The major factor influencing the outcome of thrombolytic therapy for
acute myocardial infarction is not door-to-needle time, as Harvey White
claims, but pain-to-needle time. The largest component of the overall
delay from onset to thrombolytic treatment is attributable to the
patient's delay in calling for medical help. There is then an appreciable
delay between calling for an ambulance or a doctor and arr...
The major factor influencing the outcome of thrombolytic therapy for
acute myocardial infarction is not door-to-needle time, as Harvey White
claims, but pain-to-needle time. The largest component of the overall
delay from onset to thrombolytic treatment is attributable to the
patient's delay in calling for medical help. There is then an appreciable
delay between calling for an ambulance or a doctor and arriving at the
hospital - the call-to-door time. Probably little can be done to shorten
patient delay, so in assessing the emergency response of the health-care
system to a patient with suspected acute MI, it is better to exclude that
element of the delay over which the system has no control and start the
audit clock when the patient first makes contact with any sector of the
health service. This is acknowledged in the National Service Framework for
coronary heart disease recently launched by the Government Department of
Health in England which lays down various standards to be met, including a
rigorous 60-minute call-to-needle time. This forces us to look out of the
front door of the hospital to see what avoidable delays are encountered by
the patient before arrival at hospital. There is not a lot of point in
"busting a gut" to achieve a door-to-needle time of <_30 minutes="minutes" if="if" the="the" patient="patient" has="has" already="already" taken="taken" an="an" hour="hour" or="or" more="more" to="to" get="get" emergency="emergency" department="department" after="after" summoning="summoning" help.="help." p="p"/> A recently published audit showed that with a "scoop and run" policy
in urban areas only 15% of patients had a call-to-needle time within 60
minutes.[1] By contrast, in an audit of prehospital thrombolysis, 75% of
call-to-needle times were within 60 minutes, and that was in a rural area.[2] So the message is that we have to look to prehospital thrombolysis to
maximise the potential benefit of early thrombolysis.
And the benefit of earlier thrombolysis is very much greater than the
1.6/1000/h quoted. For reasons given elsewhere the FTT estimate is wrong,[3] and the best estimate we have of the time related benefit is more
that 10 times as great, at 21/1000/h.[4]
References
(1) Birkhead JS, et al. Trends in the provision of thrombolytic
treatment between 1993 and 1997. Heart 1999;82:438-42.
(2) Rawles J, et al. Call to needle times after acute myocarial infarction
in urban and rural areas in northeast Scotland: prospective observation
study. BMJ 1998;317:576-8.
(3) Rawles J. What is the likely benefit of earlier thrombolysis? Eur Heart J 1996;17:991-5.
(4) Boersma E, et al. Early thrombolytic treatment in acute myocardial
infarction: reappraisal of the golden hour. Lancet 1996;348:771-5.
Looking at the problem from a metabolic perspective it would seem to
me that the therapeutic objective in these patients might be to achieve
the highest cardiac reserve at rest by increasing the nutrient energy
density per unit volume of flowing blood. This should optimise their
capacity for increasing ATP resynthesis by oxidative phosphorylation in
response to a sudden increase in need for energy f...
Looking at the problem from a metabolic perspective it would seem to
me that the therapeutic objective in these patients might be to achieve
the highest cardiac reserve at rest by increasing the nutrient energy
density per unit volume of flowing blood. This should optimise their
capacity for increasing ATP resynthesis by oxidative phosphorylation in
response to a sudden increase in need for energy from ATP hydrolysis
precipitated by physical exertion or even metabolic exertion such as that
induced by eating.
Perhaps this is what is being achieved in inotrope-dependent
patients, an infusion of adrenaline in a ambulatory patient increasing
glucose uptake and utilisation. If so an infusion of glucose, K+ and
insulin might be safer and even more effective option than inotropes for
it should not increase myocardial workload as much [1]. [It is the
dynamics of energy demand/supply balance that is critical, the time taken
in restoring tissue pH to baseline levels possibly being the critical
measurable variable in these patients].
From my conversation with a cardiac surgeon at the Texas Heart
Institute, administering an inotrope to patients awaiting cardiac
transplantation is a very risky business because it can precipitate fatal
myocardial events. Certainly an IV infusion of adrenaline is not without
risk. He was also of the opinion that these patients, whose cardiac index
can be much less than two, might do better without any inotropes.
Might the degree of lipid shift present at rest be the determining
factor in the energy demand/supply balance of these patients. The higher
the degree of shift the greater the nutrient energy density per unit
volume of blood available for delivery to tissues and hence need for a
increase in cardiac output to deliver the nutrient needed for ATP
resynthesis? If so might an IV infusion of omega-3-fatty acids be of
therapeutic benefit in these patients? The danger is that, being an
uncoupler, polyunsaturated fatty acid supplementation might have an
adverse effect upon outcome if not in the short-term then in the longer-
term [2].
Intelligent exploration of the metabolic options for treating
patients is dependent upon the ability to measure and monitor their
effects sensitively and objectively both at the systemic and the regional
level. Pharmacological interventions could cause sudden and variable
changes in either direction. Until this is done the effects of any
pharmacological intervention will be unpredictable especially in patients
such as these with such compromised myocardial tissue energetics.
References
(1). Glucose-K+-insulin and/or omega-3 fatty acid infusions for
prolonged anaesthesia/surgery?
Richard G Fiddian-Green (2 August 2004) eLetter re: T Tsubo, T Kudo, A
Matsuki, and T Oyama
Decreased glucose utilization during prolonged anaesthesia and surgery
Can J Anesth 1990; 37: 645-649
(2). Might polyunsaturated fatty acid supplementation in infant formula
be harmful?
Richard G Fiddian-Green
bmj.com, 2 May 2003 eLetter re: J S Forsyth, P Willatts, C Agostoni, J
Bissenden, P Casaer, and G Boehm
Long chain polyunsaturated fatty acid supplementation in infant formula
and blood pressure in later childhood: follow up of a randomised
controlled trial
BMJ 2003; 326: 953
We read with interest the review of congenitally bicuspid aortic
valve by Ward.[1] The complications of congenitally bicuspid aortic
valve, including aortic stenosis, aortic regurgitation and aortic
dissection, are well documented in this review.
It is interesting to note the association of congenitally bicuspid
aortic valve with aortic medial disease (cystic medial necrosis),
coarct...
We read with interest the review of congenitally bicuspid aortic
valve by Ward.[1] The complications of congenitally bicuspid aortic
valve, including aortic stenosis, aortic regurgitation and aortic
dissection, are well documented in this review.
It is interesting to note the association of congenitally bicuspid
aortic valve with aortic medial disease (cystic medial necrosis),
coarctation and congenital aortic arch abnormalities.[2][3] Some
investigators have postulated a common pathogenesis of aortic valve and
aorta diseases with evidence that the aortic valve and portions of the
aorta may share a common embryonic origin.[4]
We recently studied the degree of aortic medial degenerative changes
associated with congenitally bicuspid and tricuspid aortic valves in
patients with aortic stenosis, who died shortly after aortic valve
replacement.[5] Patients with aortic dissection were excluded. The
association between bicuspid aortic valve and dissection, and thus with
aortic medial degenerative changes (cystic medial necrosis), is usually
derived from case reports or series of patients dying from or being
operated upon for aortic dissection. We thought that the data were
probably biased to reflect patients with severe medial disease, and thus
we decided to re-evaluate these changes in patients without dissection.
To our surprise, computer aided morphometry demonstrated that the
aortas of congenitally bicuspid aortic valve patients had less elastic
tissue than those patients with tricuspid aortic valves. Routine
histological evaluation by light microscopy of the same aortic sections,
even with the use of elastic stains, did not demonstrate a significant
difference.
These independent findings also support the echocardiographic
observations of Pachulski and colleagues, who demonstrated an association
of aortic dilatation with bicuspid aortic valve in the absence of
hemodynamic valvular abnormalities.[6]
We agree with the conclusions of Ward.[1] Patients with congenitally
bicuspid aortic valve may be prone to aortic degeneration with age and
should be closely monitored. Alterations in the aortic media may be part
of the disease spectrum of congenitally bicuspid aortic valve.
John P. Veinot M.D., FRCPC Assoc. Professor Pathology University of Ottawa
University of Ottawa Heart Institute
Ottawa Hospital Ottawa, Ontario, Canada
REFERENCES
1. Ward C. Clinical significance of the bicuspid aortic valve. Heart
2000;83:81-85.
2. Roberts WC. The congenitally bicuspid aortic valve: a study of 85
autopsy cases. Am J Cardiol 1970;26:72-83.
3. Larson EW, Edwards WD. Risk factors for aortic dissection: A necropsy
study of 161 cases. Am J Cardiol 1984;53:849-855.
4. Schievink WI, Mokri B. Familial aorto-cervicocephalic arterial
dissections and congenitally bicuspid aortic valve. Stroke 1995;26:1935-
1940.
5. Parai JL, Masters RG, Walley VM, Stinson WA, Veinot JP. Aortic medial
changes associated with bicuspid aortic valve: Myth or reality ? Can J
Cardiol 1999;15:1233-1238.
6. Pachulski RT, Weinberg AL, Chan KL. Aortic aneurysm in patients with
functionally normal or minimally stenotic bicuspid aortic valve.
Am J Cardiol 1991;67:781-782.
The excellent review by Ward on the clinical significance of the
bicuspid aortic valve (Heart 2000;83:81-85) is of great
interest and value. The extensive reference list as well put a good bit
of the pertinent bicuspid valve literature in one place. The paper adds
greatly to our knowledge.
However, without critiquing every issue in the paper, there are two
areas in particular I would...
The excellent review by Ward on the clinical significance of the
bicuspid aortic valve (Heart 2000;83:81-85) is of great
interest and value. The extensive reference list as well put a good bit
of the pertinent bicuspid valve literature in one place. The paper adds
greatly to our knowledge.
However, without critiquing every issue in the paper, there are two
areas in particular I would like to discuss. As a pediatric cardiologist
who has been in one division for 40 years, there is considerable natural
history which has been learned, although, perhaps in order to make my
statements I would really have to work in one place for 70 years.
I have seen a huge number of patients with a true bicuspid aortic
valve and I have never seen a patient with a dissecting aneurysm. As Dr.
Ward states, the reason for the reported high incidence of aortic
dissection in the presence of an aortic bicuspid aortic valve is unclear,
particularly since the author states that the bicuspid valve is usually
normally functioning. Although the post bicuspid valve dilatation of the
ascending aorta in the presence of systemic hypertension certainly makes
the environment possible, Dr. Ward’s paper makes no mention as to whether
he has personally seen a patient with dissection. The estimated
incidence of 5% of patients with bicuspid valve having
dissection of the aorta seems very much too high.
The second issue refers to whether or not the patient born with
bicuspid aortic valve and no stenosis is expected to progress to reach
real aortic stenosis as the patient ages in the absence of infective
endocarditis. The accepted knowledge over the years has been that the
elderly with calcific aortic stenosis began with a bicuspid aortic valve,
including the valve with no stenosis to begin with. Evidence for such has
never been documented and perhaps cannot, unless a 100 year prospective
study is planned and funded. The implication of Dr. Ward’s article is not
quite that, for he doesn’t really discuss the patient with bicuspid aortic
valve and no stenosis. He only states, appropriately, that patients with
mild aortic stenosis are expected to progress in adulthood, even patients
with echocardiographic mean gradient of less than 25 mmHg. However, this
does not answer the question as to whether the patients with true bicuspid
aortic valve and no stenosis are expected to progress. In order to
discuss this issue, one needs the physical examination. Is there
a difference in natural history between the patient with true bicuspid
aortic valve with no stenosis and a true bicuspid aortic valve with mild
stenosis? In the early two decades of my 40 years, the diagnosis of
bicuspid aortic valve without stenosis was made by recognizing an aortic
ejection click with no heart murmur. I accept that occasionally an error
can be made in that the presumed aortic ejection click is in actual fact
an unusually loud tricuspid valve component of a normally split first
sound. But in the recent two decades, with echocardiography, confirmation
has been readily available. The patient with a bicuspid aortic valve and
mild aortic stenosis is diagnosed by having the aortic ejection click
plus a normally split second sound and an aortic stenosis murmur at the
second right interspace that is significant but usually stops clearly
before aortic valve closure. The latter will usually have a mean gradient
of less than 25 mmHg in the echo, just as will obviously the patient with
no stenosis. Dr. Ward because of the nature of his review does not
separate these groups. In my 40 years, I have seen many patients with
mild stenosis progress, but I have seen none with no stenosis progress.
In addition, the subgroup of patients with coarctation of the aorta has a
very high incidence of bicuspid valve without stenosis. I have never seen
one of these develop aortic stenosis either.
I realize that 40 years is not 70 years, but since it is unlikely to
be able to find all these patients with no stenosis for an associate to
follow for 30 or 40 more years answering the question for certain at this
time appears unlikely. However, it would be in cumbent upon all of us to
modify what we teach our students and what we advise our families. As far
as we know, the bicuspid aortic valve without stenosis remains without
stenosis.
Sincerely,
Jerome Liebman MD
Division of Pediatric Cardiology
Professor of Pediatrics
Rainbow Babies & Children’s Hospital
Case Western Reserve University
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.
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.
Of the paper-based coronary heart disease (CHD) risk prediction
methods, the modified Sheffield tables,[1] which include the patient's
HDL cholesterol, and the revised charts published by the joint British
societies[2] most accurately classify subjects' risks. In our evaluation
of their performance,[3] the only statistically significant difference
between them was the lower specificity of the modi...
Of the paper-based coronary heart disease (CHD) risk prediction
methods, the modified Sheffield tables,[1] which include the patient's
HDL cholesterol, and the revised charts published by the joint British
societies[2] most accurately classify subjects' risks. In our evaluation
of their performance,[3] the only statistically significant difference
between them was the lower specificity of the modified Sheffield tables,
which in turn gives them a significantly higher false positive rate than
the joint British societies' charts [3.8% (95% confidence interval 2.4 -
5.2%) vs 1.2% (0.5 - 1.9%)]. In context, false positive means a subject
whose 10 year CHD risk calculated with the Framingham equation is
<_30 but="but" who="who" is="is" scored="scored" by="by" the="the" risk="risk" table="table" chart="chart" as="as" having="having" a="a" of="of" _30="_30" or="or" higher.="higher." use="use" modified="modified" sheffield="sheffield" tables="tables" rather="rather" than="than" joint="joint" british="british" societies="societies" charts="charts" will="will" necessity="necessity" lead="lead" to="to" higher="higher" prescribing="prescribing" costs="costs" and="and" we="we" think="think" that="that" this="this" may="may" be="be" some="some" importance="importance" purchasers="purchasers" health="health" care.="care." p="p"/> Nonetheless, Wallis et al are quite correct in their assertion that
calculated CHD risks in the false positives identified by the modified
Sheffield tables approach the 30% risk threshold, and therefore treating
these patients may be no bad thing. Since the Sheffield group were
instrumental in setting the 30% treatment threshold in the first place, it
is interesting that they now believe that this risk level is
"conservative", by which we imagine they mean it is too high. The
rationale for choosing the current 30% threshold was based on the
Sheffield group's assessment of the affordability of statin treatment at
various risk levels.[4] Costs of treatment are heavily dependent upon the
price of the drugs, which have fallen substantially since the original
risk threshold was set. We agree with the Sheffield group that the 30%
risk threshold is now too high. However, we believe that it would be more
transparent were the CHD risk threshold for primary prevention to be
formally reduced, rather than covertly lowering it by using a risk
prediction method with a poor specificity.
Lower risk thresholds can be accommodated with the current joint
British charts, but the Sheffield tables would have to be drafted again.
We are also not convinced that the ability of the Sheffield tables to be
reproduced on a 'single page' is a particularly persuasive argument: the
latest edition of the British National Formulary seems to have been able
to publish the joint British societies' charts, in full and in colour.
AF Jones WA Bartlett
Department of Clinical Biochemistry, Birmingham Heartlands and
Solihull NHS Trust Birmingham B9 5SS, UK
FL Game
Department of Diabetes and Endocrinology, Nottingham City Hospital
Hucknall Road, Nottingham NG5 1PB, UK
GR Bayly
Department of Chemical Pathology, Bristol Royal Infirmary Bristol
BS2 8HW, UK
References
(1) Wallis EJ, Ramsay LE, Ul Haq IU, et al. Coronary and
cardiovascular risk estimation for primary prevention: validation of the
new Sheffield table in the 1995 Scottish health survey population. BMJ
2000;320:671-76.
(2) Wood D, Durrington P, Poulter N, et al. Joint British
recommendations on prevention of coronary heart disease in clinical
practice. Heart 1998;80(Suppl 2):S1-S29.
(3) Jones AF, Walker J, Jewkes C, et al. Comparative accuracy of
cardiovascular risk prediction methods in primary care patients. Heart
2001;85:37-43.
(4) Haq IU, Ramsay LE, Pickin DM, et al. Lipid-lowering for
prevention of coronary heart disease:what policy now? Clin Sci
1996;91:399-413.
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.
The major factor influencing the outcome of thrombolytic therapy for acute myocardial infarction is not door-to-needle time, as Harvey White claims, but pain-to-needle time. The largest component of the overall delay from onset to thrombolytic treatment is attributable to the patient's delay in calling for medical help. There is then an appreciable delay between calling for an ambulance or a doctor and arr...
Dear Editor,
Looking at the problem from a metabolic perspective it would seem to me that the therapeutic objective in these patients might be to achieve the highest cardiac reserve at rest by increasing the nutrient energy density per unit volume of flowing blood. This should optimise their capacity for increasing ATP resynthesis by oxidative phosphorylation in response to a sudden increase in need for energy f...
To the Editor;
We read with interest the review of congenitally bicuspid aortic valve by Ward.[1] The complications of congenitally bicuspid aortic valve, including aortic stenosis, aortic regurgitation and aortic dissection, are well documented in this review.
It is interesting to note the association of congenitally bicuspid aortic valve with aortic medial disease (cystic medial necrosis), coarct...
Dear Editor:
The excellent review by Ward on the clinical significance of the bicuspid aortic valve (Heart 2000;83:81-85) is of great interest and value. The extensive reference list as well put a good bit of the pertinent bicuspid valve literature in one place. The paper adds greatly to our knowledge.
However, without critiquing every issue in the paper, there are two areas in particular I would...
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...
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,
Of the paper-based coronary heart disease (CHD) risk prediction methods, the modified Sheffield tables,[1] which include the patient's HDL cholesterol, and the revised charts published by the joint British societies[2] most accurately classify subjects' risks. In our evaluation of their performance,[3] the only statistically significant difference between them was the lower specificity of the modi...
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...
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