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.
I enjoyed reading the recent article on the worldwide perspective of valve disease by Soler-Soler and Galve from Barcelona, Spain.[1] But I was surprised that no mention was made of mitral valve prolapse (MVP) anywhere in their article.
MVP is the commonest valve disorder in the United States as well as in many parts of the world.[2] It also has a prevalence of 4.3% in Spain (see table).
I enjoyed reading the recent article on the worldwide perspective of valve disease by Soler-Soler and Galve from Barcelona, Spain.[1] But I was surprised that no mention was made of mitral valve prolapse (MVP) anywhere in their article.
MVP is the commonest valve disorder in the United States as well as in many parts of the world.[2] It also has a prevalence of 4.3% in Spain (see table).
Prevalence (%) of mitral valve prolapse
Male
Female
Overall
Australia*
4
4
4
Brazil
-
-
4
Britain*
-
2
-
Britain
-
-
5
Britain**
3.9
5.2
4.5
Canada*
-
-
22
China (Hans in Sichuan)*
2.2
6.3
4.3
China (Kazaks in Xinjiang)
2.8
7.7
5.3
China (schoolchildren in Guangdong)
-
-
1.9
Denmark*
-
-
7
Ethiopia*
15.4
9.1
13.3
France
-
-
6
Germany*
6.89
13.84
9.8
Hong Kong (Chinese)
7.2*
8
7.7*
5.4**
6.4**
5.8**
India (outpatient)
-
2.7
-
India*
-
16
-
Israel
-
-
5
Italy
0.7
3.3
1.8
Italy (Blacks)
-
-
1.4
Italy (athletes)
-
-
10
Japan (schoolchildren)
0.78
1.26
1
Japan**
1x***
4X***
7.5
Japan*
11
8
11
Korea
3.3
10
6.7
Libya*
-
-
16.9
Poland
-
-
4
Russia*
-
-
2.64
Russia (high altitude)*
-
-
1.7-10.9
Saudi Arabia*
7.4
12
-
Spain
1x***
2x***
4.3
South Africa
-
-
14.3
South Africa (Blacks)
-
-
17.9
Sweden*
7
8
7.4
Turkey*
-
-
7.6
USA
3
6.2-17
-
USA (Blacks)
9
24
17
USA (health survey)
-
15.4
-
USA (non-careseeking adolescents)
2.25
6.16
4.18
USA (children)*
31
38
35
Yugoslavia (schoolchildren)
1.9*
12.8*
7.8*
-
-
18.1
Modified from reference 2.
*Echocardiographic study; **Necropsy study; ***Expressed as a ratio.
MVP is the commonest cause of mitral regurgitation in the United States and other developed countries[3] [4] as well as in the developing countries such as China.[5] [6] One of the serious complications of mitral regurgitation is atrial fibrillation which usually persists even after successful corrective surgery of the mitral valve and often recurs after pharmacologic or electric cardioversion.[7] Although postoperative atrial fibrillation can be successfully managed by antiarrhythmic drugs and long-term anticoagulant therapy to prevent thromboembolism, these therapeutic modalities are not without side-effects, torsades de pointes and bleeding, respectively. However, it was gratifying that the adjunctive use of the Cox maze procedure reported recently from the Mayo clinic increased the restoration of sinus rhythm to 82% of their patients.[8]
MVP is also the commonest cause of infective endocarditis.[9][10][11] The microbial agents causing infective endocarditis on prolapsing mitral valve are similar to those that infect valves deformed by congenital or rheumatic processes.[12] Although streptococci viridans are the most common organisms, coagulase-negative staphylococcal endocarditis is not an infrequent occurrence in patients with MVP. Recognition of the occurrence of endocarditis due to coagulase-negative staphylococci in patients with MVP is important for several reasons. First, blood cultures positive for these organisms are frequently disregarded in patients without prosthetic heart valves or intravascular catheters. Second, the indolent course of some coagulase-negative staphylococcal endocarditis may delay consideration of the correct diagnosis, particularly in patients without congenital or rheumatic heart disease. Finally, even with effective antimicrobial therapy on the basis of in vitro studies, the clinical course may be prolonged and characterized by multiple responses to and relapses following drug withdrawal.
Thus it was most unfortunate that such an important valve disease as MVP was inadvertently omitted from discussion in this otherwise comprehensive review of the subject.[1]
Tsung O. Cheng, M.D.
Professor of Medicine Division of Cardiology
The George Washington University Medical Center 2150 Pennsylvania Avenue, N.W. Washington, DC 20037, USA
2. Cheng TO, Barlow JB: Mitral leaflet billowing and prolapse. Its prevalence around the world. Angiology 1989;40:77-87.
3. Cheng TO: Mitral valve prolapse: an overview. J Cardiol 1989;19 (Suppl 21):3-20.
4. Danielsen R, Nordrehaug JE, Vik-Mo H: High occurrence of mitral valve prolapse in cardiac catheterization patients with pure isolated mitral regurgitation. Acta Med Scand 1987;221:33-38.
5. Zhou LY, Hu RD: Floppy valve syndrome: a clinicopathological analysis of 16 cases. Chin J Intern Med 1986;25:149-151.
6. Cheng TO: Mitral valve prolapse. A review. Chin J Intern Med 1988;27:56-60, 126-129.
7. Cheng TO: Combined mitral valve repair and the Cox maze procedure for mitral valve prolapse and regurgitation and associated atrial fibrillation. J Thorac Cardiovasc Surg 2000;119:634.
8. Handa N, Schaff HV, Morris JJ, Anderson BJ, Kopecky SL, Enriquez-Sarano M: Outcome of valve repair and the Cox maze procedure for mitral regurgitation and associated atrial fibrillation. J Thorac Cardiovasc Surg 1999;118:628-635.
9. McKinsey DS, Ratts TE, Bisno AL: Underlying cardiac lesions in adults with infective endocarditis. The changing spectrum. Am J Med 1987;82:681-688.
10. Atkinson JB, Virmani R: Infective endocarditis: changing trends and general approach for examination. Hum Pathol 1987;18:603-608.
12. Barlow JB, Cheng TO: Mitral valve billowing and prolapse. In: Cheng TO: The International Textbook of Cardiology. New York: Pergamon Press, 1987:497-524.
Iemura et al's hypothesis that endothelial dysfunction is associated with coronary aneurysms which have regressed after Kawasaki disease (KD) is interesting[1]; however, there are two issues with respect to their study design that need to be considered, in addition to the issues reported before.[2, 3]
(1) Is endothelial dysfunction associated with regressed coronary aneurysms per se late after KD?
Iemura et al's hypothesis that endothelial dysfunction is associated with coronary aneurysms which have regressed after Kawasaki disease (KD) is interesting[1]; however, there are two issues with respect to their study design that need to be considered, in addition to the issues reported before.[2, 3]
(1) Is endothelial dysfunction associated with regressed coronary aneurysms per se late after KD?
Iemura et al showed that acetylcholine-induced vasodilatation is impaired in regressed coronary aneurysms (groups 1 and 2) but there is preserved vasodilatation in patients without coronary involvement during the acute illness of KD (group 3). This could be explained either by the direct effect of the regressed aneurysm or the difference among the study groups (groups 1 and 2 versus group 3). The Kawasaki vasculitis was severe enough to cause coronary aneurysms in some segments during the acute illness.
Although in Fig 1 Iemura et al showed that there is acetylcholine-induced vasoconstriction in the regressed aneurysm, readers might note that the rest of the segments in the right coronary artery without coronary lesions from the onset, including segments remote from the regressed aneurysms, also seem to constrict in response to acetylcholine. This might suggest that the regressed aneurysm per se does not impair endothelial function after KD.
Iemura et al did not present any data analysing the acetylcholine-elicited responses in normal segments from disease onset in groups 1 and 2; therefore the alternative hypothesis remains possible i.e. that coronary segments, regardless of their association with regressed aneurysms, constrict in response to acetylcholine in patients with a history of severe Kawasaki vasculitis. Consistent with this hypothesis, previous reports concluded that endothelial function is impaired in unaffected coronary segments and brachial arteries (usually uninvolved with aneurysms during the acute illness) in patients with severe acute Kawasaki vasculitis in the long term follow up period:
1.5-12.5 years (mean (SE) 6.5 (1.1)) after acute KD in Mitani et al[2]
5.3-17.1 years (median 11.3) after KD in Dhillon et al[4]
16-28 years old (mean 22) at the time of examination in Kamiya et al[5]
1-14 years old (median: 3.5) at the time of examination in Sano et al[6]
(2) Is endothelial function entirely preserved in KD patients without coronary involvement during the acute illness (group 3)?
This is an issue that we did not specifically address in our previous study.[2] Iemura et al showed that coronary arteries normally dilate in response to acetylcholine in patients without coronary lesions during the acute illness (group 3) on the basis of analysing multiple coronary segments.[1] However, in KD patients some coronary segments (ie, proximal segments) are characteristically more susceptible to severe abnormalities than others in terms of morphological, angiographic findings and vasomotor function.[2, 7, 8] Abnormal vasomotor function might be unmasked by specifically focusing on some "susceptible" segments in group 3, as we did in uninvolved proximal coronary segments in patients with coronary aneurysms in other segments.[2] An alternative hypothesis that some susceptible segments are associated with impaired acetylcholine-induced vasodilatation even in group 3 remains to be tested.
Iemura et al's conclusion might not be consistent with a previous report showing that endothelial function is impaired in KD patients without aneurysms in any segment during the acute illness.[4] This inconsistency remains to be addressed.
References
1. Iemura M, Ishii M, Sugimura T, et al. Long term consequences of regressed coronary aneurysms after Kawasaki disease: vascular wall morphology and function. Heart 2000;83:307-11.
2. Mitani Y, Okuda Y, Shimpo H, et al. Impaired endothelial function in epicardial coronary arteries after Kawasaki disease. Circulation 1997;96:454-61.
3. Mitani Y. Coronary endothelial dysfunction after Kawasaki disease. J Am Coll Cardiol 2000;35:821-3
4. Dhillon R, Clarkson P, Donald AE, et al. Endothelial dysfunction late after Kawasaki disease. Circulation 1996;94:2103-6.
5. Kamiya Y, Onouchi Z, Hamaoka K. Arteriosclerosis long after Kawasaki disease: endothelial function. Acta Cardiol Paediat Jpn 1997;13:252 (Japanese).
6. Sano T, Tagawa T, Itagaki Y, et al. Endothelial dysfunction after Kawasaki vasculitis. Jpn Circ J 1999;63:338 (Japanese).
7. Naoe S, Takahashi K, Masuda H, et al. Kawasaki disease: with the particular emphasis on arterial lesions. Acta Pathol Jpn 1991;41:785-97.
8. Kato H, Sugimura T, Akagi T, et al. Long-term consequences of Kawasaki disease: a 10-21 year follow-up study of 594 patients. Circulation 1996;94:1379-85
Kurbaan and Sutton provide a balanced view of the role of pacing in
vasovagal syncope[1] - a common but complex and challenging medical
condition.
However, we feel that attention should be drawn to the methodological
problems that bedevil interpretation of the North American Vasovagal
Pacemaker Study (VPS).[2] This was not a randomised study of cardiac
pacing, but rather a randomised trial...
Kurbaan and Sutton provide a balanced view of the role of pacing in
vasovagal syncope[1] - a common but complex and challenging medical
condition.
However, we feel that attention should be drawn to the methodological
problems that bedevil interpretation of the North American Vasovagal
Pacemaker Study (VPS).[2] This was not a randomised study of cardiac
pacing, but rather a randomised trial of pacemaker prescription and
implantation. The control group did not undergo an operation with
subsequent reprogramming to an "inactive" mode, and so did not receive the
attendant medical follow-up afforded the paced group.
Recent data from a trial examining the role of cardiac pacing in
hypertrophic cardiomyopathy have clearly demonstrated the profound placebo
effect of pacemaker implantation[3] on both symptoms and objective
echocardiographic evidence of outflow tract obstruction. These
improvements were apparent despite programming the pacemaker to an
inactive mode. There is no direct evidence from the North American study
that it was appropriate pacemaker therapy that was the cause of the
reduction in symptoms seen in the paced group. Patients were highly
selected and very symptomatic, with an imbalance in symptom burden between
the 2 arms that would favour pacing (median number of lifetime episodes 14
paced versus 35 non-paced). The only way to address these issues
satisfactorily would be by implanting systems in all patients, and blindly
randomising groups to "active" or "inactive" pacing.
For the present we agree that "there are limitations to the benefits
of pacing in vasovagal syncope", particularly in young patients whom would
be subject to a lifelong burden of cardiac pacing with its inevitable
complications. Several alternative approaches are available, and should
be tried first. Leaving aside pharmacological treatment,[4] simple
orthostatic training[5] has demonstrated a greater reduction in symptom
burden than that seen in the North American VPS. This technique is both
simple and proved to be extremely effective: over a median follow-up of 18
months, spontaneous syncope was seen in 0% versus 56% in the trained and
control group respectively.
Until further randomised data become available, pacemaker
implantation should be regarded as a last resort in vasovagal syncope.
Dr Adrian Morley-Davies
Senior Registrar, Department of Cardiology
Glasgow Royal Infirmary, Glasgow G31 2ER, UK
Dr J Byrne
Specialist Registrar in Cardiology, Department of Cardiology
Western Infirmary, Glasgow
References
1. Kurbaan AS, Sutton R. Pacing for vasovagal syncope. Heart 1999;
82:649-50.
2. Connolly SJ, Sheldon RS, Roberts R. The North American Vasovagal
Pacemaker Study: A randomised trial of permanent cardiac pacing for the
prevention of vasovagal syncope. JACC 1999; 33:16-20.
3. Linde C, Gadler F, Kappenberger L, Ryden L. Placebo effect of
pacemaker implantation in obstructive hypertrophic cardiomyopathy. Am J
Cardiol 1999; 83:903-7.
5. Di Girolamo E, Di Iorio C, Leonzio L, Sabatini P, Barsotti A.
Usefulness of a tilt-training program for the prevention of refractory
neurocardiogenic syncope in adolescents: a controlled study. Circulation
1999; 100:1798-801.
We share many of the reservations that Morley-Davies and Byrne have
regarding the North American Vasovagal Pacemaker Study (VPS).[1] However,
this study should be considered in the context of the other available data
supporting the role of pacing in selected patients. We also are
interested in the study by Di Girolamo et al[2] suggesting a benefit for
orthostatic training in those with neurocardio...
We share many of the reservations that Morley-Davies and Byrne have
regarding the North American Vasovagal Pacemaker Study (VPS).[1] However,
this study should be considered in the context of the other available data
supporting the role of pacing in selected patients. We also are
interested in the study by Di Girolamo et al[2] suggesting a benefit for
orthostatic training in those with neurocardiogenic (vasovagal) syncope.
However, they do not classify the tilt test induced haemodynamic responses
seen in their population. In those with vasovagal syncope the different
haemodynamic collapse patterns seen on tilt testing[3] may have a very
useful role in identifying not only those who may benefit from pacing but
also those in whom pacing may be inappropriate even as a 'last resort'.
The consensus is that pacing is of the greatest benefit in those with a
predominantly bradycardiac (cardioinhibitory) response on tilt testing.
Furthermore, the population in Di Girolamo et al's study[2] is not
comparable to that in VPS and most other studies of pacing in vasovagal
syncope. The former's population were all adolescents (mean age 16
years), whereas much older patients were recruited into VPS (mean age 43
years). Our experience suggests that many adolescents will over time
'grow out of' their fainting episodes. Hence, in the majority of cases
our advice to this group is simply reassurance.
Since the beginning of 1997 we have run a prospective register of the
all tilt tests that we have undertaken including the management suggested.
Up until December 1999 over 600 patients had been tilted. Of these 186
were under 35 years of age. Only 5 (2.7%) of these young patients have
been paced. In each cases multiple non-pacing strategies (though not
orthostatic training) were attempted prior to offering pacing.
In selected patients with vasovagal syncope pacing offers excellent
symptomatic relief, enabling a return to normal life.
Dr A S Kurbaan
Department of Cardiology, London Chest Hospital,
London E2 9SX, UK
Dr R Sutton
Department of Cardiology, Royal Brompton Hospital,
London SW3 6NP, UK
References
1. Connolly SJ, Sheldon R, Roberts RS, Gent M on behalf of the
Vasovagal Pacemaker Study investigators. The North American Vasovagal
Pacemaker Study (VPS). A randomised trial of permanent cardiac pacing for
the prevention of vasovagal syncope. J Am Coll Cardiol 1999;33:16-20.
2. Di Girolamo E, Di Iorio C, Leonzio L, Sabatini P, Barsotti A.
Usefulness of a tilt training program for the prevention of refractory
neurocardiogenic syncope in adolescents: a controlled study. Circulation
1999;100:1798-1801
3. Kurbaan AS, Franzén A-C, Bowker TJ, Williams TR, Kaddoura S,
Petersen MEV, Sutton R. Usefulness of tilt test induced patterns of heart
rate and blood pressure using a two stage protocol with glyceryl
trinitrate provocation in patients with syncope of unknown origin. Am J
Cardiol 1999;84:695-670.
We thank Dr. Pocar and his colleagues for contributing their
experience with another case of cardiocutaneous fistula [1], which
confirms several points that we and others have previously discussed [2]
[3] [4]. The clinical presentation of cardiocutaneous fistula is usually
slow and indolent but may rapidly deteriorate. Therefore, when this
diagnosis is established elective operation should be perfo...
We thank Dr. Pocar and his colleagues for contributing their
experience with another case of cardiocutaneous fistula [1], which
confirms several points that we and others have previously discussed [2]
[3] [4]. The clinical presentation of cardiocutaneous fistula is usually
slow and indolent but may rapidly deteriorate. Therefore, when this
diagnosis is established elective operation should be performed without
undue delay, to excise the fistulous tract and remove the infected foreign
bodies. With medical therapy alone the infection cannot be eradicated. The
natural progression of the disease may lead to catastrophic hemorrhage and
grim outcome, as occurred in the case illustrated by Pocar M, et al. [1]
and previous reports [3]. Meticulous surgical technique should always be
employed during left ventricular aneurysm repair to prevent this rare but
serious complication.
Peter G. Danias, MD, PhD
Cardiology Division, Department of Medicine
Beth Israel Deaconess Medical Center and Harvard Medical School
330 Brookline Avenue, Boston, Massachusetts 02215, USA
Dr. Danias is partially supported by the Clinical Investigator Training
Program: BIDMC - Harvard/MIT Health Sciences and Technology - Pfizer Inc.
References
1. Pocar M, Donatelli F, Grossi, A. Cardiocutaneous fistula following
left ventricular aneurysmectomy. Heart Rapid Response, 17 May 2000.
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...
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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
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...Dear Editor
Kurbaan and Sutton provide a balanced view of the role of pacing in vasovagal syncope[1] - a common but complex and challenging medical condition.
However, we feel that attention should be drawn to the methodological problems that bedevil interpretation of the North American Vasovagal Pacemaker Study (VPS).[2] This was not a randomised study of cardiac pacing, but rather a randomised trial...
Dear Editor,
We share many of the reservations that Morley-Davies and Byrne have regarding the North American Vasovagal Pacemaker Study (VPS).[1] However, this study should be considered in the context of the other available data supporting the role of pacing in selected patients. We also are interested in the study by Di Girolamo et al[2] suggesting a benefit for orthostatic training in those with neurocardio...
Dear Editor,
We thank Dr. Pocar and his colleagues for contributing their experience with another case of cardiocutaneous fistula [1], which confirms several points that we and others have previously discussed [2] [3] [4]. The clinical presentation of cardiocutaneous fistula is usually slow and indolent but may rapidly deteriorate. Therefore, when this diagnosis is established elective operation should be perfo...
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