results and suggesting that both parents, the child, and any other siblings might come to us for further lipid testing, or attend their family doctor. In those who returned to us, we measured total cholesterol level, as well as HDL cholesterol and triglyceride levels, in a venous blood sample by standard methods. LDL cholesterol level was calculated by the Friedewald formula,10 and we also measured serum apo B, apo A-I and Lp(a) by the methods outlined above.7-9 The parents of children with apo B levels and apo B : apo A-I ratios below the established cut-off points were also sent a letter explaining that their children's levels currently fell below the recall criteria. These families were sent a healthy lifestyle pamphlet specifically directed to maintaining a low level of cardiovascular risk; they were also asked if they would like to volunteer as a healthy control family and have complete lipid profiles measured as above. Statistical analysis As the distributions of age, apo B and apo A-I levels, and apo B : apo A-I ratios were normal, analyses by parametric methods were appropriate. We used one-way analysis of variance (ANOVA) for comparisons of measured quantitative variables when there were more than two groups; for example, when children were divided according to high apo B, high apo B : apo A-I ratio, or both, as categorical variables, and levels of total cholesterol and LDL cholesterol, and total cholesterol to HDL cholesterol ratio as the continuous outcome variables. When the comparison was between two groups -- for example, when lipid values were compared in girls and boys as categorical determinants -- Student's t test was used.11 We employed a chi-squared comparison for assessing associations between categorical variables, and used the SPSS statistical software package for all analyses.12 Ethical approval The study was approved by the ethics committee of the University of New South Wales. Results Initial testing The parental consent rate to initial testing was 63.9%. There were 6992 children aged 5-13 years available for testing, 3501 (50.1%) boys and 3491 (49.9%) girls. Only 41 children (0.6%) failed to provide an adequate finger-prick blood sample on the day, leaving a total population of 6951 children tested. Recall population The cut-off point for apo B level was set at 0.550 g/L or more and for the apo B : apo A-I ratio 1.200 or more. We recalled 1465 children (or 21.1% of the population tested). Of these recalls, 65.3% were for elevated apo B only (Criterion 1), 19.6% for elevated apo B and apo B : apo A-I ratio (Criterion 2), and 15.1% for elevated apo B : apo A-I ratio only (Criterion 3). In all, 458 of the children recalled returned with their families to our laboratory for lipid studies (31.2% compliance rate). To obtain an assessment of how many may have been seen by their family doctor (the other option we suggested), we contacted 205 of the remaining 1007 families. Among these, 118 had seen their family doctor for follow-up, and 89 had either moved or were not interested in further testing. This suggested an overall compliance rate of about 70%, if this sample was representative. Of the non-recalled "normal" population of 5486 (78.9%), only 151 families (2.7%) volunteered for lipid testing, an insufficient number for meaningful statistical analysis. Predictive value We used the results of the 458 children who returned for a full lipid profile to assess the positive predictive value of our screening method. The National Heart Foundation of Australia recommends a total cholesterol level of 4.5 mmol/L as the upper limit for children in this age range.13 With a level of over 4.5 mmol/L as the endpoint, Criterion 1 (elevated apo B only) had a positive predictive value of 84% (95% confidence interval [CI], 80%-88%), and with Criterion 2 (elevated apo B level and apo B : apo A-I ratio combined) the predictive value increased to 90% (95% CI, 85%-95%). However, Criterion 3 (elevated apo B : apo A-I ratio only) yielded only 66% (95% CI, 54%-77%), possibly reflecting children with low HDL cholesterol and normal total cholesterol levels. Raising the cut-off point did not substantially improve the positive predictive value of our screening method. When the cut-off point for apo B was increased from 0.550 g/L to 0.700 g/L, for example, the positive predictive value of Criterion 2, the most strongly predictive, only increased to 94% (95% CI, 91%-97%). ANOVA confirmed the association between high apo B levels from analysis of dried blood spot and an adverse lipid profile, and also that a combined high apo B level and apo B : apo A-I ratio was a stronger predictor. In this analysis, criteria established by high apo B, high apo B : apo A-I ratio and a combination of both were determinant categorical variables, and the total cholesterol and LDL cholesterol levels and total chol es terol to HDL cholesterol ratio were the continuous outcomes. Total (P < 0.0006) and LDL cholesterol (P < 0.0014) levels and the total cholesterol to HDL cholesterol ratio (P < 0.0006) were all significantly higher in Criterion 2 than in Criterion 1 or Criterion 3 (Table 2). Sex, age and ethnicity There was a highly significant difference in the apo B and apo B : apo A-I ratio levels between boys and girls (P < 0.00001 for each) (Figures 1 and 2), but no difference (P = 0.6) in apo A-I levels (data not shown). The girls had consistently higher apo B levels and apo B : apo A-I ratios over the age range studied (Figures 1 and 2). This resulted in a significant difference in the recall rate between girls and boys (chi-squared = 23.362; P < 0.00001). This sex difference was also reflected in the total cholesterol levels of children returning for further lipid tests (data not shown). As shown in Figures 1 and 2, there was a downward trend in apo B level and an upward one in apo B : apo A-I ratio in boys over the age range screened, while the opposite was observed in girls; but levels were relatively consistent in both between the ages of 6 and 10 years. Most of the 6951 children screened were white (71.1%); the remainder were of diverse ethnic origins (Table 1). The mixed-race group (8.3% of the total) included white/Asian (28.2%), white/Arabic (17.8%), white/South American (10.7%), and other combinations (56.7%). As age was a significant contributor to apo B concentrations, we compared the "age adjusted apo B levels" for both boys and girls to assess potential differences between major ethnic groups (Figure 3). Indian children had the highest apo B levels, followed by white children. Asian children had the lowest levels and these were significantly different from those of the Indian, white, mixed-race and South American children (P < 0.00001 for each). We did not include black, Australian Aboriginal or Pacific Islander ethnic groups in this analysis because of small numbers and highly skewed age distributions. In all ethnic groups, girls had higher levels than boys (Figure 3). Discussion We have established previously that apolipoprotein measurements provide a convenient and effective approach to the detection of dyslipidaemia,14 and that apo B levels in children are correlated with the occurrence of coronary events in their grandparents, which highlights the relevance of measurements in children to assessing risk of vascular disease in older family members.15 We have also established a clear-cut association between increased apo B levels and apo B : apo A-I ratios and body mass index in Australian children.16 Here, we extend these find ings by demonstrating the feasibility of screening of schoolchildren's capillary blood apolipoprotein levels as an approach to family-based primary coronary prevention. Although we do not have adequate data to determine the sensitivity or specificity of our screening method, the presence of both an elevated apo B level and raised apo B : apo A-I ratios had a positive predictive value of 90% for the detection of elevated total serum cholesterol level. Raising the apolipoprotein cut-off points only improved the predictive value to 94%. This method identified elevated apolipoprotein levels in 21.1% of our population, of whom 90% had elevated total cholesterol levels. Screening for apolipoprotein levels may be more relevant than screening for total cholesterol levels alone, as total cholesterol level does not show the interrelations between levels of the atherogenic LDL and the antiatherogenic HDL cholesterol.17 In a small number of children (0.48%) apo B levels were elevated without elevation of total cholesterol level.18 These families were also provided with dietary and lifestyle advice as this may also be associated with increased cardio vascular risk. Our findings clearly show highly significant differences between boys and girls at this age, with girls having higher apo B levels and apo B : apo A-I ratios than boys. We suspect this biological difference, which was evident before the onset of puberty in both boys and girls, to be hormonally based, although we have no data to support this. The vari ation in apolipoprotein levels within the age range studied could also be hormonally based. Whatever the mech anisms, these same age-related sex differences have been identified in several other studies in children.19,20 The consistency of these results clearly indicates a need to have different cut-off points in boys and girls for elevated apolipoprotein levels. Our results also define the age range (between 6 and 10 years) when levels are most stable and most appropriate for screening, findings which will be incorporated into future studies. There were uniform sex-related differences in apolipoprotein levels in each of the racial groups in our population, as well as very significant differences in levels between the various ethnic groups, as has also been found in previous studies.21,22 In our population, Indian and white children had the highest apo B and apo B : apo A-I ratios and Asian children had the lowest. It is well established that Chinese and Japanese populations have much lower cholesterol levels than whites and a correspondingly lower prevalence of coronary artery disease. Indian populations have a higher prevalence of cardiovascular disease.23 While these variations may relate to the genetic background of each ethnic group, diet and lifestyle undoubtedly make major contributions, and this is particularly evident in non-Western groups who have moved to live in a Western society. The higher prevalence of coronary disease in Indians living in the United Kingdom, for example, is well documented.24 Ethnic differences may become blurred with time if dietary habits become more uniform, and this has occurred among Asians emigrating to the United States and the United Kingdom; within a generation they acquired local lifestyles and a correspondingly higher prevalence of coronary artery disease than that in the communities they had left.25,26 In conclusion, our study demonstrates the feasibility of conducting a program of measuring apolipoprotein levels in capillary blood samples to assess lipid profiles in children to facilitate family-based coronary prevention. It documents wide acceptance by both schools and parents. Implicit in such a study is the potential for a multiplier effect in that, if a child has an elevated apolipoprotein level and therefore an adverse lipid profile, it is very likely that this will also be seen in at least one parent and other siblings.27 Our ongoing screening program requires the establishment of a concurrent intervention program to improve dietary and lifestyle habits of affected children and their parents. This is of more immediate relevance to affected parents as they are approaching the age of overt coronary disease. However, the program provides an ideal opportunity to establish healthy lifestyles in young children at a time of easy acceptance, and with the potential for preventing a disorder that may have its origins in childhood.28 References Heart and Stroke Facts. A report by the National Heart Foundation of Australia. Canberra: NHFA, 1996. Stary HC. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis 1989; 9(1 Suppl): I19-I32. Tracy RE, Newman WP, Wattigney WA, Berenson GS. Risk factors and atherosclerosis in youth autopsy findings of the Bogalusa Heart Study. Am J Med Sci 1995; 310(Suppl 1): S37-S41. Berenson GS, Wattigney WA, Bao W, et al. Rationale to study the early natural history of heart disease: the Bogalusa Heart Study [review]. Am J Med Sci 1995; 310(Suppl 1): S22-S28. Sanchez-Bayle M, Gonzalez-Requjo A, Ruiz-Jarabo C, et al. Serum lipids and lipoproteins in Spanish children and adolescents: a 5 year follow-up. Acta Paediatr 1996; 85: 292-294. Bao W, Srinivassan SR, Berenson GS. Tracking of serum apolipoproteins A-I and B in children and young adults: the Bogalusa Heart Study. J Clin Epidemiol 1993; 46: 609-616. Wang XL, Dudman NP, Wilcken DE. Enzyme-linked immunosorbent assay of apolipoprotein B in blood spotted onto filter paper, suitable for neonatal screening. Clin Chem 1989; 35: 1000-1004. Wang XL, Dudman NP, Blades BL, Wilcken DE. Changes in the immunoreactivity of apo A-I during storage. Clin Chem 1989; 179: 285-293. Wang XL, Wilcken DE, Dudman NP. An indirect sandwich ELISA for Lp(a) in serum and dried blood spots. Clin Chim Acta 1992; 207: 73-86. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502. Norusis MJ. General factorial analysis of variance. SPSS for Windows Advanced Statistics, release 6.0. Chicago: SPSS Inc, 1993: 31-56. McNeil D. Statistical methods II: one-way analysis of variance. In: McNeil D, editor. Epidemiological research methods. New York: John Wiley & Sons, 1996: 66-71. National Diet and Heart Disease Advisory Committee, National Heart Foundation of Australia. Guide to plasma lipids for doctors. Curr Therap 1992; 10(Suppl 1): S1-S8. Wang XL, Wilcken DE, Dudman NP. Apolipoprotein A- I and B and the B/A-I ratio in the first year of life. Pediatr Res 1991; 30: 544-549. Wilcken DEL, Wang XL, Greenwood J, Lynch JF. Lipoprotein (a) and apolipoproteins B and A-I in children and coronary vascular events in their grandparents. J Pediatr 1993; 123: 519-526. Wilcken DE, Lynch JF, Marshall MD, et al. Relevance of body weight to apolipoprotein levels in Australian children. Med J Aust 1996; 164: 22-25. Taylor CJ, Olpin S, Rattenbury J, et al. Familial hyper cholesterolaemia: pilot study to identify children at risk. J Clin Pathol 1993; 46: 730-733. Grundy S. Small LDL. Atherogenic dyslipidaemia and the metabolic syndrome. Circulation 1997; 95: 1-4. Resnicow K, Morley-Kotchen J, Wynder E. Plasma cholesterol levels of 6585 children in the United States: results of the know your body screening in five states. Pediatrics 1989; 84: 969-976. Christensen B, Glueck C, Kwiterovich P, et al. Plasma cholesterol and triglyceride distributions in 13,665 children and adolescents: the Prevalence Study of the Lipid Research Clinics Program. Pediatr Res 1980; 14: 194-202. Zhang W, Evans AE, Cambien F, et al. Distribution of lipid variables in subjects in Belfast, Northern Ireland and Taiyuan, PR China. Atherosclerosis 1993; 102: 175-180. Freedman DS, Lee SL, Byers T, et al. Serum cholesterol levels in a multiracial sample of 7,439 preschool children from Arizona. Prev Med 1992; 21: 162-176. Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians: thoughts on pathogenesis, prevention, and therapy. Coronary Artery Disease in Asian Indians (CADI) Study [review]. Clin Cardiol 1995; 18: 131-135. Bhatnagar D, Anand IS, Durrington PN, et al. Coronary risk factors in people from the Indian subcontinent living in west London and their siblings in India. Lancet 1995; 345: 405-409. Egusa G, Murakami F, Ito C, et al. Westernized food habits and concentration of serum lipids in the Japanese. Atherosclerosis 1993; 100: 249-255. Robinson D, Kawamura T, Hinohara S, Sakamoto Y. Levels of cardiovascular risk factors in Japanese people living in the UK. J Cardiovasc Risk 1995; 2: 449-458. Shaukat N, de Bono DP, Jones DR. Like father like son? Sons of patients of European or Indian origin with coronary artery disease reflect their parents' risk factor patterns. Br Heart J 1995; 74: 318-323. Resnicow K, Cross D, Lacosse J, Nichols P. Evaluation of a school-site cardiovascular risk factor screening intervention. Prev Med 1993; 22: 838-856. (Received 15 Apr, accepted 15 Oct, 1997) Authors' details Department of Cardiovascular Medicine, Prince Henry and Prince of Wales Hospitals, Sydney; and Community Health Services and Programs, South Eastern Sydney Area Health Service, Royal South Sydney Hospital, Sydney, NSW. Judith F Lynch, HTech, Heart Health Education Program Co-ordinator; Michelle D Marshall, BSc, Scientific Officer; Xing L Wang, PhD, Research Fellow; David E L Wilcken , MD, FRACP, Visiting Professor of Medicine. Reprints will not be available from the authors. Correspondence: Professor D E L Wilcken, Department of Cardiovascular Medicine, Room 163, Clinical Sciences Building, Prince Henry Hospital, Little Bay, Sydney, NSW 2036. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Judith F Lynch · Michelle D Marshall · Xing L Wang

Notable Case Ephedrine abuse causing acute myocardial infarction Jerome G L Cockings and Michael A Brown "On the street", the more expensive illegal psychostimulants, such as cocaine or amphetamine, may be mixed with or substituted for cheaper drugs such as ephedrine -- with added risk to the user. We report diffuse myocardial injury in a 25-year-old man who presented with pulmonary oedema after intravenously injecting himself with ephedrine, believing it to be amphetamine. MJA 1997; 167: 199-200 Introduction - Clinical record - Discussion - References - Authors' details - - Articles on similar material Introduction The abuse of psychostimulants, such as cocaine and amphetamines, is of concern in Australia -- they are among the most widely used of the illicit drugs after cannabis.1 Occupational use of stimulant drugs is also a problem -- there have been accidents involving heavy transport vehicles whose drivers had taken ephedrine.2 In addition, ephedrine may be taken by "recreational" drug abusers when it is mixed with or substituted for other illicit drugs such as amphetamines. Ephedrine has both cardiovascular and central nervous system effects, but, although the cardiovascular risks of major psychostimulants such as cocaine are well known,3 little has been reported for ephedrine. We report a patient who injected himself intravenously with ephedrine, sustaining diffuse myocardial injury which resolved with inotropic support and ventilation. Clinical record A 25-year-old man with a history of intravenous psychostimulant abuse presented to hospital with progressive dyspnoea two hours after injecting himself intravenously with a solution of a white powder he believed was amphetamine. He had no other medical history of note, was a non-smoker and had previously been well. There was no family history of sudden cardiac death. Serum lipid levels were not measured. On examination he was conscious but tachypnoeic and cyanosed. He was afebrile, tachycardic (pulse, 140 beats/min), normotensive (110/70 mmHg) and hypoxic (Pao2, 49 mmHg), with hypocapnia (Paco2, 33 mmHg), a mild alkalosis (pH, 7.45) and a pronounced leukocytosis (44 x 106 cells/L). He had a reduced cardiac output (2.2 L/min; normal range, 4.5-6.5 L/min), with a pulmonary artery occlusion pressure (an estimate of left atrial pressure) of 30 mmHg. There was bilateral "bat's wing" opacification on chest x-ray, consistent with a clinical diagnosis of pulmonary oedema. Within an hour of admission and treatment with diuretic and oxygen, further deterioration with cardiogenic shock necessitated intubation, ventilation and admission to an intensive care unit. Initially, the lungs were poorly compliant (49 mL/cmH2O; normal range, 70-100 mL/cmH2O) and the alveolar-arterial (A-a) O2 gradient was elevated (260 mmHg; normal range, < 50 mmHg when on 80% O2). He received continuous inotropic support with adrenaline, initially at 38 µg/min, which was steadily reduced over three days. By Day 3, his cardiac output was 5.5 L/min without inotropes. His respiratory function and gas exchange improved steadily and he was extubated on Day 5. Results of microbiological investigations (tracheal aspirate, blood culture and urine culture) were negative and antibiotics were not given. On admission, electrocardiograms revealed widespread ST-segment depression with T-wave inversion, consistent with subendocardial infarction and ischaemia. A posterior infarction could not be excluded. The peak serum creatine kinase (CK) level was 2360 U/L (normal range, 20-130 U/L) (CK-MB isozyme fraction, 6.1%; normally < 2%), with rises in serum levels of aspartate aminotransferase (to 222 U/L [normal range, < 45 U/L]) and lactate dehydrogenase (to 612 U/L [normal range, 110-230 U/L]). A technetium Tc 99m perfusion scan of the myocardium showed mild tracer uptake in the left myocardium and more intense uptake in the posterolateral wall, consistent with diffuse myocardial damage and an acute posterolateral infarction. Echocardiography soon after admission showed severe left ventricular dysfunction in all areas except the apex (which showed near-normal contractility), with a poor overall ejection fraction. There was mild mitral regurgitation with no vegetations. Right ventricular function was normal. On Day 6, mild to moderate impairment of left ventricular function was still present, maximum at the base, with mild ventricular dilatation. The patient continued to improve and was discharged from hospital nine days after admission. Laboratory analysis of the unused white powder identified only ephedrine. On review one month later the patient was symptom-free. The resting electrocardiogram showed non-specific ST-segment and T-wave changes. Exercise testing, carried out according to the Bruce protocol,4 was 13.5 min in duration and limited by fatigue. His peak heart rate was 192 beats/min, with no chest pain or ST-segment or T-wave changes. He attained an estimated oxygen consumption of 49 mL/kg per min (normal range, 50-70 mL/kg per min) and an aerobic capacity of 106% of the predicted value. At two months, echocardiography showed normal left ventricular function but persistent trivial mitral regurgitation with a minor prolapse of the anterior leaflet. The patient was counselled about the health risks (such as the risk of bacterial endocarditis) of continuing to inject illegally obtained drugs. Discussion Our patient presented with diffuse myocardial injury consistent with sympathomimetic abuse -- the agent was identified as ephedrine. He recovered adequately after intensive treatment. The stimulatory central nervous system effects of ephedrine -- increased arousal, restlessness and insomnia -- have been recognised for many years. Preparations of the herb ephedra were used in ancient Chinese medicines, and ephedrine, the active alkaloid, was identified in the late 19th century.5 Ephedrine is a direct agonist of both alpha and beta sympathetic receptors and an indirect adrenoreceptor agonist, causing release of noradrenaline from presynaptic sympathetic nerve terminals. Its cardiovascular effects include tachycardia, increased inotropy, arterial vasoconstriction and hypertension,6 and these are the effects for which it is used therapeutically. Amphetamine and pseudoephedrine have similar actions, although amphetamine has more pronounced central nervous system effects.7 Ephedrine is widely available, but despite the potential for abuse that this creates there are few reports of its cardiovascular risks. Bruno et al. described two cases of intracranial haemorrhage and one of a thalamic infarct following excessive ephedrine ingestion,6 highlighting the potential dangers of non-prescribed self-administration of this drug. Chronic cardiomyopathy was documented after long-term ingestion of ephedrine in a cough mixture.8 Myocardial injury occurred after ephedrine given therapeutically for hypotension during labour,9 and coronary artery spasm leading to myocardial injury has been described with pseudoephedrine ingestion.10 The mechanism of the myocardial injury caused by ephedrine overdose is probably similar to that caused by cocaine -- intense diffuse vasoconstriction of both the coronary and the systemic arterial systems, decreasing myocardial perfusion, increasing afterload, and increasing myocardial oxygen utilisation.3 Although severe hypertension would be expected with ephedrine overdose, and may have been present in our patient soon after the injection of ephedrine, on presentation he had severe acute left ventricular failure with a consequent fall in contractility and blood pressure. This necessitated inotropic support rather than the use of vasodilators. Various other factors may have contributed to the myocardial injury in our patient. There may have been contaminants in the syringe, and the injection of insoluble particulate matter may have caused vascular occlusion. This could have been compounded by catecholamine-enhanced platelet aggregation induced by ephedrine. Further, although no other agents were identified in the remaining unused powder, the original injection may have included another myotoxin. Pre-existing coronary artery disease was unlikely in an otherwise healthy young non-smoker. A coronary angiogram was not performed. Although the leukocytosis was pronounced, this was consistent with the severe physiological stress. Nevertheless, in the absence of any other antecedent events or prior myocardial disease, this case report strongly suggests that the acute myocardial infarction was precipitated by the self-injection of ephedrine. "On the street", small quantities of a cheaper drug such as ephedrine may be mixed with stimulants such as amphetamine. This case illustrates the risks associated with the total substitution of ephedrine and the subsequent injection of what is likely to have been a high dose of this drug. References Australian Social Issues Research 1991. Report on the national campaign against drug abuse. Sydney: Social Issues Household Survey 1985-1991. Canberra: AGPS, 1991. Staysafe Committee of NSW 1992. Staysafe 19: Alcohol and other drugs on NSW roads 1. The problem and countermeasures. Sydney: NSW Parliament, 1992. Goldfrank LR, Hoffman RS. The cardiovascular effects of cocaine. Ann Emerg Med 1991; 20: 165-175. Bruce RA. Exercise testing of patients with coronary artery disease. Principles and normal standards for evaluation. Ann Clin Res 1971; 3: 323-332. Kalix P. The pharmacology of psychoactive alkaloids from Ephedra and Catha. J Enthnopharmacol 1991; 32: 201-208. Bruno A, Nolte KB, Chapin J. Stroke associated with ephedrine use. Neurology 1993; 43: 1313-1316. Gawin FH, Ellinwood EH. Cocaine and other stimulants: actions, abuse and treatment. N Engl J Med 1988; 318: 1173-1182. To LB, Sangster JF, Rampling D, Cammens I. Ephedrine-induced cardiomyopathy. Med J Aust 1980; 2: 35-36. Menegakis NE, Amstey MS. Case report of myocardial infarction in labour. Am J Obstet Gynecol 1991; 165: 1383-1384. Weiner I, Tilkian AG, Palazzolo M. Coronary artery spasm and myocardial infarction in a patient with normal coronary arteries: temporal relationship to pseudo-ephedrine ingestion. Cathet Cardiovasc Diagn 1990; 20: 51-53. (Received 27 Feb, accepted 12 June 1997) Authors' details Royal Adelaide Hospital, Adelaide, SA. Jerome G L Cockings, FFICANZCA, FANZCA, Senior Registrar in Intensive Care; Michael Brown, MD, FRACP, Consultant Cardiologist. Reprints will not be available from the authors. Correspondence: Dr J G L Cockings, Consultant Intensivist, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102. E-mail: J. Cockings@mailbox.uq.edu.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Michael A Brown

Reducing the burden of chronic heart failure It's time to adopt new management strategies MJA 1997; 167: 61-62 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". - ©MJA1997 Chronic heart failure (CHF) is a major public health problem.1 The disease is associated with poor prognosis2 and markedly reduced quality of life. Unlike other cardiovascular conditions, it is increasing in incidence and prevalence.1,3 Its management imposes a substantial burden on the health care system, accounting for 1%-2% of total health care costs in industrialised nations.4 About 70% of these costs are related to hospitalisation. Most epidemiological data on heart failure have come from the United States and Europe. In Australia, carefully conducted studies of the incidence, prevalence and hospitalisation rates of CHF have been sadly lacking. Thus, the report by Blyth et al. in this issue of the Journal5 is welcome as it provides us with local data on the impact of CHF in the hospital setting. Their findings confirm the massive burden that heart failure imposes on the patient and the health care system. What can we do to contain or even reverse this situation? Despite therapeutic advances, CHF remains a disease with unacceptably high mortality rates, poor quality of life and massive socioeconomic cost. The current approach to managing heart failure comprises non-pharmacological interventions (sodium restriction, alcohol abstention, exercise), drug therapies and, in selected patients, surgery. Surgery has a limited role: if objective evidence exists of reversible ischaemia and/or hibernating myocardium, coronary artery bypass grafting should be considered. Several new surgical approaches may also be useful as long-term therapy in some patients, including cardiomyoplasty, ventriculectomy and insertion of a left ventricular assist device. Transplantation is an extremely effective therapy, but limited by donor organ availability, and the age and comorbidities of many patients with CHF. Drug therapies have a substantial impact on disease outcomes. Angiotensin-converting enzyme (ACE) inhibitors relieve symptoms, improve quality of life and prolong survival.6,7 Digoxin has no overall effect on mortality,8 but may be of symptomatic benefit in patients receiving ACE inhibitor therapy.9 However, mortality remains high even in CHF patients receiving the best available drug therapy. In the CONSENSUS study of patients with severe heart failure, 12-month mortality was almost 50% despite patients receiving diuretics, digoxin and high doses of ACE inhibitors.7 New drugs are continually being evaluated in CHF. Many provide short-term symptomatic benefit, but at the expense of long-term increases in mortality: these include non-digitalis inotropic agents (milrinone, xamoterol, ibopamine, vesnarinone) and direct-acting vasodilator drugs (flosequinan).10 New drugs that appear to offer symptomatic benefit without adverse mortality outcomes include b -adrenoceptor-blocking agents (specifically, carvedilol) and angiotensin II receptor antagonists (specifically, losartan). Recent studies have suggested prolonged survival in chronic heart failure with both agents.11-12 Despite these therapeutic advances, CHF remains a disease with unacceptably high mortality rates, poor quality of life and massive socioeconomic cost. Effective new management strategies are urgently required. In most patients heart failure is a complex disorder requiring an integrated treatment strategy. Physicians, general practitioners, nurse practitioners, nutritionists, physiotherapists and psychologists need to be drawn together to maximise thera peutic benefits to the patient. One approach has been to establish multidisciplinary clinics where patients have access to dedicated physicians, dietary expertise, literature about the disease, behaviour modification interventions and exercise programs. Patients are encouraged to become active participants in managing their disease. They are asked to weigh themselves regularly, monitor dietary sodium intake, watch closely for signs of fluid accumulation or changing symptoms and to interact frequently by telephone with members of the multidisciplinary team. The nurse practitioner regularly checks on patient status and addresses specific enquiries. This approach brings together the skills of multiple health care providers in an environment of frequent and regular appraisal of the patient. Outcomes from pilot studies of this approach have included reduced dietary salt intake, improved compliance with drug therapies, improved patient well-being, and reduced hospitalisations.13,14 In one study, emergency department visits were reduced by 67% and hospitalisations by 87%.14 This was found to be highly cost-effective. Heart failure remains a major clinical challenge for health care professionals in the 1990s. It is no longer sufficient to manage the hospitalised patient well; the real goal of treatment is to address the health of people with heart failure in the community so that they do not require hospital admission. Henry Krum Associate Professor of Medicine, Clinical Pharmacology Unit Department of Epidemiology and Preventive Medicine, and Department of Medicine Monash University, Alfred Hospital, Melbourne, VIC Garg R, Packer M, Pitt B, Yusuf S. Heart failure in the 1990s: evolution of a major public health problem in cardiovascular medicine. J Am Coll Cardiol 1993; 22 (4 Suppl A): 3A-5A. Franciosa JA, Wilen M, Ziesche S, et al. Survival in men with severe left ventricular failure due to either coronary heart disease or idiopathic dilated cardiomyopathy. Am J Cardiol 1983; 51: 831-836. Schocken DD, Arrieta MI, Leaverton PE. Prevalence in mortality rate of congestive heart failure in the United States. J Am Coll Cardiol 1992; 20: 301-306. McMurray J, Hart W. The economic impact of heart failure on the UK National Health Service . Eur Heart J 1993; 14 Suppl: 133. Blyth FM, Lazarus R, Ross D, et al. Burden and outcomes of hospitalisation for congestive heart failure. Med J Aust 1997: 167; 67-70. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316: 1429-1435. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336: 525-533. Packer M, Gheorgiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin converting enzyme inhibitors. N Engl J Med 1993; 329: 1-7. Niebauer J, Coats AJS. Treating chronic heart failure: time to take stock. Lancet 1997; 349: 966-967. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996; 334: 1349-1355. Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997; 349: 747-752. Rich MW, Beckham V, Wittenberg C, et al. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995; 333: 1190-1195. West JA, Miller NH, Parker KM, et al. A comprehensive management system for heart failure improves clinical outcomes and reduces medical resource utilization. Am J Cardiol 1997; 79: 58-63. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Henry Krum

Burden and outcomes of hospitalisation for congestive heart failure Fiona M Blyth, Ross Lazarus, David Ross, Michael Price, Gary Cheuk and Stephen R Leeder For editorial comment see Krum Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Abstract Objective: To describe the hospital burden and health outcomes associated with admission for congestive heart failure (CHF). Design and setting: Descriptive follow-up study in a tertiary-level metropolitan teaching hospital. Patients: Acute adult inpatients with a clinical diagnosis of CHF for more than 24 hours admitted to Westmead Hospital, Sydney, during the four months from September 1993 to January 1994. At baseline, 122 patients were assessed; 88 patients were assessed at four-month follow-up. Interventions: Usual clinical care. Main outcome measures: Length of stay; hospital bed-days; readmissions; mortality; health related quality of life (SF-36); patient knowledge. Results: The average age of subjects was 73.4 years. Many were using informal domiciliary care before admission. Mean length of stay for the baseline admission was 13.8 days, accounting for 7.6% of hospital separations and 1683 hospital bed-days, or 4.2% of bed-days for all inpatients aged 65 years and over. Fifteen patients were readmitted for CHF during the following four months, with a total of 26 CHF-related admissions. Twenty-one patients (17.2%) died during the course of the study. Quality of life at baseline was poor compared with population normative data, with a slight improvement among survivors at four-month follow-up. Patient knowledge of CHF was poor in a subsample survey ( n = 24). Conclusions: CHF represents a significant burden to patients (through morbidity and mortality), their carers (through provision of daily care), and hospitals (through multiple admissions for acute decompensation). It is difficult to monitor the hospital burden of CHF using routine data sources. MJA 1997; 167: 67-70 Introduction Congestive heart failure (CHF) has been estimated to affect 3%-5% of those aged over 65 years, and 10% of those over 75 years.1 It is the fastest growing cardiovascular disorder in the United States,2 the only one increasing in incidence and prevalence,3 and the leading cause of hospital admission and readmission in Americans aged over 65 years.4 In 1990, CHF cost the US economy $US8 billion, and accounted for five million hospital bed-days.5,6 In Scotland, CHF hospital discharge rates have risen in a decade to be almost equal to those for myocardial infarction.7 In the United Kingdom, the National Health Service spends £360 million per year in diagnosis and management, on a par with spending on stroke or asthma. Most of this expenditure is on hospital admissions.8 As there is little information available on the outcomes of current hospital management of CHF patients,9,10 we describe the health outcomes of a cohort of patients hospitalised with CHF, and the impact of their hospitalisation on a health service. Methods All acute adult patients admitted to Westmead Hospital during four months (September 1993 to January 1994) with a clinical diagnosis of CHF, or who developed CHF of more than 24 hours' duration during an admission, were eligible for inclusion in the study. The diagnosis of CHF was made by medical staff on clinical grounds. Additional eligibility criteria were fluency in English and absence of significant cognitive impairment. Two cardiology-trained research nurses implemented an active daily case-finding strategy to overcome the difficulties encountered in identifying CHF patients from existing record systems. Diagnostic codes are generally not added to the patient's medical record until some time after discharge. Patients were identified by review of the computerised admissions log, medical record chart audit in the relevant ward areas, and consultation with medical staff. Potential subjects were assessed for their general condition and fluency in English and, if appropriate, screened for cognitive impairment by means of the Mini-Mental State examination.11 Informed consent was then sought. If patients were unable to participate fully, consent was sought to review their medical record and follow them up four months later to ascertain vital status. Baseline data were collected by interview, medical record review and self-administered questionnaires. Data were collected on demographic characteristics, domiciliary arrangements, current and past medical history, clinical severity of heart failure (according to the New York Heart Association [NYHA] criteria for grading functional incapacity of patients with cardiac disease), investigations, drug treatment, hospital resource use, formal and informal use of domiciliary care, and health-related quality of life (HRQOL) before admission (measured with the SF-36 [Medical Outcomes Study 36 Item Short Form Health Survey]).12 Patient knowledge about CHF was assessed by a short questionnaire in a subset of 24 consecutive patients. Four months after baseline admission, subjects were contacted by telephone to arrange follow-up by questionnaire. Data were sought on health status, HRQOL, current treatment, and domiciliary arrangements. The hospital's computer system was searched for any readmissions during the follow-up period. All analysis was performed using SAS version 6.08 for Windows.13 Two-sample t tests were used to assess the statistical significance of differences between groups, with adjustments made for multiple comparisons. SF-36 data were scored and subscales were calculated with the recommended scoring algorithm.12 Westmead Hospital Human Research Ethics Committee approved the study, and informed consent was obtained from all participating patients. Results There was no "gold standard" available for checking the accuracy and completeness of study case ascertainment methods. However, a list was assembled of all separations from Westmead Hospital during the study recruitment period with a principal diagnosis code for CHF (ICD-9 codes 428.0, 428.1, 428.9). These were then cross-checked against a list of study subjects. This list identified seven patients who were not identified by study case-finding methods. These were considered "missed" potential cases, but represented a small proportion of this group (4.3%). During the study recruitment period, 154 patients met the required clinical criteria and 122 (79%) consented to participate. Participation and follow-up are detailed in Box 1. Sample characteristics: Women made up 54.9% of the study participants. The mean age was 73.4 years (range, 24-97 years); women were older on average than men (76.8 compared with 69.4 years; P = 0.0001). Most patients had a history of established CHF; 35.2% were undergoing their first hospital admission for CHF. Only 1.8% of patients were NYHA grade I on baseline admission, 12.3% grade II, 64.4% grade III, and 17.5% grade IV (4% lacked data for NYHA classification). Thirty-eight patients had their ejection fraction measured at the baseline admission, with a mean value of 35% (range, 9%-74%). Ischaemic heart disease (58.2%) and hypertension (39.3%) were major aetiological factors in CHF. The cohort was cared for by cardiologists (n = 74; 60.7%), and geriatricians (n = 48; 39.3%). Admission diagnoses are shown in Box 2 (below). When admission diagnoses were compared with ICD-9 codings on the medical record, 39 (86.6%) of the 45 with heart-failure-specific admission diagnoses and 30 (78.9%) of the 38 with suggestive diagnoses had a CHF-related ICD-9 code (428, 428.0, 428.1, 428.9) in one of the first six ICD-9 coding positions. Preadmission characteristics: Data were available for 99 subjects: 88 lived in private accommodation, 50 reported needing regular help from family or friends with general housekeeping, and 23 reported needing help with supervision of medication. Length of stay: The study participants accounted for 7.6% of hospital separations (excluding day-only patients). The mean length of stay during the baseline admission was 13.8 days (SD = 12.1). Length of stay had a markedly skewed distribution (median, 10 days; range, 2-66 days). Overall, the sample accounted for 1683 bed-days during baseline admissions and 10.6% of hospital bed-days associated with the geriatricians and cardiologists who participated in the study. Of those patients aged 65 years and over admitted during the same period, the CHF cohort accounted for 4.2% of bed-days. Readmissions: During the follow-up period, there were 73 readmissions to Westmead Hospital from the study cohort, 26 due to a further episode of CHF in 15 patients. A total of 171 bed-days were used for CHF-related readmissions by the 14 patients for whom data were available. Deaths: Twenty-one patients died during the study (17.2%). Changes in domicile: Eight patients (8.1%) were discharged to a higher level of domiciliary care, suggesting a decline in independence and increased use of health and/or community services. Quality of life: Data on HRQOL before admission were obtained from 84 of the 85 subjects at baseline (Box 3). Mean SF-36 subscale scores for these subjects were generally low, particularly for subscales with physical health components. For each subscale there was a wide range of scores, indicating substantial variability in health-related quality of life before admission. Compared with Australian normative SF-36 data for men and women aged 65 years and over,14 the study cohort reported significantly lower mean HRQOL for all subscales. Follow-up SF-36 data were obtained for 58 subjects (Box 4). Patients with missing follow-up data had either died before follow-up (n = 15) or were too unwell to fill in the form (n = 6). In that sense, the SF-36 results at follow-up represent the "survivor" population within the study cohort. Mean follow-up subscale scores in survivors were somewhat higher compared with their baseline scores. The smallest improvements were in the subscales related to physical health. Improvements in the Social Function, Vitality and Mental Health subscales were statistically significant. Patient knowledge: The 24 patients who completed the questionnaire were similar to the CHF cohort in age, sex, length of stay, and type of treating specialist. Nineteen had been admitted to hospital previously for CHF. Only 11 knew that they had been diagnosed as having heart failure. Although 16 agreed that patients with heart failure would need to take medication permanently, six thought that CHF was unlikely to recur. Nineteen agreed that shortness of breath and 15 agreed that ankle swelling were important symptoms, but only four recognised that rapidly increasing weight was important. Discussion CHF has a significant impact on hospital services. The study cohort contributed significantly to adult bed-days attributable to participating clinicians. A substantial proportion (12.3%) of the cohort was readmitted with CHF within four months of their baseline admission, suggesting an annual readmission rate of around 36%. This compares with an annual readmission rate of nearly 20% in the SOLVD (Studies of Left Ventricular Dysfunction) registry study cohort, who were younger.10 CHF admissions show seasonal variations, with a winter peak that is probably associated with chest infection. Therefore, the impact of CHF on acute hospital services may be even greater at that time of year. The 48 subjects (39.3%) who were admitted under the care of geriatricians were, by hospital admission policy, those aged over 65 with serious comorbidity and/or likely to represent a placement problem after discharge. Many required substantial help with tasks essential for independent living, and most of this help was provided informally. This was clearly a group that would require increased resources with deteriorating health. HRQOL was generally poor in the study participants compared with normative data,14 probably reflecting the combined effects of disease severity and comorbidity. There was limited improvement between baseline and follow-up, particularly in the subscales related to physical health, perhaps indicating that at baseline the lower limits of some SF-36 subscales did not adequately reflect the subjects' condition (i.e., a "floor" effect was operating). The mean changes in scores over time were small, but underlying this was great variability between individuals. At the time of this study there were few educational resources for CHF patients. This is surprising, as CHF is a chronic condition with acute exacerbations that may be ameliorated by early recognition and intervention, and which requires compliance with medication. Some CHF patients may avoid hospital admission by timely intervention prompted by self-monitoring of signs and symptoms. Seventy-six subjects (62.3%) had a recorded history of acute deterioration lasting for more than 24 hours, suggesting a possible opportunity for early recognition and intervention. The patient knowledge survey was limited, but it demonstrated an apparent lack of understanding of key features of CHF. Recent acute illness could have contributed to this. That almost a quarter of the cohort required daily help with taking medications has implications for the targeting of educational interventions. For elderly patients experiencing readmissions for CHF, the risk of dying in the near future and the palliative nature of treatment are additional issues which may need to be explored. This study was constrained, for practical reasons, by reliance on a clinical diagnosis of CHF. In a larger study with more resources, verification of diagnosis and more detailed examination of diagnostic coding practices would be desirable, and would allow identification of subgroups of particular clinical interest. Diagnostic coding practices in routine record keeping do not facilitate monitoring of the public health impact of CHF. A hospital admission for CHF may be assigned a principal ICD-9 code which reflects the underlying cause of CHF, and secondary ICD-9 codes are sometimes used to identify a past medical history of CHF rather than a feature of the current admission. In this study, poor health represented a further barrier to study participation and monitoring outcomes. Most losses to follow-up resulted from death or worsening health. During the study 21 subjects (17.2%) died. This represents a poor survival rate, worse than for many malignancies of adulthood. Cause of death was not ascertained, but in the SOLVD registry cohort10 most deaths were due to progressive CHF. In addition, sudden death occurs in CHF patients at five times the rate in the general population of the same age.15 Chronic CHF represents a significant burden to patients (through morbidity and mortality), their carers (through provision of daily care), and the hospital system (through multiple admissions for acute decompensation). Acknowledgements We acknowledge the contribution of Moira Hewitt, RN, and Jeanette Bunn, RN, to the Westmead CHF Outcomes study, and study coinvestigator Dr Julia Lowe from the Newcastle Heart Failure Group. This study was funded by the NSW Health Department's Health Outcomes Program. References Failure to treat heart failure [editorial]. Lancet 1992; 330: 278-279. Mortality from congestive heart failure --United States, 1980-1990. MMWR Morb Mortal Wkly Rep 1994; 43: 77-81. Yamani M, Massie BM. Congestive heart failure: insights from epidemiology, implications for treatment. Mayo Clin Proc 1993; 68: 1214-1218. Gooding J, Jette AM. Hospital readmissions among the elderly. J Am Geriatr Soc 1985; 33: 595-601. National Centre for Health Statistics, Graves EJ. National Hospital Discharge Survey: Annual Summary, 1990. Vital Health Stat [13] 1992; 112: 28. Munoz E, Chalfin D, Birnbaum E, et al. Hospital costs, resource characteristics, and the dynamics of death for patients with a primary diagnosis of congestive heart failure. N Y State J Med 1989; 89: 60-63. McMurray J. Trends in hospitalisation for heart failure in Scotland 1980-1990. Eur Heart J 1993; 14: 1158-1162. McMurray J, Hart W. The economic impact of hearfailure on the U K National Health Service. Eur Heart J 1993; 14 Suppl: 133. Parameshwar J, Poole-Wilson PA, Sutton GC. Heart failure in a district hospital. J R Coll Physicians Lond 1992; 26: 139-142. Bourassa MG, Gurne O, Bangdiwala SI, et al. for the SOLVD investigators. Natural history and patterns of current practice in heart failure. J Am Coll Cardiol 1993; 22 Suppl A: 14A-19A. Folstein MF, Folstein SE, McHugh PR. "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-198. Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 health survey: manual and interpretation guide. Boston: The Health Institute, New England Medical Centre, 1993 . SAS for the Microsoft Windows Environment, Version 6. Cary, NC: SAS Institute Inc, 1993. Stevenson CE. SF-36: Interim norms for Australian data. Canberra: Australian Institute of Health and Welfare, 1996. Kannel WB, Ho K, Thom T. Changing epidemiologic features of cardiac failure. Br Heart J 1994; 72 Suppl: S3-S9. (Received 8 Oct 1996, accepted 10 Apr 1997) Authors' details Westmead Hospital, Sydney, NSW. Fiona M Blyth, FAFPHM, Registrar, Department of Public Health and Community Medicine. Ross Lazarus, FAFPHM, Senior Lecturer in Epidemiology, Department of Public Health and Community Medicine, University of Sydney at Westmead Hospital. David Ross, FRACP, Head, Department of Cardiology. Michael Price, FRACP, Head, Geriatric Medicine Unit. Gary Cheuk, FRACP, Registrar, Geriatric Medicine Unit. Stephen R Leeder, FRACP, PhD, FAFPHM, Professor of Public Health and Community Medicine, University of Sydney at Westmead Hospital. Reprints will not be available from the author. Correspondence: Dr F M Blyth, Department of Public Health and Community Medicine, Westmead Hospital, Westmead, NSW 2145. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Fiona M Blyth · Ross Lazarus · David Ross · Michael Price · Gary Cheuk · Stephen R Leeder

Withdrawal of nifedipine capsules: jeopardising the treatment of acute severe hypertension in pregnancy? Mark A Brown, Lesley M E McCowan, Robyn A North, Barry N Walters (for the Council of the Australasian Society for the Study of Hypertension in Pregnancy) Short-acting oral nifedipine has been withdrawn from the Australian market because of reports of its adverse effects after long-term treatment in non-pregnant patients with heart disease. This will have a major impact on the treatment of acutely hypertensive pregnant women, in whom the drug has proven to be safe, effective and easy to administer. Should pregnant women be forced to use less suitable agents, thus threatening their own and their babies' health? (MJA 1997; 166: 640-643) Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Introduction - Antihypertensive medications in pregnancy - Adverse effects of nifedipine - Risk-benefit analysis of nifedipine in pregnancy - Withdrawal of nifedipine from the Australian market - Conclusions - Acknowledgement - References - Authors' details Make a comment - - ©MJA1997 Introduction Pre-eclampsia is the development of hypertension after 20 weeks' gestation in a woman with no known history of hypertension or renal disease, whose blood pressure was normal in the first half of the pregnancy and returns to normal after delivery.1 Despite advances in maternal and neonatal care, it remains an important cause of maternal morbidity (and sometimes mortality) and of fetal prematurity, growth retardation and perinatal death. The dangers of cerebral haemorrhage in pre-eclampsia and of convulsions (eclampsia) have led to the belief that severe hypertension (systolic blood pressure 170 mmHg and/or diastolic blood pressure 110 mmHg) should be treated promptly in pre-eclamptic women. However, the ability to treat acute hypertensive crises in pregnancy is about to be retarded considerably because of recommendations by the Australian Drug Evaluation Committee (ADEC) to withdraw short-acting nifedipine capsules,2 one of the most common drugs for treating acute severe hypertension in pregnancy, effective from 1 May 1997. Antihypertensive medications in pregnancy There are only a few options for the treatment of acute severe hypertension in pregnancy. Nifedipine (given orally or sublingually) and hydralazine (given intravenously or, sometimes, intramuscularly) are the most commonly used agents. They have both been endorsed for use for severe hypertension in pregnancy by the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) on the basis of clinical studies and extensive clinical experience by members of the ASSHP and other societies.1 Intravenous diazoxide was one of the earliest drugs to be used.3 It is effective but can cause sudden maternal hypotension, maternal hyperglycaemia and fetal hypoglycaemia, uterine atony and fetal distress. It is best given as incremental small-dose boluses to avoid a sudden drop in blood pressure. Intravenous labetalol has been used less widely but is at least as effective as intravenous diazoxide.3 Its safety in preterm infants has been questioned,4 with higher perinatal mortality than in subjects given hydralazine in one study. Intravenous glyceryl trinitrate is a potential candidate for treating severe hypertension in pregnancy.5 It has not yet been used widely and there is a risk that its predominant venodilator effect could reduce preload and compromise an already threatened cardiac output.6 Intravenous sodium nitroprusside is an excellent drug for acute severe hypertension, but its use in pregnancy is precluded by the risk of fetal cyanide toxicity.7 Adverse effects of nifedipine Unfortunately, some authors fail to discriminate between pregnant and non-pregnant subjects when providing recommendations about the continued use of nifedipine capsules. For example, Grossman et al. did a MEDLINE search of articles from 1966 to 1994 using the terms "side-effects" and "nifedipine" to document serious adverse effects with oral or sublingual nifedipine.8 They recommended that, given the seriousness of the reported adverse cardiac events and the lack of any clinical documentation attesting to a benefit, the use of nifedipine capsules for hypertensive emergencies and pseudoemergencies should be abandoned. Only one case of fetal distress was reported in this review9 (although we have noted three other cases), in a pregnant woman whose blood pressure fell from 150/115 mmHg to 90/55 mmHg, hardly a surprising event and one which could have occurred with any drug which lowered the blood pressure to this extent. A more disturbing report by Rehman et al. noted that 98% of hospitalised patients receiving nifedipine capsules failed to have a bedside evaluation and only half had had their blood pressure followed up within an hour of treatment.10 This is poor medical practice and a good reason to improve medical education, but not a reason to withdraw a drug from the market. Risk-benefit analysis of nifedipine in pregnancy Many small studies, comprising a total of about 150 pregnant women, have shown that nifedipine will acutely lower maternal blood pressure within 30 minutes of administration, without compromising the fetus.11-22 In studies involving approximately 200 pregnant women treated with nifedipine over a longer period, no adverse fetal effects were recorded.12,23-27 Three case reports (of four patients) have, at the same time, reported the potential risk of sudden hypotension following the use of nifedipine in severe pre-eclampsia, particularly when combined with magnesium sulfate (used parenterally as convulsion prophylaxis in pre-eclampsia).9,28,29 However, in a more recent prospective study, 10 women with severe pre-eclampsia already receiving intravenous magnesium sulfate were given between 10 mg and 40 mg nifedipine orally. Blood pressure was well controlled in each woman, none had significant hypotension and there was no fetal distress.30 Sudden hypotension has been reported with other antihypertensive drugs used to acutely lower blood pressure in pregnancy, including hydralazine.3,31 The risk of sudden hypotension with any form of acute antihypertensive therapy can be minimised by concomitant plasma volume expansion1,20,32 and avoidance of diuretics, as pre-eclampsia is a volume-contracted state compared with normal pregnancy.33 Several studies have found that nifedipine lowers maternal blood pressure without adversely affecting uteroplacental blood flow.13,14,17,23,34 Several studies have compared intravenous hydralazine with nifedipine in pre-eclampsia;12,19,20,35 all showed nifedipine to be of equal or greater efficacy and safety for both mother and fetus. Visser and Wallenburg observed similar maximum reductions in blood pressure during administration of each drug, but greater falls in pulmonary capillary wedge pressure as well as increased occurrence of fetal distress in women receiving hydralazine.20 In one randomised trial, there were fewer preterm infants and less acute fetal distress in the group of women given nifedipine than in the group of women given intravenous and then oral hydralazine.12 The most recent and largest studies showed that maternal and fetal outcomes were similar in pregnant women with severe hypertension (diastolic blood pressure > 120 mmHg) who received either sublingual nifedipine or intravenous hydralazine.36 The authors concluded that sublingual nifedipine may be advantageous "for use by midwives who work in rural areas where speed is essential in reducing acute hypertension . . ." Nifedipine also relaxes the myometrium, and therefore has a potentially important role in the treatment of preterm labour. In five separate randomised trials involving a total of 290 women, nifedipine was as effective as ritodrine for tocolysis and was associated with fewer serious maternal side effects.37-41 No adverse fetal effects were attributable to nifedipine in studies reporting on more than 350 women treated with the drug in preterm labour.42 Recent prospective data have provided further support for the safety of nifedipine, even when used in early pregnancy.43 Withdrawal of nifedipine from the Australian market The "position of comfort" -- that nifedipine can be used safely and easily in an emergency (before insertion of an intravenous cannula) -- has been lost. The plan to withdraw nifedipine capsules arose out of concern over the potential adverse effects (myocardial infarction, death) in non-pregnant patients with hypertension and ischaemic heart disease receiving long-term treatment with the drug.44-46 In New Zealand, the Ministry of Health has stated that nifedipine and some other calcium antagonists are contraindicated in pregnancy.47 There is no basis for this pronouncement in studies of nifedipine use in human pregnancy. As nifedipine was never officially listed in the Australian Register of Therapeutic Goods for use in pregnancy, clinicians cannot argue to retain the drug for the treatment of hypertension in pregnancy. The simple solution could be to accept defeat and rely on parenteral hydralazine. However, the most recent preparation of this drug is not marketed for intramuscular use (presumably because of its variable absorption), so that treatment must be delayed until an intravenous cannula is inserted. This delay adds to the dangers of severe hypertension for the pregnant woman. Moreover, it has been speculated that parenteral hydralazine will also be withdrawn shortly as it has been superseded by better drugs with fewer side-effects in non-pregnant patients. We now face the following situation: nifedipine capsules have been withdrawn from sale, and it is possible that intravenous hydralazine and diazoxide will also be withdrawn from the Australian market. Intravenous labetalol is not available in Australia, and magnesium sulfate, while known to have some blood pressure lowering effects, is not a sufficiently powerful antihypertensive agent for treatment of severe hypertension in pre-eclampsia. Therefore, intravenous sodium nitroprusside and glyceryl trinitrate will be the only agents left for the treatment of acute severe hypertension in pregnancy. The former can induce fetal cyanide toxicity, while the latter has been subject to far fewer studies in pregnancy than nifedipine, hydralazine or diazoxide -- and both drugs require highly skilled dose titration. Why do pregnant women now face the very real prospect that we will no longer be able to treat their severe hypertension as efficiently as before? In part, this relates to the bureaucratic nature of administering such matters -- if a drug has not been officially listed for an approved indication in the Australian Register of Therapeutic Goods (and nifedipine was never listed for use in pregnancy), then, despite widespread clinical use for that purpose, it can be withdrawn from the market by the pharmaceutical regulatory authorities. To be fair, this is probably the safest approach overall. At the same time, however, this situation highlights deficiencies in clinical and scientific interaction among clinicians, pharmaceutical companies and government agencies. The pharmaceutical company concerned has long known that nifedipine was being used for treating severe hypertension in pregnancy. They, of course, could not endorse such an action, but could have worked with clinicians to study the clinical outcomes in a proper manner, leading to an application for approval of a new indication. They chose not to do so. We clinicians are as much at fault here for not taking such an initiative when the company failed to do so. ADEC tried to balance these issues in its most recent consideration of the problem, but had no option other than to withdraw nifedipine capsules from sale. In New Zealand, nifedipine capsules are now available only in hospitals, which limits the access of rural practitioners to this drug. Perhaps this situation should force us to reconsider the speed at which we need to lower blood pressure in pre-eclampsia. Pregnancy outcomes are very good when severe hypertension is treated rapidly (over 20-30 minutes) and cerebral haemorrhage and eclampsia are now relatively rare. This does not mean there is necessarily a causal relationship between such treatment and the low rates of intracerebral haemorrhage and eclampsia. However, it would be difficult to prove a causal relationship because of the rarity of these complications as well as the ethical problems involved in randomising severly hypertensive pregnant women to a trial comparing rapid reductions in blood pressure (e.g., using nifedepine) with slower reductions (e.g., using oral clonidine or methyldopa). Conclusions The "best case" scenario is that withdrawal from sale of nifedipine capsules and intramuscular hydralazine will leave Australian clinicians with only intravenous diazoxide and intravenous hydralazine to fill an essential therapeutic niche (with intravenous labetalol still available in New Zealand). None of these drugs can be given urgently in hospitals without resident medical staff, and even in the larger tertiary hospitals resident medical staff can be delayed in other wards or operating theatres. Such delays could result in serious complications for the pregnant woman and her baby. The "worst case" scenario is that none of these drugs (nifedipine, labetalol, hydralazine or diazoxide) will be available for the treatment of acute severe hypertension in pregnancy. Pregnant women will then suffer from inadequate treatment or be exposed to the side effects of the remaining antihypertensive drugs, which are currently not recommended for use in pregnancy. Is all this enough to justify continued availability of short-acting nifedipine in pregnant women in Australia and New Zealand? Most clinicians would rapidly respond "yes" as they continue to practise medicine as both an art and a science. The "art" of using nifedipine successfully in pregnancy is well known to most of us, but, although the above review of the available literature shows that nifidepine capsules are as safe as any other drugs currently used to treat acute severe hypertension in pregnancy, we have failed to gather the science to a sufficient extent. We hope our patients will not suffer as a result of our combined shortfalls. Acknowledgement We thank Mrs Jodie Hendley for assistance in preparing this manuscript. References Brown MA, Buddle ML. Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features. Med J Aust 1996; 165: 360-365. Australian Drug Evaluation Committee. Resolution No. 5857. Commonwealth of Australia Gazette No. GN 10, 25 October 1995. (See also Resolution No. 7129. 5-6 December 1996.) Michael CA. Intravenous labetalol and intravenous diazoxide in severe hypertension complicating pregnancy. Aust N Z J Obstet Gynaecol 1986; 26: 26-29. Visser W, Wallenburg HCS. Should labetalol be used in severe early onset preeclampsia patients? Protagonist and presentations. Proceedings of the 8th World Congress on Hypertension in Pregnancy; 1992 Nov 8-12; Buenos Aires, Argentina. Abstract 104: 290. Ramsay B, de Belder A, Campbell S, et al. A nitric oxide donor improves uterine artery diastolic blood flow in normal early pregnancy and in women at high risk of pre-eclampsia. Eur J Clin Invest 1994; 24: 76-78. Visser W, Wallenburg HCS. Central hemodynamic observations in untreated preeclamptic patients. Hypertension 1991; 17: 1072-1077. Baker A. Management of severe pregnancy induced hypertension, or gestosis, with sodium nitroprusside. Anaesth Intensive Care 1990; 18: 361-365. Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudo emergencies? JAMA 1996; 276: 1328-1331. Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol 1993; 100: 959-961. Rehman F, Mansoor GA, White WB. Inappropriate physician habits in prescribing oral nifedipine capsules in hospitalised patients. Am J Hypertens 1996; 9: 1035-1039. Walters BNJ, Redman CWG. Treatment of severe pregnancy-associated hypertension with the calcium antagonist nifedipine. Br J Obstet Gynaecol 1984; 91: 330-336. Fenakel K, Fenakel G, Appelman Z, et al. Nifedipine in the treatment of severe preeclampsia. Obstet Gynecol 1991; 77: 331-337. Hanretty KP, Whittle MJ, Howie CA, Rubin PC. Effect of nifedipine on Doppler flow velocity waveforms in severe preeclampsia. BMJ 1989; 299: 1205-1206. Lindow SW, Davies N, Davey DA, Smith JA. The effect of sublingual nifedipine on uteroplacental blood flow in hypertensive pregnancy. Br J Obstet Gynaecol 1988; 95: 1276-1281. Duggan PM, McCowan LME, Stewart AW. Antihypertensive drug effects on placental flow velocity waveforms in pregnant women with severe hypertension. Aust N Z J Obstet Gynaecol 1992; 32: 335. Lurie S, Fenakel K, Friedman A. Effect of nifedipine on fetal heart rate in the treatment of severe pregnancy-induced hypertension. Am J Perinatal 1990; 7: 285-286. Pirhonen JP, Erkkola RU, Ekblad UU. Uterine and fetal flow velocity waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine. Obstet Gynecol 1990; 76: 37-41. Puzey MS, Ackovic KL, Lindow SW, Gonin R. The effect of nifedipine on fetal umbilical artery Doppler waveforms in pregnancies complicated by hypertension. S Afr Med J 1991; 79: 192-194. Seabe SJ, Moodley J, Becker P. Nifedipine in acute hypertensive emergencies in pregnancy. S Afr Med J 1989; 76: 248-250. Visser W, Wallenburg HCS. A comparison between the haemodynamic effects of oral nifedipine and intravenous dihydralazine in patients with severe preeclampsia. J Hypertens 1995; 13: 791-795. Childress CH, Katz VL. Nifedipine and its indications in obstetrics and gynaecology. Obstet Gynecol 1994; 83: 616-624. Levin AC, Doering PL, Hatton RC. Use of nifedipine in the hypertensive diseases of pregnancy. Ann Pharmacother 1994; 28: 1371-1378. Moretti MM, Fairlie FM, Akl S, et al. The effect of nifedipine therapy on fetal and placental Doppler waveforms in pre-eclampsia remote from term. Am J Obstet Gynecol 1990; 163: 1844-1848. Constantine G, Beevers DG, Reynolds AL, Luesley DM. Nifedipine as a second line antihypertensive drug in pregnancy. Br J Obstet Gynaecol 1987; 94: 1136-1142. Greer IA, Walker JJ, Bjornsson S, Calder AA. Second line therapy with nifedipine in severe pregnancy induced hypertension. Clin Exp Hypertens Pregnancy 1989; B8: 277-292. Sibai BM, Barton JR, Akl S, et al. A randomized prospective comparison of nifedipine and bed rest versus bed rest alone in the management of preeclampsia remote from term. Am J Obstet Gynecol 1992; 167: 879-884. Jayawardana J, Lekamge N. A comparison of nifedipine with methyldopa in pregnancy induced hypertension. Ceylon Med J 1994; 39: 87-90. Hata T, Manabe A, Hata K, Kitao M. Changes in blood velocities of fetal circulation in association with fetal heart rate abnormalities: effect of sublingual administration of nifedipine. Am J Perinatal 1995; 12: 80-81. Waisman GD, Mayorga LM, Camera MI, et al. Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia? Am J Obstet Gynecol 1988; 159: 308-309. Scardo JA, Vermillion ST, Hogg BB, Newman RB. Haemodynamic effects of oral nifedipine in pre-eclamptic hypertensive emergencies. Am J Obstet Gynecol 1996; 175: 336-340. Vink GJ, Moodley J, Philpott RH. Effect of dihydralazine on the fetus in the treatment of maternal hypertension. Obstet Gynecol 1980; 55: 519-522. Paterson-Brown S, Robson SC, Redfern N, et al. Hydralazine boluses for the treatment of severe hypertension in pre-eclampsia. Br J Obstet Gynaecol 1994; 101: 409-413. Brown MA, Gallery EDM. Volume homeostasis in normal pregnancy and pre-eclampsia. Baillieres Clin Obstet Gynaecol 1990; 8: 287-310. Hirose S, Yamada A, Kasugai M, et al. The effect of nifedipine and dipyridamole on the Doppler blood flow waveforms of umbilical and uterine arteries in hypertensive pregnant women. Asia-Oceania J Obstet Gynaecol 1992; 18: 187-193. Martins-Costa S, Ramos JG, Barros E, et al. Randomised, controlled trial of hydralazine versus nifedipine in pre-eclamptic women with acute hypertension. Clin Exp Hypertens Pregnancy 1992; B11: 25-44. Jegasothy R, Paranthaman S. Sublingual nifedipine compared with intravenous hydralazine in the acute treatment of severe hypertension in pregnancy: potential for use in rural practice. J Obstet Gynaecol Res 1996; 22: 21-24. Bracero LA, Leikin E, Kirshenbaum N, Tejani N. Comparison of nifedipine and ritodrine for the treatment of preterm labour. Am J Perinatol 1991; 8: 365-369. Meyer WR, Randall HW, Graves WL. Nifedipine versus ritodrine for suppressing preterm labor. J Reprod Med 1990; 35: 649-653. Ferguson JE, Dyson DC, Schutz T, Stevenson DK. A comparison of tocolysis with nifedipine or ritodrine: an analysis of efficacy and maternal, fetal and neonatal outcome. Am J Obstet Gynecol 1990; 163: 105-111. Kupferminc M, Lessing JB, Yaron Y, Peyser MR. Nifedipine versus ritodrine for suppression of preterm labor. Br J Obstet Gynaecol 1993; 100: 1090-1094. Read MD, Wellby DR. The use of a calcium antagonist (nifedipine) to suppress preterm labour. Br J Obstet Gynaecol 1986; 93: 933-937. Ray D, Dyson D. Calcium channel blockers. Clin Obstet Gynecol 1995; 38: 317-322. Magee LA, Schick B, Donnenfeld AE, et al. The safety of calcium channel blockers in human pregnancy: a prospective, multicenter cohort study. Am J Obstet Gynecol 1996; 174: 823-828. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 275: 620-625. Buring JE, Glynn RJ, Hennekens CH. Calcium channel blockers and myocardial infarction. A hypothesis formulated but not yet tested. JAMA 1995; 274: 654-645. Horton R. Spinning the risks and benefits of calcium antagonists. Lancet 1995; 346: 586-587. New Zealand Ministry of Health. Managing high blood pressure in pregnancy. Prescriber Update 1994; 7: 2-10. (Received 26 Aug 1996, accepted 28 Jan 1997) Authors' details Departments of Medicine, Renal Medicine and Obstetrics, St George Hospital, Kogarah, NSW. Mark A Brown, FRACP, MD, Associate Professor of Medicine. Department of Obstetrics and Gynaecology, University of Auckland School of Medicine, National Women's Hospital, Auckland, NZ. Lesley M E McCowan, FRCOG, FRNZCOG, Senior Lecturer in Obstetrics and Gynaecology; Robyn A North, PhD, FRACP, Senior Lecturer in Obstetric Medicine. King Edward Memorial Hospital for Women, Perth, WA. Barry N Walters, FRACP, Physician in Obstetric Medicine. Council of the Australasian Society for the Study of Hypertension in Pregnancy, 145 Macquarie Street, Sydney, NSW 2000. No reprints will be available. Correspondence: Dr M A Brown, Departments of Medicine, Renal Medicine and Obstetrics, St George Hospital, Kogarah, NSW 2217. To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia. We appreciate your comments.

Mark A Brown · Robyn A North · Barry N Walters

Salt intake, cardiovascular disease and public health We need to do more than take the salt shaker off the table MJA 1997; 166: 396 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". - - ©MJA1997 The contribution of dietary salt intake to cardiovascular morbidity and mortality is a subject of ongoing discussion and controversy.1,2 What is unquestionable is that the average salt intake of most people in most nations exceeds physiological requirements (10-20 mmol/day) by a factor of between five and 30, and this relatively high intake contributes significantly to the average blood pressure of a population, and hence to the prevalence of hypertension.3 The relationship between blood pressure levels and morbidity and mortality from heart attack and stroke suggests that any reduction in levels of salt intake in a population would result in a corresponding reduction in cardiovascular morbidity and mortality. For example, it has been argued that a mean reduction in sodium intake of 50 mmol per day across the whole population in the United Kingdom would reduce coronary death rates there by 16% and stroke death rates by 22%, and create substantial monetary savings from the reduced prevalence of these and related diseases.4 there is unlikely to be much further progress in reducing Australians' salt intake unless more low-salt foods which are easily identifiable and affordable become available Such epidemiological observations have led national and international health authorities to set targets for reductions in population salt consumption.5,6 The Australian Government has set a target sodium intake of 100 mmol per day to be achieved by the year 2000. It is reasonable to ask whether this target (or any other for salt intake) is justified on public health grounds and whether it is achievable. For such a target to be appropriate requires that it be both safe and cost effective in reducing cardiovascular morbidity and mortality . Despite the consistent epidemiological data and experimental evidence, clinical trial data are limited. There are no randomised controlled trials of effects of varying sodium intake on cardiovascular outcome other than on blood pressure levels per se. However, there is experimental and limited clinical trial data suggesting that salt intake influences left ventricular mass independently of blood pressure,7 which is relevant in that left ventricular hypertrophy is itself a powerful predictor of cardiovascular morbidity and mortality. Is a target of 100 mmol/day realistic in countries like Australia? In this issue of the Journal Beard et al. have attempted to measure salt intake in an Australian population sample in the light of our national target for the year 2000. Using 24-hour urine collections to estimate sodium excretion, they found that only 6% of men and 36% of women had reached the year 2000 target. As only 52% of the eligible population were studied and as there was underepresentation of younger people and lower socioeconomic groups, these figures are likely to underestimate the true levels of sodium intake and to overestimate the extent to which the target was reached. Interestingly, among both men and women, and among both those who did and those who did not comply with the sodium intake target, most stated that they never or rarely added salt to food. This apparent anomaly may raise doubts about the reliability of the participants' reports, but is probably more readily explained by the poor reliability of a single 24-hour urine specimen for estimating usual sodium intake, and the high proportion of dietary salt hidden in food.8 The actual values for the percentage of the population complying with targets should perhaps be taken with "a pinch of salt", while the estimates of population average salt intake are in accord with other Australian data and those from countries (such as the United States) with similar dietary habits and are probably realistic. If the target of less than 100 mmol/day is desirable for most of the population why are we so far from achieving it, and is it realistic? As Beard et al. point out, at least 75% of salt in the British diet and those of other affluent societies comes from processed foods.8 Given the proportion of participants in the study by Beard et al. who claim not to add salt to food or in cooking, the figure may be higher in Australia. Bread is a major source of dietary salt, along with canned foods and preserves. Take-away foods are more likely to be salted, and the growing habit of eating out leaves the consumer with less control over salt intake. The smaller body mass, and hence lower total food consumption, of women compared with men may at least partly explain their lower salt intake -- perhaps the target for sodium intake for women should be lower than that for men. Beard et al. point out that there has been relatively little publicity about the national dietary target for salt and that, although some food manufacturers have taken initiatives to reduce salt use, shoppers receive relatively little advice or encouragement. The picture is perhaps not quite as bleak as it seems. The National Heart Foundation and State health departments have long been publicising the benefits of reducing salt intake as part of a more general healthy diet that includes eating more fresh fruit and vegetables and reducing saturated fat intake. These measures may have much greater value in cardiovascular health if adopted in combination with other lifestyle changes.9-11 However, there is unlikely to be much further progress in reducing Australians' salt intake unless more low-salt foods which are easily identifiable and affordable, as well as being economically viable for the food industry, become available. This will require more concerted efforts and cooperation between the food industry, government, consumers and food scientists. Novel approaches should be explored, such as the use of salt substitutes, which has resulted in long term blood pressure reduction in older patients with hypertension in Holland.12 Perhaps it is timely that the National Health and Medical Research Council consider a fresh approach to the problem that includes working with the food industry and food scientists to make it easier for consumers to reduce unnecessarily high and harmful levels of salt intake. A randomised controlled trial that showed that reducing salt intake decreased morbidity and mortality would undoubtedly dispel any lingering doubts on this issue and accelerate efforts. While purists might argue that such evidence should be as rigorously demanded of lifestyle changes as of new drugs or surgery, in the case of dietary salt we are in something of a "Catch-22" situation -- it is unlikely that an adequate trial could be mounted unless low salt foods were much more widely available than they are at present. However, a precedent for major public health initiatives in the absence of definitive clinical trial data has been set with the multitude of campaigns against cigarette smoking. The cumulative evidence for the benefits of moderating dietary salt intake is sufficient to justify more active public health initiatives now. Lawrie J Beilin Professor, Department of Medicine, University of Western Australia, Perth, WA Dyer AR, Stamler R, Elliot P, Stamler J. Dietary salt and blood pressure. Nature Med 1995; 1: 994-996. Wardener HL, Kaplan NM. On the assertion that a moderate restriction of sodium intake may have adverse health effects. Am J Hypertension 1993; 6: 810-814. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results of 24 hour urine sodium and potassium excretion. BMJ 1988; 297: 319-328. Law MR, Frost CD, Wald MJ. By how much does dietary salt lower blood pressure? III. Analysis of data from trials of salt reduction. BMJ 1991; 302: 819-823. National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group report on primary prevention of hypertension. Arch Intern Med 1993; 153: 186-208. Health Targets and Implementation (Health for All) Committee. Health for all Australians. Canberra: AGPS, 1988: 38. Langenfeld MRW, Schmeider RE. Salt and left ventricular hypertrophy: what are the links? J Hum Hypertens 1995; 9: 909-916. James WPT, Ralph A, Sanchez-Castillo CP. The dominance of salt in manufactured food in the sodium intake of affluent societies. Lancet 1987; 1: 426-429. Ascherio A, Rimm EB, Giovanucci EL, et al. A prospective study of nutritional factors and hypertension among US men. Circulation 1992; 86: 1475-1484. Beilin LJ. Non-pharmacological management of hypertension: optimal strategies for reducing cardiovascular risk. J Hypertens 1994; 12 Suppl 10: S71-S81. Jennings GL, Sudhir K. Initial therapy of primary hypertension. Med J Aust 1990; 152: 198-203. Geleeijnse JM, Witteman JCM, Bak AAA, et al. Reduction in blood pressure with a low sodium, high potassium, high magnesium salt in older subjects with mild to moderate hypertension. BMJ 1994; 309: 436-440. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Lawrie J Beilin

The Hobart Salt Study 1995: few meet national sodium intake target Trevor C Beard, David R Woodward, Peter J Ball, Helen Hornsby, Richard J von Witt and Terence Dwyer MJA 1997; 166: 404 For editorial comment see Beilin Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Statistical analysis - Results - Sodium and potassium excretion - Discretionary use of salt - Discussion - Public health implications - Conclusion - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objective: To estimate 24-hour sodium and potassium excretion in an urban Australian population. Design and setting: Cross-sectional survey of an urban population in Hobart, Tasmania, in 1995. Participants: Systematic sample (87 men, 107 women) from the Commonwealth Electoral Roll of people aged 18-70 years on 30 June 1995 whose residential address was within 10 km of the Hobart General Post Office. Main outcome measure: Conformity with the national target for sodium intake for the year 2000 of ≤100 mmol/day. Results: The target was met by 6% of men and 36% of women. This difference between the sexes was significant ( P < 0.001), while differences between age groups and socioeconomic levels were not significant. Conclusion: Our findings confirm the low level of conformity with the national sodium target reported by the handful of Australian studies over the past decade. Given the major community costs associated with hypertension, our results highlight the need for effective and properly monitored action to reduce sodium intakes. MJA 1997; 166: 404-407 Introduction Many health problems are associated with the current sodium intake of people in Western societies.1 In 1988, an Australian target for a lower sodium intake was set for the express purpose of reducing the prevalence of hypertension.2 Although other factors, such as excess body weight, inadequate exercise, excess alcohol, low dietary potassium and "psychological influences", may contribute to hypertension,3 Australia's national target for sodium intake (≤100 mmol/day)2 is accepted internationally.4-6 Further, it is supported by the discovery that the usual human salt intake in Western diets induces hypertension in chimpanzees, and that this is reversed when they return to their natural diet.7 The effect of low dietary potassium on health has received less attention, but there is good evidence that potassium intake should at least equal sodium intake in molar units.8,9 Potassium predominates in unsalted foods because it is the major intracellular cation in the living tissues of both plants and animals. Thus, virtually all the natural foods available to mammals have a molar sodium to potassium ratio of less than 1.0. The human body must have evolved on this dietary ratio; its inversion is recent in phylogenetic terms, unnecessary and probably unsafe.8,9 Published data on current intakes of sodium and potassium among Australians are very few, and usually based on small samples10-12 We report electrolyte excretion data obtained from 194 Hobart residents for a behavioural study in 1995. Our estimates are based on 24-hour excretion of these electrolytes in the urine (widely accepted as the preferred method of assessment of intake).13,14 Methods People aged 18-70 years on 30 June 1995 and residing within 10 km of the Hobart General Post Office were selected from the Commonwealth Electoral Roll (revised to February 1995) as follows. Every 500th person on the roll was selected for contact or, if ineligible, replaced by the next eligible person. A letter inviting participation was mailed to each person, outlining the study (including the need to attend for interview and to provide a 24-hour urine sample) and enclosing a reply-paid envelope. Those failing to reply were sent a second letter two weeks later, followed, if necessary, by a telephone call within a further 10 days. Unpredictable variability in sodium excretion (a confounder in the behavioural study) was reduced by excluding volunteers with serious intercurrent illness, pregnancy, breast-feeding or use of potassium supplements, diuretics or other drugs likely to affect sodium excretion. We estimated socioeconomic status by the postcode of the participant's address, using the Index of Relative Socioeconomic Disadvantage (IRSD);15 data for specific postcodes were supplied by the Australian Bureau of Statistics. Suburbs whose postcodes had an IRSD ≤ 1000 (the national mean score) were classified as "lower socio economic status", and those with an IRSD ≥ 1000 as "higher socioeconomic status". Two subjects listed a GPO box address and were not assigned a socio economic status rating. At interview, we collected demographic and anthropometric data and a short medical history. Participants completed a food-frequency questionnaire and answered behavioural and cognitive questions, which will be reported elsewhere. Each participant received detailed verbal and written instructions on how to make a complete 24-hour collection of urine; all were asked to collect urine on weekdays, and women of reproductive age were asked to avoid collection during the premenstrual week, when sodium retention may occur.16 Participants collected urine in 2 L plastic containers containing 20 mL of 6 molar hydrochloric acid and returned them promptly. Urine volume was estimated by weighing. For 82 of the 194 samples the estimated volume was adjusted to 24 hours because of longer or shorter actual collection times; the maximum adjustment was 175 minutes over the 24 hours (12.2%), and only five adjustments exceeded 5%. The samples, identified only by code numbers, were diluted with neutral pH buffer and analysed for sodium and potassium by ion-selective electrodes on a Kodak Ektachem 750 XRC analyser (Johnson & Johnson Clinical Diagnostics, Rochester, NY, USA) and, for creatinine, by the Ektachem method also. Laboratory results were sent to those participants who requested them. A duplicate of every tenth sample was sent for analysis under a different code number for quality assurance. We calculated imprecision of laboratory measurements from the differences between results for duplicate samples using the formula published for the Intersalt study.17 The coefficients of variation for laboratory imprecision were 0.6% for sodium, 1.1% for potassium and 5.4% for creatinine. The protocol was approved by the University of Tasmania Committee on Ethical Aspects of Human Experimentation, and all subjects gave written informed consent. Statistical analysis We used SPSS18 to analyse the data; P< 0.05 was used as the criterion of statistical significance. Differences between sexes, age groups and socioeconomic status levels were assessed by t tests (for mean sodium and potassium excretion rates) and by chi-squared tests (for compliance with targets for sodium and sodium to potassium ratio). Results Of 619 individuals originally selected, 167 (27%) were uncontactable despite active follow-up, 80 (13%) were ineligible because they had moved out of the target area, 151 (24%) declined to take part, 18 (3%) were eliminated by our exclusion criteria (nine for medications, five for illness, and four for pregnancy or lactation), and nine participated incompletely. The remaining 194 (31% of the initial sample, or 52% of those known to be eligible) were interviewed and provided a 24-hour urine collection. Box 1 (below) compares sociodemographic characteristics for these 194 participants with those of the other 425 people originally selected. The two groups had a similar sex distribution, but participants were significantly older and had higher socioeconomic status. For participants, the sex ratio was similar in both age divisions (43% men in the 18-44 years group and 46% men in the 45-70 years group), and in both socioeconomic groups (47% and 44% men in the lower and higher socioeconomic status groups, respectively). While we do not have birthplace data for the non-participants, most participants were born in Australia (83%) or in the United Kingdom or Ireland (12%). Sodium and potassium excretion Twenty-four-hour sodium excretion was greater in men (range, 39-337 mmol) than in women (26-241 mmol), and the mean sodium intake (as reflected by this excretion rate) was 52 mmol higher in men than in women, a highly significant difference (P< 0.001). Only 6% of men, compared with 36% of women, met the Australian national target (≤ 100 mmol/day), represented by the vertical line in the Figure, and this difference was also significant at P< 0.001. Differences between age groups and socioeconomic status groups were not significant at the P< 0.05 level (Box 2, below). The mean potassium intake in men was 9 mmol higher than in women (P = 0.03), but differences between age groups and socioeconomic status groups were not significant (Box 2, above). Only 5% of men and 19% of women met the recommendation8,9 that the sodium to potassium ratio should not exceed 1.0 (diagonal line in the Figure); this sex difference was significant (P = 0.002). Differences were not statistically significant between younger and older participants (P = 0.33), and were on the margin of significance for socioeconomic status levels (P = 0.05). Discretionary use of salt Most of our 194 participants claimed that they never or rarely added salt at the table (51% of men and 73% of women), and that they never or rarely cooked with salt (54% of men and 61% of women). Compliers and non-compliers with the sodium target gave similar answers about the use of salt: 66% of compliers and 62% of non-compliers rarely or never added salt at the table, and 57% of compliers and 58% of non-compliers rarely or never cooked with salt. Discussion Despite our relatively low response rate, Box 1 shows that our participants had a similar sex ratio to that of a systematic sample from the Hobart electoral roll, and we found that sex differences in electrolyte excretion were significant. Although our sample was biased in terms of age and socioeconomic status, the effect of age and socioeconomic status on electrolyte excretion in the participants barely reached significance (Box 2), and hence these biases are unlikely to have influenced our findings. If the participants were unrepresentative in some other way -- more health-conscious, for example -- our data could underestimate sodium excretion and overestimate compliance with the sodium target. It is difficult to be certain of the completeness of 24-hour urine collections. Para-aminobenzoic acid has been used as a marker in overseas studies,19 but is not approved for use with healthy volunteers in Australia. Creatinine excretion is a customary indicator of completeness, but no standard cut-off points exist.19 As both undercollection and overcollection could have affected our results, we repeated the t-test analyses of Box 2 after excluding subjects whose creatinine outputs were in the lowest and highest 2.5% for men and women. For both sodium and potassium the changes in means and standard deviations were negligible, indicating no serious problem with outliers. Moreover, the range of excretion rates of each electrolyte in each sex remained unaltered. Accuracy and imprecision of assays are also important determinants of data quality. As reported in our Methods, duplicate assays indicated acceptable imprecision -- the laboratory is a participant in the Royal College of Pathologists of Australasia-Australian Association of Clinical Biochemists Quality Assurance Scheme and is accredited by the National Association of Testing Authorities. Few other Australian studies have been reported. In one, estimates based on food-frequency questionnaires were somewhat lower than ours,12 but urinary excretion is considered a more valid indicator of intakes.13,14 A Hobart study in 1989, with a similar protocol for sample selection and urine collection,10 found mean sodium and potassium excretion rates in men of 160 mmol/day and 77 mmol/day, respectively, compared with 124 mmol/day and 66 mmol/day in women. In Sydney, in 1992, Notowidjojo and Truswell11 found mean sodium and potassium excretion rates of 164 mmol/day and 74 mmol/day in men and 133 mmol/day and 66 mmol/day in women. These two studies support our conclusion that average intakes in Australia -- especially among men -- are substantially above the national target. Public health implications Meta-analysis by Law et al. indicates that a 50 mmol decrease in community sodium intake could reduce mortality from heart disease by 16% and from stroke by 22%.20 The annual cost to Australia of heart disease, stroke and hypertension was recently estimated at $1198 million, $666 million and $546 million, respectively.21 If a lower salt intake reduced prevalence as much as it reduced mortality, the saving from 16% less heart disease and 22% less stroke and hypertension would be $458 million annually, with added savings from reduced prevalence of other conditions.1 In the United Kingdom the complete elimination of table salt and cooking salt would reduce mean sodium intake by only about 15%.22 This figure might be even lower in Australia, as this and other studies show that most people already avoid adding salt to their food.23,24 The main source of dietary sodium -- at least 75% of the total -- is processed foods, and a major reduction depends on changing their composition.21 Government initiatives have been limited to recommending a lower salt content in processed foods,25 setting a national target for sodium intake of ≤100 mmol/day,2 and publishing the dietary guideline Choose low salt foods and use salt sparingly.26 Food manufacturers have made some commendable initiatives, but they depend on consumer demand, and little has been done to inform the public about the national target for sodium intake. Although some low-salt processed foods are available and labelled in accordance with the food regulations, shoppers receive little specific advice or encouragement to reduce their sodium intake by choosing them. Conclusion By setting a national sodium-intake target, Australian health authorities have accepted that excessive dietary sodium is an important health issue, with significant morbidity, mortality and economic costs. Our results indicate the need for an active campaign to promote and monitor the nation's sodium target effectively. Acknowledgements This study was carried out with an educational grant from the National Heart Foundation of Australia, and financial assistance towards the purchase of computer equipment was received from Sizzler Restaurants and from Salt Skip Incorporated. We are indebted to Leigh Blizzard, statistician at the Menzies Centre, for statistical advice. References Antonios TFT, MacGregor GA. Deleterious effects of salt intake other than effects on blood pressure. Clin Exp Pharmacol Physiol 1995; 22: 180-184. Health Targets and Implementation (Health For All) Committee. Health for all Australians. Canberra: AGPS, 1988: 38. WHO/ISH Statement Committee. Prevention of hypertension and associated cardiovascular disease: a 1995 statement. Clin Exper Hypertension 1996; 18: 581-593. National Research Council. Committee on diet and health. Implications for reducing chronic disease risk. Washington DC: National Academy Press, 1989: 16-17. World Health Organization. Diet, nutrition, and the prevention of chronic diseases. WHO Technical Report No. 797. Geneva: WHO, 1990: 61. Committee on Medical Aspects of Food Policy. Nutritional aspects of cardiovascular disease. Department of Health and Social Security. Report on health and social subjects No. 46. London: HMSO, 1994: 138. Denton D, Weisinger R, Mundy NI, et al. The effect of increased salt intake on blood pressure of chimpanzees. Nature Med 1995; 1: 1009-1016. Truswell AS. Potassium. In: Truswell AS, Dreosti IE, English RM, et al., editors. Recommended nutrient intakes: Australian papers. Sydney: Australian Professional Publications, 1990: 191-198. Stamler J, Rose G, Stamler R, et al. Intersalt study findings: public health and medical care implications. Hypertension 1989; 14: 570-577. Beard TC, Eickhoff R, Mejglo ZA, et al. Population-based survey of human sodium and potassium excretion. Clin Exp Pharmacol Physiol 1992; 19: 327-330. Notowidjojo L, Truswell AS. Urinary sodium and potassium in a sample of healthy adults in Sydney, Australia. Asia Pacific J Clin Nutr 1993; 2: 25-33. Baghurst KI, Crawford D, Worsley A, et al. The Victorian nutrition survey: a profile of the energy, macronutrient and sodium intakes of the population. Community Health Studies 1988; 12: 42-54. Caggiula AW, Wing RR, Nowalk MP, et al. The measurement of sodium and potassium intake. Am J Clin Nutr 1985; 42: 391-398. Hunter D. Biochemical indicators of dietary intake. In: Willett W, editor. Nutritional epidemiology. New York: Oxford University Press, 1990: 143-216. Australian Bureau of Statistics. Socio-economic indexes for areas. Canberra: ABS, 1990. MacGregor GA, Markandu ND, Roulston JE, et al. Is idiopathic oedema idiopathic? Lancet 1979; 1: 397-400. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ 1988; 297: 319-328. SPSS for Windows, release 6.1 [computer program]. Chicago: SPSS Inc, 1994. Bingham SA, Cummings JH. The use of creatinine output as a check on the completeness of 24-hour urine collections. Hum Nutr Clin Nutr 1985; 39C: 343-353. Law MR, Frost CD, Wald MJ. By how much does dietary salt lower blood pressure? III. Analysis of data from trials of salt reduction. BMJ 1991; 302: 819-823. National Heart Foundation of Australia. Heart and stroke facts report. Canberra: The Foundation, 1995. James WPT, Ralph A, Sanchez-Castillo CP. The dominance of salt in manufactured food in the sodium intake of affluent societies. Lancet 1987; 1: 426-429. Bennett SA, Magnus P. Trends in cardiovascular risk factors in Australia. Med J Aust 1994; 161: 519-527. Thomson A, Rundle S, Singh BB, et al. Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality? Aust N Z J Med 1995; 25: 290-296. National Health and Medical Research Council. Report of the working party on sodium in the Australian diet. Canberra: AGPS, 1984: 4. National Health and Medical Research Council. Dietary guidelines for Australians. Canberra: AGPS, 1992: 70-83. (Received 24 Jun, accepted 4 Nov, 1996) Authors' details Menzies Centre for Population Health Research, University of Tasmania, Hobart, TAS. Trevor C Beard, OBE, MB BChir, MPH, Senior Research Fellow; Helen Hornsby, BA(Hons), Research Assistant; Terence Dwyer, MD, MPH, Director. Division of Biochemistry, University of Tasmania, Hobart, TAS. David R Woodward, PhD, Senior Lecturer. Department of Psychology, University of Tasmania, Hobart, TAS. Peter J Ball, BSc, MA, Senior Lecturer. Department of Clinical Chemistry, Royal Hobart Hospital, Hobart, TAS. Richard J von Witt, FRCPath, FRCPA, Director. Reprints: Dr T C Beard, Menzies Centre for Population Health Research, 17 Liverpool Street, Hobart, TAS 7000. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Trevor C Beard · David R Woodward · Peter J Ball · Helen Hornsby · Terence Dwyer

Helping heart attack victims to save their own lives Reperfusion techniques can save both lives and heart muscle, but the key is prompt treatment MJA 1997; 166: 228 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". - - ©MJA1997 The outlook for a person in the early hours after the onset of a myocardial infarction remains grim. Of the 40% who will die in the first month, a third will die in the first hour and up to a half in the first day.1 While some deaths are sudden and not amenable to treatment, the outcome in many cases can be improved by appropriate modern medical treatment, such as defibrillation and coronary reperfusion strategies, if administered early enough. publicise the symptoms of a possible heart attack, emphasise the importance of reporting them, and ensure that the message is aimed at all educational levels The risk of sudden cardiac death from ventricular fibrillation can be reduced by access to and use of a defibrillator. Coronary care ambulances with skilled paramedical staff have saved many lives since their introduction to Australia in the late 1960s.2 Increasingly, strategic placement of semi-automatic defibrillators -- for example, in large passenger aircraft and football stadiums -- is being considered, to further improve out-of-hospital survival. Once the patient reaches hospital, modern reperfusion strategies such as thrombo lysis and acute angioplasty can save lives, limit myocardial damage and reduce subsequent cardiac disability.3,4 Improved understanding of myocardial infarction from angiographic and postmortem studies has reaffirmed that most cases are indeed due to coronary thrombosis. The need to achieve coronary reperfusion as early as possible has long been recognised from pathophysiological studies and clinical trial experience.3,4 Since the mid 1980s, thrombolytic therapy has been studied in over 200 000 patients,3 and a recent overview has shown very clearly that streptokinase and recombinant tissue plasminogen activator (t-PA) are effective thrombolytic agents in acute myocardial infarction. Their appropriate use in patients with suspected myocardial infarction can save 20-30 lives per 1000 patients treated over the first 35 days,3 and there is the prospect of even better outcomes with new thrombolytic agents. More recently, reperfusion with acute coronary angioplasty has been shown to be equivalent to thrombolysis in most centres and to have superior outcomes in some centres, particularly those with a high level of expertise and readily available angioplasty services.4 The use of intracoronary stents adjunctive to angioplasty may improve even further the early outcome, with a reduced risk of late restenosis. The average loss of life per hour of delay of thrombolytic therapy is 1.6 lives per 1000 patients treated.3 The myocardial infarction triage and intervention trial in Seattle demonstrated even more accurately the importance of urgent treatment in the first hour.5 For patients surviving to hospital and being treated within 70 minutes of symptom onset, the 28-day mortality rate was 1.2% and only 5% of the left ventricular mass was infarcted; those treated later than 70 minutes had a mortality rate of 8.7% and 11% of myocardium was infarcted. These benefits were demonstrated with thrombolytic regimens now known to achieve early patency and restoration of normal coronary blood flow in less than half the patients treated. With the more aggressive reperfusion strategies now available the prospects are even brighter. The first hour after the onset of coronary thrombosis is indeed the "golden hour" of opportunity for preserving heart muscle and saving lives. These developments represent a quantum shift in what can be achieved in treating coronary thrombosis. Clinical management which allowed a passive acceptance of inevitable cardiac damage and high mortality rates is now out of date. The aim now is preservation of both life and myocardium by early restoration of coronary blood flow. From a mortality rate for hospitalised patients of 30% in the 1960s to 10%-15% after the introduction of coronary care units, a 28-day death rate of below 5% should now be achievable for coronary care patients after their first myocardial infarct.6,7 Given what can be achieved with early treatment, the reluctance of patients who suffer a heart attack to present to hospital is disappointing. Previous Australian studies8,9 have shown avoidable delays in presentation of up to several hours from the onset of symptoms. In this issue of the Journal Dracup and colleagues provide further evidence of this risk-taking behaviour -- they report an unusually long median delay of 6.4 hours, even longer than the approximately two-hour delay reported by Leitch et al.8 in a Sydney-based study in 1989 and the approximately 1.2-hour delay found by Bett et al.9 in a study of 22 centres in 1988-89. The difference is probably partly due to differences in the definition of time of onset. Dracup et al. report the duration from onset of the first symptoms until hospital presentation, whereas Leitch et al. reported the time of onset of the symptom which initiated action until hospital presentation8 (which does not take into account the duration of any preceding intermittent symptoms), and Bett et al. reported the time from onset of the symptom which initiated action to when "help was first sought"9 (as opposed to hospital presentation). Thus, the latter studies would be expected to give a shorter average interval than that reported by Dracup et al. It is noteworthy that Dracup et al. conducted their study before the May 1996 Heart Foundation Heart Week campaign, which emphasised how to recognise symptoms of heart attack, with posters and television commercials depicting squeezing chest pain as a python-like grip, and the need for early action by patients suffering symptoms of a heart attack. Dracup et al. found that the patients who recognised their symptoms as cardiac in origin had only one-third the response time of those who did not. It would be interesting to see if a follow-up study showed any effect of the 1996 campaign. Although the complex human response to chest pain is more likely to be instinctive rather than knowledge-based,9 Dracup and colleagues provide further useful insight into factors that cause delay. The independent predictors of delay were educational status (slower response times in less educated patients), a desire not to cause trouble, failure to recognise symptoms as being cardiac in origin, and an intermittent pattern of symptoms. The message for future public education campaigns is clear -- publicise the symptoms of a possible heart attack, emphasise the importance of reporting them (no-one ever died of embarrassment), and ensure that the message is aimed at all educational levels. The message for health professionals is especially clear -- a third of patients reported that they learnt about heart attack symptoms from a health professional. Doctors and nurses dealing with existing heart patients or those with substantial risk factors for myocardial infarction have many opportunities to educate patients about heart attack symptoms and to give clear instructions on how -- and why -- they should summon an ambulance and get to a hospital fast. Paul E Langton Cardiology Research Fellow, Sir Charles Gairdner Hospital, Perth, WA Peter L Thompson Clinical Professor, Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Perth, WA Tunstall-Pedoe H, Kuulasmaa K, Amouzel P, et al. Myocardial infarction and coronary deaths in the World Health Organization MONICA project. Circulation 1994; 90: 563-612. O'Rourke MF. Acute myocardial infarction: prehospital coronary care. In: Thompson PL, editor. Coronary care manual. London: Churchill-Livingstone, 1997: 429-433. Fibrinolytic Therapy Trialists Collaborative Group. Fibrinolytic therapy -- indications in suspected acute myocardial infarction. Lancet 1994; 343: 311-322. Ryan TJ, Anderson JL, Autman EM, et al. ACC/AHA Guidelines for the management of patients with acute myocardial infarction: executive summary. Circulation 1996; 94: 2341-2350. Weaver WD, Cerqueria M, Hallstrom AP, et al. for the MITI project group. Prehospital-initiated v. hospital-initiated thrombolytic therapy. The myocardial infarction triage and intervention (MITI) trial. JAMA 1993; 270: 1211-1216. DeVreede JJM, Gorgels AP, Verstraaten GMP, et al. Did prognosis after myocardial infarction change during the past 30 years? J Am Coll Cardiol 1991; 18: 698-706. Jamrozik K, Broadhurst R, Parsons RW, et al. Ten year trends in medical management and case fatality in acute myocardial infarction [abstract]. J Am Coll Cardiol 1996; 27: 278A. Leitch JW, Birbara T, Freedman B, et al. Factors influencing the time from onset of chest pain to arrival at hospital. Med J Aust 1989; 150: 6-8. Bett N, Aroney G, Thompson PL. Impact of a national education campaign to reduce patient delay in possible heart attack. Aust N Z J Med 1993; 23: 157-161. Reprints: Dr P E Langton, Sir Charles Gairdner Hospital, Verdun Street, Nedlands, WA 6009. - - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Paul E Langton · Peter L Thompson

Australian patients' delay in response to heart attack symptoms Kathleen Dracup, Sharon M McKinley and Debra K Moser MJA 1997; 166: 233 For comment see Langton and Thompson Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Statistical analyses - Results - Associations with delay time - Discussion - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objectives: To examine delay in seeking treatment among patients with an evolving acute myocardial infarction (MI), and to identify factors which contributed to this delay. Design: Patient interview combined with medical record review. Participants and setting: 317 patients with confirmed diagnosis of acute MI interviewed within 72 hours of admission to three hospitals. Main outcome measures: Delay from onset of symptoms to arrival at hospital, and cognitive, emotional, sociodemographic and clinical factors which contributed to increased prehospital delay. Results: Median prehospital delay was 6.4 hours; 41% of patients delayed less than four hours, while 28% delayed less than two hours. Prehospital delay was increased in patients with fewer years of education (P = 0.001), lower income (P = 0.003) and transportation to the hospital by private car rather than ambulance (P = 0.02). Delay time was increased by several cognitive and emotional processes (P < 0.001), such as waiting to see if symptoms would go away, being too embarrassed to ask for assistance, and not recognising the importance of symptoms. Delay time was increased with heartburn, breathlessness or intermittent symptoms and decreased with sweating and dizziness (P < 0.05). Independent predictors of increased prehospital time (P < 0.01) were fewer than 10 years of education, not wanting to trouble anyone, failing to recognise the symptoms of delay, and the intermittent nature of symptoms. Conclusion: Over 50% of acute MI patients delay seeking treatment by six hours or more. Many factors related to cognitive and social processes that contribute to this delay may be remediable with appropriate patient and community education. MJA 1997; 166: 233-236 Introduction Every year in Australia approximately 22 000 people suffer a heart attack and approximately half of these die. Most of these deaths occur out of hospital.1 The high mortality associated with acute myocardial infarction (MI) is dismaying, given that major large-scale clinical trials have shown that thrombolytic therapy can significantly reduce mortality from MI.2 With this therapy, the shorter the interval between the onset of symptoms and when the drug is given, the better the outcome.2 If therapy is started within three hours of symptoms, mortality is reduced by 23%;3 this becomes 45% if started within one hour of symptoms.3 Similarly, the earlier the treatment, the better the resulting cardiac function and the lower the incidence of morbidity after MI.4 Prehospital delay is known to be a substantial problem. Median delay times ranging from just under two hours5 to six-and-a-half hours have been reported.6 Overall, approximately 25%-50% of MI patients delay seeking medical care for cardiac symptoms for more than six hours.7,8 In other countries, the factors associated with increased prehospital delay are being older; being female; having a clinical history of hypertension, diabetes, angina or congestive heart failure; having low emotional or somatic awareness; consultation with a spouse or other relative; consultation with a doctor; and self-treatment. Decreased prehospital delay occurs when there is haemodynamic instability, large infarct size, sudden onset of severe chest pain, recognition of symptoms as heart-related and consultation with a non-relative.8,9 We do not know if the characteristics that contribute to delay in seeking treatment for acute MI symptoms are similar for Australian patients. Such information is important for designing appropriate patient and community education programs. Therefore our aims were, firstly, to describe prehospital delay time in Australian patients experiencing symptoms of evolving acute MI and, secondly, to identify the cognitive, emotional, sociodemographic and clinical factors which contribute to this delay. Methods We gained appropriate institutional ethics committee review and approval for the study from the study hospitals and the University of Technology, Sydney. Eligible patients admitted to three hospitals between 1 March and 31 July 1995 were invited to participate in the study and gave written informed consent. Patients were eligible if they were able to read and write English, lived independently, were free from malignancy or other complicating illness, alert and orientated, were within 24 and 72 hours of hospital admission, and had a diagnosis of acute MI, determined by:Chest pain lasting longer than 20 minutes; Serial electrocardiographic evidence of acute MI (i.e., appearance of new Q waves in at least two leads of a 12-lead standard electrocardiogram); and Elevations in serum creatine kinase-MB consistent with evolving MI. Only patients with Q-wave MI were studied. Patients were excluded if they were being mechanically ventilated. The hospitals were two metropolitan university-affiliated city teaching hospitals and a district hospital, chosen because their geographical catchment areas were relatively small, so transportation time would not add significantly to the time between symptom onset and arrival at the hospital. We reviewed medical records to obtain sociodemographic and clinical data. We assessed information about the cognitive, emotional and social processes surrounding the decision to seek treatment using the Response to symptoms questionnaire, designed to obtain information about patient delay and factors contributing to delay in six domains: (1) context in which MI symptoms appeared; (2) antecedents of symptoms; (3) affective response to symptoms; (4) behavioural response to symptoms; (5) cognitive response to symptoms; and (6) the response of others to patient symptoms.10 Based on growing evidence that cognitive, symptom-appraisal and social factors may be more important determinants of delay than knowledge about appropriate re sponse to symptoms,10 we modified the instrument to further assess cognitive, symptom-appraisal and social factors surrounding a patient's decision to seek care for acute MI symptoms. The resulting instrument assesses factors surrounding the onset of acute MI symptoms, the response of others to symptoms, and the patient's response to symptoms. We established the time from symptom onset to hospital admission by reviewing the medical record for the time stated in the admission record by the admitting physician and the time of admission to the hospital. Also, each patient was asked about the time of first symptoms. If symptoms had come and gone, patients were carefully interviewed to determine the nature of those symptoms and the exact time that cardiac symptoms began. Where the patient's account differed from the time recorded by the admitting doctor, cardiac enzymes and serial electrocardiograms were reviewed to identify the most likely time of symptom onset. The value that most closely matched the expected clinical course reflected in the tests was chosen. Patients were asked if they wanted to complete the questionnaire themselves or if they wanted the researcher to read the questions; 96% chose the latter. Statistical analyses Independent t tests or analysis of variance (with post-hoc t tests adjusted for multiple comparisons) were used to assess the impact of sociodemographic, clinical, cognitive and social factors. Delay time was markedly skewed, so we used square root transformations to obtain a normal distribution, and all analyses were performed on transformed values. Multiple logistic regression and χ2 tests were used to determine odds ratios for delays of more than two hours among several sociodemographic, clinical, social and cognitive variables. Variables that were significantly different (P < 0.05) on delay time were entered into the forward stepwise logistic regression. Criteria for entry and removal of variables were based on the likelihood ratio test, with enter and remove limits set at P < 0.05 and P > > 0.05. Results Of 321 eligible patients approached, 317 agreed to participate in the study; four declined, giving fatigue as a reason. Patients were predominantly older (mean, 63 years; standard deviation, 12 years), male, married and white. There was diversity in years of formal education and socioeconomic status. Most patients experienced their symptoms at home and most went to hospital by ambulance (Box 1). Many patients were at greater than average risk for suffering an acute MI, with previous medical histories of angina pectoris (43%), MI (28%), hypertension (53%) and/or diabetes mellitus (19%). Most MIs were inferior (46%) or anterior (32%). Median prehospital delay time was 6.4 hours (interquartile range, 1.9-19.9 h; mean, 17.3 h). Only 14% of patients arrived within one hour of the onset of symptoms, 28.5% within two hours and 41% within four hours. However, 54% arrived at the hospital more than six hours after first experiencing cardiac symptoms. One hundred and fifty-three patients (48%) received thrombolytic therapy; 29 within one hour of the onset of symptoms. Associations with delay time Sociodemographic factors: Box 1 shows that there were differences in delay time according to education, annual income and use of ambulance. There was no significant association with sex, age, ethnicity, the location where symptoms occurred or whether or not a spouse was present when they occurred. Symptoms and pain: We examined breathlessness, fatigue, weakness, vague chest discomfort, chest pain, neck pain, arm numbness, pain between shoulder blades, back pain, nausea, feeling that something was wrong, dia phoresis, feeling clammy, heartburn, and dizziness. Delay time was less if patients were dia phoretic (P = 0.001) or experienced dizziness (P = 0.03) and increased if they were breathless (P = 0.03) or experienced heartburn (P = 0.03). The remaining symptoms made no difference to delay times. If symptoms were intermittent, patients took longer to seek treatment (P = 0.0001), while those who believed their symptoms to be cardiac in nature delayed for shorter times (P = 0.001). However, 60% originally attributed their symptoms to another cause (e.g., muscle pain, fatigue, indigestion). Patients who appraised their pain as very serious delayed a shorter time than patients who appraised their pain as not serious (P = 0.001). However, patients who rated their initial chest pain as severe had similar delay times to patients who rated their pain as mild (P = 0.644). Knowledge of coronary heart disease: There were no differences in the average time to arrival at hospital related to previous myocardial infarction, previous cardiac surgery, diabetes mellitus, hypertension or angina. Forty per cent of patients reported that their source of information about MI symptoms was television or reading; 27% received their information from a friend; 23% from a doctor; and 10% from a nurse. Sixteen per cent of patients knew about thrombolysis therapy for acute MI and these, on average, came to the hos pital earlier than patients who did not know about this treatment (P = 0.001). Cognitive and psychological factors: Box 2 (below) shows significant associations between patients' responses and delays in seeking medical treatment. Independent predictors of delay: We tested factors that were significant on univariate analyses in a multiple regression model. The five independent predictors of delay are shown in Box 3. Discussion In 317 patients admitted to hospital for evolving acute MI, we found that median prehospital delay was 6.4 hours. Almost 60% of patients delayed more than four hours, while more than 70% delayed longer than two hours. These times are substantially longer than those recorded in most studies from other countries,4-6,8,11 as well as those documented in previous Australian studies.12,13 The disparity between this and previous Australian studies is un doubtedly related to a difference in the definitions used to characterise prehospital delay. In the first Australian study, time from symptom onset to the first attempt to get help was reported.12 In the second, the definition of total delay time was the period from the onset of chest pain to arrival at hospital; where there were multiple episodes of chest pain, the time from the last episode of pain was used.13 Both variations in definitions would shorten reported delay time relative to the definition we used. It is unlikely that longer transportation times to the hospital contributed to longer delay times in our study because of the geographic situation of the participating hospitals and the high rate of ambulance use. Moreover, all studies on this topic have found that home-to-hospital time, as well as in-hospital time, play a minor role in the delay that occurs before definitive treatment.8,14,15 We included only those patients who survived to hospital admission and who met our inclusion criteria, and hence our patients were clearly not representative of all patients with acute MI. Unfortunately, approximately 30% of such patients die of sudden cardiac death before reaching the hospital,1 and we excluded patients because they were unable to respond to questions within the designated 72 hours of hospital admission (e.g., because they required mechanical ventilation or had compromised mental status). In the past, most researchers have focused on identifying patients who are more likely to delay a decision to come to the hospital because of various sociodemographic and clinical characteristics. In our study, the most important factor predicting delay was years of formal education, a characteristic that health professionals cannot alter. However, it may be linked with other characteristics (e.g., income, age, coping styles or other underlying cognitive mechanisms affecting delay), some of which may be amenable to change. Many of our patients had difficulty identifying their symptoms as cardiac in nature, initially thinking they were gastrointestinal, musculoskeletal, or fatigue. Many patients knew the classic signs of acute MI but did not know the diversity of its presentation, notably its often intermittent nature. Patients should be told that the symptoms may come on gradually or may not be constant, as many believe that MI is accompanied by sudden, crushing chest pain and unconsciousness. As in other studies,5,12,16,17 experience of a previous MI did not result in patients coming to the hospital sooner. Thus, the public, particularly patients at high risk for a future MI, need to be informed that the manifestations of an evolving MI may vary, even within the same individual, and should be clear about the actions to take if and when symptoms occur. In most studies in the United States, less than half of MI patients arrive by ambulance,18 whereas in our study most patients in all three hospitals used this means of transportation. Ambulance is preferable to other types of transportation because of the early treatment available and because delay times are usually reduced.18 From the accounts of patients in this study, doctors and nurses played minimal roles in providing information about the symptoms of MI, compared with knowledge gained from television, reading and friends. Counselling strategies tested in other clinical populations support the assumption that individuals who are prepared for certain signs and symptoms will delay less in seeking care than individuals who have no such preparation.19-21 They also suggest that health professionals should take a more proactive and intensive approach to educating patients about the nature of MI signs and symptoms and the steps to take to receive early treatment. These data also indicate the opportunity for professional organisations to enhance the knowledge and beliefs of patients by community educational programs via television, radio and newspapers. Very few patients knew about thrombolysis and its effectiveness in treating acute MI, but those who did presented sooner than those who did not. Based on these findings, health care professionals should emphasise the rationale for early treatment to patients at high risk for future MI, and public campaigns should advertise the benefit of seeking early treatment. Patients need to know that their decision to seek immediate treatment has important future rewards as this may override whatever trepidation they experience in acknowledging that they might be having a heart attack. In summary, almost all the significant predictors of delay we identified related to social and cognitive processes that might be amenable to change. Health care professionals should recognise the reluctance of patients to recognise MI symptoms as cardiac and provide them with the necessary guidance, so that they will seek care as soon as possible. The availability of newer forms of treatment, particularly thrombolytic therapy, provides a compelling reason for physicians and nurses to encourage patients and their families to seek care early to preserve ischaemic myocardium and reduce infarct size in the face of an evolving MI. Acknowledgements Funding for this study was provided by a Fulbright Foundation Senior Scholars grant and from the L W Hassenplug Chair funds. We thank the following nurses who assisted with data collection: Patricia Cameron, Marie Droulers, Cameron Goodear, Jennifer Kidd, Jacqueline Padley, Rebecca Scammell and Jennifer Williams. References Heart and stroke facts. Canberra: National Heart Foundation of Australia, 1995. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311-322. Gruppo Italiano per lo Studio della Stretochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-401. Simoons ML, Serruys PW, Brand MVD, et al. Early thrombolysis in acute myocardial infarction: Limitation of infarct size and improved survival. J Am Coll Cardiol 1986; 7: 717-721. Maynard C, Althouse R, Olsufka M, et al. Early versus late hospital arrival for acute myocardial infarction in the western Washington thrombolytic therapy trials. Am J Cardiol 1989; 63: 1296-1300. Cooper RS, Simmons B, Castaner A, et al. Survival rates and prehospital delay during myocardial infarction among black persons. Am J Cardiol 1986; 57: 208-211. Dracup K, Moser D. Treatment seeking behavior among those with symptoms and signs of acute myocardial infarction. Heart Lung 1991; 20: 570-575. GISSI-Avoidable Delay Study Group. Epidemiology of avoidable delay in the care of patients with acute myocardial infarction in Italy. Arch Intern Med 1995; 155: 1481-1488. Dracup K, Moser D, Eisenberg M, et al. Causes of delay in seeking treatment for symptoms of acute myocardial infarction. Soc Sci Med 1995; 40: 379-392. Burnett RE, Blumenthal JA, Mark DB, et al. Distinguishing between early and late responders to symptoms of acute myocardial infarction. Am J Cardiol 1995; 75: 1019-1022. Schwarz B, Schoberberger R, Rieder A, Dunze M. Factors delaying treatment of acute myocardial infarction. Eur Heart J 1994; 15: 1595-1598. Bett N, Aroney G, Thompson P. Impact of a national educational program to reduce patient delay in possible heart attack. Aust N Z J Med 1993; 23: 157-161. Leitch JW, Birbara T, Freedman B, et al. Factors influencing the time from onset of chest pain to arrival at the hospital. Med J Aust 1989; 150; 6-8. Schroeder JS, Lamb IH, Hu M. The pre-hospital course of patients with chest pain: analysis of the prodromal, symptomatic, decision-making, transportation and emergency room periods. Am J Med 1978; 64: 742-748. Schmidt SB, Borsch MA. The prehospital phase of acute myocardial infarction in the era of thrombolysis. Am J Cardiol 1990; 65: 1411-1415. Turi ZG, Stone PH, Muller JE, et al. Implications for acute intervention related to time of hospital arrival in acute myocardial infarction. Am J Cardiol 1986; 58: 203-209. Weilgosz ATJ, Nolan RP, Earp JA, Biro E. Reasons for patients' delay in response to symptoms of acute myocardial infarction. Can Med Assoc J 1988; 139: 853-857. Meischke H, Ho MT, Eisenberg MS, et al. Reasons patients with chest pain delay or do not call 911. Ann Emerg Med 1995; 25: 193-197. Bandura A. Self-efficacy; toward a unifying theory of behavior change. Psychol Bull 1977; 84: 191-198. Bailey WC, Richards JM Jr, Brooks CM, et al. A randomized trial to improve self-management practices of adults with asthma. Arch Intern Med 1990; 150: 1664-1667. Avis NE, Smith DW, McKinlay JB. Accuracy of perceptions of heart attack risks: what influences perceptions and can they be changed? Am J Public Health 1989; 17: 1608-1611. (Received 28 Mar, accepted 20 Nov, 1996) Authors' details University of California, Los Angeles, CA, USA. Kathleen Dracup, RN, DNSc, L W Hassenplug Professor of Nursing. University of Technology, Sydney, and Royal North Shore Hospital, Sydney, NSW. Sharon M McKinley, RN, PhD, Professor of Critical Care Nursing. College of Nursing, Ohio State University, Columbus, OH, USA. Debra K Moser, RN, DNSc, Assistant Professor. Reprints: Professor S M McKinley, Level 6, Royal North Shore Hospital, St Leonards, NSW 2065. E-mail: smckinle AT doh.health.nsw.gov.au - - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Kathleen Dracup · Sharon M McKinley · Debra K Moser

Clinical Practice Clinical exercise stress testing -- Safety and performance guidelines* The Cardiac Society of Australia and New Zealand Clinical exercise testing has wide application in medicine, including the assessment of functional capacity, ventilatory function, gas exchange, muscle function, and endocrine and metabolic function, and as a test for claudication in peripheral vascular disease. The major use of exercise testing, however, is as a stress test in patients with known or suspected coronary artery disease. This article outlines the minimum safety and performance guidelines for exercise stress testing with electrocardiography, although many of the safety guidelines are common to other types of exercise tests, particularly exercise stress scintigraphy and echocardiography. MJA 1996; 164: 282-284 Introduction - Exercise equipment - Electrocardiograph (ECG) - Blood pressure measurement - Documentation - Postexercise period - Resuscitation equipment - Personnel - References - Authors' details - - Articles on similar material Introduction Clinical exercise stress testing with exercise electrocardiography is usually performed in patients with known or suspected coronary artery disease (see Box 1). It is thus not without risk: one in 10 000 people will die, and two to three in 10 000 will have a major morbid event such as myocardial infarction, a major arrhythmia requiring resuscitation, severe hypotension, severe heart failure or unstable angina pectoris. (The complication rates may be higher in some laboratories because of the mix of referred patients.) Those who perform exercise stress testing must thus be able to recognise and exclude patients at high risk, and have the clinical skills and equipment to recognise and deal effectively with complications. They should also obtain informed consent from the patient before performing the test. Exercise equipment Energy expenditure is best quantified by measurement of oxygen consumption (Vo2), expressed in METS, during exercise. A MET unit is the energy expenditure at rest, equivalent to an oxygen uptake of approximately 3.5 mL O2 per kilogram bodyweight per minute. This is the most precise measurement of metabolic load, and therefore cardiovascular load, and can vary considerably between individuals with differing exercise efficiency working at the same treadmill or cycle ergometer setting. Vo2 is not usually measured directly; energy expenditure in METS can be estimated from nomograms1 which assume that energy expenditure can be quantified as watts (cycle ergometer) or as speed and grade (treadmill). Treadmills must be motorised and calibrated, and should be capable of providing measured increases in speed and gradient. The treadmill speed can be easily checked by measuring the visible length of belt, multiplying by two, and multiplying this by manually counted belt revolutions/ minute to give km/hour. Treadmill inclination can be checked by a protractor. Cycle ergometers must be able to vary the external workload and quantify it in watts. Preference is for electrical or mechanical braking, although wind-braking is probably adequate. Thumb-screw braking is not adequate as the load cannot be quantified and is not reproducible. Simple step devices (including "Masters two-step"), or any other form of non-quantified and unmonitored exercise, are not adequate for clinical exercise stress testing. Equipment should be serviced on a regular basis to ensure performance within specifications. Electrocardiograph (ECG) Use 12-lead ECG equipment, recording on a 3-channel device with adequate low frequency and phase response. Devices which record only one or three ECG leads, even if these are bipolar chest leads, are not adequate. If the device provides computer-averaged complexes, raw ECG traces should also be inspected at each stage of exercise, or at least every three minutes, to avoid incorrect interpretation resulting from noise or artefact. Electrodes must be firmly fixed to the patient's skin with adhesive or continuous suction, and have good contact with the ECG lead, to prevent movement artefact in the ECG trace. Use an alcohol solution to remove oil from the patient's skin and abrade the horny layer of the epidermis with fine sandpaper or a disposable abrasive device. Record a standard supine ECG (with limb leads on the limbs) for each patient, and an additional supine ECG with the limb electrodes on the torso if this is where they will be placed during exercise. Monitor the ECG continuously during the exercise period and for five minutes after the cessation of exercise on a video display of two or three leads, preferably selected to be semiorthogonal (i.e., an inferior lead, V5, and V1 or V2). Monitoring a single lead is suboptimal for detecting arrhythmias and ischaemic patterns during exercise. Monitoring devices should have a memory loop capable of providing hard copy or storing rhythm traces on request by the operator. Record further ECGs with the patient upright; during each stage of exercise (or at least every three minutes); at peak exercise; immediately upon cessation of exercise; and at least twice during the post- exercise period. Blood pressure measurement Measure blood pressure before, during (ideally every minute but at least every three minutes, coinciding with each stage of exercise) and after exercise (at least two measurements). If possible, a measurement should be made at peak exercise. Additional measurements may be required depending on clinical circumstances. Documentation Document the resting and peak heart rate and blood pressure, and any abnormalities of these or the ECG. The peak rate-pressure product (heart rate x systolic blood pressure) should be calculated as this provides the best estimate of myocardial load. Question the patient about symptoms such as angina, anginal equivalents, shortness of breath, presyncope and claudication during and after exercise. Identify the major symptom which limits exercise and record its intensity, at least descriptively, but ideally with a quantitative measure such as the Borg scale2 (see Box 2). Also record the duration of exercise and the maximum workload achieved. Postexercise period Patients should be observed for at least 10 minutes after cessation of exercise. Continue ECG monitoring for at least five minutes, or longer if clinically indicated. The duration of ECG monitoring may be abbreviated to three minutes in special circumstances, such as thallium scintigraphy, when imaging must commence as soon as possible after exercise. In such cases, the patient should be closely observed for the first 10 minutes after exercise. Resuscitation equipment Exercise stress test laboratories must be adequately equipped to provide advanced life support in the event of a cardiac arrest (see Box 3). The exercise room must be sufficiently large to allow the patient to be removed from the treadmill or cycle and be placed on the ground for resuscitation if complications occur. All resuscitation equipment must be easily accessible and maintained and tested on a regular basis. Personnel Two people (at least one of whom is a registered medical practitioner, see Box 4) should be present in the exercise room at all times during exercise stress testing and the immediate postexercise period. Both should be trained in cardiopulmonary resuscitation and in the recognition of the major arrhythmias and ischaemic patterns on the ECG. No regular specific courses are currently available in exercise stress testing. The assistant for exercise stress testing should be a professional person with training in an area related to health (e.g., ECG technician, graduate of a course approved by the Australian Association for Exercise and Sports Sciences, coronary care-trained nurse, physiotherapist, occupational therapist). He or she must be able to perform cardiopulmonary resuscitation, obtain a high quality ECG trace, and recognise the major arrhythmic and ischaemic ECG and clinical manifestations likely to occur during exercise stress testing. He or she should also have observed exercise stress tests under the supervision of a cardiologist and performed tests under supervision of an experienced assistant. A retraining program in cardiopulmonary resuscitation should be undertaken every two years. References The Committee on Exercise, American Heart Association. Exercise testing and training of apparently healthy individuals: a handbook for physicians. Dallas, TX: American Heart Association, 1972: 13. Noble BJ, Borg GAV, Jacobs I, et al. A category-ratio perceived exertion scale: relationship to blood and muscle lactates and heart rate. Med Sci Sports Exerc 1983; 15: 523-528. * Adapted from a Cardiac Society guideline document, copies of which are available from Professor Freedman. Authors' details 145 Macquarie Street, Sydney, NSW 2000. The Cardiac Society of Australia and New Zealand. No reprints will be available. Correspondence: Professor Ben Freedman, Honorary Secretary. ©MJA 1998 Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1998 Medical Journal of Australia. 1: Indications for exercise stress testing* As a diagnostic test in patients with suspected coronary artery disease (e.g., men with symptoms that are atypical for myocardial ischaemia, patients with symptoms consistent with recurrent exercise-induced cardiac arrhythmias). To assist in identifying patients with documented coronary artery disease who are at high risk (e.g., due to advanced disease and/or left ventricular dysfunction). To evaluate patients after coronary artery bypass surgery or angioplasty. To quantify a patient's functional capacity, prognosis or response to therapies, and to follow the natural course of disease at appropriate intervals (e.g., after uncomplicated myocardial infarction, in selected patients with congenital heart disease). General contraindications Unstable angina prior to a period of stabilisation Untreated life-threatening arrhythmias Uncompensated severe congestive heart failure Advanced atrioventricular heart block Acute myocarditis Critical aortic stenosis * Adapted from: Guidelines for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Cardiovascular Procedures (Subcommittee on Exercise Testing). J Am Coll Cardiol 1986; 8: 725-738. Back to text 2: Borg scale2 for ratings of perceived exertion 0Nothing at all0.5 Very, very weak1 Very weak2 Weak3 Moderate4 Somewhat strong5 Strong67 Very strong8910 Very, very strong(maximal)Back to text 3: Essential resuscitation equipment Defibrillator with electrogel or electrode pads Suction (motor driven or gas cylinder [Venturi] device with appropriate plastic or metal suckers) Airway plus self-inflating ventilation bag Oxygen and appropriate masks Drugs, intravenous cannulas and giving sets, including atropine, lignocaine, adrenaline, and sotalol or amiodarone for intravenous use, a β2-agonist inhaler (e.g., salbutamol), and short-acting nitrates (e.g., sublingual glyceryl trinitrate or isosorbide dinitrate, or glyceryl trinitrate spray) Alarm to summon nearby personnel and a telephone to call an intensive care ambulance in the event of an emergency Back to text 4: Medical practitioners supervising exercise stress tests should be able to: Evaluate indications for exercise stress testing and recognise contraindications. Interpret all the major abnormalities that can be detected on 12-lead electrocardiography, particularly those associated with ischaemic heart disease; those likely to preclude interpretation of the exercise ECG; those which might indicate deferral of the exercise test; and the tachy- and bradyarrhythmias that may occur during exercise. Differentiate ischaemic from non-ischaemic symptoms during exercise. Perform basic and advanced life support with skill in an emergency situation, and show evidence of continuing competence by, for example, attending retraining courses at two-yearly intervals. Demonstate previous experience in exercise stress testing supervised by a cardiologist, including determination of the most appropriate protocol for individual patients. Back to text

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