Nava and coworkers[1] and Martini and coworkers[2] described a
single patient with the diagnois of right ventricular dysplasia who,
retrospectively analyzed by the same authors, may have suffered from the
syndrome of right bundle branch block, ST segment elevation and sudden
death, now known as Brugada disease.
As they have no genetic analysis
on that patient (to exclude among others Naxos syndrome) t...
Nava and coworkers[1] and Martini and coworkers[2] described a
single patient with the diagnois of right ventricular dysplasia who,
retrospectively analyzed by the same authors, may have suffered from the
syndrome of right bundle branch block, ST segment elevation and sudden
death, now known as Brugada disease.
As they have no genetic analysis
on that patient (to exclude among others Naxos syndrome) their recent
letter to Heart[3] ads only confusion to an excellent study by Viskin and
coworkers.[4] Their speculations on the mechanisms of right ventricular
dysplasia and Brugada disease are no more than speculations and devoid of
any scientific basis.
Prof Dr Pedro Brugada
Cardiovascular Research and Teaching Institute Aalst Belgium
References
(1) Nava A, Canciani B, Schiavinato ML, Martini B, Buja GF, La repolarisation precoce
dans le precordiales droites: trouble de la conduction intraventriculaire droite? Correlations
de l'electrocardiographie- vectorcardiographie avec l'electro- physiologie. Mises a Jour
Cardiologiques 1988;17:157-9.
(2) Martini B, Nava A, Thiene G, et al. Ventricular fibrillation without apparent heart
disease: description of six cases. Am Heart J 1989;11:1203-9.
(3)Martini B, Nava A, Cannas S. There is not a single typical ECG pattern for the syndrome of sudden
death, RBBB, and ST elevation [Rapid response]. Heart 15 August 2000.
(4) Viskin S, Fish R, Eldar M, et al. Prevalence of the Brugada sign in idiopathic ventricular
fibrillation and healthy controls. Heart 2000;84:31-6.
The article by Viskin et al[1] adds some confusion to the definition of "the typical" electrocardiographic pattern associated with the syndrome of sudden death and right bundle branch delay described by Nava and Martini in 1988-1989,[2, 3] by Aihara in 1990, and by Brugada in 1992. As clearly documented,[3] three (and not one as discussed by Viskin et al) of six patients with aborted sudden death showed differe...
The article by Viskin et al[1] adds some confusion to the definition of "the typical" electrocardiographic pattern associated with the syndrome of sudden death and right bundle branch delay described by Nava and Martini in 1988-1989,[2, 3] by Aihara in 1990, and by Brugada in 1992. As clearly documented,[3] three (and not one as discussed by Viskin et al) of six patients with aborted sudden death showed different degrees of right bundle branch block, left axis deviation, prolonged PR interval and ST segment elevation. Two more patients had mild isolated ST elevation with T inversion. The same polymorphic patterns were lately documented either with standard electrocardiography or after class 1C drugs (in subjects with normal ECG or minor ST-T abnormalities), either in Brugada's or other series.[4] Thus a typical sign of the syndrome is a fascinating but not confirmed statement.
Viskin probably wants to emphasise the first and the most popular electrocardiogram of the syndrome, which is the one published in 1988[1] and 1989 (patient 3 of figure 1 in reference 2), and reprocessed by Brugada on his web site.
This electrocardiogram shows an R' wave in V1 (incorrectly called J wave), very similar to an incomplete right bundle branch block, followed by a coved ST elevation.
It must be remembered that the typical J wave is those recorded in leads II, III, aVF, V5-V6 in vagotonia, and other pathological conditions.[5] Thus R' in V1 is an atypical J wave, or something else.
Different from a right bundle branch delay, the atypical J wave seen in V1 shows neither a late and slurred S wave in V6, or the typical vectorcardiographic terminal loop.[1] Late potentials often characterise this pattern, but are absent in pure incomplete right bundle branch block. Thus the trace proposed by Viskin et al in figure 2 as the typical sign of the syndrome is, in reality, a typical incomplete right bundle branch block, while the trace presented in figure 3A closely resembles a true atypical J wave with coved ST elevation, and not a questionable sign.
This does not means that Viskin et al's patients do not have the syndrome, because this is not characterised by a single electrocardiographic pattern, but by polymorphic right bundle branch delays with ST elevation.[2] The latter can be the only basal abnormality, with the atypical J wave appearing spontaneously, or being induced after class 1C drugs.
The significance of all the electrocardiographic patterns of the syndrome, particularly of the atypical J wave and coved ST elevation, is strongly debated. Brugada favours a functional repolarisation abnormality, while we think, according to electrical and anatomic demonstration, that it represents an organic depolarisation abnormality.[4]
This can be easily demonstrated by recording late potentials. As mentioned before, in patients with the discussed "typical" electrocardiogram late potentials are almost always present, clearly demonstrating that the atypical J wave and coved ST elevation is due to a delayed QRS activity, probably of the outflow tract of the right ventricle.[4]
Please contact Dr Martini for a copy of the figure described below (unfortunately we cannot support illustrations in Rapid Responses)
The atypical J wave with coved ST elevation in V1, is identical in these two subjects with the syndrome. The trace on the left is the patient of Brugada described in Heart[6] after ajmaline; this pattern was ascribed to a functional repolarisation abnormality. The trace on the right is that of an apparently normal patient, belonging to a family affected by a minor form of right ventricular cardiomyopathy. This patient has a very positive late potentials study, indicating that the atypical J wave and ST elevation, both spontaneous and drug inducible, represents a late depolarisation abnormality of the cardiac activity, probably at the right ventricular outflow tract level. A repolarisation abnormality can never induce late potentials.
Bortolo Martini MD* Andrea Nava MD+ Sergio Cannas MD*
*Department of Cardiology, Ospedale Civile di Thiene
+Department of Cardiology, University of Padua
Correspondence to:
Bortolo Martini MD
Via Gioberti 9
36016 Thiene (VI), Italy
Fax +39 445 368537
References
(1) Viskin S, Fish R, Eldar M, et al. Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls. Heart 2000;84:31-6.
(2) Nava A, Canciani B, Schiavinato ML, Martini B, Buja GF, La repolarisation precoce dans le precordiales droites: trouble de la conduction intraventriculaire droite? Correlations de l'electrocardiographie- vectorcardiographie avec l'electro- physiologie. Mises a Jour Cardiologiques 1988;17:157-9.
(3) Martini B, Nava A, Thiene G, et al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J 1989;11:1203-9.
(4) Martini B, Corrado D, Nava A, Thiene G. Syndrome of right bundle branch block, ST segment elevation and sudden death: evidence of an organic substrate. In: Nava A, Thiene G, eds. Arrhythmogenic right ventricular cardiomyopathy. Elsevier 1997:438-53.
(5) Yan GX, Antzelevitch C. Cellular basis for the electrocardiographic J wave. Circulation 1996;93:372-9.
(6) Brugada P. Brugada syndrome: an electrocardiographic
diagnosis not to be missed. Heart 2000;84:1-3.
We read with interest the article by Kubler et al[1]
concerning 3 patients with platypnoea-orthodeoxia syndrome. As reported,
this syndrome is infrequent and the diagnosis can be difficult. It
is characterised by dyspnoea and arterial hypoxaemia induced by upright
position that resolved by recumbency. This is usually the consequence of
right-to-left shunt at the atrial level. Such shunting is frequent in...
We read with interest the article by Kubler et al[1]
concerning 3 patients with platypnoea-orthodeoxia syndrome. As reported,
this syndrome is infrequent and the diagnosis can be difficult. It
is characterised by dyspnoea and arterial hypoxaemia induced by upright
position that resolved by recumbency. This is usually the consequence of
right-to-left shunt at the atrial level. Such shunting is frequent in
patients with congenital heart defects when there is high pulmonary artery
pressure and patent foramen ovale/atrial septal defect (PFO/ASD) but
usually there is no postural change for both dyspnoea and hypoxaemia.
More
surprisingly are the normal right-sided pressures associated with this
syndrome. Moreover, due to the high prevalence of PFO in the "normal" population
(between 25 and 33%) we might expect to observe more and
more patients with this syndrome.
In our experience, this syndrome is not extremely rare; we
collected 18 patients with similar symptoms (10 female and 8
male, meand (SD) age 71 (6) years).[2] Most of them presented with
variable dyspnoea on exercise and/or hypoxaemia. In fact, the postural
character was present in only 55% of our
group, and can be masked when the patient cannot be weaned off the
ventilator! Some of the patients had a history of stroke or
paradoxical embolism (27%).
It is possible that the concept of platypnoea
-orthodeoxia may be too restrictive. In this population, the first
diagnosis advocated is usually pulmonary embolism and this has led to
various investigations. In fact, transthoracic but mainly transoesophageal
echocardiography, as reported by Kubler et al is the most common examination to depict the PFO and interatrial right-to-left shunt. In this
setting, cardiac catheterization is not necessary to confirm the
diagnosis. In contrast, we recommend
transcatheter PFO/ASD occlusion instead of surgery. Indeed, a significant
number of patients are quite debilitated or sick and surgical closure would
increase their risk.
The literature describes many devices that have been
successfully used to close such defects. This technique is easy to perform,
does not require general anaesthesia, and provides complete correction. In
our experience, device implantation was performed successfully in all but 1 patient.
Another interest of cardiac catheterization is to reveal
the underlying causes responsible for this interatrial right-to-left
shunting. First, there is frequently a haemodynamic pressure gradient
between both atria favouring a right-to-left shunt noticed in late
diastole or early systole. Also been reported is lower right atrial
pressure or equal to the left atrial pressure. It is probable that
significant amount of blood flow from the inferior vena cava can easily cross a PFO by
kinetic energy without need of a favourable pressure gradient between both
atria. Second, there is frequently a preferential blood flow streaming
from inferior vena cava, or more rarely from superior vena cava,
towards the left atrium through a PFO. In our experience, we have noticed
frequently horizontalization of the atrial septum so that the PFO is
placed directly in line with the blood flow from the inferior vena cava. This can be the
consequence of different causes such as classic pneumonectomy or
lobectomy, cyphoscoliosis, or ascending aorta aneurysm displacing the
atrial septal orientation. The dilatation of ascending aorta due to age
seems to be in our experience the most frequent cause responsible for this
syndrome.
We hope that publication in Heart of 3 cases of platypnoea-orthodeoxia will heighten awareness of this complication. When this
syndrome is suspected, we strongly recommend transoesophageal echocardiography
with contrast study to depict the interatrial right-to-left shunt and propose transcatheter PFO occlusion. The true incidence of
this syndrome remains to be established and a registry of the complication
would be of interest.
F GODART
C REY
Department of Paediatric Cardiology
CHRU de Lille, 59037 Lille cedex
France
(2) Godart F, Rey C, Prat A, et al. Atrial right-to-left shunting causing
severe hypoxaemia despite normal right-sided pressures. Report of 11
consecutive cases corrected by percutaneous closure. Eur Heart J 2000;21:483-9.
We appreciate the kind comments of Dr Mitani regarding
our article in the March 2000 issue of Heart and for
sharing their experiences with us.[1]
In group 1 and 2 patients who had regressed coronary aneurysm after Kawasaki disease, there was significantly more vascular constriction with acetylcholine and poorer dilatation with isosorbide
dinitrate at the regressed site, than in group 3 patient...
We appreciate the kind comments of Dr Mitani regarding
our article in the March 2000 issue of Heart and for
sharing their experiences with us.[1]
In group 1 and 2 patients who had regressed coronary aneurysm after Kawasaki disease, there was significantly more vascular constriction with acetylcholine and poorer dilatation with isosorbide
dinitrate at the regressed site, than in group 3 patients
who had no coronary artery lesions after Kawasaki disease.
Fourteen patients in group 1 and group 2 in the acute stage
of illness had coronary artery lesions on one side of the
coronary artery but no coronary artery lesion on the
opposite side.
We also evaluated the vascular function of
these sites (n = 19) using intracoronary infusion of
acetylcholine chloride and isosorbide. The mean (SD)
change in the coronary artery diameter after infusion of
acetylcholine was 12.5 (3.0)% in group 1 and 2, and
11.3 (5.6)% in group 3. The mean (SD) change in the
coronary artery diameter after infusion of isosorbide
dinitrate was 17.3 (9.5)% in group 1 and 2, and 18.0
(8.2)% in group 3. There was no significant difference in
responses to the infusion of either acetylcholine or
isosorbide dinitrate between these two groups.
These
findings suggested that such coronary arteries had finctionally normal
endothelium and smooth muscle even in
patients with a history of severe Kawasaki vasculitis.
The coronary arteries in group 3 patients had normal
responses to the infusion of either acetylcholine or
isosorbide dinitrate, according to the analysis of multiple
coronary artery segments involving proximal coronary artery
segments. We assessed differences in responses to the
infusion of acetylcholine or isosorbide dinitrate
between proximal coronary artery segments and distal
coronary artery segments in group 3 patients and in controls. The mean (SD) change in the coronary artery
diameter after infusion of acetylcholine was 11.9 (3.5)% at
the proximal artery coronary segments and 12.8 (4.0)% at
the distal coronary artery segments in group 3. The mean
(SD) change in the coronary artery diameter after infusion
of isosorbide dinitrate was 16.8 (4.2)% at the proximal
coronary artery segments and 17.1 (8.0)% at the distal
coronary artery segments in group 3.
These results
suggested that there was no significant difference in
responses to the infusion of either acetylcholine or
isosorbide dinitrate between the proximal coronary artery
segments and the distal coronary artery segments in group 3
patients. Similar findings were found in the control
patients.
In a new study,[2] we investigated
the vascular morphology of the coronary artery, in 6
Kawasaki disease patients who had completely normal first
coronary angiography findings, using intravascular
ultrasound imaging; we found no differences in wall
morphology between the proximal coronary artery segments
and the distal coronary artery segments.
From the basis of our studies, we conclude that long-term
persistent coronary aneurysms and regressed coronary
aneurysms after Kawasaki disease exhibit vascular
dysfunction.[1-5] These patients should be counseled to
avoid potential risk factors for atherosclerosis, and they
should be advised that long-term follow-up is needed into
adulthood. However, patients with normal coronary arteries after
Kawasaki disease had no significant difference from the
controls in response to either acetylcholine or isosorbide
dinitrate infusion. These findings suggested that such
coronary arteries had normal function of the endothelium
and smooth muscle even in the long term.
References
(1) Iemura M, Ishii M, Sugimura T, Akagi T, Kato H. Long-
term consequences of regressed coronary aneurysms after
Kawasaki Disease: vascular wall morphology and function.
Heart 2000;83:307-11.
(2) Ishii M, Hashino K, Iemura M, Yamakawa R, Muta H, Himeno
W, Akagi T, Kato H. Long-term consequences of coronary
aneurysms after Kawasaki disease: vascular wall morphology
and endothelium function (abstract). J Am Coll Cardiol 2000;35:513A.
(3) Yamakawa R, Ishii M, Sugimura T, Akagi T, Eto G, Iemura
M, Tsutsumi T, Kato H. Coronary endothelial dysfunction
after Kawasaki disease: evaluation by intracoronary
injection of acetylcholine. J Am Coll Cardiol 1998;31:1074-
80.
(4) Sugimura T, Kato H, Inoue O, et al. Vasodilatory
response of the coronary arteries after Kawasaki disease:
evaluation by intracoronary injection of isosorbide
dinitrate. J Pediatr 1992;121:684-8.
(5) Sugimura T, Kato H, Inoue O, Fukuda T, Sato N, Ishii M,
Takagi J, Akagi T, Maeno Y, Kawano T, Takagishi T, Sasaguri
Y. Intravascular ultasound of coronary arteries in
children: assessment of the wall morphology and the lumen
after Kawasaki disease. Circulation 1994;89:258-65.
I read with interest Kübler’s review[1] and Willenheimer and colleagues’ viewpoint[2] on a similar theme about the application of drug trial results in
clinical practice, an area that remains controversial.
Florey’s penicillin trial in the 1940s only involved 8 mice. The mice were
inoculated with streptococci and only the four that were treated survived.
Such simplistic demonstration of a positive...
I read with interest Kübler’s review[1] and Willenheimer and colleagues’ viewpoint[2] on a similar theme about the application of drug trial results in
clinical practice, an area that remains controversial.
Florey’s penicillin trial in the 1940s only involved 8 mice. The mice were
inoculated with streptococci and only the four that were treated survived.
Such simplistic demonstration of a positive drug effect is unfortunately
not possible in preventative cardiovascular medicine where multiple
factors are at work. The advent of modern drug trials however has allowed
the efficacy of many cardiac drugs to be proved, but only with an
assumption of homogeneity in large numbers of study patients. The call for
more “overly” inclusive trials by Willenheimer and colleagues such as the
HOPE study could potentially be problematic. This empirical approach
“treats the many to benefit the few”. This invariably removes the need for
any understanding of the individual pathophysiologic process resulting in
unnecessary multiple drug therapy in many patients. Also, this encourages
an unhealthy “pill-pushing” culture and not enough on the need for
lifestyle modification. For example, the benefit of cholesterol lowering
with a statin is completely negated by smoking.[3]
For a given drug trial, theoretically there will be 4 outcome groups:
(a) those who survive because of a positive drug effect
(b) the vast
majority whose survivals are not dependent on treatment
(c) those whose
deaths are contributed by adverse drug reactions
(d) those whose
deaths are inevitable; either due to inadequate drug effect or alternate
pathophysiology.
If (a) > (c) then (a) divided by (a) + (c) + (d) gives
the relative risk reduction, in many positive cardiovascular trials, this
being greater than 25%. The problem is, it is necessary to treat a large
number of patients to uncover a drug effect.
As pointed out by
Willenheimer and colleagues, the survival of “32” out of 696 heart failure
patients treated in the US carvedilol trial established the statistical
efficacy of the drug. In other words, 19 out of every 20 patients treated
did not benefit from the drug as a whole (the inverse of number needed to
treat). Unfortunately, it is not possible to distinguish (a) from
(b) patients. There is therefore room to find reliable markers of drug
efficacy (or the lack of) to monitor the progress of drug treatment. The
lack of drug efficacy in (c) and (d) patients should perhaps be more
carefully explored clinically, and post-mortems should be carried out if
feasible. Some would argue that the (b) patient population would also
benefit from drug-induced alteration of the disease process. This however
has not yet been borne out in population mortality curves which appear to
have flattened out.[4]
Pitt O Lim
Department of Clinical Pharmacology and Therapeutics
Ninewells Hospital
Dundee, DD1 9SY UK
References
(1) Kubler W. Treatment of cardiac diseases: evidence based or
experience based medicine? Heart 2000;84:134-6.
(2) Willenheimer R, Dahlof B, Gordon A. Clinical trials in cardiovascular
medicine: are we looking for statistical significance or clinical
relevance? Heart 2000;84:129-33.
(3) Isles CG, Norrie J. Lipid lowering drugs for patients who continue to
smoke? Heart 2000;83:619-20.
(4) Fuster V. Epidemic of cardiovascular disease and stroke: the three main
challenges: presented at the 71st scientific sessions of the American
Heart Association - Dallas, Texas. Circulation 1999;99:1132-7.
The recent article by Ghuran and Nolan is a valuable review about cardiovascular effects of recreational drugs.[1] We would like to provide additional information, not included in the review, about the induction of changes in the QT interval by some recreational substances.
The long QT syndrome has been associated with the occurrence of ventricular tachyarrhythmias (torsades de pointes). Considering the s...
The recent article by Ghuran and Nolan is a valuable review about cardiovascular effects of recreational drugs.[1] We would like to provide additional information, not included in the review, about the induction of changes in the QT interval by some recreational substances.
The long QT syndrome has been associated with the occurrence of ventricular tachyarrhythmias (torsades de pointes). Considering the substances of abuse, to our knowledge, at least cocaine, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and alcohol[2] can induce changes in the QT/QTc interval. There are published clinical case reports describing this kind of change for MDMA,[3, 4] and for cocaine it has also been described the presence of torsades de pointes in a patient with idiopathic long QT syndrome.[5]
In addition we would like to present results of the ECG-recording obtained during a clinical trial where MDMA was administered. Eight healthy male recreational users of MDMA participated in a randomized, double blind, cross-over and placebo controlled study. All subjects received, in different experimental sessions, a single oral dose of placebo, MDMA 125 mg; MDMA 75 mg and d,l-amphetamine 40 mg. A 12 lead-electrocardiogram (50 mm/sec) was performed prior treatment (baseline measure) and 1, 2, 4, 8 and 24 hours after drug administration. Cycle length (RR) and QT interval were measured manually by the same blinded investigator. Both measures were performed in all 12 leads of each ECG recording. Corrected QT was calculated with Bazett's formula. Interlead QTc dispersion was determined as the longest minus the shortest QTc on the 12-lead ECG. Changes in the T wave and appearance of U waves were also considered. Individual changes after each treatment conditions were evaluated according to criteria suggested by the Committee for Proprietary Medicinal Products (CPMP).[6] Other details of the trial have been previously published.[7] The table shows the number of subjects (maximal 8) who fulfil any criteria for prolonged cardiac repolarisation:
Mean QTc values (ms; n = 8) for each administered substance
Criteria
Placebo
MDMA 125 mg
MDMA 75 mg
Amphetamine
QTc between 431-450 ms*
0
1 (446 ms)
0
0
QTc change from baseline*
Between 30-60 ms
0
2
3
1
> 60 ms
0
1
0
0
QTc dispersion > 100 ms*
0
3
1
0
T wave changes
0
2
2
2
U wave appearance
0
2
1
1
*Following CPMP criteria
The maximal effects were observed two hours after MDMA administration and returned to normal values at 4-8 hours. For amphetamine the maximal effects were observed lately, 8 to 24 hours after drug administration. Although the magnitude of mean QTc increase was not clinically relevant, individual data of some subjects might be interpreted as important "warning" signs of possible malignant arrhythmia in accordance to the CPMP recommendation. The mean QTc increase observed for MDMA is similar to that described after the administration of therapeutic doses of prescription drugs as terfenadine or cisapride in clinical trials.
The administration of a single oral dose of MDMA, in the range of those consumed recreationally, produce a slight increase of QTc. Although these changes are mild in magnitude, MDMA could enhance the risk of ventricular arrhytmia in subjects with genetic predisposition to present an acquired long QT syndrome, and/or when used in combination with other well known arrhythmogenic drugs.
Supported by grants FIS 97/1198, CIRIT 1997SGR00077, ISC-III-97/4344 and Plan Nacional sobre Drogas (Madrid).
Magí Farré
Marta Mas
Lluis Molina
Jordi Camí
Units of Pharmacology and Cardiology
IMIM-Hospital del Mar, UAB - UPF
Barcelona, Spain
References
(1) Ghuran A, Nolan J. Recreational drug misuse: issues for the cardiologist. Heart 2000;83:627-33.
(2) Rossinen J, Sinisalo J, Partanen J, et al. Efects of acute alcohol infusion on duration and dispersion of QT interval in male patients with coronary artery disease and in healthy controls. Clin Cardiol 1999;22:591-4.
(3) Maxwell DL, Polkey MI, Henry JA. Hyponatremia and catatonic stupor after taking "ecstasy". BMJ 1993;307:1399.
(4) Drake WM, Broadhurst PA. QT-interval prolongation with ecstasy. S Afr Med J 1996;86:180-1.
(5) Schrem SS, Belsky P, Schwartzman D, et al. Cocaine-induced torsades de pointes in a patient with the idiopathic long QT syndrome. Am Heart J 1990;120:980-4.
(6) Committee for Proprietary Medicinal Products (CPMP). The assessment of the potential for QT interval prolongation by non-cardiovascular medicinal products. London: Commission of the European Communities, 1997 (Available from URL: http://www.eudra.org/en_home.htm).
(7) Mas M, Farré M, de la Torre R, et al. Cardiovascular and neuroendocrine effects, and pharmacokinetics of MDMA in humans. J Pharmacol Exp Ther 1999;290:136-45.
In the case report by Sutaria et al (Heart 2000;83:97-98) an acute anterior MI complicated the routine administration of ergometrine after a
spontaneous vaginal delivery. A peak creatinine kinase (CK) of 9858 U/l
was reported (CK-MB fraction 8%) with the apparent implication that this
CK rise reflected solely myocardial damage. The myometrium, however, is a
source of CK and childbirth results in six fold...
In the case report by Sutaria et al (Heart 2000;83:97-98) an acute anterior MI complicated the routine administration of ergometrine after a
spontaneous vaginal delivery. A peak creatinine kinase (CK) of 9858 U/l
was reported (CK-MB fraction 8%) with the apparent implication that this
CK rise reflected solely myocardial damage. The myometrium, however, is a
source of CK and childbirth results in six fold rise in maternal CK
activity[1] and this rise starts to occur within thirty minutes of
delivery.[2] The increase in CK is higher in surgical compared to vaginal
deliveries.
References
1. Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry.
2nd ed. Philadelphia: WB Saunders; 1986.
2. Jouppila R, Jouppila P, Koivisto M, Virkkunen L, von Wendt L,
Pakarinen A. Maternal, foetal and neonatal blood creatinine-phosphokinase
activities and creatinine-phosphokinase co-enzymes after labour with and
without epidural analgesic and after caesarean section. Acta Anaesth Scand
1978;22:491-496
I read, with great interest the article by Alp et al comparing
intravenous and oral flecainide for the cardioversion of acute atrial
fibrillation.[1] However, the article concludes that if a patient
converts, there is no difference in the percentage of cardioversion by
either route (even though the numbers presented tend to favour the oral
route). But it fails to mention if there was any differences...
I read, with great interest the article by Alp et al comparing
intravenous and oral flecainide for the cardioversion of acute atrial
fibrillation.[1] However, the article concludes that if a patient
converts, there is no difference in the percentage of cardioversion by
either route (even though the numbers presented tend to favour the oral
route). But it fails to mention if there was any differences between those
who reverted to normal sinus rhythm compared to those who did not.
Particularly, since the reported span of time of the duration of AF is so
broad (1 to 40 hours) was there any relation between the length of the
arrhythmia and the propensity to cardiovert? This stems directly from the
postulate that the sooner therapy is started, the better the chances at
cardioversion are.
Another unclear point is whether the patients were known to be
paroxysmallly fibrillating or whether all of them were "completely" new
"fibrillators". If the former is correct, were they on any medications
(beta blockers, ACE inhibitors, etc) and were there any differences in the
rate they reverted to normal sinus rhythm?
Benjamin Mazouz MD
Psagot, D.N. Mizrach Binyamin
ISRAEL 90-624
The Heiden Department of Cardiology
3-5 Strauss Street
Jerusalem
ISRAEL 91-004
Reference
(1) Alp NJ, Bell JA, Shai M. Randomised double blind trial of oral
versus intravenous flecainide for the cardioversion of acute atrial
fibrillation. Heart 2000;84:37-40.
Cowie's editorial envisages a clinical role for measurement of brain
natriuretic peptide (BNP) in the near future.[1] However, while the
potential for risk stratification and monitoring of treatment in patients
with heart failure is encouraging, we would urge caution regarding the
diagnostic utility of plasma BNP concentration.
There is little doubt that the diagnosis of heart failure is
difficult -...
Cowie's editorial envisages a clinical role for measurement of brain
natriuretic peptide (BNP) in the near future.[1] However, while the
potential for risk stratification and monitoring of treatment in patients
with heart failure is encouraging, we would urge caution regarding the
diagnostic utility of plasma BNP concentration.
There is little doubt that the diagnosis of heart failure is
difficult - only about a third of patients referred for echocardiography
or to a cardiology clinic with suspected heart failure turn out to have
left ventricular systolic dysfunction.[2, 3] Nor is there any doubt that
a definitive diagnosis is important, as the institution of appropriate
treatments may have a significant impact on survival as well as symptoms,
while exclusion of left ventricular systolic dysfunction as a cause of
symptoms allows other investigations and treatment to be planned.
However, many echocardiography departments are becoming overwhelmed. Thus
a simple test that can "rule in" or "rule out" left ventricular
systolic dysfunction has considerable appeal.
In the assessment of any diagnostic test, it is useful to consider
both the properties of the test (sensitivity and specificity) and the
baseline probability of the diagnosis (ie, the probability before the test
result is known). The use of decision analysis, based upon Bayesian
statistics is invaluable in this regard and is recommended in standard
textbooks of evidence-based medicine.[4]
Plasma natriuretic peptides are highly sensitive (over 90%) but only
moderately specific (approximately 60%) tests for left ventricular
systolic dysfunction.[5] As a consequence low plasma concentrations of
natriuretic peptides will be helpful in "ruling out" the diagnosis of
left ventricular systolic dysfunction but high concentrations will be of
little value as they may be associated with a number of other diagnoses.[1] Hence, while plasma BNP concentrations will be very helpful in
screening large numbers of patients where the overall prevalence of left
ventricular systolic dysfunction is low,[5] their use in the
investigation of patients with suspected heart failure will be much more
limited.
In a study of patients referred to outpatients with suspected
heart failure, we found that 15% of those with a normal plasma brain
natriuretic peptide concentration had left ventricular systolic
dysfunction.[3]
A further important question is whether BNP provides additional
information aborve and beyond that given by current investigations. In
our study, the use of plasma BNP concentration did not add significantly
to more simple "tests" - a history of previous myocardial infarction and
an electrocardiogram.[3] While history and an electrocardiogram are
mainstays of the investigation of the breathless patient, a false negative
rate for plasma BNP concentration of approximately 15% is too high to
obviate the need for echocardiography in such individuals.
We believe that in the setting of patients with "suspected heart failure", an echocardiogram rather than plasma brain natriuretic peptide
concentration remains the investigation of choice. Despite the exciting
potential for estimating prognosis and adjusting treatment, there is
currently no role for measurement of brain natriuretic peptide in routine
clinical practice.
References
(1) Cowie MR. BNP: soon to become a routine measure in the care of
patients with heart failure? Heart 2000:83:617-18.
(2) Francis CM, Caruana L, Kearney P, et al. Open access echocardiography
in management of heart failure in the community. BMJ 1995;310:634-6.
(3) Landray MJ, Lehman R, Arnold IR. Measuring brain natriuretic peptide
in suspected left ventricular systolic dysfunction in general practice:
cross-sectional study. BMJ 2000;320:985-6.
(4) Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-based
medicine. How to practice and teach EBM. Churchill Livingstone 1998:118-28.
(5) McDonagh TA, Robb SD, Murdoch DR, et al. Biochemical detection of left-
ventricular systolic dysfunction. Lancet 1998;351:9-13.
Martin J Landray
Lecturer in Medicine
University of Birmingham
Birmingham B15 2TH, UK
Richard Lehman
General Practice Principal
Hightown Surgery
Banbury OX16 9DB, UK
Ian Arnold
Consultant Cardiologist
Horton Hospital
Oxford Radcliffe Hospitals NHS Trust
Banbury OX16 9AL, UK
We read with interest the case report by Codispoti et al, depicting
an association of pulmonary atresia and intact inter-ventricular septum
(PAIS) with persistent pulmonary hypertension of the newborn. In our
study of 24 autopsied cases of PAIS, we found four cases (16.7%) with
persistence of fetal circulation. All were a few days old with varying
degrees of ventricular hypoplasia and tricuspid steno...
We read with interest the case report by Codispoti et al, depicting
an association of pulmonary atresia and intact inter-ventricular septum
(PAIS) with persistent pulmonary hypertension of the newborn. In our
study of 24 autopsied cases of PAIS, we found four cases (16.7%) with
persistence of fetal circulation. All were a few days old with varying
degrees of ventricular hypoplasia and tricuspid stenoses. As a protocol
followed at our centre, sections of the lungs (average six) are studied in
all autopsied congenital heart diseases and hence we feel that this
association may not be as uncommon as suggested by the authors.
Taking into consideration the physiology of PAIS, the patent ductus
arteriosus supplies the pulmonary arterial tree in a retrograde fashion
and is responsible for the infrequency of pulmonary arterial hypoplasia
and development of collaterals. However, with persistent pulmonary
hypertension of the newborn, the retrograde blood flow would decrease and
there may even be a right to left shunt at the ductal level. Hence such
neonates will not only have a bad post operative course after correction
as occurred in the authors' case but would also have higher pre-operative
morbidity. It would, therefore, be important to consider them as a subset
of PAIS.
Reference
1. Codispoli M, Burns JE, Haworth SG, Simpson D, Mankad PS. Persistent
pulmonary hypertension of the newborn association with pulmonary atresia
and intact ventricular septum. Heart 1999;82:531-3.
Nava and coworkers[1] and Martini and coworkers[2] described a single patient with the diagnois of right ventricular dysplasia who, retrospectively analyzed by the same authors, may have suffered from the syndrome of right bundle branch block, ST segment elevation and sudden death, now known as Brugada disease.
As they have no genetic analysis on that patient (to exclude among others Naxos syndrome) t...
The article by Viskin et al[1] adds some confusion to the definition of "the typical" electrocardiographic pattern associated with the syndrome of sudden death and right bundle branch delay described by Nava and Martini in 1988-1989,[2, 3] by Aihara in 1990, and by Brugada in 1992. As clearly documented,[3] three (and not one as discussed by Viskin et al) of six patients with aborted sudden death showed differe...
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Dear Editor:
We appreciate the kind comments of Dr Mitani regarding our article in the March 2000 issue of Heart and for sharing their experiences with us.[1]
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Dear Editor
I read, with great interest the article by Alp et al comparing intravenous and oral flecainide for the cardioversion of acute atrial fibrillation.[1] However, the article concludes that if a patient converts, there is no difference in the percentage of cardioversion by either route (even though the numbers presented tend to favour the oral route). But it fails to mention if there was any differences...
Cowie's editorial envisages a clinical role for measurement of brain natriuretic peptide (BNP) in the near future.[1] However, while the potential for risk stratification and monitoring of treatment in patients with heart failure is encouraging, we would urge caution regarding the diagnostic utility of plasma BNP concentration.
There is little doubt that the diagnosis of heart failure is difficult -...
Dear Editor
We read with interest the case report by Codispoti et al, depicting an association of pulmonary atresia and intact inter-ventricular septum (PAIS) with persistent pulmonary hypertension of the newborn. In our study of 24 autopsied cases of PAIS, we found four cases (16.7%) with persistence of fetal circulation. All were a few days old with varying degrees of ventricular hypoplasia and tricuspid steno...
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