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
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.
We agree that cystic medial necrosis may in a small number
of patients be the cause of spontaneous coronary artery dissection.[1]
However, the pathogenesis of spontaneous coronary artery dissection
remains
poorly understood. Indeed, no uniform histological findings have been
identified and it is improbable that a single mechanism operates in all
these
patients. Our patient had none of the featur...
We agree that cystic medial necrosis may in a small number
of patients be the cause of spontaneous coronary artery dissection.[1]
However, the pathogenesis of spontaneous coronary artery dissection
remains
poorly understood. Indeed, no uniform histological findings have been
identified and it is improbable that a single mechanism operates in all
these
patients. Our patient had none of the features of Marfans syndrome, and as
there was no histopathological analysis, the aetiology remains a subject
of
speculation.
The high mortality associated with this condition necessitates urgent
coronary angiography to confirm the diagnosis. In patients surviving the
initial episode, and subsequently remain asymptomatic, medical therapy is
safe and compatible with good long term outlook. However, in those with
ongoing symptoms of myocardial ischaemia consideration should be given to
coronary revascularisation, though technically difficult in some cases, as
the only means to improve outcome in this usually fatal condition.
Reference
(1) Basso C, Morgagni GL, Thiene G. Spontaneous coronary artery
dissection: a neglected case of acute myocardial ischaemia. Heart
1996;75:451-4.
We read with interest Professor Treasure's recent paper on the
cardiovascular surgical aspects of Marfan syndrome.[1] We wish to add to
the discussion by raising the significant cardiovascular risks faced by
Marfan patients during pregnancy, a problem that he touched on in a
previous editorial.[2] This is an important and controversial issue in the
management of adult cardiovascular manifestations of Marfa...
We read with interest Professor Treasure's recent paper on the
cardiovascular surgical aspects of Marfan syndrome.[1] We wish to add to
the discussion by raising the significant cardiovascular risks faced by
Marfan patients during pregnancy, a problem that he touched on in a
previous editorial.[2] This is an important and controversial issue in the
management of adult cardiovascular manifestations of Marfan syndrome,
which is not mentioned in his recent and otherwise excellent review.
It is well recognised that, apart from the 50% risk of passing on
this autosomal dominant condition, pregnancy itself is associated with
increased risk of cardiovascular, most particularly aortic, events.[3] [4]
The majority of patients with no or only mild aortic dilatation have an
uncomplicated and uneventful pregnancy.[5] However, the higher risk of
catastrophic cardiovascular events in women with moderate to severe aortic
or mitral valve pathology, and particularly in those with evidence of
significant aortic dilatation, necessitates very close multidisciplinary
monitoring during pregnancy, with timely intervention to safeguard the
wellbeing of both mother and foetus.
Before pregnancy, any woman with a diagnosis of Marfan syndrome
should be evaluated clinically and echocardiographically to assess the
degree of cardiovascular symptoms and pathology. If at most, the
cardiovascular problems are mild, and the aortic root diameter is under 4
cm,[3] then female Marfan patients wanting children should be counselled
to reproduce early if possible, with warning of a small but potential risk
during pregnancy. Those with significant cardiovascular problems and/or a
dilated aortic root should be counselled against pregnancy. Despite this,
controversy remains with respect to those asymptomatic women with an
aortic root diameter between 4-5 cm who, mindful of the potential risks,
wish to become pregnant. The choice remains between offering pre-
conception prophylactic surgery, and that of allowing pregnancy to take
place with reassurance of a stringent and regular high-risk follow-up in a
dedicated multidisciplinary unit. The former choice poses the dilemma of
inflicting peri- and post-operative surgical morbidity in an otherwise
young and healthy individual whose aorta may not necessarily ever dilate
to a point requiring surgery. The latter risks accelerated aortic
dilatation, possibly complicated by dissection, during pregnancy and the
need for aortic surgery with maternal and foetal morbidity.
During pregnancy, any patient with Marfan syndrome requires regular
echocardiography to check valvular pathology and any significant increase
in aortic dimensions. Cardiovascular complications can occur early on in
pregnancy as significant cardiac output and plasma volume changes can be
seen as early as the 6th gestational week.[3] Due to the ability of beta-
blockers to slow the rate of aortic dilatation,[6] their continued use is
recommended in Marfan women during pregnancy.[7]
When possible, labour should be allowed to proceed naturally to a
vaginal delivery, but there should be a low threshold for caesarean
section in the event of foetal mal-position, distress or significant
maternal hypertension. Epidural anaesthesia is recommended in order to
minimise the rise in blood pressure accompanying pain and anxiety of
labour. It may also be prudent to administer prophylactic antibiotics in
women with evidence of mitral valve prolapse in the context of the low but
potentially serious consequence of bacteraemia associated with
instrumental delivery.
Finally, whilst the majority of female Marfan patients go through
pregnancy without significant problems, it is important to keep in mind
that no Marfan patient can be reassured of an event free pregnancy. Major
aortic events have been described in Marfan patients with normal aortic
roots in and out of pregnancy.[8] [9]
Kumud Dhital
Eric Rosenthal
Adult Congenital Heart Disease Clinic
Guy's Hospital St Thomas Street
London SE1 9RT, UK
References
(1) Treasure T. Cardiovascular surgery for Marfan syndrome. Heart
2000;84:674-8.
(2) Treasure T. Elective replacement of the aortic root in Marfan's
syndrome. Br Heart J 1993;69:101-3.
(3) Pyeritz RE. Maternal and fetal complications of pregnancy in the
Marfan syndrome. Am J Med 1981;71:784-90.
(4) Lipscomb KJ, Smith JC, Clarke B, et al. Outcome of pregnancy in
women with Marfan's syndrome. Br J Obstet Gynaecol 1997;104:201-6.
(5) Rossiter JP, Repke JT, Morales AJ, et al. A prospective
longitudinal evaluation of pregnancy in the Marfan syndrome. Am J Obstet
Gynecol 1995;173:1599-606.
(6) Shores J, Berger KR, Murphy EA, et al. Progression of aortic
dilatation and the benefit of long-term b-adrenergic blockade in Marfan's
syndrome. N Engl J Med 1994;330:1335-41.
(7) Elkayam U, Ostrzega E, Shotan A, et al. Cardiovascular problems
in pregnant women with the Marfan syndrome. Ann Intern Med 1995;123:117-
22.
(8) Rosenblum NG, Grossman AR, Gabbe SG, et al. Failure of serial
echocardiographic studies to predict aortic dissection in a pregnant
patient with Marfan's syndrome. Am J Obstet Gynecol 1983;146:470-1.
(9) Murgatroyd F, Child A, Poloniecki J, et al. Does routine
echocardiographic assessment of the aortic root diameter help predict the
risk of dissection in the Marfan syndrome? Eur Heart J 1991;12;410.
I agree wholeheartedly with many of Dr Rawles' comments. There are
five components of delay in the "pain-to-needle" time. My editorial
focused on administration of thrombolytic therapy in the emergency
department, and as such I did not discuss other important components of
delay.
Patient delays in summoning medical assistance have proven to be very
difficult to influence. Delays in the arr...
I agree wholeheartedly with many of Dr Rawles' comments. There are
five components of delay in the "pain-to-needle" time. My editorial
focused on administration of thrombolytic therapy in the emergency
department, and as such I did not discuss other important components of
delay.
Patient delays in summoning medical assistance have proven to be very
difficult to influence. Delays in the arrival of medical assistance have
been improved by dispatching an ambulance immediately to the patient.
There may be further delays at the scene for history-taking, physical
examination and procedures to be undertaken, but these may prove
worthwhile if treatment can be expedited as a result. For instance, the
recording of an electrocardiogram may allow confirmation of the diagnosis
of threatened myocardial infarction, enabling pre-hospital thrombolysis to
be undertaken - and as Dr Rawles points out, this has real advantages.
Transport delays are essentially unmodifiable. This leaves delays in
hospital, which I discussed in my editorial.
I strongly support the use of pre-hospital thrombolysis in rural
areas[1] and in cases where transport delays are likely to exceed one
hour.[2]
The issue of just how many lives are saved per hour less of treatment
delay is controversial because no trials have randomised the timing of
thrombolysis. In the FTT overview, which examined all available data from
randomized trials of >1,000 patients, regression analysis showed that
there was an approximate straight-line relationship between treatment
delay and mortality, and we calculated that for every hour less of delay
prior to treatment, 1.6 lives were saved per 1,000 patients randomised.[3]
It is incorrect to simply connect the data points (including the 50%
reduction in the first hour in the GISSI-1 trial[4]) and to ascribe larger
reductions for each hour less of delay prior to treatment. In a weighted
regression analysis of eight trials, Boersma et al concluded that a one-
hour delay may result in 21 lives lost per 1,000 patients treated.[5]
In the GREAT trial, which was led by Dr Rawles, 311 patients who were
more than 30 minutes' travelling time away from hospital were randomised
to receive either pre-hospital or in-hospital thrombolysis. The "door-to-
needle" time of those treated in-hospital (which was the focus of my
editorial) was 87 minutes.[6] A meta-analysis of six pre-hospital
thrombolysis trials, including the GREAT trial, calculated that there was
a 17% reduction (95% confidence interval 2-30%) in short-term mortality
with pre-hospital thrombolysis, equating to about 16 lives saved per 1,000
patients treated.[7]
It should be noted that there were often marked door-to-needle delays
prior to in-hospital thrombolysis in these trials, meaning that the
overall difference in the time to treatment between pre- and in-hospital
thrombolysis was approximately 60 minutes. In the largest of these trials
(the European Myocardial Infarction Project, which randomized 5,469
patients) the difference was 55 minutes, but no significant reduction in
mortality was shown with pre-hospital thrombolysis, leading to the
conclusion that perhaps the difference has to be greater than this to
translate into a survival benefit.[8]
I believe that the appropriate paradigm is not actually "time from
onset of ischaemia to treatment", as Dr Rawles asserts, but rather, "time
from the onset of ischaemia to the opening of the infarct-related artery
and achievement of myocyte reperfusion". The primary goal of treatments
for patients with acute myocardial infarction should be to shorten this
time as much as possible.
Dr Rawles sees little point in reducing the door-to-needle time if
the patient has already taken an hour or more to get to the emergency
department, but I disagree. Any reduction in the delay between the onset
of ischaemia and opening of the infarct-related artery is important to
reduce mortality, preserve left ventricular function and improve quality
of life. Our goal, therefore, should be to reduce all components of delay
in the time from the onset of ischaemia to opening of the infarct-related
artery and achievement of myocyte perfusion.
Harvey D White
Cardiology Department
Green Lane Hospital
Auckland, New Zealand
References
(1) White HD. Prehospital thrombolysis [editorial]. NZ Med J. In
press 2001.
(2) White HD, Van de Werf FJJ. Thrombolysis for acute myocardial
infarction. Circulation 1998;97:1632-46.
(3) Fibrinolytic Therapy Trialists' (FTT) Collaborative Group.
Indications for fibrinolytic therapy in suspected acute myocardial
infarction: collaborative overview of early mortality and major morbidity
results from all randomised trials of more than 1000 patients. Lancet
1994;343:311-22.
(4) Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto
Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in
acute myocardial infarction. Lancet 1986;i:397-402.
(5) Boersma E, Maas ACP, Deckers JW, et al. Early thrombolytic
treatment in acute myocardial infarction: reappraisal of the golden hour.
Lancet 1996;348:771-5.
(6) The GREAT Group. Feasibility, safety, and efficacy of domiciliary
thrombolysis by general practitioners: Grampian Region Early Anistreplase
Trial. Br Med J 1992;305:548-53.
(7) Morrison LJ, Verbeek PR, McDonald AC, et al. Mortality and
prehospital thrombolysis for acute myocardial infarction: a meta-analysis.
JAMA 2000;283:2686-92.
(8) The European Myocardial Infarction Project Group. Prehospital
thrombolytic therapy in patients with suspected acute myocardial
infarction. N Engl J Med 1993;329:383-9.
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.
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
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Dear Editor,
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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...
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