more_vertA month after my father died of heart failure in a cardiac intensive-care unit in my hometown, I flew back to Baltimore to finish my final year of medical school. Although I was apprehensive about returning to the hospital, I knew that the full schedule would be a welcome distraction. Still, I was surprised how easily I fell back into the old routine of attending morning rounds, admitting patients, writing progress notes, and presenting cases to the head physician.
Preference: Cardiology and Cardiac Surgery
99
Warfarin or excipient allergy: a clinical dilemma resolved
A 57-year-old Asian woman was referred for surgical ablation of atrial fibrillation (AF), coronary revascularisation and mitral valve surgery. She had a history of paroxysmal AF, previous stroke, coronary artery disease and severe mitral regurgitation. In the work-up for surgery, she developed recurrent, pruritic maculopapular rashes involving her trunk and upper limbs on two occasions within 3 days of initiating oral anticoagulation with warfarin (Marevan, Aspen) for AF. There were no other changes to the patient’s longstanding medication regimen during this period. Her regular medications consisted of aspirin 100 mg and perindopril arginine 2.5 mg in the morning, and atorvastatin 80 mg at night. Long-term anticoagulation with warfarin was necessary due to planned mechanical valve replacement and ongoing paroxysmal AF. Subsequently, she was referred to a clinical immunologist for assessment of her reaction to warfarin. Since allergic reactions to warfarin are rare, a reaction to one of the dyes in the tablet was considered.
The patient had been taking all three strengths of Marevan tablets (1 mg, 3 mg and 5 mg), which contain a number of excipients (Box). Initial drug challenge commenced with Coumadin 1 mg (Bristol-Myers Squibb) tablets, as these did not contain any shared excipients. She tolerated this for 1 week and subsequently the dose was increased to three 1 mg tablets of Coumadin. She remained symptom-free and reached a therapeutic international normalised ratio. It was therefore deemed safer to avoid Marevan 1 mg and 3 mg tablets and the Coumadin 2 mg tablet, which shared the colouring constituent indigo carmine (132). She later underwent mitral valve replacement with a mechanical valve, closure of the left atrial appendage, surgical ablation and coronary revascularisation. She currently remains rate-controlled at 7 months follow-up with therapeutic anticoagulation on Coumadin 1 mg tablets.
“Warfarin allergy” can be due to the coumarin structure or the excipients introduced for colouring and safety.1 While this has previously been documented, excipients are rarely considered as a possible cause of allergic reaction in common practice.1,2 Importantly, not all allergies are attributed to the coumarin structure, and it is possible to have dermatological adverse reactions to the colouring dyes in warfarin.1,3 In our patient, we strongly suspect indigo carmine (FD&C Blue No. 2). Blue dyes have previously been implicated as the cause of urticarial rashes in patients taking synthyroid tablets.4 Although there was no objective confirmation of causality (eg, patch testing), the clinical presentation coupled with a high score of 9 on the Naranjo probability scale is compelling, although not conclusive.5 With this in mind, we suggest that excipient allergy should be considered in patients with a reaction to warfarin, and dye-free preparations can be administered as a therapeutic alternative.
1
Excipient dyes used in Coumadin and Marevan brands
|
Brand/strength |
Tablet colour |
Active ingredient |
Dye |
||||||||||||
|
|
|||||||||||||||
|
Coumadin 1 mg |
Light tan |
Warfarin sodium |
Amaranth (123)Quinoline Yellow (104) |
||||||||||||
|
Coumadin 2 mg |
Lavender |
Warfarin sodium |
Amaranth (123)Indigo Carmine (132) |
||||||||||||
|
Coumadin 5 mg |
Green |
Warfarin sodium |
Quinoline Yellow (104)Brilliant Blue FCF (133) |
||||||||||||
|
Marevan 1 mg |
Brown |
Warfarin sodium |
Iron Oxide Yellow (172)Iron Oxide Red (142)Indigo Carmine (132) |
||||||||||||
|
Marevan 3 mg |
Blue |
Warfarin sodium |
Indigo Carmine (132) |
||||||||||||
|
Marevan 5 mg |
Pink |
Warfarin sodium |
Erythrosine (127) |
||||||||||||
|
|
|||||||||||||||
|
Other excipients (all strengths): Coumadin — lactose, starch (tapioca, stearic acid and magnesium stearate); Marevan — lactose, starch (maize and pregelatinised maize, sodium starch and magnesium stearate). |
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Steroid-induced cardiomyopathy
Clinical record
In December 2012, a 30-year-old man was admitted via the emergency department of our tertiary hospital with atrial fibrillation (AF), new-onset biventricular cardiac failure, acute renal failure and elevated liver function test results.
He presented with a 2-week history of dyspnoea, palpitations and epigastric discomfort. An electrocardiogram confirmed AF with a rapid ventricular response, and he was subsequently admitted to hospital. His initial heart rate varied between 120 and 140 beats/min and his blood pressure was 140/90 mmHg. He had distended jugular veins and cardiac examination revealed a gallop rhythm and an apical pansystolic murmur. His lungs were clear to auscultation and he had no peripheral oedema.
The patient was a successful bodybuilder and strongman. Over the past 12 months, he had taken testosterone 1.5 g per week, trenbolone 500 mg per week, methandrostenolone 40 mg daily, anastrozole 0.5 mg daily and naproxen 1.1 g daily in preparation for a national championship competition. The products were obtained through other users at the gym where the patient trained. He had ceased all the above supplements about 6 weeks before his admission. He was 141 kg at the time of presentation.
Further questioning elicited that he had taken anabolic steroids for about 7 years leading up to his presentation. He stated that he had only recently started taking trenbolone. Further examination did not reveal any evidence of gynaecomastia, testicular atrophy or acne.
His social history was otherwise unremarkable. There was no history of heavy alcohol use, smoking or illicit drugs. There was no family history of cardiomyopathy. There were no signs and symptoms of a viral illness.
Fifteen months before presentation, he had a transthoracic echocardiogram for hypertension, which revealed normal biventricular size and systolic function, normal biatrial size, normal diastolic function and normal valve function. At the time, he also underwent a treadmill stress echocardiogram, for which he exercised for 8 min 50 s on a 2-minute Bruce protocol, achieving 100% maximum predicted heart rate and 14.5 metabolic equivalents. There was no evidence of inducible ischaemia.
Initial laboratory tests showed an increased haemoglobin level (192 g/L [reference interval (RI), 130–180 g/L]) with a normal haematocrit level (0.54 L/L [RI, 0.40–0.54 L/L]); renal dysfunction (creatinine level, 138 μmol/L [RI, 62–106 μmol/L]) with normal electrolytes; a mildly increased level of high-sensitivity troponin T (26 ng/L [RI, < 15 ng/L]) with no subsequent increase; and increased liver enzyme levels (alanine aminotransferase [ALT], 207 U/L [RI, < 41 U/L]; aspartate aminotransferase [AST], 116 U/L [RI, < 40 U/L]). However, his albumin and bilirubin levels and international normalised ratio were normal. Initial therapy included metoprolol and anticoagulation with low molecular weight heparin.
The patient underwent transoesophageal echocardiography on Day 3 of his admission. This showed severe global biventricular dysfunction, moderate to severe mitral regurgitation as a result of annular dilatation, biatrial enlargement, and the presence of spontaneous echo contrast in the left atrial appendage without thrombus. Electrical cardioversion was performed, resulting in sinus tachycardia; however, AF recurred within 24 hours. Pharmacological therapy to promote sinus rhythm included intravenous amiodarone (300 mg immediately, followed by 1200 mg over 24 hours) followed by oral loading (400 mg three times a day).
Our patient was given carvedilol and ramipril. However, he deteriorated on Day 4, developing hypotension (blood pressure, 80/50 mmHg) and renal dysfunction (creatinine level, 267 μmol/L), and a worsening of his liver function (ALT, 1857 U/L; AST, 1697 U/L). Low-dose dobutamine infusion was started and continued for 72 hours, resulting in excellent diuresis and improvement in his clinical condition with recovery of liver and kidney function.
Investigations to exclude a secondary cause of cardiomyopathy included thyroid function tests, iron studies and plasma metanephrine tests, which all returned normal results.
- angiotensin-converting enzyme inhibitor: ramipril 5 mg daily;
- β-blocker: carvedilol uptitrated to 50 mg twice daily;
- aldosterone antagonist: initially spironolactone 25 mg daily, subsequently changed to eplerenone 25 mg daily because of gynaecomastia;
- amiodarone to maintain sinus rhythm: initially 200 mg daily, reduced to 100 mg daily, and eventually stopped because of hyperthyroidism;
- anticoagulation for AF: initial warfarin therapy now changed to aspirin; and
- testosterone replacement (125 mg per week) for rebound low serum testosterone.
He had serial transthoracic echocardiograms, with improvement documented in left ventricular structure and function (Box).
Our patient was treated for a dilated cardiomyopathy as a result of anabolic steroid use. He has now stopped taking anabolic steroids for 18 months. He weighs 122 kg; however, through a different training regimen, he can lift the same weight as he did when he was 141 kg.
Previous work has shown that the use of supraphysiological testosterone doses results in increased fat-free mass, muscle size and strength in men.1 Studies have also shown that despite education about the potential side effects of anabolic steroids, many users will continue their practice.2
Cardiomyopathy, including ventricular hypertrophy and dilatation, is a complication of anabolic steroid use that has previously been described.3,4 Anabolic steroids are thought to cause changes in heart muscle structure through their effect on androgen receptors expressed on cardiac myocytes.3
Of note also is the regimen of anabolic steroid use in our patient. The amount of testosterone used was about 15–20 times that used for testosterone replacement therapy, and methandrostenolone is not recommended owing to its potential for hepatotoxicity.5 Oestrogen blockade with anastrozole aims to prevent gynaecomastia resulting from anabolic steroid misuse, while also increasing serum testosterone levels.6 Trenbolone is a veterinary grade anabolic steroid used for cattle growth, but has been used in a hazardous way by sports competitors and bodybuilders.7
Our case highlights an interesting presentation of a dilated cardiomyopathy with acute decompensated heart failure 6 weeks after cessation of anabolic steroids in a patient who had performed physically at an elite level only 2 weeks before admission. Further inhospital decompensation may have been precipitated by the acute effect of β-blocker therapy on cardiac output in this context, reducing the heart rate when stroke volume was extremely low. Definitive management involved cessation of the offending agents, exclusion of other reversible causes of heart failure, and initiation of conventional heart failure therapy. Awareness of the harmful cardiac effects of anabolic steroid use must be promoted within the medical profession and among potential users so that such cases can be prevented.
Lessons from practice
- Anabolic steroid use and misuse is an important issue in the bodybuilding community.
- Anabolic steroid use and misuse is an important potential cause of dilated cardiomyopathy.
- The mainstay of treatment involves abstinence from the offending agent, as well as initiation of conventional heart failure therapy.
- The recent addition of trenbolone to the patient’s steroid regimen potentially contributed to his presentation.
Echocardiogram results
|
Date |
LVEF |
LVEDD (mm) |
LVMI (g/m2) |
||||||||||||
|
|
|||||||||||||||
|
17/12/12∗ |
<15% |
|
|
||||||||||||
|
30/01/13 |
40% |
64 |
185 |
||||||||||||
|
08/07/13 |
54% |
61 |
165 |
||||||||||||
|
02/12/13 |
60% |
60 |
152 |
||||||||||||
|
25/03/14 |
63% |
59 |
147 |
||||||||||||
|
|
|||||||||||||||
|
LVEF = left ventricular ejection fraction (reference interval [RI], >55%). LVEDD = left ventricular end diastolic diameter (RI, <55 mm). LVMI = left ventricular mass index (RI, <127 g/m2). |
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Rheumatic heart disease in Indigenous children in northern Australia: differences in prevalence and the challenges of screening
Indigenous Australians (Aboriginal Australians and/or Torres Strait Islander peoples) suffer high rates of acute rheumatic fever (ARF) and its sequel, rheumatic heart disease (RHD).1,2 Estimates of RHD prevalence have relied on register data collected for clinical purposes or on intermittent enhanced surveillance projects,3 and have suggested that 1%–2% of Indigenous Australians living in northern and central Australia have RHD.
Screening for RHD provides an opportunity to accurately define the current disease burden, as well as to identify children with undiagnosed disease who may benefit from early treatment. A number of studies have shown that cardiac auscultation lacks the sensitivity and specificity required for screening for RHD and should no longer be used for this purpose.4–6 Portable echocardiography has emerged as a more valuable tool, and its usefulness was enhanced by the publication of the World Heart Federation (WHF) criteria for the echocardiographic diagnosis of RHD in 2012 (Box 1).7
We recently published the results of an echocardiographic screening study of more than 5000 school-aged children, including nearly 4000 Indigenous children living in four regions of northern and central Australia.8 We used the WHF criteria to compare the echocardiographic findings of children at high and low risk of RHD (as defined by the RHD Australia guidelines9). We found that the overall prevalence of definite RHD in high-risk Indigenous children (8.6 per 1000) was comparable with previous register-based estimates from the Northern Territory. Definite RHD was not identified in any low-risk non-Indigenous children.
This study is methodologically the most rigorous exploration of echocardiographic screening yet conducted, and the first cross-sectional survey of the prevalence of RHD in Australia. However, we did not report the data in sufficient detail to maximise its relevance for local RHD control in Australia. In this article, we describe the prevalence of definite and borderline RHD in Indigenous children from the Top End of the NT, Central Australia, Far North Queensland (FNQ), including the Torres Strait, and the Kimberley region of Western Australia. By comparing the findings in different regions and describing some of the challenges of the screening process, we aim to inform decision making about the potential impact and usefulness of echocardiographic screening for RHD in different Australian regions.
Methods
Design, setting and participants
The study design and population and the sample size calculation have been described previously.8 Briefly, we performed screening echocardiograms on 3946 Indigenous children aged 5–15 years living in remote communities in northern Australia. Thirty-two communities were selected from four geographical regions (Box 2). Children were identified by the enrolment records of participating schools and were recruited at school or by approaching their families. Written informed consent was obtained from parents or guardians, and written consent was also obtained from children who were at least 13 years old.
The study was conducted from September 2008 to November 2010. Ethics approval was obtained from the Human Research Ethics Committee of the Northern Territory Department of Health and Community Services, the Central Australian Human Research Ethics Committee, the Cairns and Hinterland Health Service District Human Research Ethics Committee, the James Cook University Human Ethics Committee, the University of Western Australia Human Research Ethics Committee, and the Western Australian Aboriginal Health Information and Ethics Committee.
Echocardiography protocol, reporting and definitions
Screening echocardiograms were performed by cardiac sonographers according to an abbreviated protocol that focused on the mitral and aortic valves. Sonographers were provided with a list of features that prompted a more detailed, comprehensive echocardiogram, also performed at the time of screening, if required. Screening echocardiograms were recorded to DVD and reported offsite by a pool of 14 cardiologists according to our standardised electronic protocol. These data were used post hoc to determine whether children met the WHF definitions of definite or borderline RHD.
Clinical follow-up
Separate to reporting for research purposes, all comprehensive echocardiograms were sent to a local cardiologist to guide clinical management of the participant. The cardiologist provided a written report that included the echocardiographic findings and recommendations for follow-up, including secondary prophylaxis. Reports were sent to the primary health care team, who used existing clinical services to coordinate the necessary referrals.
Socioeconomic comparisons
We explored whether differences in RHD prevalence between regions could be attributed to socioeconomic or demographic factors. No information about socioeconomic factors was collected from individual participants. Instead, we used publicly available statistics to compare the socioeconomic characteristics of the participating schools and communities. Information about school attendance and the Indigenous status of enrolled students, as well as Index of Community Socio-Educational Advantage (ICSEA10) scores were obtained for each participating school from the Australian Government’s MySchool website.11 The ICSEA is a measure of the educational advantage of the students enrolled at a particular school, based on information about each student’s family background (including parental occupation and level of education). The median value of the scale is 1000 with an SD of 100.
Information about household crowding and Socio-Economic Indexes for Areas (SEIFA12) scores were obtained for each participating community from the Australian Bureau of Statistics 2011 census data.13 Two SEIFA scores were analysed: the Index of Relative Social Disadvantage (IRSD) and the Index of Relative Social Advantage and Disadvantage (IRSAD). These indices summarise socioeconomic information about the people and households in a geographical area, and scales are standardised with a mean value of 1000 and an SD of 100.
ICSEA, IRSD and IRSAD scores were assigned to individuals according to their school or community and to calculate aggregate scores for each of the four study regions.
Statistical analysis
Statistical analysis was performed with the Stata statistical package (version 12.1; StataCorp). Descriptive data are presented as medians and interquartile range (IQR) for non-normally distributed variables. Medians were compared with the Mann–Whitney U test (for two groups) or the Kruskal–Wallis test (for more than two groups). Categorical variables were compared with the χ2 test. RHD prevalence (with 95% CIs) was calculated for the entire study sample and for each of the four regions. Multivariate logistic regression was used to compare the proportion of children with RHD in each region. Socioeconomic variables were compared by means of ANOVA (IRSAD, IRSD and ICSEA) or Kruskal–Wallis and Mann–Whitney U tests (household crowding).
Results
The demographic characteristics of the 3946 remote Indigenous children who had a screening echocardiogram are presented in Box 3. Forty-one per cent of the FNQ participants were identified as Torres Strait Islanders or Aboriginal and Torres Strait Islanders, whereas more than 99% of the other groups were identified as Aboriginal only.
Despite the similar age and sex distribution of all four groups, children from the Top End of the NT had a significantly lower median body weight and body mass index than children from the other three regions (compared with Central Australia and FNQ, P < 0.001; with the Kimberley, P = 0.004; Box 3).
Of the 569 comprehensive echocardiograms performed (13.3% of children screened), significantly more were undertaken in FNQ (17.2%) than in other jurisdictions (P < 0.001 compared with the Kimberley, P < 0.001; with Central Australia, P = 0.002; with the Top End, P = 0.26; Box 3). In the FNQ group, more Torres Strait Islander children (20.4%) required a comprehensive echocardiogram than did non-Torres Strait Islander children (14.9%, P < 0.001).
Prevalence of RHD based on the WHF criteria
The prevalence of definite and borderline RHD in each region is presented in Box 4. The prevalence of definite RHD was higher in Top End children than in children from the three other jurisdictions combined (odds ratio [OR], 2.3; 95% CI, 1.2–4.6, P = 0.01). This difference was not observed in the borderline RHD category.
We have previously reported that 18 of the 34 children (52.9%) who met the criteria for definite RHD were new cases (no previous history of ARF or RHD);8 the majority (93.9%) of children meeting the criteria for borderline RHD were also new cases. The prevalence of previously undiagnosed definite RHD detected in the entire study sample by screening was 4.6 per 1000 (95% CI, 2.7–7.2); for the Top End, the prevalence of new cases of definite RHD was 7.0 per 1000 (95% CI, 2.8–14.4).
Comparison of the socioeconomic profiles of the four regions
Thirty-eight schools from 32 communities participated in the screening study. Mean and median ICSEA, IRSD and IRSAD scores for each region are presented in Box 5. The Top End communities had significantly lower mean ICSEA, IRSD and IRSAD scores (ANOVA), and significantly higher levels of household crowding (Kruskal–Wallis, Mann–Whitney U tests) than the other regions (P < 0.05 for all comparisons; Top End versus other regions combined or individually). Top End schools also had significantly lower median ICSEA scores than the other regions combined and than each of Central Australia and FNQ (for each comparison, P < 0.001), but not when compared with Kimberley schools (P = 0.43).
Discussion
This is the first prospective screening survey for RHD in Indigenous Australian children, and the first study to provide reliable information about the epidemiology of RHD in children from FNQ and the Kimberley region of Western Australia. Our previous report confirmed that the prevalence of RHD is high in Indigenous children, and that the overall prevalence of definite RHD in school-aged children (8.6 per 1000) is comparable with figures from developing countries.14–18 Although this figure is similar to previous estimates of the prevalence of RHD in the NT,1,2,19 there are important differences between the four regions when examined individually.
The most striking difference is the higher prevalence of definite RHD in children from the Top End of the NT. The prevalence of 15.0 per 1000 is two to three times higher than in other regions, and nearly triple the previously published estimates of RHD prevalence in Top End children (5.8 per 100020). Two more recent audits of the NT register have been undertaken, but only the combined data from the Top End and Central Australia have been published,1,19 reporting an RHD prevalence of 8.5 per 1000 in Indigenous children aged 5–14 years in the NT. Our study suggests that this significantly underestimates the burden of disease in the Top End, and that disease epidemiology may be different in the Top End and Central Australia.
This difference has not previously been reported, and reasons for a higher disease burden in the Top End are not clear. However, some features of our study sample may be relevant. We noted that the growth parameters of Top End children were significantly lower than those of children in the other regions, and that the participating Top End communities had the highest number of people per household, a mean of 6.3 persons, compared with the Australian average of 2.6 persons per household.12 In addition, the ICSEA, ISRD and IRSAD scores were also lowest in our Top End sample, between three and five SDs below the Australian average. It was striking how far below the Australian mean these scores were in all regions, highlighting the extreme disadvantage experienced in remote Aboriginal communities. We attempted to quantify the relationship between definite RHD and the four socioeconomic measures by logistic regression, but the small number of cases of definite RHD prevented this.
These observations suggest that the participating communities from the Top End were the most disadvantaged of the remote Indigenous communities we surveyed. Given that poverty-related factors, such as overcrowded housing, are known to be significant risk factors for ARF and RHD,21–23 extreme disadvantage would provide a plausible explanation for the higher prevalence of RHD in the Top End. Other possibilities include inherent differences in host susceptibility or in circulating strains of group A Streptococcus (GAS), but data are not available for the four sampled regions to explore these hypotheses. One NT study that investigated the diversity of GAS strains in the NT did not find “NT-endemic” strains, and the authors concluded that the high burden of GAS disease was more probably related to poor living conditions than to bacterial factors.24
Selection bias may also contribute to the observed differences in RHD prevalence. Given the logistical challenges of surveying a large number of Indigenous children in remote areas, we were unable to select communities at random. We instead carefully selected communities of different sizes and from different areas in the same geographic region to provide as broad a sample as possible (Box 2).
Only about 50% of school-enrolled children were screened in our study (although the percentages in Box 5 are slight underestimates, because the school enrolment record includes children of all ages, some of whom were not eligible for our study). Given that the average daily attendance in participating schools was 69%, this result is understandable, and indicates our efforts to maximise recruitment.
Whether the children we screened were representative of all children in the participating communities is an important question. We were unable to collect information about children who had not consented to the study, but Box 3 shows that there were no differences in the sex or age distributions of the samples from each region. It is probable that these figures (equal sex and normal age distributions) are representative of the communities as a whole, and that selection bias is unlikely to explain the observed differences in RHD prevalence.
However, selection bias may have resulted in an overall underestimation of RHD prevalence. A school-based approach to screening is practical, but potentially excludes those most at risk of disease, such as children who are too sick to attend school, or who live in the most marginalised families. This may have resulted in underestimation of the full burden of RHD in remote Indigenous communities.
The number of new cases detected is a crucial element in evaluating the usefulness of any screening program. More than half of the children meeting the criteria for definite RHD were new cases (Box 4), with an overall prevalence of 4.6 new cases per 1000 children screened. This figure was substantially higher in the Top End cohort, and our results suggest that for every 1000 Top End children screened, 7 new cases of definite RHD would be detected, equivalent to about 50 new cases in this population. This information is critical for evaluating the cost-effectiveness of screening, and we are currently analysing the data.
We encountered a number of practical difficulties that have implications for future echocardiographic screening in remote Australia. The logistical challenges of travel to remote communities are clear; travel by road is slow and sometimes impossible, and travel by plane is expensive, requiring chartered flights to isolated areas not served by commercial flights. After staff had arrived in the communities, the biggest challenge was finding and obtaining consent from the children to be screened, as school attendance was poor. We tried to include absentees by extending our screening activities beyond the school grounds, which was time-consuming and inefficient.
The most significant challenges faced by this study related to clinical follow-up and communication with families and health care providers. A total of 569 children (14.4%, Box 3) had comprehensive echocardiograms that required timely review by an offsite cardiologist to guide clinical management. This considerably increased the workload of local cardiologists, and it frequently took weeks to months for reports to be completed. Once available, the reports themselves often generated confusion and frustration for health care providers, as illustrated by a qualitative survey of health care providers in three participating screening sites.25 The WHF diagnostic criteria had not yet been published when our study commenced, so there was uncertainty about the significance of minor echocardiographic changes in an otherwise healthy child. This resulted in many paediatric cardiology referrals, which often challenged the capacity of local services.25 If echocardiographic screening is to become feasible as a routine approach, a technical aspect that must be refined is thus to reduce the number of comprehensive echocardiograms that require review by a cardiologist. Ensuring that health systems are equipped to deal with the additional increase in case numbers is vital before initiating routine screening activity.26
The impact of screening on the families of 68 children in our study was explored by Wark and colleagues with a Quality of Life (QOL) questionnaire.25 Although there was no difference in the overall QOL summary scores, carers of children with possibly abnormal echocardiograms had poorer QOL scores in subscales pertaining to general health perception and parental emotional impact. In contrast, a study by a New Zealand group27 surveyed 114 families who had participated in a more recent school-based echocardiographic screening program, and found unanimous support for the program. The authors concluded that the screening process had no negative effects, nor were there short-term adverse effects in the families of children with abnormal results, in terms of either health perception or of parental anxiety.
The timing of the two studies and methodological differences may explain these contrasting findings. In the New Zealand study, screening and reporting occurred within a much shorter time period, and clinical follow-up was performed by clinicians who were directly involved in the research process. In addition, the WHF criteria had been published before the study commenced, reducing diagnostic uncertainty regarding the significance of minor echocardiographic abnormalities and facilitating appropriate clinical follow-up.
In summary, our study identified a previously unrecognised difference in the prevalence of RHD in four remote regions of northern Australia. The prevalence of definite RHD in Top End children was nearly twice as high as that in the other three regions, and this may be related to socioeconomic factors. We estimate that 4–8 per 1000 Indigenous children in remote communities have undetected RHD that could be identified by echocardiographic screening. Whether such screening should be recommended will require further and careful consideration of its cost-effectiveness, feasibility, sustainability and impact on primary and specialist health care services. We are currently preparing a cost-effectiveness analysis that will allow us to make informed recommendations regarding RHD screening to national policymakers.
1
Echocardiographic criteria for rheumatic heart disease (RHD) in individuals aged ≤ 20 years
Definite RHD (one of the following features):
- Pathological mitral regurgitation and at least two morphological features of RHD of the mitral valve;
- Mitral stenosis mean gradient ≥ 4 mm Hg;∗
- Pathological aortic regurgitation and at least two morphological features of RHD of the aortic valve;†
- Borderline disease of both the aortic valve and mitral valve.†
Borderline RHD (one of the following features):
- At least two morphological features of RHD of the mitral valve without pathological mitral regurgitation or mitral stenosis;
- Pathological mitral regurgitation;
- Pathological aortic regurgitation.
∗Congenital mitral valve anomalies must be excluded.
†Bicuspid aortic valve, dilated aortic root and hypertension must be excluded.
†Combined aortic and mitral regurgitation in high prevalence regions and in the absence of congenital heart disease is regarded as rheumatic. The four Doppler echocardiographic criteria for pathological mitral regurgitation are that it be seen in two views; in at least one view, jet length ≥ 2 cm; velocity ≥ 3 m/s for one complete envelope; and pan-systolic jet in at least one envelope. The criteria for pathological aortic regurgitation are that it be seen in two views; in at least one view, jet length ≥ 1 cm; velocity ≥ 3 m/s in early diastole; and pan-diastolic jet in at least one envelope). Adapted from Reményi et al.7
2
Northern Australian sites where echocardiographic screening for rheumatic heart disease was undertaken for this study
3
Demographic characteristics of Indigenous children screened for rheumatic heart disease
|
Characteristic |
Top End (n = 1000) |
Central Australia (n = 895) |
Far North Queensland (n = 1265) |
Kimberley (n = 786) |
P |
||||||||||
|
|
|||||||||||||||
|
Number (%) |
|||||||||||||||
|
Sex |
|||||||||||||||
|
Male |
497 (49.7%) |
479 (53.5%) |
641 (50.7%) |
389 (49.5%) |
0.30∗ |
||||||||||
|
Female |
503 (50.3%) |
416 (46.5%) |
624 (49.3%) |
397 (50.5%) |
|||||||||||
|
Ethnicity |
|||||||||||||||
|
Aboriginal |
998 (99.8%) |
892 (99.7%) |
746 (59.0%) |
786 (100.0%) |
|||||||||||
|
Torres Strait Islander |
2 (0.2%) |
2 (0.2%) |
303 (24.0%) |
0 |
< 0.001∗ |
||||||||||
|
Aboriginal and Torres Strait Islander |
0 |
1 (0.1%) |
216 (17.1%) |
0 |
|||||||||||
|
Comprehensive echocardiogram performed, n (%) |
153 (15.3%) |
111 (12.4%) |
217 (17.2%) |
88 (11.2%) |
< 0.001∗ |
||||||||||
|
Median (interquartile range) |
|||||||||||||||
|
Age (years) |
9.4 (7.4–11.6) |
9.3 (7.3–11.3) |
9.2 (7.2–11.2) |
9.3 (7.3–11.5) |
0.15† |
||||||||||
|
Weight (kg) |
26.5 (21.1–35.5) |
29.8 (22.9–40.8) |
28.5 (21.8–39.5) |
27.4 (21.7–39.0) |
< 0.001† |
||||||||||
|
Height (cm) |
133.0 (121.9–147.0) |
135.0 (123.0–149.0) |
133.4 (120.1–145.8) |
133.0 (121.4–148.2) |
0.01† |
||||||||||
|
BMI (kg/m2) |
15.1 (14.0–16.6) |
16.2 (14.9–18.9) |
16.2 (14.7–19.0) |
15.7 (14.4–17.9) |
< 0.001† |
||||||||||
|
|
|||||||||||||||
|
BMI = body mass index. |
|||||||||||||||
4
Cases of rheumatic heart disease (RHD) in Indigenous children from four remote regions of northern Australia
|
Top End |
Central Australia |
Far North Queensland |
Kimberley |
Total |
P (χ2) |
||||||||||
|
|
|||||||||||||||
|
Definite RHD |
|||||||||||||||
|
New cases |
7 |
4 |
5 |
2 |
18 |
||||||||||
|
Known cases |
8 |
2 |
1 |
5 |
16 |
0.06 |
|||||||||
|
Prevalence |
15.0/1000 |
6.7/1000 |
4.7/1000 |
8.9/1000 |
8.6/1000 |
||||||||||
|
95% CI |
8.4–24.6 |
2.5–14.5 |
1.7–10.2 |
3.6–18.2 |
6.0–12.0 |
||||||||||
|
Borderline RHD |
|||||||||||||||
|
New cases |
17 |
14 |
23 |
8 |
62 |
||||||||||
|
Known cases |
1 |
1 |
2 |
0 |
4 |
0.41 |
|||||||||
|
Prevalence |
18.0/1000 |
16.8/1000 |
19.8/1000 |
10.2/1000 |
16.7/1000 |
||||||||||
|
95% CI |
10.7–28.3 |
9.4–27.5 |
12.8–29.0 |
4.4–20.0 |
13.0–21.2 |
||||||||||
|
Total screened |
1000 |
895 |
1265 |
786 |
3946 |
||||||||||
|
|
|||||||||||||||
5
Comparison of the socioeconomic characteristics of the four screening regions
|
Top End |
Central Australia |
Far North Queensland |
Kimberley |
||||||||||||
|
|
|||||||||||||||
|
Number of Indigenous children aged 5–14 years who were screened |
1000 |
895 |
1265 |
786 |
|||||||||||
|
Number of participating communities |
7 |
10 |
7 |
8 |
|||||||||||
|
Number of participating schools |
7 |
14 |
8 |
9 |
|||||||||||
|
Estimated number of Indigenous students enrolled in participating schools (all ages)∗ |
1765 |
1744 |
2635 |
1250 |
|||||||||||
|
Estimated percentage of enrolled Indigenous students who were screened |
56.7% |
51.3% |
48.0% |
62.9% |
|||||||||||
|
Average school attendance in participating schools11 |
65.0% |
68.0% |
79.0% |
67.0% |
|||||||||||
|
ICSEA score of participating schools11 |
|||||||||||||||
|
Mean (SD) |
576 (38) |
643 (79) |
622 (80) |
583 (48) |
|||||||||||
|
Median (IQR) |
569 (556–590) |
631 (566–712) |
587 (581–592) |
567 (557–612) |
|||||||||||
|
IRSAD score of participating communities12 |
|||||||||||||||
|
Mean (SD) |
631 (67) |
734 (96)† |
759 (180) |
711 (28) |
|||||||||||
|
Median (IQR) |
688 (580–690) |
695 (655–831) |
678 (644–913) |
694 (694–758) |
|||||||||||
|
IRSD score of participating communities12 |
|||||||||||||||
|
Mean (SD) |
533 (104) |
676 (122)† |
712 (224) |
650 (33) |
|||||||||||
|
Median (IQR) |
606 (443–641) |
618 (570–795) |
621 (585–903) |
628 (628–704) |
|||||||||||
|
Number of people per household in participating communities12 |
|||||||||||||||
|
Mean (SD) |
6.3 (0.9) |
4.8 (1.1)† |
4.5 (0.5) |
4.8 (0.7) |
|||||||||||
|
Median (IQR) |
6.8 (5.1–7.0) |
5.0 (4.1–5.9) |
4.2 (4.0–5.0) |
4.6 (4.3–5.6) |
|||||||||||
|
|
|||||||||||||||
|
ICSEA = Index of Community Socio-Educational advantage; IRSAD = Index of Relative Social Advantage and Disadvantage; IRSD = Index of Relative Social Disadvantage; IQR = interquartile range. |
|||||||||||||||
[Department of Ethics] Delayed consent: will there be a shift in approach for US primary percutaneous coronary intervention trials?
No doubt the HEAT-PPCI (How Effective Are Antithrombotic Therapies in Primary PCI) study presented at the American College of Cardiology 2014 Scientific Sessions in March, 2014, continues to elicit much controversy and discussion—and not limited to the outcome of the trial. HEAT-PPCI reported that unfractionated heparin (UFH) outperformed bivalirudin for 28 days outcome in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).
[Perspectives] Salim Yusuf: global leader in cardiovascular disease research
Salim Yusuf, Executive Director of the Population Health Research Institute and Professor of Medicine at McMaster University, does not have to worry about being low profile, as any search on Medline reveals hundreds of results. But this one-time doyen of clinical trials in cardiology has broadened his perspective in more recent times towards global epidemiological research, partly shaped by his curiosity about the high burden of cardiovascular disease (CVD) in his native India, which was a trigger for the seminal INTERHEART study, undertaken in 52 countries, and published in The Lancet in 2004.
[Comment] Cardiology: a call for papers
Are you seeking high exposure for your research? Do you have a Late-Breaking Clinical Trial that will be presented at the American College of Cardiology meeting, to be held during April 2–4, 2016 in Chicago, USA? Are you anxious that deadlines are tight for coincident publication and presentation? Then submit your paper as a fast track to The Lancet by March 1, 2016 for thorough, but speedy, peer review.
[Comment] Open questions for non-infarct-related arteries in STEMI
Few questions in cardiology have received more disparate answers and caused such sudden reversals in official guidelines as that of the best treatment of clinically significant lesions in non-infarct-related arteries, which affect more than half of patients with ST-elevation myocardial infarction (STEMI). Findings of large meta-analyses show that simultaneous multivessel percutaneous coronary intervention (PCI) has a worse outcome than does PCI of the infarct-related artery alone.1,2 Staged PCI for treatment of clinically significant lesions in non-infarct-related arteries is still recommended in current European Society of Cardiology guidelines for STEMI, published in 2012.
[Comment] ADVICE on adenosine to improve atrial fibrillation ablation
Atrial fibrillation is the most common cardiac arrhythmia.1 Since it was first described in 1998, pulmonary vein isolation has evolved to become a routine procedure for patients with atrial fibrillation.2 Nevertheless, many patients need repeated ablation procedures because of recurrence of atrial fibrillation, which in most cases is associated with reconnection of previously isolated pulmonary veins.3 Thus, for paroxysmal atrial fibrillation, one of the major challenges is to develop strategies to reduce pulmonary vein reconnection.
Emergency: real stories from Australia’s emergency department doctors
Edited by Dr Simon Judkins, 2015, Penguin Random House, RRP $32.99, 260 pages
Review by Adrian Rollins, editor, Australian Medicine
It’s not surprising so many television dramas are set in hospital emergency departments, where life is portrayed at being lived at an intensity well beyond the norm.
In this celluloid world, every day is filled with raw human emotions, adrenaline-pumping action, wrenching life-and-death decisions, and a heady mix of tragedy and triumph against the odds.
This may be one of the rare instances where reality matches – and in some cases, exceeds – the imagination of the dramatists.
In Emergency, 26 physicians give outsiders an intriguing glimpse into what it really means to be on the medical frontline.
In well-crafted and frequently moving accounts, they relay both the what of the job – retrieving everyone from toddlers to octogenarians from the brink of death – and its consequences: the lasting emotional effects of these experiences, which are often pushed to one side in the heat of the moment, but resonate loudly in the all-too rare moments for quiet reflection.
Take the story of the emergency doctor dangling over the edge of a conveyor belt to comfort a trapped worker whose legs have been crushed and amputated in a garbage compactor.
Or the physician who finds himself wading through puddles of blood to treat a stream of bullet-riddled gang members brought to hospital from the badlands of Cape Town.
Or the gut-wrenching realisation for a resuscitation team that, despite their herculean efforts, they have been unable to revive a two-year-old who strangled herself playing with a cord dangling from the blinds above her bed.
The stories in the collection traverse the breadth and depth of emergency medicine practice.
Readers are transported from major Australian city hospitals to the PNG highlands, to Uluru, Sydney Harbour and bleak industrial estates.
They witness the exhilaration that comes from saving a life, and the trauma that can accompany losing one.
They also get a glimpse into the challenges of practising this exacting craft – the marathon hours, the high levels of stress, the frustrations caused by inadequate resources, the seemingly endless demand for help, and the lack of time and space to reflect.
But what shines through, and what television scriptwriters tend to overlook, is the commitment to patients that overwhelms all else.
It is what drove Dr Mark Little to try just one more time after 75 minutes of failed attempts to revive a 60-year-old builder who had suffered a cardiac arrest – this time to succeed.
It is apparent in the tortured reaction of staff to the death of a toddler, despite their valiant attempts.
“This is fucked,” Dr Judkins recalls one nurse saying. “Why does this happen? This is not right.”
“This is why we do the job,” he responds, articulating his philosophy that, while they were unable to save this particular life, they had the skill to save others, “and that’s incredible”.
AMA Vice President Dr Stephen Parnis, an emergency physician in Melbourne, says it is not just about saving lives.
Relating the experience of advising and supporting a favourite uncle during a four-year battle with bile duct cancer, Parnis reflects that some of the most rewarding aspects of the job come from caring for the dying: “To ease their anxiety and pain, to calm their fears, to share that time with them, is a privilege”.
Practising emergency medicine is not for everyone, and the risk of burnout can be high.
The hours are long and often unsociable – after all, medical emergencies can happen any time – and the demands can be relentless.
But it is clear that for those who shared their experiences in Emergency, the connection with patients, the chance to save lives – or, on occasion, to ease death – and the satisfaction that comes from working as part of a well-drilled team, more than make up for these inconveniences.