The comparison of the mathematical accuracy of paper-based tables or
charts for estimating coronary (CHD) or cardiovascular (CVD) risk by Jones
et al[1] is extremely valuable, but their conclusion that the revised
Joint British Societies chart has the best combination of sensitivity and
specificity is surprising. When the SMAC guidance[2] based on the
original Sheffield table[3] was issued in 1997 the recom...
The comparison of the mathematical accuracy of paper-based tables or
charts for estimating coronary (CHD) or cardiovascular (CVD) risk by Jones
et al[1] is extremely valuable, but their conclusion that the revised
Joint British Societies chart has the best combination of sensitivity and
specificity is surprising. When the SMAC guidance[2] based on the
original Sheffield table[3] was issued in 1997 the recommendations on
statin treatment for primary prevention extrapolated well beyond the trial
evidence then available. It was therefore appropriate to use a risk
assessment method with high specificity, at the expense of sensitivity if
necessary, to ensure that all those treated with statins had high CHD risk.[4] The situation now is entirely different. There is evidence for the
efficacy of statins in patients at a lower cholesterol threshold and at
CHD risk as low as 6% over 10 years.[5] Current British Guidelines[6]
advise treatment at an extremely conservative CHD risk threshold of 30%
over 10 years, recognising that the number of high risk people in our
population precludes treatment at a lower threshold because of the total
cost and workload involved.
To implement guidelines which are already
very conservative it is critical that the CHD risk assessment method used
should miss as few people who ought to be treated as possible, i.e. it
should have high sensitivity. Risk assessment methods with low sensitivity
will add conservatism to guidelines that are already very conservative.
Specificity is less important provided that people with very low risk are
not identified for treatment.[4] The modified Sheffield table[7] was
therefore designed to have high sensitivity with some sacrifice of
specificity, within reason.
Turning to the findings of Jones et al,[1] the updated New Zealand
table had sensitivity of 75% for 5 year CVD risk 20%, which is equivalent
to the 10 year CHD risk 30% threshold for statin treatment. This method
would deny statin treatment to fully one quarter of those eligible for
treatment. The revised Joint British Societies chart had sensitivity 85%
for 10 year CHD risk 30%, and would therefore deny statin treatment to
one sixth (15%) of those who ought to have statin treatment. The modified
Sheffield table had a significantly higher sensitivity for this CHD risk
threshold (91%) and would therefore ensure statin treatment of
significantly more of the high-risk people who should be treated. We have
shown elsewhere[7] that those ‘missed’ by the modified Sheffield table
all lie only marginally above the 30% threshold, and that those treated
‘incorrectly’ all have 10 year CHD risk between 20-30% - a level at which
statin treatment is readily justifiable.[5]
Doctors who wish to use a paper-based CHD risk assessment method to
implement the Joint British Societies guidelines and National Service
Framework for CHD should use the method with highest sensitivity, which is
the modified Sheffield table.[1][8] Unlike the other risk assessment
methods studied by Jones et al[1] the Sheffield table is also a highly
accurate screening tool for lipid measurement[7] and summarises the Joint
British Societies guidelines[6] on a single page.[7]
Erica J Wallis
Lawrence E Ramsay Peter R Jackson
References
(1) Jones AF, Walker J, Jewkes C, Game FL, Bartlett WA, Marshall T,
Bayly GR. Comparative accuracy of cardiovascular risk prediction methods
in primary care patients. Heart 2001;85:37-43.
(2) Standing Medical Advisory Committee. The use of statins. London:
Department of Health, 1997 (11061 HCD Aug 97(04).
(3) Ramsay LE, Haq IU, Jackson PR, Yeo WW, Pickin DM, Payne JN.
Targeting lipid-lowering drug therapy for primary prevention of coronary
disease: an updated Sheffield table. Lancet 1996;348:387-8.
(4) Haq IU, Ramsay LE, Jackson PR, Wallis EJ. Prediction of coronary
risk for primary prevention of coronary heart disease: a comparison of
methods. Q J Med 1999;92:379-85.
(5) Downs GR, Clearfield M, Weiss S, Whitney E, Shapiro DR, Beere PA
et al for the AFCAPS/TexCAPS Research Group. Primary prevention of acute
coronary events with lovastatin in men and women with average cholesterol
levels: results of AFCAPS/TexCAPS. JAMA 1998;279:1615-22.
(6) Wood D, Durrington P, Poulter N, McInnes G, Rees A, Wray R on
behalf of the British Cardiac Society, British Hyperlipidaemia
Association, British Hypertension Society and endorsed by the British
Diabetic Association. Joint British recommendations on prevention of
coronary heart disease in clinical practice. Heart 1998;80(suppl 2):S1-29.
(7) Wallis EJ, Ramsay LE, Haq IU, Ghahramani P, Jackson PR, Rowland-
Yeo K, Yeo WW. Coronary and cardiovascular risk estimation for primary
prevention: validation of a new Sheffield table in the 1995 Scottish
Health Survey population. BMJ 2000;320:671-6.
(8) Wallis EJ, Ramsay LE, Yikona JINM, Jackson PR. Comparison of CHD
risk estimation methods. Authors did not use the latest version of the
Sheffield table. BMJ 2000;321:175.
I was surprised that Missouris and colleagues in their case
report failed to mention cystic medial necrosis as a cause
of spontaneous coronary artery dissection.[1] This disease
requires histologic confirmation and is characterised by
focal fragmentation of elastic fibers, loss of smooth muscle
cells of the media and the accumulation of acid
mucopolysaccharides. Mandatory exclusion of Marfan syndrome,
his...
I was surprised that Missouris and colleagues in their case
report failed to mention cystic medial necrosis as a cause
of spontaneous coronary artery dissection.[1] This disease
requires histologic confirmation and is characterised by
focal fragmentation of elastic fibers, loss of smooth muscle
cells of the media and the accumulation of acid
mucopolysaccharides. Mandatory exclusion of Marfan syndrome,
histologically similar, is based on clinical features and
genetic testing.
Although the authors' approach was successful, attempts to
revascularise jeopardised myocardium in these cases, either
by balloon angioplasty or surgery, can be hazardous. In case
of spontaneous dissection of a coronary artery over its full
length, failure to dilate or bypass the real lumen can
indeed have disastrous consequences.[2]
References
(1) Missouris CG, Ring A, Ward D. A young woman with chest
pain. Heart 2000;84:e12.
(2) Conraads VM, Vorlat A, Colpaert CG, Rodrigus IE, De Paep
R, Moulijn AC, Vrints CJ. Spontaneous dissection of three
major coronary arteries subsequent to cystic medial
necrosis. Chest 1999;116:1473-5.
The Guideline for the management of patients with acute coronary syndromes
without persistent ECG ST segment elevation[1] gives excellent and timely
advice, but there is one area which continues to cause confusion, and that
concerns the diagnosis of "myocardial infarction".
The International Redefinition of Myocardial Infarction[2] states that
an infarct has occurred when there has been a typical rise...
The Guideline for the management of patients with acute coronary syndromes
without persistent ECG ST segment elevation[1] gives excellent and timely
advice, but there is one area which continues to cause confusion, and that
concerns the diagnosis of "myocardial infarction".
The International Redefinition of Myocardial Infarction[2] states that
an infarct has occurred when there has been a typical rise and gradual
fall in serum troponin in association with ischaemic symptoms and/or
ischaemic changes on the ECG. The document makes two further key
statements. Firstly it defines an increase in serum troponins as a
measurement “exceeding the 99th centile of a reference control group”.
Secondly it acknowledges that “any amount of necrosis caused by ischaemia
should be labelled as an infarct.”
As troponins are highly sensitive and specific markers for myocardial
damage, application of this redefinition will result in an immediate
doubling or tripling of the infarct rate in District General Hospitals as
they switch over from CK-MB to troponins (data from internal audit, West
Suffolk Hospital). The Guideline however continues to use the Braunwald
classification, 3 and talks in terms of “unstable angina with positive
troponins”.
Whilst the immediate management of such patients is not at issue, the
terminology has become confusing, and the question of where and when to
draw the line for myocardial infarction requires clarification. This
diagnosis has major implications for occupation, driving, insurance and
psychology. If the troponins are elevated and the patient has ischaemic
symptoms, should we continue to talk in terms of “unstable angina” or
should we accept the Redefinition and be telling at least twice as many
patients as we used to that they have had a heart attack?
David Hildick-Smith
Peter Glennon
Cardiac Unit, Papworth Hospital
Cambridge CB3 8RE, UK
References
(1) Guideline for the management of patients with acute coronary
syndromes without persistent ECG ST segment elevation. Heart 2001;85:133-42.
(2) Myocardial infarction redefined--a consensus document of The Joint
European Society of Cardiology/American College of Cardiology Committee
for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-69.
(3) Braunwald E. Unstable angina. A classification. Circulation 1989;80:410-14.
Thank you for sending us the letter from Hildick-Smith and Glennon
and
inviting a response. The Guideline for the management of patients with
acute coronary syndromes without persistent ECG ST segment elevation
(Heart
2001;85:133-142) was based on the deliberations of a working party which
met
in October 1999, and on a review of the literature up to December 1999.
The
paper referred to by Hildick-Smith a...
Thank you for sending us the letter from Hildick-Smith and Glennon
and
inviting a response. The Guideline for the management of patients with
acute coronary syndromes without persistent ECG ST segment elevation
(Heart
2001;85:133-142) was based on the deliberations of a working party which
met
in October 1999, and on a review of the literature up to December 1999.
The
paper referred to by Hildick-Smith and Glennon (Myocardial infarction
redefined--a consensus document of The Joint European Society of
Cardiology/American College of Cardiology Committee for the redefinition
of
Myocardial infarction J Am Coll Cardiol 2000;36:959-69) was of course
published subsequently in September 2000.
The points raised in the letter from Hildick-Smith and Glennon are
interesting but do not affect the recommendations for clinical management
of
patients with acute coronary syndromes, or the conclusions of the
Guideline.
While we agree that with the advent of troponins there needs to be a
redefinition of myocardial infarction, we do not feel it appropriate to
enter into correspondence here in that process. We will be taking up
these
points and others in a separate paper in due course.
We thank Underwood for his kind comment about our study[1] which
demonstrated an absence of gender bias in the investigation and management
of patients referred to our open access chest pain clinic. We can
reassure him that this study relied on routinely collected data and
clinical staff were not aware that they would be under scrutiny with
regard to gender bias. Also, primary physicians had guide...
We thank Underwood for his kind comment about our study[1] which
demonstrated an absence of gender bias in the investigation and management
of patients referred to our open access chest pain clinic. We can
reassure him that this study relied on routinely collected data and
clinical staff were not aware that they would be under scrutiny with
regard to gender bias. Also, primary physicians had guidelines as to
which patients could be referred and an exclusion was limited mobility.
Furthermore, the supervising cardiology specialist registrars made
management decisions based on individual clinical judgement although, as
stated, these decisions were checked by consultants. As can be deduced
from our results, only patients who actually had an exercise test were
included in the study and therefore, patients who were not exercised
because of abnormal resting electrocardiograms were excluded.
His comments about the role of treadmill exercise testing, myocardial
perfusion imaging (MPI) and coronary arteriography are also timely as the
establishment of open access clinics in the United Kingdom has become a
priority since the publication of the National Service Framework for
coronary heart disease.[2] In summary, Underwood contends that
Southampton had a low use of MPI, that a high proportion of women referred
for coronary arteriography had normal coronary arteries and that if MPI
were used more frequently, "inappropriate" coronary arteriography could be
avoided and large cost savings could be made.
An ideal diagnostic test would be one which provides the most
information for the least cost and at low risk to the patient. There is
no doubt that MPI provides valuable prognostic information which may be
superior to that obtained by coronary arteriography. However, it has a
high radiation burden and requires expensive equipment and in the United
Kingdom, is not as widely available as coronary arteriography.[3] The
serious complication rate for coronary arteriography has been estimated at
1% with a mortality rate of 1 in 2000.[3] However, it uniquely provides
the anatomical data required for revascularisation by coronary artery
bypass surgery or percutaneous transluminal coronary angioplasty.
In our study, we showed that for men, treadmill exercise testing had
a high positive predictive value of 95.2%. At the end of our study
period, 286 men had had coronary arteriography of which 170 (59.4%) were
referred for revascularisation for either symptomatic or prognostic
reasons. It could be argued therefore, that if MPI had been carried out
instead of arteriography, then approximately 40% of men may have been
spared arteriography. However, 60% of men would have had an additional
investigation and because of this, they would have waited longer for
revascularisation. In our centre, the waiting time for MPI is x months.
In contrast to men, the positive predictive value for treadmill
exercise testing in women was only 72% and as it is known that false
positive rates are higher in women, the British Cardiac Society guidelines
do suggest that MPI should be carried out as a first line investigation
for chest pain in women.[3] However, from personal experience, we know
that this is not common practice in the UK and that this is partly because
of limited availability. Also, the open access chest pain clinics being
established as part of the National Service Framework will all use
treadmill testing for initial diagnosis and none are restricted to men.
In our study, all women with 2 mm or more of ST depression on their
electrocardiogram during their exercise test who were referred for further
investigation were referred for arteriography rather than MPI. Of these,
56% were referred for revascularisation. Therefore, the argument as to
whether these women should have had MPI first is the same as that for all
men who were referred for arteriography. Similarly, for women who had ST
depression of less than 2mm and who were referred for arteriography, the
intervention rate was 42.3%. For those women who had no electrocardiogram
changes and who were referred for arteriography, the intervention rate was
only 13%. For this group, it would seem that MPI would perhaps have been
more appropriate. Of all women referred for arteriography in our series,
we found that 56.2% had normal coronary arteries. This is similar to the
50% of women undergoing diagnostic arteriography in the CASS study[4] but
greater than the 30.7% found in the RITA study.[5] However, this latter
study included patients with myocardial infarction and unstable angina.
These high rates of normal arteriographic findings are likely to reflect
the low positive predictive value of exercise testing in women rather than
indiscriminate referral for arteriography. For instance, of the women who
had MPI in our study, only 3.9% were reported to have findings compatible
with coronary artery disease (data not originally reported). This
suggests that women suspected of having a low probability for coronary
artery disease were referred for MPI while women thought to have a greater
probability were referred for arteriography. Underwood reports in the
EMPIRE study that centres which used MPI had a normal angiogram rate of
26% while those that did not had a rate of 43%.[6] However, these figures
are not comparable to ours since they are not sex specific. If we were to
combine our results for men and women, then 29.3% of all patients
undergoing arteriography had normal results!
Underwood estimates that based on the EMPIRE results, Southampton
could save £65,000 a year if MPI were to be used more frequently. We do
not agree with this claim. The main deficiencies of the EMPIRE study are
that it was a retrospective notes trawl; it was relatively small with 8
centres in 4 countries recruiting an average of only 49 patients each and
hypothetical rather than actual costs were used in financial calculations.
We are told that there were "discrepant results" when each centre supplied
information on costs and charges. They estimated that exercise tests, MPI
and coronary arteriography cost £70, £220 and £1,100 respectively.
However, the assumed cost of angiography is excessive, now being as low as
£700 in most high volume centres. If we applied these figures to our
female population, then the cost for the investigations which actually
occurred is £149,190 (601 exercise tests, 137 arteriograms, 51 MPI
studies). If we then consider a situation where every woman had an
exercise test, where women who were actually referred for arteriography
had MPI instead and where only those women who were referred for
revascularisation had arteriography, then the cost would be £114,930 (601
exercise tests, 45 arteriograms, 188 MPI studies). This figure is likely
to be higher in real life because it does not take into account false
positive MPI results e.g. those due to breast shadows, which could lead to
further investigation by arteriography. Also, it does not take into
account situations where arteriography rather than MPI is indicated for
clinical reasons. It can be seen that cost savings can be made but not on
the scale claimed.
In the EMPIRE study, Underwood concedes that there are no randomised
trials assessing the cost-effectiveness of strategies of investigation in
patients with symptoms suggestive of coronary artery disease. This
situation is still true. Even without such studies, common sense tells us
that there are situations where the use of MPI is valuable. For instance,
in patients thought to have a low probability of coronary artery disease,
a normal MPI result would indicate an extremely good prognosis. On the
other hand, in patients thought to be at high risk from coronary events,
then coronary arteriography would be more appropriate regardless of sex,
poor mobility or abnormal resting electrocardiogram. The question as to
whether all women who have a history suggestive of angina should have MPI
as a first investigation rather than an exercise test has never been asked
in any study and we stand by our assertion that further research is
needed.
References
(1) Wong Y, Rodwell A, Dawkins S, Livesey SA, Simpson IA. Sex
differences in investigation results and treatment in subjects referred
for investigation of chest pain. Heart 2001;85:149-52.
(2) Anon. National Service Framework for Coronary Heart Disease.
Modern standards and service models. Department of Health, March, 2000.
(3) de Bono D. Investigation and management of stable angina: revised
guidelines 1998. Heart 1999;81:546-55.
(4) Kennedy JW, Killip T, Fisher LD, Alderman EL, Gillespie MJ, Mock
MB. The clinical spectrum of coronary artery disease and its surgical and
medical management. Circulation 1982;66(Suppl 3):16-23.
(5) Henderson RA, Raskino CL, Hampton JR. Variations in the use of
coronary arteriography in the UK: the RITA trial coronary arteriogram
register. Q J Med 1995;88:167-73.
(6) Underwood SR, Goodman B, Salyani S, Ogle JR, Ell PJ. Economics of
Myocardial Perfusion Imaging in Europe - the EMPIRE study. Eur Heart J
1999;20:157-65.
Wong and colleagues very nicely demonstrate the absence of gender
bias in investigation and management of 1522 patients referred by primary
care physicians to an open access chest pain clinic.[1] This is very
reassuring but their results raise an important issue concerning the
strategies of investigation used in their clinic. To summarise their data:
Wong and colleagues very nicely demonstrate the absence of gender
bias in investigation and management of 1522 patients referred by primary
care physicians to an open access chest pain clinic.[1] This is very
reassuring but their results raise an important issue concerning the
strategies of investigation used in their clinic. To summarise their data:
Table: Investigations in Southampton
Male (%)
Female (%)
Exercise ECG
100
1000
Myocardial perfusion imaging
8
5
Coronary arteriogram
31
23
Unfortunately, we are not told the criteria used by the trainee
cardiologists who staffed the clinic when deciding which patients went
from the exercise ECG to further investigation, and so we presume that it
was a matter of individual clinical judgement rather than a predetermined
strategy. This raises the question of whether the clinical staff were
aware that their decisions would become a matter of scrutiny with regard
to gender bias but, to be fair, we should assume that all concerned were
satisfied that this was not a source of positive discrimination.
More importantly, it is clear that the main strategy of investigation
was to submit all patients to an exercise ECG (presumably including those
with abnormal resting ECGs and those with restricted exercise tolerance
for non-cardiac reasons), to move to angiography if further investigation
was required, and in very few patients was myocardial perfusion imaging
(MPI) deemed appropriate. Many factors may underlie this choice of
strategy, including local availability of MPI and funding arrangements,
but the strategy was not in line with current British Cardiac Society
guidelines on investigation of possible angina.[2] These state that when
a patient presents with chest pain suggestive of coronary artery disease,
the initial stress test should be myocardial perfusion imaging in females,
in those with an abnormal resting ECG, and in those who are unable to
perform dynamic exercise. If coronary artery disease is confirmed then
medical management may be appropriate without the need for angiography if
the risk of coronary events is not high. The American guidelines are
similar although they do not specifically mention females.[3]
Admittedly, recruitment of patients to the Southampton study started
before these guidelines were published but the guidelines were based upon
previously established knowledge and practice.
It is relevant to compare the Southampton practice with that in eight
other European centres reported in the EMPIRE study.[4] This was a study
of the cost-effectiveness of strategies of investigation in patients newly
presenting with chest pain, although not to an open access chest pain
clinic. The study involved two centres in each of four European
countries, one in each country being a routine user of MPI and one using
it less frequently (“non-user”). The percentage of patients undergoing
MPI in the user centres was 59% of males and 49% of females. In the non-
user centres it was 18% and 13% respectively, thus Southampton is a more
extreme non-user of MPI than any of the centres in the EMPIRE study. In
the EMPIRE patients without coronary artery disease there was a 34% saving
of costs over two years in the user centres compared with the non-users
for the same clinical outcome. Much of this saving arose from avoiding
inappropriate coronary angiography in patients without CAD or with only
mild CAD, as illustrated by a rate of normal diagnostic coronary
angiograms in the MPI user centres of 26% compared with 43% in the non-
user centres. In Southampton, the normal coronary angiography rate in
women was 56%, a figure that must alarm many observers, although it was
considerably lower at 16% in men.
Without further information it is not possible to calculate the
potential financial savings in Southampton, but the figures suggest that
at least 500 patients without CAD are investigated in Southampton each
year because of chest pain. Applying the EMPIRE data to this population
suggests that a saving of £65,000 might be made each year and this would
be more than enough to provide sufficient MPI capacity if such does not
already exist.
Wong and colleagues conclude that further research is needed into how
best to investigate women with chest pain. I submit that there has
already been considerable research in this area[5-8] and that strategies
in line with the recommendations of the British and American cardiac
societies would have allowed the chest pain clinic in Southampton to have
achieved similar results in a more cost-effective manner.
References
(1) Wong Y, Rodwell A, Dawkins S, Livesey SA, Simpson IA. Sex differences of investigation results and treatment in subjects referred for investigation of chest pain. Heart 2001;85:149-52.
(2) de Bono D. Investigation and management of stable angina: revised guidelines 1998. Heart 1999;81:546-55.
(3) Gibbons RJ, Chatterjee K, Daley J, et al. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. Circulation 1999;99:2829-48.
(4) Underwood SR, Godman B, Salyani S, Ogle JR, Ell PJ. Economics of myocardial perfusion imaging in Europe – the EMPIRE study. Eur Heart J 1999;20:157-66.
(5) Cerqueira MD. Diagnostic testing strategies for coronary artery disease: special issues related to gender. Am J Cardiol 1995;75:D52-60.
(6) Hachamovitch R, Berman DS, Kiat H, et al. Effective risk stratification using exercise myocardial perfusion SPECT in women: gender-related differences in prognostic nuclear testing. J Am Coll Cardiol 1996;28:34-44.
(7) Shaw LJ, Heller GV, Travin MI, et al. Cost analysis of diagnostic testing for coronary artery disease in women with stable chest pain. J Nucl Cardiol 1999;6:559-69.
(8) Shaw LJ, Hachamovitch R, Berman DS, et al. The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterisation ischaemia. J Am Coll Cardiol 1999;33:661-9.
We read with interest the ‘electronic’ case report posted recently by Yeih and colleagues on aconitine poisoning.[1] They describe in detail the mechanism by which aconitine is purported to cause severe cardiotoxicity. We recently encountered a patient who had taken aconite in an attempted suicide. A magnesium sulphate infusion was employed with apparent success.
We read with interest the ‘electronic’ case report posted recently by Yeih and colleagues on aconitine poisoning.[1] They describe in detail the mechanism by which aconitine is purported to cause severe cardiotoxicity. We recently encountered a patient who had taken aconite in an attempted suicide. A magnesium sulphate infusion was employed with apparent success.
Case Report
A 23 year old man was admitted to our hospital with chest pain, vomiting and confusion. He admitted to haven taken an unknown quantity of ‘aconite’ (common name for Aconitum species) some four hours prior to his admission. Additionally, he complained of abdominal colic, blurred vision and perioral paraesthesia. On arrival, his pulse was 180; blood pressure un-recordable; Glasgow Coma Scale 14/15 (confused, hallucinating). Initial blood investigations exhibited mild (pre-) renal impairment, a leucocytosis and serial blood gas assays demonstrated initially a compensated metabolic acidosis and later a mixed respiratory and metabolic acidosis. The initial ECG exhibited an irregular, predominately narrow complex tachycardia at the rate of approximately 200 beats per minute. Close inspection revealed a marked enhancement of cardiac automaticity with multifocal atrial and ventricular depolarisations.
In essence, he showed the typical features of potentially fatal aconitine poisoning. Initial therapy focused on good supportive care, but in addition, we administered ‘prophylactic’ magnesium sulphate (8 mmol bolus, followed by an infusion of 62 mmol) – this was started six hours after the initial ingestion of aconitine. Subsequently, he did require ventilation in order to maintain a safe airway during gastric lavage as well as to correct the respiratory acidosis. He also received a brief period of ionotropic support. One and half hours after the administration of magnesium, his rhythm returned to a sinus tachycardia, with some abnormal P wave morphology but no ectopy. Subsequently his ECG completely normalised. The rest of his stay was uneventful and he went on to make a full recovery.
Discussion
As a consequence of the sodium channel activation, aconitine induces automaticity of the myocardium, predisposing to arrhythmias. These usually take the form of ventricular arrhythmias, including bi-directional tachycardias and torsades des pointes. Magnesium acts as a fast sodium channel blocker,[2] and hence has a theoretical role in the treatment of aconitine poisoning. Conventional anti-arrhythmics have generally been disappointing, as has been described previously.[3] [4] One other reported example of successful use of magnesium was after several other anti-arrhythmic drugs had failed in a patient with torsades des pointes.[5] This appears to be the first time that magnesium has been used first-line with some success.
Most anti-arrhythmic drugs have shown little consistent effect in the treatment of aconitine poisoning,[6] but, with perhaps the exception of amiodarone, all risk Q-T prolongation, an important mechanism in the development of ventricular tachyarrhythmias. By contrast, side effects from magnesium are few, minor and self-limiting. It would seem reasonable to consider magnesium as first line therapy in cases of aconitine poisoning.
Simon Conroy MB ChB MRCP
Specialist Registrar
Kettering General Hospital NHS Trust
The study by Hetmanski investigates the use of plasma BNP to detect
low left ventricular ejection fraction in a cohort of patients in the
community on frusemide.[1] The study showed a poor, albeit statistically
significant, correlation between plasma BNP and left ventricular ejection
fraction. The area under the receiver operating curve for BNP was only
0.587, and the authors conclude that the "accuracy o...
The study by Hetmanski investigates the use of plasma BNP to detect
low left ventricular ejection fraction in a cohort of patients in the
community on frusemide.[1] The study showed a poor, albeit statistically
significant, correlation between plasma BNP and left ventricular ejection
fraction. The area under the receiver operating curve for BNP was only
0.587, and the authors conclude that the "accuracy of BNP concentrations
to provide a measure of left ventricular ejection fraction and help
diagnose heart failure is not as good as previously reported".[1]
This study correctly acknowledges that primary care patients in whom
there is a clinical suspicion of heart failure differ in several important
aspects from patients in clinical trials: they tend to be elderly,
commonly have comorbid conditions, and the symptoms of heart failure are
frequent and often mild, making diagnosis difficult. However, this study
has several important limitations.
The first problem is that of patient selection. Although the
community setting is relevant and topical, we question the authors'
assumption that the majority of patients prescribed loop diuretics in
primary care would have the clinical syndrome of heart failure. Loop
diuretics are widely used in hypertension and for the empirical treatment
of ankle swelling of uncertain cause. Little is known about the prevalence
of heart failure in patients prescribed loop diuretics, but it may not
differ significantly from age-matched community controls. The presence of
echocardiographic left ventricular systolic dysfunction in community-based
patients treated with loop diuretics in previous reports varies from 26%[2]
to 41%.[3]
Secondly, of the 1425 patients prescribed diuretics identified from
practice registers and invited to take part in the study, only 653 (46%)
consented and underwent echocardiography and BNP measurement. It may be
possible that the patients with heart failure in the original cohort did
not take part in the study.
Thirdly, recent studies have demonstrated that BNP levels are
decreased by frusemide.[4-7] A major part of the therapeutic regimen used
in the BNP-guided treatment trial by Troughton et al[7] was an increase in
diuretic therapy to decrease the BNP level. Therefore, the influence of
diuretic therapy on BNP will impair the performance of BNP as a diagnostic
test in the study by Hetmanski et al.[1] The diagnostic efficacy of BNP
measurement performed during the first presentation of patients with
symptoms is still unknown.
Fourthly, there is confusion between the identification of left
ventricular systolic dysfunction and the diagnosis of the clinical
syndrome of heart failure. We believe that the goal of a diagnostic test
in the community is to aid recognition of the clinical syndrome of heart
failure so that appropriate further investigations, treatment and follow-
up can be instituted. This still remains the potential value of a
biochemical diagnostic tool such as BNP. BNP could well complement, rather
than replace, echocardiographic assessment of the left ventricle.[8] Left
ventricular systolic dysfunction on echo overlaps with but is not
synonymous with the clinical syndrome of heart failure. This study, by
using an arbitrary left ventricular ejection fraction (LVEF) cut-off of
40%, will have missed many patients with the clinical syndrome of heart
failure including those with diastolic dysfunction, an important
consideration in the community and in elderly patients.[9] Echocardiograhic
assessment of the LV in this study depends on an arbitrary LV ejection
fraction cut-off to "rule in" or "rule out" left ventricular systolic
dysfunction. Any chosen level of LVEF cut-off - usually adopted from
mechanistic clinical trials - will have a unique ROC curve reflecting the
changing relationship between diagnostic sensitivity and specificity at
any particular level of LVEF. In reality, improved recognition of the
clinical syndrome of heart failure may prove more useful.
Community studies of the effectiveness of BNP measurement for the
diagnosis of the clinical syndrome of heart failure are still needed.
These studies must be carefully conducted randomised controlled trials
which recognise the contribution of heart failure with preserved systolic
function in this group and utilise a pragmatic definition of the syndrome
of heart failure appropriate for primary care.
Dr SP Wright
Research Fellow in Cardiovascular Medicine
Department of Medicine
Dr RN Doughty
New Zealand National Heart Foundation BNZ Senior Fellow
Department of Medicine
Dr A Pearl
Research Fellow
Department of General Practice and Primary Health Care
School of Medicine and Health Sciences
University of Auckland
Private Bag 92019, Auckland, New Zealand
References
(1) Hetmanski D, Sparrow N, Curtis S, Cowley A. Failure of plasma
brain natriuretic peptide to identify left ventricular systolic
dysfunction in the community. Heart 2000;84:357-60.
(2) Francis C, Caruana L, Kearney P, Love M, Sutherland G, Starkey I, et
al. Open access echocardiography in management of heart failure in the
community. BMJ 1995;310:634-6.
(3) Wheeldon N, MacDonald T, Flucker C, McKendrick A, McDevitt D, Struthers
A. Echocardiography in chronic heart failure in the community. Quart J Med 1993;86:17-23.
(4) Murdoch D, McDonagh T, Byrne J, Blue L, Farmer R, Morton J. Titration
of vasodilator therapy in chronic heart failure according to plasma brain
natriuretic peptide concentration. Am Heart J 1999;138:1128-32.
(5) Northridge D, Newby D, Rooney E, Norrie J, Dargie H. Comparison of the
short-term effects of candoxatril, an orally active neutral endopeptidase
inhibitor, and frusemide in the treatment of patients with chronic heart
failure. Am Heart J 1999;138:1149-57.
(6) Kelly R, Struthers A. Risk assessment of left ventricular systolic
dysfunction: drug treatment might be contaminating factor [letter]. BMJ
2000(321):111.
(7) Troughton R, Frampton C, Yandle T, Espiner E, Nicholls M, Richards A.
Treatment of heart failure guided by plasma aminoterminal natriuretic
peptide (N-BNP) concentrations. Lancet 2000;355:1126-30.
(8) Struthers A. Further defining the role for natriuretic peptide levels
in clinical practice [editorial]. Eur Heart J 1999;20:712-4.
(9) Tresch D, McGough M. Heart failure with normal systolic function: a
common disorder in older people. J Am Geriatr Soc 1995;43:1035-42.
I read with interest this case report from Hirooka and colleagues.[1]
Myocardial contrast echocardiography (MCE) allows the assessment of
myocardial perfusion, however, several technical issues remain unresolved
and artifacts are quite common.
It is highly debatable whether the perfusion defect shown represents
myocardial ischemia due to systolic compression of the LAD septal
branches. If that w...
I read with interest this case report from Hirooka and colleagues.[1]
Myocardial contrast echocardiography (MCE) allows the assessment of
myocardial perfusion, however, several technical issues remain unresolved
and artifacts are quite common.
It is highly debatable whether the perfusion defect shown represents
myocardial ischemia due to systolic compression of the LAD septal
branches. If that were the case, the bottom right picture also shows a
perfusion defect in the basal and mid-portion of the contra-lateral wall,
which cannot be explained by the angiographic findings and more likely
represents an artifact commonly seen in the basal portions of the LV.
Destruction of the microbubbles due to vigorous myocardial contraction may
explain the findings.
It is possible that MCE, due to its sampling rate, may allow us to
assess phasic changes in myocardial blood volume (MBV).[2] However, from
the physiologic standpoint, it is difficult to conceive that
autoregulation of the coronary microcirculation is absent and systolic
compression of the LAD septal branches would simultaneously cause such
dramatic reduction of MBV.
MCE is an emerging technique with great clinical potential for the
assessment of myocardial perfusion. At the current stage of the MCE
technology, and to facilitate its progress and acceptance within the
cardiology community, caution must be exercised to avoid conclusions,
especially when based upon a case report.
References
(1) Hirooka K, Masakazu Y, Miyatake K. Visualisation of systolic
myocardial perfusion defect induced by septal squeezing. Heart
2000;84:482.
(2) Kaul S, Jayaweera AR. Coronary and myocardial blood volumes:
noninvasive tools to assess the coronary microcirculation? Circulation
1997;96:719–24.
Chest radiography, to which not even a passing allusion was made in a recent report on misdiagnosis of heart failure,[1] has now been accorded its rightful status in the recognition of this syndrome.[2] Unlike some of the clinical stigmata of pulmonary disease, which have been accorded an importance, in the undergraduate curriculum, disproportionate to their relationship to evidence-based medicine,[3] the radiogra...
Chest radiography, to which not even a passing allusion was made in a recent report on misdiagnosis of heart failure,[1] has now been accorded its rightful status in the recognition of this syndrome.[2] Unlike some of the clinical stigmata of pulmonary disease, which have been accorded an importance, in the undergraduate curriculum, disproportionate to their relationship to evidence-based medicine,[3] the radiographic stigmata of severe chronic left ventricular failure (LVF), although not instilled to the same extent, nevertheless have the merit of having been evaluated for sensitivity, specificity, and positive predictive value, yielding values of 65%, 80%, and 89% respectively, for pulmonary vascular redistribution, and 27%, 87%, and 83%, respectively, for interstitial oedema in the presence of pulmonary capillary wedge pressure > 18 mmHg.[4]
On a 4-point scale of severity, a comparison between clinical and radiographic parameters for LVF generated a concordance which differed by no more than 1 grade, in 94% of instances.[5] Analysis of radiographic parameters also revealed greater interobserver agreement for recognition of interstitial oedema as opposed to pulmonary vascular redistribution (95% vs 74%).[4]
In consequence, this parameter (together with alveolar oedema) deserves recognition in the entirety of its protean manifestations which include, not just the Kerley B lines and "bat's wing" appearance mentioned by the author,[2] but also lower zone "mottled" as well as confluent opacities (some of which may be asymmetrical),[6] and right upper zone opacities (attributable to underlying mitral regurgitation),[6,7] all of which have the potential to be misattributed to pulmonary sepsis.[6]
Overdiagnosis also needs to be avoided, especially in pulmonary embolism (PE), where instead of a positive correlation between clinical and radiographic severity,[5] the degree of breathlessness far outstrips abnormalities (if any) seen on X-ray.
Radiographic abnormalities common to heart failure and PE include pleural effusions which, in heart failure, are reported (sic) more likely to be either bilateral (73%) or right sided (19%), than left sided (9%),[8] a preferential distribution not documented in PE.
References
(1) Caruana L, Petrie MC, Davie AP, McMurray JJV. Do patients with suspected heart failure and preserved left ventricular systolic function suffer from "diastolic heart failure" or from misdiagnosis? A prospective study. BMJ 2000;321:215-19.
(2) Struthers AD. The diagnosis of heart failure. Heart 2000;84:334-8.
(3) McAlister FA, Strauss SE, Sackett DL, on behalf of the CARE-COAD Group. Why we need large, simple studies of the clinical examination: the problem and proposed situation. Lancet 1999;354:1721-4.
(4) Butman SM, Ewy GA, Standen JR, Kern KB, Hahn E. Bedside cardiovascular examination in patients with severe chronic heart failure: importance of rest or inducible venous distention. J Am Coll Cardiol 1993;22:969-74.
(5) Forrester JS, Diamond GA, Swan HJC. Correlative classification of clinical and hemodynamic function after acute myocardial infarction. Am J Cardiol 1977;39:137-45.
(6) Fraser RS, Colman N, Muller NL, Pare PD. Pulmonary edema. In: Diagnosis of Diseases of the Chest. 4th ed, Vol III. WB Saunders Company: Philadelphia, London, Toronto, Montreal, Sydney, Tokyo. pp 1946-2017.
(7) Brander L, Kloeter U, Henzen C, Briner V, Stulz P. Right-sided pulmonary oedema. Lancet 1999;354:1440.
(8) Weiss JM, Spodick DH. Laterality of pleural effusions in congestive heart failure. Am J Cardiol 1984;53:951.
The comparison of the mathematical accuracy of paper-based tables or charts for estimating coronary (CHD) or cardiovascular (CVD) risk by Jones et al[1] is extremely valuable, but their conclusion that the revised Joint British Societies chart has the best combination of sensitivity and specificity is surprising. When the SMAC guidance[2] based on the original Sheffield table[3] was issued in 1997 the recom...
I was surprised that Missouris and colleagues in their case report failed to mention cystic medial necrosis as a cause of spontaneous coronary artery dissection.[1] This disease requires histologic confirmation and is characterised by focal fragmentation of elastic fibers, loss of smooth muscle cells of the media and the accumulation of acid mucopolysaccharides. Mandatory exclusion of Marfan syndrome, his...
The Guideline for the management of patients with acute coronary syndromes without persistent ECG ST segment elevation[1] gives excellent and timely advice, but there is one area which continues to cause confusion, and that concerns the diagnosis of "myocardial infarction".
The International Redefinition of Myocardial Infarction[2] states that an infarct has occurred when there has been a typical rise...
Thank you for sending us the letter from Hildick-Smith and Glennon and inviting a response. The Guideline for the management of patients with acute coronary syndromes without persistent ECG ST segment elevation (Heart 2001;85:133-142) was based on the deliberations of a working party which met in October 1999, and on a review of the literature up to December 1999. The paper referred to by Hildick-Smith a...
Dear Editor,
We thank Underwood for his kind comment about our study[1] which demonstrated an absence of gender bias in the investigation and management of patients referred to our open access chest pain clinic. We can reassure him that this study relied on routinely collected data and clinical staff were not aware that they would be under scrutiny with regard to gender bias. Also, primary physicians had guide...
Wong and colleagues very nicely demonstrate the absence of gender bias in investigation and management of 1522 patients referred by primary care physicians to an open access chest pain clinic.[1] This is very reassuring but their results raise an important issue concerning the strategies of investigation used in their clinic. To summarise their data:
Table: Investigations in Southampton...
We read with interest the ‘electronic’ case report posted recently by Yeih and colleagues on aconitine poisoning.[1] They describe in detail the mechanism by which aconitine is purported to cause severe cardiotoxicity. We recently encountered a patient who had taken aconite in an attempted suicide. A magnesium sulphate infusion was employed with apparent success.
Case Report
A 23 year o...
The study by Hetmanski investigates the use of plasma BNP to detect low left ventricular ejection fraction in a cohort of patients in the community on frusemide.[1] The study showed a poor, albeit statistically significant, correlation between plasma BNP and left ventricular ejection fraction. The area under the receiver operating curve for BNP was only 0.587, and the authors conclude that the "accuracy o...
I read with interest this case report from Hirooka and colleagues.[1] Myocardial contrast echocardiography (MCE) allows the assessment of myocardial perfusion, however, several technical issues remain unresolved and artifacts are quite common.
It is highly debatable whether the perfusion defect shown represents myocardial ischemia due to systolic compression of the LAD septal branches. If that w...
Chest radiography, to which not even a passing allusion was made in a recent report on misdiagnosis of heart failure,[1] has now been accorded its rightful status in the recognition of this syndrome.[2] Unlike some of the clinical stigmata of pulmonary disease, which have been accorded an importance, in the undergraduate curriculum, disproportionate to their relationship to evidence-based medicine,[3] the radiogra...
Pages