1254
The research in our laboratory was partly supported by grant GM23200
from the National Institutes of Health. J. M. R. is a recipient of an
International Fellowship from the Fogarty International Center, National
Institutes of Health.
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1. KerrJF, Wyllie AH, Currie AR. Apoptosis: a basic biological
phenomenon with wide-ranging implications in tissue kinetics. Br J
Cancer 1972; 26: 239-57.
2. Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated
with endogenous endonuclease activation. Nature 1980; 284: 555-56.
3. Golstein P, Ojcius DM, Young JD. Cell death mechanisms and the
immune system. Immunol Rev 1991; 121: 29-65.
4. Cohen JJ, Duke RC, Fadok VA, Sellins KS. Apoptosis and programmed
cell death in immunity. Annu Rev Immunol 1992; 10: 267-93.
5. Orrenius S, McConkey DJ, Bellomo G, Nicotera P. Role of CA2+ in
toxic cell killing. Trends Pharmacol Sci 1989; 10: 281-85.
6. Arends MJ, Morris RG, Wyllie AH. Apoptosis: the role of the
endonuclease. Am J Pathol 1990; 136: 593-608.
7. Knight CR, Rees RC, Griffin M. Apoptosis: a potential role for cytosolic
transglutaminase and its importance in tumour progression. Biochim
Biophys Acta 1991; 1096: 312-18.
8. Brach MA, de Vos S, Gruss HJ, Hermann F. Prolongation of survival of
human polymorphonuclear neutrophils by granulocyte-macrophage
colony-stimulating factor is caused by inhibition of programmed cell
death. Blood 1992; 80: 2920-24.
9. Oren M. The involvement of oncogenes and tumor suppressor genes in
the control of apoptosis. Cancer Metastasis Rev 1990; 11: 141-48.
10. Evan GI, Wyllie AH, Gilbert CS, et al. Induction of apoptosis in
fibroblasts by c-myc proteins. Cell 1992; 69: 119-28.
11. Korsmeyer SJ. Bcl-2: an antidote to programmed cell death. Cancer
Surveys 1992; 15: 105-18.
12. Finke J, Firtzen R, Ternes P, et al. Expression of bcl-2 in Burkitt’s
lymphoma cell lines: induction by latent Eptein-Barr virus genes. Blood
1992; 80: 459-69.
13. Bissonette RP, Echeverri F, Mahboubi A, Green DR. Apoptotic cell
death induced by c-myc is inhibited by bcl-2. Nature 1992; 359:552-54.
14. McDonnel TJ, Korsmeyer SJ. Progression from lymphoid hyperplasia to
high grade lymphoma in mice transgenic for the t(14;18). Nature 1991;
349: 254-56.
15. Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene.
Nature 1991; 351: 453-56.
16. Yonish-Rouach E, Resnitsky D, Lotem J, Sachs L, Kimchi A, Oren M.
Wild type p53 induces apoptosis of myeloid leukaemia cells that is
inhibited by interleukin-6. Nature 1991; 353: 345-47.
ARRHYTHMIA OCTET
Investigation of palpitations
The uncomfortable of a beating heart-
awareness
palpitations-is a commoncomplaint that can occur under
normal or abnormal circumstances. For example, normal
palpitations occur with exercise, emotions, and stress, or
after taking substances that increase adrenergic tone or
diminish vagal activity (coffee, nicotine, and adrenergic or
anticholinergic drugs). Normal palpitations are recognised
as such because individuals who experience them realise or
are told that something happened to accelerate the normal
rhythm of the heart. However, some people find sinus
tachycardia troublesome enough to seek medical attention.
In other situations palpitations are clearly abnormal. The
heart beat, which is felt for no apparent reason, may be fast,
or strong and slow, or feel like a missed or extra beat.
Although these abnormal palpitations usually point to a
cardiac arrhythmia, this is not always the case. Moreover,
many patients with arrhythmias do not have palpitations but
manifestations such as syncope, shock, and chest pain
(sudden death is also possible). We will discuss the approach
to the patient who seeks medical attention because of a
17. Hickman JA. Apoptosis induced by anticancer drugs. Cancer Metastasis
Rev 1992; 11: 121-39.
18. Beutler E. Cladribine (2-chlorodeoxyadenosine). Lancet 1992; 340:
952-56.
19. Carrera CJ, Piro LD, Saven A, Beutler E, Terai C, Carson DA.
2-chlorodeoxyadenosine chemotherapy triggers programmed cell
death in normal and malignant lymphocytes. Adv Exp Med Biol 1991;
309A: 15-18.
20. Pantaleo G, Graziosi C, Fauci AS. The immunopathogenesis of human
immunodeficiency virus infection. N Engl J Med 1993; 328: 327-35.
21. Groux H, Torpier G, Monté D, Mouton Y, Capron A, Ameisen JC.
Activation-induced death by apoptosis in CD4+ T cells from human
immunodeficiency virus-infected asymptomatic individuals. J Exp
Med 1992; 175: 331-40.
22. Terai C, Kornbluth RS, Pauza CD, Richman DD, Carson DA.
Apoptosis as a mechanism of cell death in cultured T lymphoblasts
acutely infected with HIV-1. J Clin Invest 1991; 87: 1710-14.
23. Banda NK, Bernier J, Kurahara DK, et al. Crosslinking CD4 by human
immunodeficiency virus gp120 primes T cells for activation induced
apoptosis. J Exp Med 1992; 38: 252-56.
24. Watanabe-Fukunaga R, Brannon CI, Copeland NG, Jenkins NA,
Nagata S. Lymphoproliferation disorder in mice explained by defects
in Fas antigen that mediates apoptosis. Nature 1992; 356: 314-17.
25. Cohen PL, Eisenberg RA. The lpr and gld genes in systemic
autoimmunity: life and death in the Fas lane. Immunol Today 1992; 13:
427-28.
26. Graninger WB. Transcriptional overexpression of the proto-oncogene
bcl-2 in patients with systemic lupus erythematosus. Wien Klin
Wochenscher 1992; 104: 205-07.
27. Strasser A, Whittingham S, Vaux DL, et al. Enforced BCL2 expression
in B-lymphoid cells prolongs antibody responses and elicits
autoimmune disease. Proc Natl Acad Sci USA 1991; 88: 8661-65.
28. Martin DP, Ito A, Horigome K, Lampe PA, Johnson EM Jr.
Biochemical characterization of programmed cell death in NGF-
deprived sympathetic neurons. J Neurobiol 1992; 23: 1205-20.
29. Garcia I, Martinou I, Tsujimoto Y, Martinou JC. Prevention of
programmed cell death of sympathetic neurons by the bcl-2 proto-
oncogene. Science 1992; 258: 302-04.
30. Mattson MP, Cheng B, Davis D, Bryant K, Leibenburg I, Rydel RE.
Beta-amyloid peptides destabilize calcium homeostasis and render
human cortical neurons vulnerable to excitotoxicity. J Neuroscience
1992; 12: 376-89.
31. Rosenberg MB, Friedmann T, Robertson RC, et al. Grafting genetically
modified cells to the damaged brain: restorative effects of NGF
expression. Science 1988; 242: 1575-78.
history of palpitations, with special emphasis on the history,
physical examination, and 12-lead electrocardiogram
(ECG) because they are simple and inexpensive diagnostic
tools that are available to most physicians.
History
Although the physical examination and ECG will provide
important diagnostic information, most patients are initially
seen by physicians after the palpitations have ceased
spontaneously. Consequently the history becomes the most
important diagnostic weapon in such cases. These points are
ADDRESSES: Cardiovascular Centre, OLV Hospital, Aalst,
Belgium (Pedro Brugada, MD, Erik Andries, MD); Bayindir Medical
Centre, Ankara, Turkey (Sinan Gürsoy, MD); and Arrhythmia Unit,
Department of Cardiology, Hospital Clínic, University of
Barcelona, Spain (Josep Brugada, MD). Correspondence to Prof Pedro
Brugada, Cardiovascular Centre, OLV Hospital, Moorselbaan 164, 9300
Aalst, Belgium.

TABLE I-DIAGNOSIS OF GENERAL PRACTITIONER IN 223
CONSECUTIVE PATIENTS WITH PROVEN PAROXYSMAL
REGULAR TACHYCARDIA BUT NO HISTORY OF SYNCOPE OR
CARDIAC ARREST
clearly illustrated by the data shown in table I on general
practitioners’ initial diagnoses in 223 patients with proven
abnormal tachycardias. When the patient was seen during
an episode a cardiac arrhythmia was readily diagnosed. By
contrast, at other times the diagnosis was seldom suspected.
None of these patients had a history of cardiac arrest or
syncope; their main complaint was paroxysmal palpitations.
The elements summarised in table 11 are an essential part
of the history in patients with paroxysmal palpitations.
Nevertheless, the diagnostic value of some of these elements
is questionable or has, in our opinion, been overemphasised.
TABLE II-ELEMENTS IN HISTORY OF PATIENT WITH
COMPLAINTS OF PAROXYSMAL PALPITATIONS
For example, medical students are commonly taught that
polyuria follows an episode of supraventricular tachycardia
(SVT).2 However, less than 5% of our patients with
documented paroxysmal SVT, and none of those with
permanent, incessant SVT, have such a history.
Characteristics of palpitations
Patients with paroxysmal palpitations may describe them
as rapid or slow, regular or irregular (table III). Rapid
irregular palpitations suggest atrial fibrillation with its
typical irregular and fast ventricular rate, but can be a
manifestation of atrial tachycardia or flutter with a variable
degree of atrioventricular conduction. They may also be
provoked by multiple premature beats. Rapid regular
palpitations occur during supraventricular or ventricular
tachycardia with a regular rate. With palpitations of this
nature it is important to ask some additional questions. We
have found it very helpful to know whether the patient feels
the palpitations only in the chest or also in the neck, since we
have shown3that patients with neck palpitations are most
likely to have atrioventricular nodal re-entrant tachycardia.
Patients with SVT with an accessory pathway do not
TABLE III-SUSPECTED DIAGNOSIS BASED ON THE
CHARACTERISTICS OF PALPITATIONS
1255
experience neck palpitations. The underlying reason is that,
during atrioventricular nodal re-entrant tachycardia, atria
and ventricles contract simultaneously, causing pronounced
reflux of blood into the superior vena cava and the feeling of
neck palpitations. Because the patient may look like a frog
under these circumstances we call them "frog positive". The
longer interval between ventricular and atrial contraction
(RP interval) during tachycardia with an accessory
atrioventricular pathway results in less or no reflux in the
superior vena cava, so the patient does not experience neck
palpitations-"frog negative". Thus, a frog-positive patient
immediately raises the suspicion of atrioventricular nodal
tachycardia.
Patients with ventricular tachycardia (VT) sometimes
have slow irregular neck palpitations and regular rapid chest
palpitations. This combination comes about because
atrioventricular dissociation during tachycardia, with the
sinus rhythm causing contraction of the atria against a closed
atrioventricular valve.
TABLE IV-FREQUENCY OF PALPITATIONS DURING
VENTRICULAR TACHYCARDIA IN PATIENTS WITHOUTSYNCOPE
OR CARDIAC ARREST ACCORDING TO AETIOLOGY OF
ARRHYTHMIA
Palpitations are not always present in patients with VT;
the mechanical performance of the heart (left ventricular
function) must be sufficiently good to produce them. Table
Iv gives data on the frequency of palpitations in 197 patients
with sustained VT of various aetiologies. Palpitations
occurred in all those with VT and a normal heart (idiopathic
VT) and in patients with VT caused by right ventricular
dysplasia, a disease that affects the right ventricle but does
not usually damage left ventricular function.4 By contrast,
only 6% of 97 patients with sustained, non-syncopal VT
caused by an old myocardial infarction (a disease that
profoundly affects left ventricular function) complained of
palpitations during the arrhythmia. Of 36 consecutive
patients with ventricular fibrillation late after myocardial
infarction, none had the feeling of rapid heart action before
the cardiac arrest. The first symptom was loss of
consciousness in all cases. Thus, as previously mentioned,
the absence of palpitations does not exclude a cardiac
arrhythmia as the cause of certain symptoms such as
syncope. Very severe arrhythmias, because they usually
occur in very diseased hearts, will not cause palpitations.
Mode of onset of palpitations
An abrupt onset of palpitations suggests paroxysmal
abnormal tachycardia, although palpitations caused by sinus
tachycardia during anxiety likewise start abruptly.s By
contrast, paroxysmal SVT or VT may be preceded by a
progressive onset of palpitations if they start during exercise.
Thus, although an abrupt onset is regarded as typical for a
cardiac arrhythmia, there are many exceptions.
Mode of termination of palpitations
As with the onset of palpitations, an abrupt termination
suggests an abnormal cause but likewise there are many
exceptions. A high adrenergic tone caused by the arrhythmia
1256
often results in sinus tachycardia immediately after
termination of a sustained tachycardia, especially when the
tachycardia was very fast or lasted for a long time. The sinus
tachycardia may make it impossible for the patient to
perceive the end of tachycardia as "abrupt". Conversely,
sinus tachycardia can terminate abruptly, particularly in
well-trained athletes with high vagal tone.
Initiating factors
Most patients with paroxysmal cardiac arrhythmias are
unable to recognise a unique precipitating factor. Occasional
patients seem to experience their arrhythmias more
frequently during exercise or emotions (suggesting a role of
the adrenergic system) or at rest or after exercise (suggesting
a role of the vagus). Separate adrenergic and vagal induced
arrhythmias may exist,6but most patients seem to fall in a
"mixed" category. This is important, because some
researchers have suggested that adrenergic-induced
arrhythmias should be treated with beta-blockers whereas
vagal-induced arrhythmias should be treated with drugs
such as disopyramide that have vagolytic effects. We have
not been impressed with the results of treatment according
to this approach. Rather, we find that patients with
vagal-induced arrhythmias do not necessarily respond to
vagolytic agents, and likewise those with adrenergic-
dependent arrhythmias do not always improve with beta-
blockers.
Recognition of initiating factors may have been important
in the past when curative therapies were not available and
when the only means of preventing recurrence was to advise
patients to avoid coffee, alcohol, tobacco, exercise, or any
form of stress. Although the benefit of these measures has
never been proven, clinicians should try and determine
whether there are any precipitating factors since this
knowledge will sometimes have therapeutic relevance.
Associated symptoms
Palpitations are neither the only nor the unique symptom
caused by cardiac arrhythmias. As mentioned above,
palpitations may be totally absent during the most severe
cardiac arrhythmias, and, conversely, may be caused by a
sinus tachycardia devoid of any pathological significance.
Symptoms associated with palpitations vary enormously
and there is a very important subjective factor in their origin.
Chest pain, anxiety, fear, and dizziness are commonly
experienced at the onset and termination of tachycardias.
They have no further relevance with the exception of true
syncope. Syncope in patients with ventricular arrhythmias
carries a bad prognosis.7 A patient with syncope during VT
has very fast VT, very bad left ventricular function, or both.8
In patients with syncopal VT and a normal heart (idiopathic
VT), syncope is exclusively related to a fast heart rate.
Treatment with antiarrhythmic drugs slows the rate of VT
sufficiently to prevent the syncope, even when the VT
recurs.9 By contrast, syncope during VT in patients with an
abnormal heart may be caused by a fast or a slow VT in a
heart with poor mechanical performance.8 Antiarrhythmic
drugs often fail to slow down the VT sufficiently in these
cases to prevent further syncopal episodes and sudden
death. Antiarrhythmic agents may also adversely affect left
ventricular function. Recurrence of VT during
antiarrhythmic drug treatment, even when the rate is slower
than before treatment, may not only cause another syncopal
episode but also sudden death. Patients with syncopal SVT
resemble those with syncopal VT and a normal heart.
Syncope caused by SVT is usually a manifestation of a very
fast heart rate (eg, during atrial fibrillation with rapid
ventricular rates because of anterograde conduction over an
accessory pathway) and not of poor left ventricular
function In these patients, antiarrhythmic drugs can fully
control the syncopal episodes despite recurrences of the
arrhythmia. Of course, curative approaches like
radiofrequency ablationll are preferred to palliative
treatment with antiarrhythmic drugs.
Frequency of episodes and effects on quality of life
The more frequently a cardiac arrhythmia occurs, the
more likely it is to have an impact on quality of life and
health. Moreover, quality of life will also be affected by the
severity of the symptoms. Patients with SVT causing
palpitations that last for only a few seconds may not regard
that as a problem if the arrhythmia always stops
spontaneously, even when they have very frequent episodes,
whereas less frequent episodes of SVT lasting for hours may
be far more troublesome.
The impact of an arrhythmia on quality of life influences
therapeutic decisions. We classify our patients in four
categories depending on their symptoms. Category I
patients have a completely symptomless cardiac arrhythmia
or an arrhythmia substrate (accessory pathway) that poses
no danger in terms of producing syncope or sudden death or
heart dilation in the long term ("tachycardiomyopathy").
Category II patients are likewise symptom free, but they
have an arrhythmia or an arrhythmia substrate that can
potentially lead to syncope or sudden death, or to a
tachycardiomyopathy. Category III patients are
symptomatic because of palpitations, fear, anxiety, or other
symptoms caused by the arrhythmia, but do not have
syncope, aborted sudden death, or heart dilation caused by
the arrhythmia. Category IV patients are those who have
syncope or aborted sudden death because of the arrhythmia,
or have heart dilation caused by it (tachycardiomyopathy).
Category I patients may not need any treatment or, in case of
social or employment difficulties, the risks of therapy must
be carefully weighed against the possible benefits. Category
IV patients require immediate diagnosis and treatment.
Category II and III patients fall between these extremes.
Effects of previous treatments
Understanding the effects of previous therapy is
important for selection of a new treatment. There is little
point in trying another beta-blocker in a patient in whom
beta-blockers have previously been unsuccessful.
Moreover, the more drugs that have previously been found
unhelpful, the more difficult it becomes to find an effective
agent; in such patients other forms of treatment should be
considered straight away.
The history contains many elements that may point to a
particular diagnosis in a patient with paroxysmal
palpitations. A frog-positive patient with rapid regular
palpitations is likely to have atrioventricular nodal re-
entrant tachycardia. A frog-negative patient with irregular
rapid palpitations usually has paroxysmal atrial fibrillation.
In a frog-negative patient with regular rapid palpitations the
first thought should be circus movement tachycardia via an
accessory pathway or VT. An abrupt onset and offset of the
complaints suggests a cardiac arrhythmia, but this history is
not entirely specific nor sensitive. As mentioned above, the
most severe arrhythmias do not produce palpitations
because the heart is too sick to palpitate; they usually result

in abrupt loss of consciousness and sudden cardiac death or
undefined symptoms.
Physical examination
The findings on physical examination will differ
considerably depending on whether the patient is examined
during or after the arrhythmia episode, and on whether the
patient has structural heart disease.
Physical examination during tachycardia
Different types of cardiac arrhythmias affect not only the
heart rate but also the relation and timing of atrial and
ventricular contraction. These changes result in
recognisable physical signs that may suggest a certain
arrhythmia. The possible findings related to blood pressure,
heart sounds, and arterial and jugular venous pulsations are
summarised in table v. The ability to recognise these signs
depends on the experience and persistence of the
investigator.
Physical examination after an episode of tachycardia
In most patients with SVT who are examined outside an
episode of tachycardia there will be no abnormal findings.
Patients with atrial flutter or atrial fibrillation caused by
heart disease are an exception. During sinus rhythm the
findings will be those of the underlying disease in such
cases-eg, the typical diastolic murmur, opening snap, and
loud first heart sound of mitral stenosis. A normal physical
examination during sinus rhythm (or when the patient does
not have any complaints) does not exclude a cardiac
arrhythmia.
12-lead ECG
The 12-lead ECG helps to distinguish supraventricular
from ventricular tachycardias ’12--14 and to diagnose the type
of SVT during the arrhythmia.1s
Regular tachycardia with QRS complex
narrow
When the P wave follows the QRS complex after 140 ms,
the most likely diagnosis is circus movement tachycardia in a
retrograde direction via an accessory pathway of the Kent
type. When the P wave is in the QRS complex or absent, the
most likely diagnosis is atrioventricular nodal re-entrant
tachycardia. When the P wave follows the QRS complex
after 200 ms or more, the diagnosis is tachycardia caused by
an accessory pathway of the slow type16 or atrial
tachycardiaP A tachycardia with a ventricular rate of 150
beats/min suggests atrial flutter with 2:1 atrioventricular
conduction.
Regular tachycardia with wide QRS complex
Regular tachycardia with a wide QRS complex may be an
SVT conducted to the ventricles over the normal
atrioventricular conduction system but with
intraventricular aberrant conduction (right or left bundle
branch block) or may be a VT. The standard criteria for this
differentiation have poor sensitivity and specificity. We
lately reported simple criteria13 based on the duration of the
intrinsicoid deflection (RS interval) in the precordial leads.
We found that when a QRS complex with an RS
morphology cannot be identified in the precordial leads VI1
to V6, the diagnosis is always VT. We also found that when
one or more RS complexes can be recognised in the
precordial leads, if the interval from the beginning of the R
1257
TABLE V-PHYSICAL FINDINGS DURING SUSTAINED
TACHYCARDIAS
wave to the deepest part of the S wave is more than 100 ms,
the
diagnosis is likewise VT in virtually all cases. Other
diagnostic criteria are the presence of more QRS complexes
than P waves during tachycardia (100 % specific for VT) and
morphological criteria in the precordial leads VIand V6.14
Irregular tachycardia with narrow or wide QRS complex
An irregular tachycardia (ventricular rate fast but
changing continuously) may be caused by any SVT that is
conducted to the ventricles in a variable way, or by a VT
with an irregular rate. Only a few SVTs can be conducted
irregularly to the ventricles-atrial tachycardia, atrial
flutter, and most commonly, atrial fibrillation. When the
QRS complex is narrow, SVT is readily diagnosed. When
the QRS complex is wide, the same criteria as previously
discussed13 can be used to make the differential diagnosis
between SVT with aberrant conduction and VT.
Atrioventricular nodel re-entrant tachycardia may
occasionally be conducted irregularly to the ventricles.
Circus movement tachycardia via an accessory
atrioventricular pathway in a retrograde (orthodromic
tachycardia) or anterograde (antidromic tachycardia)
direction requires a 1:1 relation between atrial and
ventricular events and is virtually never irregular.
ECG during sinus rhythm
It is not always possible to record a full 12-lead ECG
during the palpitations. The history may be enough to
diagnose the type of arrhythmia without an ECG.3,18 In a
patient with complaints that suggest a cardiac arrhythmia
and a history of heart disease, regular palpitations are most
likely to be caused by VT, whereas irregular palpitations are
probably due to atrial fibrillation. In a patient without a
history of heart disease, regular palpitations may be caused
by any SVT except atrial fibrillation.
The ECG outside an episode of tachycardia may also offer
important information. In a patient with ventricular pre-
excitation during sinus rhythm the most likely cause of
paroxysmal palpitations is circus movement tachycardia via
the accessory pathway for retrograde conduction from
ventricles to atria. Irregular, rapid palpitations are usually
caused by trial fibrillation with anterograde conduction over
the accessory pathway. However, a normal ECG outside the
tachycardia episodes does not exclude an arrhythmia. The
patient may have VT (idiopathic) or SVT (intranodal
tachycardia, or a tachycardia via a retrograde accessory
pathway not capable of anterograde conduction-so-called
concealed accessory pathway).
After the arrhythmia has been suspected or
documented
Once a cardiac arrhythmia has been suspected by means
of history or documented with an ECG or physical
examination during an episode of tachycardia, what are the
1258
next steps? Many cardiac arrhythmias can now be treated
directly with radiofrequency ablation," so the decision to
refer the patient for an electrophysiological investigation
and, eventually, ablation should not be unnecessarily
delayed. However, some investigations may be worthwhile.
Ambulatory ECG monitoring is useful in patients with
frequent complaints but of almost no value in those with
very sporadic episodes.19 Ambulatory recordings can also be
used to reassure patients whose complaints are not caused by
an arrhythmia if these complaints occur during the
recording and are shown to be unrelated.
Transtelephonic monitoring of cardiac rhythm and event
recordings permit ECG recording at the time of an event.
Consequently, they are preferable to ambulatory
monitoring for follow-up. However, event recorders have
obvious drawbacks, the most important being the inability
to ascertain the type of arrhythmia from a transtelephonic
recording. We believe that electrophysiologial investigations
are the fastest way to confirm a diagnosis, and because of the
therapeutic possibilities (ablation) they may be the most
cost-effective way to assess a cardiac arrhythmia.
We thank Mrs Marline van Royen for her help.
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PUBLIC HEALTH
Misoprostol and illegal abortion
Brazil
We report on the determinants and consequences
of induced abortion among 803 women admitted to
hospital with abortion complications in Rio de
Janeiro, Brazil, in 1991.458 (57%) women reported
using misoprostol to induce abortion, 74% in the first
4 months of pregnancy. Doses of 200-16 800 µg
were reported, with a median of 800 µg. 65% of the
women took the drug orally, 29% used a
combination of oral and vaginal routes, and 6%
administered it intravaginally. Vaginal bleeding and
uterine cramps were the commonest reasons for
seeking hospital care. Only 8% of women reported
gastrointestinal side-effects. Misoprostol induced
vaginal bleeding within 12 h of administration in
52% of the women, but 16% waited 10 days or more
for onset of bleeding. 4% were admitted to hospital
with complete abortion. The likelihood of bleeding
starting within 12 h increased with duration of
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tachycardia: clinical course and long-term follow-up in patients
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16. Brugada P, B&auml;r FWHM, Vanagt EJ, Friedman PL, Wellens HJJ.
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in Rio de Janeiro,
gestation and it was greater when the drug was used
both orally and intravaginally. A significantly smaller
proportion of women taking misoprostol than of
those who induced abortion by catheter insertion
presented signs of infection or physical injuries or
required blood transfusion (<0&middot;0005). Among 803
women interviewed at delivery as controls, 6% had
taken misoprostol but abortion had not ensued.
Misoprostol has an important role as an abortifacient
among the women studied.
ADDRESSES: Department of Epidemiology and Quantitative
Methods, National School of Public Health Oswaldo Cruz
Foundation, Rio de Janeiro, Brazil (S. H. Costa, MSc) and
Department of Public Health and Primary Care, University of
Oxford, UK (Prof M. P. Vessey, MD, FRS). Correspondence to Ms Sarah
H. Costa, Department of Public Health and Primary Care, Gibson Building,
Radcliffe Infirmary, Oxford OX2 6HE, UK.