1. health and fitness
2. disease

European Heart Journal (2004) 25, 1310–1317
Clinical research
Heart rate is a predictor of success in the
treatment of adults with symptomatic
paroxysmal supraventricular tachycardia
, Sergio Antonio Faraguti
Piercarlo Ballo*, Daniele Bernabo
Received 24 July 2003; revised 21 April 2004; accepted 13 May 2004
Available online 20 July 2004
See page 1277 for the editorial comment on this articley
KEYWORDS
Aims To analyse whether heart rate may affect the efficacy of adenosine, verapamil
and carotid sinus massage in terminating symptomatic episodes of paroxysmal
supraventricular tachycardia (PSVT) in adults.
Methods and results The study population was selected among 175 adult patients,
affected by symptomatic PSVT. One hundred and six of them were considered eligible for
the study. Each subject received one of the following treatments: verapamil, 5 mg
intravenously (IV) in 5–10 min, followed by 1–5 lg/kg/min; adenosine, 6 mg IV, followed
by 12 mg IV after 2–3 min; carotid sinus massage. Adenosine and verapamil were
similarly effective in terminating PSVT (74.4% vs 81.8%, P ¼ 0:45). The efficacy of
carotid sinus massage was significantly lower in comparison with the other two groups
(32.4%, P ¼ 0:00032 vs adenosine and P ¼ 0:000044 vs verapamil group). At logistic
regression, PSVT rate showed a positive association with the percentage of sinus rhythm
restoration in the group who received adenosine (P ¼ 0:0004). The probability of success
in resolving the tachycardia following treatment with adenosine was >75% for heart
rates over 166 beats per minute (bpm), but rapidly decreased at lower frequencies,
reducing to 25% at 138 bpm. In the verapamil group, PSVT rate was negatively related to
the percentage of sinus rhythm restoration (P ¼ 0:018). The probability of success in
terminating PSVT following administration of verapamil was >75% for heart rates lower
than 186 bpm, but tended to decrease at faster rates, reducing to 25% at 241 bpm. No
significant effects of heart rate were observed in the carotid sinus massage group
(P ¼ 0:17). The probability curves obtained in the adenosine and verapamil group
crossed at a point corresponding to 173 bpm, which may represent a cut-off value to
predict which treatment could ensure higher rate of success.
Conclusions Heart rate predicts restoration of sinus rhythm in adult subjects with
symptomatic episodes of PSVT treated with adenosine and verapamil. Adenosine is
highly effective in PSVT characterised by fast rates, whereas the efficacy of verapamil is
increased in patients with low-frequency PSVT.
c 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights
reserved.
Adenosine;
Verapamil;
Vagal manoeuvres;
Heart rate;
Supraventricular tachycardia
Introduction
* Corresponding author. Tel.: þ39-0187-53255/299; fax: þ39-0187533456.
E-mail address: pcballo@tin.it (P. Ballo).
y
doi:10.1016/j.ehj.2004.07.003.
Paroxysmal supraventricular tachycardia (PSVT) is a
common arrhythmia which may be associated to a variety
of electrophysiological abnormalities, including increased
0195-668X/$ - see front matter c 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ehj.2004.05.011
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
Department of Cardiology, S. Andrea Hospital, La Spezia, Italy
Heart rate is a predictor of success in the treatment of adults with symptomatic paroxysmal supraventricular tachycardia
Methods
Patient selection
Male or female adult subjects, affected by symptomatic PSVT,
seen at our Department between 11 September, 2000 and 5 February, 2004 were retrospectively enrolled for this study. Patients
were considered eligible for the study if they had (1) age P 16
years, (2) sudden onset of symptoms due to the tachycardia
(subjective awareness of palpitations or rhythm irregularity or
arrhythmia-related dizziness, chest discomfort, dyspnoea, asthenia, anxiety) and (3) electrocardiographic evidence of PSVT.
Exclusion criteria were: haemodynamic instability (which was
considered an indication for immediate electrical cardioversion),
bradycardia <50 beats per minute (bpm); high-grade sinoatrial or
AV block, history of sick sinus syndrome or sinus node dysfunction,
heart failure (New York Heart Association class III or IV), asthma,
previous implantation of pacemaker or defibrillator, use of antiarrhythmics or rate-limiting drugs within the previous 15 days,
contraindications to carotid sinus massage (carotid bruit, history
of previous adverse reaction to carotid sinus massage or cerebrovascular accidents in the last three months), hypersensitivity,
intolerance or contraindications to verapamil or adenosine.
Clinical examination and ECG
All patients underwent an accurate clinical examination and a
brief and targeted history. Systemic arterial pressure was determined using standard methods, with a cuff sphygmomanometer, after 3 min of supine position. Measurements were repeated
every 3 min throughout the entire procedure. A 12-lead ECG was
registered in each subject and electrocardiographic monitoring
was maintained until completion of the therapeutic protocol.
PSVT was defined as a regular tachycardia with sudden onset, QRS
complexes of supraventricular origin (i.e., narrow complexes or
wide complexes in the presence of aberrant conduction, previous
conduction defects or suspected accessory pathways with no
evidence of AV-dissociation) and abnormal non-sinus P waves.
Study protocols
On the basis of the general clinical evaluation, each participant
in the study underwent one of the following treatments:
(1) verapamil, 5 mg intravenously (IV) in 5–10 min, followed by
1–5 lg/kg/min, based on heart rate and blood pressure; (2)
adenosine 6 mg IV, followed by a second dose of 12 mg IV after
2–3 min; (3) carotid sinus massage, applied twice for at least 5 s
on each side. Any procedure was terminated in case of success
of the treatment or if complications such as severe hypotension
(systolic blood pressure <90 mmHg), bradycardia (<50 bpm),
atrial fibrillation or flutter, high-degree AV-block or malignant
ventricular arrhythmias occurred. Success of the treatment was
defined as persistent sinus rhythm restoration, maintained for at
least 3 min after the termination of PSVT.
Statistical analysis
Data are shown as mean values±SD for continuous variables. The
comparison of normal outcomes among the three study groups
was assessed using one-way analysis of variance. Dichotomous
variables (i.e., gender and success in terminating PSVT) were
compared with use of the v2 test. Logistic regression analysis was
performed using the maximised log likelihood method, in order
to evaluate the effect of PSVT rate on the success of the treatment in each group of study. Regression co-efficients, odds ratios, 95% confidence intervals (CI) and statistical significance
were calculated for each treatment. The estimated probability
of sinus rhythm restoration was expressed as a function of heart
rate using the formula p ¼ 1 1=½expða þ b HRÞ þ 1, where p is
the probability of success, expressed as a decimal between 0 and
1, exp denotes the exponential function, a and b represent the
intercept and the slope of the logistic regression line in each
group of study, and HR indicates heart rate. The heart rate values
which corresponded to an estimated 25%, 50% and 75% probability of success were determined using the formula HR ¼
½logitðpÞ a=b, where the expression logit (p) indicates the log
odds ratio, computed as the natural logarithm of ½p=ð1 pÞ. To
obtain a direct and simplified quantification of changes in the
probability of success for any unitary variation in heart rate, a
linear approximation was assumed for the adenosine and verapamil curves in the interval between the values of heart rate
corresponding to a 25% and 75% probability of success. Linearity
in this range was tested by fitting data with use of linear regression analysis, based on the least square method. Parameter
estimates, Pearson’s correlation co-efficients and levels of significance of the regression lines were determined in both groups.
The significance level was set at 0.05. All statistical tests
were two-tailed. The SPSS software (Statistical Package for
Social Sciences, Chicago, Illinois, USA) for Windows Release
11.5.0 was used to generate the statistical analyses.
Results
Study population
One hundred and seventy-five patients met the inclusion
criteria. One subject presented severe hypotension and
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
automaticity, triggered activity and re-entry circuits
which develop in the atrial myocardium or in the atrioventricular (AV) junction.1–5 The general clinical approach
to a subject with suspected PSVT includes a brief and
targeted history and an accurate analysis of the electrocardiogram (ECG), in the attempt to differentiate PSVT
from other narrow-complex tachycardias and to choose
the most appropriate treatment.6;7 When no haemodynamic instability is present, vagal manoeuvres, adenosine
and verapamil are usually considered as the first-line
treatment of choice for PSVT,8–10 and the relative efficacy
of each has been evaluated in many studies.11–16
Both adenosine and verapamil are well known to have a
frequency-dependent effect on functional AV-nodal
properties,17–19 and the rate-dependence of depression in
AV-nodal function has been reported to play a key role in
the ability of interrupting experimental pacing-induced
PSVT.20 These findings suggest that the rate of the tachycardia may potentially affect the anti-arrhythmic efficacy
of both drugs in spontaneous PSVT. However, whether
heart rate could be a predictor of success in the treatment
of PSVT in clinical practice has never been analysed.
The aim of this study was to evaluate whether the rate
of the tachycardia may predict the restoration of sinus
rhythm in the treatment of adult subjects with symptomatic PSVT. The design of the study included two
different pharmacological protocols (i.e., adenosine and
verapamil) and one non-pharmacological approach (i.e.,
carotid sinus massage).
1311
1312
P. Ballo et al.
underwent successful DC-shock. In 23 cases, PSVT was
associated with type 2 second-grade AV-block (19 with
conduction ratio 2:1, one with conduction ratio 4:1 and
three with variable ventricular response). Twenty-two
subjects were under chronic anti-arrhythmic therapy
(eight of which were assuming verapamil, six propafenone, five amiodarone, two sotalol and one diltiazem).
Two previously untreated patients were also excluded
because one of them had spontaneously taken 300 mg of
propafenone and the other 160 mg of verapamil per os at
the onset of symptoms. Twenty-one subjects experienced spontaneous termination of PSVT during electrocardiographic monitoring before the beginning of the
treatment. One hundred and six patients were then admitted to the study group. Thirty-nine subjects received
adenosine, 33 subjects were administered verapamil and
34 underwent carotid sinus massage.
The three groups were similar as regards mean age,
gender distribution, arterial systolic and diastolic pressures and heart rate (Table 1). The percentages of success in terminating PSVT were significantly different
among the three groups (P ¼ 0:000029). A similar efficacy of treatment was observed in the group treated
with adenosine (74.4%) and among the subjects who received verapamil (81.8%, P ¼ 0:45). The percentage of
PSVT interruption in the group treated with the carotid
sinus massage was consistently lower in comparison with
the other two groups (32.4%, P ¼ 0:00032 vs adenosine
and P ¼ 0:000044 vs verapamil group). No significant
complications were observed in any subject.
Effect of heart rate
Logistic regression (Table 2) showed a significant positive
association between heart rate and the probability of
Table 1 General characteristics of the three study groups
Patients (males/females)
Age (years)
Systolic arterial pressure (mmHg)
Diastolic arterial pressure (mmHg)
Heart rate (bpm)
Adenosine
Verapamil
CSM
p Value
39 (13/26)
56.6±19.0
124.4±16.6
78.0±10.5
172.0±22.5
33 (10/23)
57.9±16.4
132.3±10.5
81.7±8.5
166.6±29.8
34 (13/21)
61.6±14.0
126.0±21.9
81.1±12.8
170.6±24.5
0.78
0.43
0.13
0.30
0.66
p Values were calculated using analysis of variance or v2 test. CSM, carotid sinus massage.
Table 2 Effect of heart rate on the probability of sinus rhythm restoration in the three groups of study, as evaluated by logistic
regression
Adenosine group
Verapamil group
CSM group
Intercept
B
SE
p Value
Odds ratio
95% CI
Overall p value
)11.698
8.546
3.087
0.077
)0.040
)0.023
0.028
0.019
0.018
0.006
0.033
0.204
1.081
0.961
0.978
1.023–1.141
0.926–0.997
0.944–1.012
0.0004
0.018
0.176
The co-efficients B represent the slopes of the relations between heart rate and the log odds ratio for the probability of success of the treatment in
each group of study. The standard error (SE) and the statistical significance of each slope are reported in the table. Odds ratio, 95% confidence
intervals (CI) and overall model significance for each study group are also shown. CSM, carotid sinus massage.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
General features and efficacy of treatment
PSVT termination in the adenosine group (Fig. 1, top
panel). The maximal effect of heart rate was observed in
the central portion of the curve, where the slope of the
relation assumed its highest values. The estimated
probability of success for the treatment with adenosine
was >75% for heart rates >166 bpm, but rapidly decreased at lower frequencies, reducing to 50% at 152
bpm – corresponding to the central inflection point of
the curve – and to 25% at 138 bpm. In the range between
138 and 166 bpm, the sigmoidal curve was well approximated by a linear relation (p ¼ 0:0183 HR – 2.2754;
r ¼ 0:99, P < 0:0001). This corresponded to an absolute
1.8% decrease in the probability of sinus rhythm restoration for any unitary decrease in heart rate – i.e., for
any reduction by one beat per minute in PSVT frequency
within that interval.
In the verapamil group, heart rate was negatively
associated with the efficacy of the treatment in interrupting PSVT (Fig. 1, middle panel). The estimated
probability of success was >75% for heart rates <186
bpm, but tended to decrease for higher values of frequency, reducing to 50% at 214 bpm and to 25% at a
frequency of 241 bpm. Similarly to the adenosine curve,
the S-shaped function was well fitted by a linear equation
in the range between 186 and 241 bpm (p ¼ 0:0094 HR þ 2:5232; r ¼ 0:99, P < 0:0001). This corresponded to
an absolute 0.9% reduction in the probability of sinus
rhythm restoration for any increase by one beat per
minute in PSVT rate.
Although the efficacy of carotid sinus massage showed
some tendency to decrease as PSVT frequency increased
(Fig. 1, bottom panel), the relation to heart rate was not
significant (Table 2). The comparison of the relations
obtained in the adenosine and verapamil groups showed
that the two curves crossed in a point which corresponded to 173.0 bpm. This represented the value of
heart rate at which the two treatments would yield a
similar percentage of success in PSVT termination
Heart rate is a predictor of success in the treatment of adults with symptomatic paroxysmal supraventricular tachycardia
Favours
Adenosine
Favours
Verapamil
Adenosine
100
Difference in the
probability of success (%)
Probability of success (%)
100
75
50
25
0
75
125
175
225
1313
275
50
0
-50
-100
75
Heart rate (bpm)
125
175
225
275
Heart rate (bpm)
Fig. 2 Comparison of the efficacy of adenosine and verapamil according
to heart rate. The plot shows the difference between the estimated
probability of sinus rhythm restoration obtained by treatment with
adenosine and that obtained by administration of verapamil, at different
values of heart rate. At a frequency approximately equal to 173 bpm,
there were no differences between the two treatments. The efficacy was
better for adenosine at faster frequencies, and better for verapamil at
slower frequencies (see text).
Verapamil
75
50
25
0
75
125
175
225
275
Heart rate (bpm)
Probability of success (%)
100
Carotid sinus massage
75
50
25
0
75
125
175
225
275
Heart rate (bpm)
Fig. 1 Effect of heart rate on the probability of sinus rhythm restoration
following treatment with adenosine (top panel), verapamil (middle panel) and carotid sinus massage (bottom panel). The heart rate values
which corresponded to an estimated 25% and 75% probability of success
are shown in each plot. In those intervals, relations were approximately
linear (see text).
(83.5%). Higher rates were then associated with better
efficacy of adenosine, whereas lower rates were associated with better efficacy of verapamil (Fig. 2).
Discussion
PSVT is a common clinical condition which may be explained by various pathophysiological mechanisms. Enhanced automaticity, triggered activity or re-entry
circuits which develop in the atrial myocardium or in the
AV-junction may be responsible for different types of
PSVT, although recent observations have suggested that
other unknown mechanisms could be involved in some
cases with peculiar electropharmacological responses.21
The most common arrhythmia mechanisms in PSVT are
AV-intranodal re-entry, which leads to AV-nodal reciprocating tachycardia,2;5;22–26 and re-entry by an accessory
AV-connection, which produces AV-reciprocating tachycardia.27;28 Atrial tachycardia is a less frequent type of
PSVT which may be underlied by focal or macro re-entrant mechanisms in different regions of the atrial tissue,29–37 whereas other PSVT types are rare. Despite
heterogeneity of pathogenesis, contemporary management of PSVT usually follows a general algorithm which
initially includes vagal manoeuvres and administration of
adenosine or verapamil.38–41 Diltiazem,42–44 b-blockers,45;46 anti-arrhythmics of class Ic47;48 and III,49–52
pharmacological associations,53;54 new selective A1 adenosine receptor agonists currently under clinical investigation55;56 and transoesophageal atrial pacing57 may
also be useful in the treatment or prevention of episodes
of PSVT in adults, and immediate electrical cardioversion
with DC-shock is recommended in case of haemodynamically compromised patients.8;58 Digoxin is the drug
of choice for supraventricular tachycardias occurring in
foetuses and may be effective in the prophylaxis of recurrences in infants and children, but has a limited role
in adults.59–61 Transoesophageal and/or endocavitary
electrophysiology are often required to determine the
exact mechanism of the arrhythmia62–64 and radiofrequency catheter ablation is generally indicated in subjects with drug-refractory arrhythmias.65–69
Adenosine and verapamil have been reported to have
similar high efficacy in terminating PSVT, with a rate of
success ranging from 59% to 100% for adenosine and from
73% to 98.8% for verapamil,11;13;42;70;71 according to the
dose and mode of administration. Vagal manoeuvres
present the advantage of being relatively simple and
non-invasive, but their efficacy seems to be quite lower
in comparison with pharmacological interventions, with
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
Probability of success (%)
100
1314
increase in the effective refractory period of the AVnode which occurs at fast heart rates may play a key role
in determining a higher efficacy of adenosine in terminating PSVT characterised by relatively high frequencies.
The efficacy of verapamil in the treatment and prophylaxis of supraventricular tachycardias is due to its
ability to produce an inhibition of the inward calcium
current I(Ca, L), secondary to the blockage of type L
calcium channels, resulting in a rate-dependent prolongation in AV-nodal conduction time and effective refractory period and yielding a decrease in the atrial
pacing rate at which AV-Wenckebach occurs.80–85 An
adjunctive anti-arrhythmic mechanism of verapamil may
be due to the inhibition of the rapid component of the
delayed rectifier potassium current I(Kr), which produces
a delay in the myocyte repolarisation process and leads
to a prolongation of the action potential and effective
refractory period.86–88 The rate-dependency of the
pharmacological effect of verapamil is probably the result of an interaction among various factors, which may
include differential effects on calcium or potassium
channels, a large constant time of adaptation due to slow
drug-specific association and dissociation kinetic to the
calcium channel,18;84;89;90 and a modulating action by the
autonomic tone.91;92 A recent study has shown that administration of verapamil in healthy adults leads to a
prolongation of the atrial effective refractory period at
low frequencies and to a shortening at high frequencies,
suggesting a predominant effect on I(Ca, L) at fast rates
and a predominant effect on I(Kr) at slow rates.93 The
report that I(Kr) may play an important role in the
electrophysiological properties of the AV-node94 may
suggest the intriguing hypothesis that a predominant
effect on the potassium channels, with subsequent increase in the effective refractory period, could exist at
slow rates in the AV-nodal tissue and play some role in
determining a higher efficacy of verapamil in low-frequency PSVT. The relation among rate-dependent and
slowly adaptive pharmacodynamic interaction with calcium channels, differential effects on calcium and potassium channels, and potentially higher efficacy in
terminating PSVT in patients with low heart frequencies
in comparison with those with high frequencies should be
evaluated in further studies.
Limitations of the study
The major limitation of this study is that the design did
not include either electrophysiological study or electrocardiographic determination of PSVT types, so that the
effect of different electrical patterns in affecting the
relationship between heart rate and success of treatment could have not been evaluated. It is well known
that different subtypes of PSVT may show unequal responsiveness to anti-arrhythmics, particularly in the case
of atrial tachycardia, which does not directly involve the
AV-node and tends to show variable sensitivity to nodal
blocking agents such as adenosine and verapamil.95;96
However, atrial tachycardia has been reported to be
relatively infrequent, accounting for only 5–15% of all
PSVTs.7;97–100 Accordingly, an a posteriori analysis in our
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
percentages of PSVT termination ranging from 6% to 22%
following carotid sinus massage.16;70;72–75 Our results
confirm the evidence that adenosine and verapamil are
similarly highly effective in terminating spontaneous
episodes of PSVT in adults, whereas carotid sinus massage is able to interrupt tachycardia in a relatively low
percentage of cases. However, our data also suggest that
the efficacy of both adenosine and verapamil is affected
by the frequency of the arrhythmia. Increasing PSVT
rates were significantly associated to higher percentages
of sinus rhythm restoration following treatment with
adenosine (Fig. 1, top panel). In contrast, the efficacy of
verapamil in restoring sinus rhythm was inversely related
to the frequency of PSVT (Fig. 1, middle panel), and no
significant effect of heart rate was observed in the group
which had undergone carotid sinus massage (Fig. 1,
bottom panel). Of note, the effect of heart rate on the
efficacy of verapamil was less in comparison with that
observed for adenosine, as shown by the milder steepness of the curve in the plots. However, the comparison
of the relations obtained in the adenosine and verapamil
groups suggested that 173 bpm could be used as the best
cut-off value to predict which treatment may ensure
higher probability of success in restoring sinus rhythm
(Fig. 2). Heart rates over this cut-off value may be associated to higher percentages of PSVT interruption by
administration of adenosine, whereas slower frequencies
may be associated to better efficacy of verapamil.
Heart rate is known to influence the pharmacodynamic effect of both adenosine and verapamil on the AVnode. It has been shown that the negative dromotropic
effect of adenosine tends to increase when the atrial
pacing cycle is progressively reduced during experimental PSVT,17 and the rate-dependent conduction slowing
seems to be more pronounced for adenosine than for
verapamil.19 Adenosine has been demonstrated to increase AV-nodal fatigue – i.e., the AV-nodal delay which
slowly develops at fast rates – and to attenuate facilitation – i.e., the tendency of short cycles to improve
subsequent nodal recovery – without directly altering
AV-nodal recovery, and this may result in frequencydependent increases in the AV-nodal conduction time
and effective refractory period. The substrate of this
phenomenon remains to be clarified, although complex
interaction among different electrophysiological and
molecular mechanisms is likely to be involved. These
include a direct effect on the activation of the inward
rectifier potassium current I(K, Ado), which produces
hyperpolarization and depression in AV-conduction,76
and an indirect effect of antagonism on catecholaminestimulated adenylate cyclase activity, which occurs
through coupling with guanosine triphosphate-binding
inhibitory proteins.77;78 A possible alternative ionic
mechanism has also recently been proposed, involving a
different adenosine-activated, time- and voltage-dependent potassium current defined Ado-I(K), which could
play a key role in determining nodal depression at lower
concentrations of the nucleoside and particularly at fast
heart rate.79 Regardless of the exact mechanism underlying these phenomena, our hypothesis is that the enhancement in the negative dromotropic effect and the
P. Ballo et al.
Heart rate is a predictor of success in the treatment of adults with symptomatic paroxysmal supraventricular tachycardia
Conclusions
In the treatment of symptomatic episodes of PSVT in
adult subjects, both adenosine and verapamil demonstrated a high rate of success in terminating the tachycardia, whereas a poor response to carotid sinus massage
was observed. The rate of the tachycardia may predict
the success of pharmacological treatment. The efficacy
of adenosine was directly related to the frequency of the
arrhythmia, so it should be considered the treatment of
choice in patients with PSVT characterised by high heart
rates. Conversely, the efficacy of verapamil seems to be
increased in patients with low-frequency PSVT, so that it
could be appropriately used as the first-line treatment in
these subjects.
References
1. Orejarena LA, Vidaillet HJR, DeStefano F et al. Paroxysmal supraventricular tachycardia in the general population. J Am Coll Cardiol
1998;31:150–7.
2. Luber S, Brady WJ, Joyce T et al. Paroxysmal supraventricular
tachycardia: outcome after ED care. Am J Emerg Med 2001;19:40–2.
3. Kadish A, Passman R. Mechanisms and management of paroxysmal
supraventricular tachycardia. Cardiol Rev 1999;7:254–64.
4. Paparella N, Alboni P. Classification and prevalence of supraventricular tachyarrhythmia. Cardiologia 1991;36:7–10.
5. Brembilla-Perrot B, Houriez P, Beurrier D et al. Influence of age on
the electrophysiological mechanism of paroxysmal supraventricular
tachycardias. Int J Cardiol 2001;78:293–8.
6. Accardi AJ, Miller R, Holmes JF. Enhanced diagnosis of narrow
complex tachycardias with increased electrocardiograph speed. J
Emerg Med 2002;22:123–6.
7. Kalbfleisch SJ, el-Atassi R, Calkins H et al. Differentiation of
paroxysmal narrow QRS complex tachycardias using the 12-lead
electrocardiogram. J Am Coll Cardiol 1999;21:85–9.
8. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Part 6: advanced cardiovascular life support:
7D: the tachycardia algorithms. The American Heart Association in
collaboration with the International Liaison Committee on Resuscitation. Circulation 2000;102:I158–65.
9. Junga G, Candinas R Schweiz. Modern therapy of paroxysmal
supraventricular tachycardia. Rundsch Med Prax 1999;88:273–7.
10. Paul T, Bertram H, Bokenkamp R et al. Supraventricular tachycardia
in infants, children and adolescents: diagnosis, and pharmacological
and interventional therapy. Paediatr Drugs 2000;2:171–81.
11. Brady Jr WJ, DeBehnke DJ, Wickman LL et al. Treatment of out-ofhospital supraventricular tachycardia: adenosine vs verapamil. Acad
Emerg Med 1996;3:574–85.
12. Gil Madre J, Lazaro Rodriguez S, Sentenac Merchan G et al. Adenosine
triphosphate in the treatment of supraventricular paroxysmal tachycardia: a comparison with verapamil. Rev Esp Cardiol 1995;48:55–8.
13. Davis R, Spitalnic SJ, Jagminas L. Cost-effective adenosine dosing
for the treatment of PSVT. Am J Emerg Med 1999;17:633–4.
14. Lee KL, Chun HM, Liem LB et al. Effect of adenosine and verapamil
in catecholamine-induced accelerated atrioventricular junctional
rhythm: insights into the underlying mechanism. Pacing Clin Electrophysiol 1999;22:866–70.
15. Kirton OC, Windsor J, Wedderburn R et al. Management of
paroxysmal atrioventricular nodal reentrant tachycardia in the
critically ill surgical patient. Crit Care Med 1997;25:761–6.
16. Lim SH, Anantharaman V, Teo WS et al. Comparison of treatment of
supraventricular tachycardia by Valsalva maneuver and carotid sinus
massage. Ann Emerg Med 1998;31:30–5.
17. Lai WT, Lee CS, Wu SN. Rate-dependent properties of adenosineinduced negative dromotropism in humans. Circulation 1994;90:
1832–9.
18. Schwarzl I, Stark U, Kasper K et al. Quantification of rate-dependent
effects of verapamil, diltiazem, and digoxin on atrioventricular
conduction. J Pharmacol Toxicol Methods 1996;36:205–10.
19. Stark G, Sterz F, Stark U et al. Frequency-dependent effects of
adenosine and verapamil on atrioventricular conduction of isolated
guinea pig hearts. J Cardiovasc Pharmacol 1993;21:955–9.
20. Nayebpour M, Billette J, Amellal F et al. Effects of adenosine on
rate-dependent atrioventricular nodal function. Potential roles in
tachycardia termination and physiological regulation. Circulation
1993;88:2632–45.
21. Chiale PA, Franco DA, Selva HO et al. Lidocaine-sensitive atrial
tachycardia: lidocaine-sensitive, rate-related, repetitive atrial
tachycardia: a new arrhythmogenic syndrome. J Am Coll Cardiol
2000;36(1):1637–45.
22. Kwaku KF, Josephson ME. Typical AVNRT – an update on mechanisms and therapy. Card Electrophysiol Rev 2002;6:414–21.
23. Nawata H, Yamamoto N, Hirao K et al. Heterogeneity of anterograde
fast-pathway and retrograde slow-pathway conduction patterns in
patients with the fast-slow form of atrioventricular nodal reentrant
tachycardia: electrophysiological and electrocardiographic considerations. J Am Coll Cardiol 1998;32:1731–40.
24. Delise P, Bonso A, Coro L et al. Pacemapping of the triangle of Koch:
a simple method to reduce the risk of atrioventricular block during
radiofrequency ablation of atrioventricular node reentrant tachycardia. Pacing Clin Electrophysiol 2001;24:1725–31.
25. Heinroth KM, Kattenbeck K, Stabenow I et al. Multiple AV nodal
pathways in patients with AV nodal reentrant tachycardia–more
common than expected. Europace 2002;4:375–82.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
study population revealed electrographic findings
suggestive for AV-nodal reciprocant tachycardia in 66
cases (62.3%), for AV-reciprocant tachycardia in 32 cases
(30.2%) and for atrial tachycardia in only eight cases
(7.5%). Also, the protocol of the study was designed
taking into account that: (1) PSVT subtype identification
by surface ECG is often difficult to perform, particularly
when the tachycardia presents high frequencies, (2)
electrophysiological tests are not routinely performed in
clinical practice, (3) although various electrocardiographic criteria have been proposed in the attempt to
distinguish different types of PSVT,100–102 about 20% of
PSVT may be incorrectly classified on the basis of the
surface ECG.7 The possibility that some cases of regular
atrial flutter with conduction ratio 2:1 have been classified as PSVT or vice versa should also be taken into
account. By design, only symptomatic episodes were included in this study, yet sub-clinical PSVT seems to be
uncommon.103 This study did not analyse the potential
effect of other clinical variables on the efficacy of the
treatment of PSVT, such as a history positive for previous
episodes of PSVT and duration of the arrhythmia. Many of
the patients with PSVT often complain of previous undocumented episodes of palpitations, and it is hard to
establish whether the arrhythmia is a relapse or a first
episode in these cases. Also, most patients with PSVT are
not able to determine the onset of the symptoms with
sufficient precision, so that introducing the duration of
the tachycardia as a study variable would have produced
a relevant risk of biases in the analysis. In addition, it
should be considered that this study was retrospective
and not randomised, so that the results have to be interpreted with caution. Lastly, the effect of heart rate
on the percentage of success in the treatment of PSVT
using other therapeutic approaches has not been evaluated. Larger prospective trials and further studies are
needed to analyse these aspects.
1315
1316
47. Reimold SC, Maisel WH, Antman EM. Propafenone for the treatment
of supraventricular tachycardia and atrial fibrillation: a metaanalysis. Am J Cardiol 1998;82:66N–71N.
48. Gambhir DS, Bhargava M, Arora R et al. Electrophysiological effects
and therapeutic efficacy of intravenous flecainide for termination of
paroxysmal supraventricular tachycardia. Indian Heart J 1995;47:
237–43.
49. Page RL, Connolly SJ, Wilkinson WE et al. Antiarrhythmic effects of
azimilide in paroxysmal supraventricular tachycardia: efficacy and
dose–response. Am Heart J 2002;143:643–9.
50. Tendera M, Wnuk-Wojnar AM, Kulakowski P et al. Efficacy and safety
of dofetilide in the prevention of symptomatic episodes of paroxysmal supraventricular tachycardia: a 6-month double-blind comparison with propafenone and placebo. Am Heart J 2001;142:93–8.
51. Pritchett EL, Wilkinson WE. Effect of dofetilide on survival in patients
with supraventricular arrhythmias. Am Heart J 1999;138:994–7.
52. Gambhir DS, Bhargava M, Nair M et al. Comparison of electrophysiological effects and efficacy of single-dose intravenous and longterm oral amiodarone therapy in patients with AV nodal reentrant
tachycardia. Indian Heart J 1996;48:133–7.
53. Price JF, Kertesz NJ, Snyder CS et al. Flecainide and sotalol: a new
combination therapy for refractory supraventricular tachycardia in
children <1 year of age. J Am Coll Cardiol 2002;39:517–20.
54. Alboni P, Tomasi C, Menozzi C et al. Efficacy and safety of out-ofhospital self-administered single-dose oral drug treatment in the
management of infrequent, well-tolerated paroxysmal supraventricular tachycardia. J Am Coll Cardiol 2001;37:548–53.
55. Lerman BB, Ellenbogen KA, Kadish A et al. Electrophysiologic effects
of a novel selective adenosine A1 agonist (CVT-510) on atrioventricular nodal conduction in humans. J Cardiovasc Pharmacol Ther
2001;6:237–45.
56. Ellenbogen KA. Randomized, double-blind, placebo-controlled study
of intravenous CVT-510 in patients with PSVT undergoing an
electrophysiologic study. Program and abstracts from American
Heart Association Scientific Sessions 2002, November 17–20, 2002;
Chicago, IL.
57. Volkmann H, Dannberg G, Heinke M et al. Termination of tachycardias by transesophageal electrical pacing. Pacing Clin Electrophysiol
1992;15:1962–6.
58. Lowenstein SR, Halperin BD, Reiter MJ. Paroxysmal supraventricular
tachycardias. J Emerg Med 1996;14:39–51.
59. Pfammatter JP, Bauersfeld U. Safety issues in the treatment of
paediatric supraventricular tachycardias. Drug Saf 1998;18:345–56.
60. Mathew J, Hunsberger S, Fleg J et al. Incidence, predictive factors,
and prognostic significance of supraventricular tachyarrhythmias in
congestive heart failure. Chest 2000;118:914–22.
61. Jaeggi E, Fouron JC, Fournier A et al. Ventriculo-atrial time interval
measured on M mode echocardiography: a determining element in
diagnosis, treatment, and prognosis of fetal supraventricular
tachycardia. Heart 1998;79:582–7.
62. Knight BP, Ebinger M, Oral H et al. Diagnostic value of tachycardia
features and pacing maneuvers during paroxysmal supraventricular
tachycardia. J Am Coll Cardiol 2000;36:574–82.
63. Matsui Y, Iwasaka T, Karakawa M et al. Left ventricular systolic time
intervals during paroxysmal supraventricular tachycardia: the difference between A-V nodal re-entry and A-V re-entry. J Cardiol
1992;22:679–85.
64. Knight BP, Zivin A, Souza J et al. A technique for the rapid diagnosis
of atrial tachycardia in the electrophysiology laboratory. J Am Coll
Cardiol 1999;33:775–81.
65. Akhtar M, Jazayeri MR, Sra J et al. Atrioventricular nodal reentry.
Clinical, electrophysiological, and therapeutic considerations. Circulation 1993;88:282–95.
66. Nakagawa H, Jackman WM. Catheter ablation of macroreentrant
atrial tachycardia in patients following atriotomy. Eur Heart J
2002;23:1566–8.
67. Kopf GS, Mello DM, Kenney KM et al. Intraoperative radiofrequency
ablation of the atrium: effectiveness for treatment of supraventricular tachycardia in congenital heart surgery. Ann Thorac Surg
2002;74:797–804.
68. Wetzel U, Hindricks G, Schirdewahn P et al. A stepwise mapping
approach for localization and ablation of ectopic right, left, and
septal atrial foci using electroanatomic mapping. Eur Heart J
2002;23:1387–93.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
26. Wu J, Zipes DP. Mechanisms underlying atrioventricular nodal
conduction and the reentrant circuit of atrioventricular nodal
reentrant tachycardia using optical mapping. J Cardiovasc Electrophysiol 2002;13:831–4.
27. Luria DM, Chugh SS, Munger TM et al. Electrophysiologic characteristics of diverse accessory pathway locations of antidromic reciprocating tachycardia. Am J Cardiol 2000;86:1333–8.
28. Davidson NC, Morton JB, Sanders P et al. Latent Mahaim fiber as a
cause of antidromic reciprocating tachycardia: recognition and
successful radiofrequency ablation. J Cardiovasc Electrophysiol
2002;13:74–8.
29. Shah DC, Haissaguerre M, Jais P et al. High-resolution mapping of
tachycardia originating from the superior vena cava: evidence of
electrical heterogeneity, slow conduction, and possible circus
movement reentry. J Cardiovasc Electrophysiol 2002;13:388–92.
30. Matsuoka K, Kasai A, Fujii E et al. Electrophysiological features of
atrial tachycardia arising from the atrioventricular annulus. Pacing
Clin Electrophysiol 2002;25:440–5.
31. Katritsis D, Giazitzoglou E, Korovesis S et al. Epicardial foci of atrial
arrhythmias apparently originating in the left pulmonary veins. J
Cardiovasc Electrophysiol 2002;13:319–23.
32. Hegbom F, Hoff PI, Rossvoll O et al. A typical P-wave morphology in
incessant atrial tachycardia originating from the right upper
pulmonary vein. Scand Cardiovasc J 2000;34:277–80.
33. Ouyang F, Ernst S, Vogtmann T et al. Characterization of reentrant
circuits in left atrial macroreentrant tachycardia: critical isthmus
block can prevent atrial tachycardia recurrence. Circulation
2002;105(23):1934–42.
34. Markowitz SM, Brodman RF, Stein KM et al. Lesional tachycardias
related to mitral valve surgery. J Am Coll Cardiol 2002;39(19):
1973–83.
35. Marrouche NF, Sippens Groenewegen A, Yang Y et al. Clinical and
electrophysiological characteristics of left septal atrial tachycardia.
J Am Coll Cardiol 2002;40(18):1133–9.
36. Dong J, Schreieck J, Ndrepepa G et al. Ectopic tachycardia
originating from the superior vena cava. J Cardiovasc Electrophysiol
2002;13:620–4.
37. Ma G, Brady WJ, Pollack M et al. Electrocardiographic manifestations: digitalis toxicity. J Emerg Med 2001;20:145–52.
38. Blomstrom-Lundqvist C, Scheinman MM, Aliot EM et al. European
Society of Cardiology Committee, NASPE-Heart Rhythm Society.
ACC/AHA/ESC guidelines for the management of patients with
supraventricular arrhythmias – executive summary. A report of the
American college of cardiology/American heart association task
force on practice guidelines and the European society of cardiology
committee for practice guidelines (writing committee to develop
guidelines for the management of patients with supraventricular
arrhythmias) developed in collaboration with NASPE-Heart Rhythm
Society. J Am Coll Cardiol 2003;42:1493–531.
39. Ferguson JD, DiMarco JP. Contemporary management of paroxysmal
supraventricular tachycardia. Circulation 2003;107:1096–9.
40. Hebbar AK, Hueston WJ. Management of common arrhythmias: Part
I. Supraventricular arrhythmias. Am Fam Physician 2002;65(15):
2479–86.
41. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Part 6: advanced cardiovascular life support:
section 5: pharmacology I: agents for arrhythmias. The American
Heart Association in collaboration with the International Liaison
Committee on Resuscitation. Circulation 2000;102:I-112–28.
42. Lim SH, Anantharaman V, Teo WS. Slow-infusion of calcium channel
blockers in the emergency management of supraventricular tachycardia. Resuscitation 2002;52:167–74.
43. Gupta A, Naik A, Vora A et al. Comparison of efficacy of intravenous
diltiazem and esmolol in terminating supraventricular tachycardia. J
Assoc Physicians India 1999;47:969–72.
44. Dougherty AH, Jackman WM, Naccarelli GV et al. Acute conversion
of paroxysmal supraventricular tachycardia with intravenous diltiazem. IV Diltiazem Study Group. Am J Cardiol 1992;70:587–92.
45. Balser JR, Martinez EA, Winters BD et al. Beta-adrenergic blockade
accelerates conversion of postoperative supraventricular tachyarrhythmias. Anesthesiology 1998;89:1052–9.
46. Barbier GH, Shettigar UR, Appunn DO. Clinical rationale for the use
of an ultra-short acting beta-blocker: esmolol. Int J Clin Pharmacol
Ther 1995;33:212–8.
P. Ballo et al.
Heart rate is a predictor of success in the treatment of adults with symptomatic paroxysmal supraventricular tachycardia
86. Yue L, Feng JL, Wang Z et al. Effects of ambasilide, quinidine,
flecainide and verapamil on ultra-rapid delayed rectifier potassium
currents in canine atrial myocytes. Cardiovasc Res 2000;46:151–61.
87. Chouabe C, Drici MD, Romey G et al. Effects of calcium channel
blockers on cloned cardiac Kþ channels IKr and IKs. Therapie
2000;55:195–202.
88. DeCoursey TE. Mechanism of Kþ channel block by verapamil and
related compounds in rat alveolar epithelial cells. J Gen Physiol
1995;106:745–79.
89. Talajic M, Nattel S. Frequency-dependent effects of calcium
antagonists on atrioventricular conduction and refractoriness:
demonstration and characterization in anesthetized dogs. Circulation 1986;74:1156–67.
90. Stark G, Schulze-Bauer C, Stark U et al. Comparison of the
frequency-dependent effects on the atrioventricular node of
verapamil, amiodarone, digoxin, and diltiazem in isolated guinea
pig hearts. J Cardiovasc Pharmacol 1995;25:330–5.
91. Lang J, Timour Chah Q, Charve P et al. Role of calcium in the ratedependent depression of atrioventricular nodal conduction in the
dog heart under vagal influence. Int J Cardiol 1987;15:65–76.
92. Qi AZ, Tuna IC, Gornick CC et al. Potentiation of cardiac electrophysiologic effects of verapamil after autonomic blockade or
cardiac transplantation. Circulation 1987;75:888–93.
93. Hassan SA, Oral H, Scharf C et al. Rate-dependent effect of
verapamil on atrial refractoriness. J Am Coll Cardiol
2003;41:446–51.
94. Sato N, Tanaka H, Habuchi Y et al. Electrophysiological effects of
ibutilide on the delayed rectifier K(+) current in rabbit sinoatrial and
atrioventricular node cells. Eur J Pharmacol 2000;404:281–8.
95. Fujino H, Fujiseki Y, Shimada M. Electrophysiologic effects of
calcium channel blockers on supraventricular tachycardia in children. J Cardiol 1989;19:307–15.
96. Bhandari AK. Atrial Tachycardia. Curr Treat Options Cardiovasc Med
1999;1:107–16.
97. Steinbeck G, Hoffmann E. ‘True’ atrial tachycardia. Eur Heart J
1998;19(Suppl E):E10–2, E48–9.
98. Simons GR, Wharton JM. Radiofrequency catheter ablation of atrial
tachycardia and atrial flutter. Coron Artery Dis 1996;7:12–9.
99. Dierkes S, Vester EG, Dobran LJ et al. Adenosine in the noninvasive
diagnosis of dual AV nodal conduction: use as a follow-up parameter
after slow pathway ablation in AVNRT. Acta Cardiol 2001;56:103–8.
100. Maglana MP, Kam RM, Teo WS. The differential diagnosis of
supraventricular tachycardia using clinical and electrocardiographic
features. Ann Acad Med Singapore 2000;29:653–7.
101. Maury P, Zimmermann M, Metzger J. Distinction between atrioventricular reciprocating tachycardia and atrioventricular node reentrant tachycardia in the adult population based on P wave
location. Should we reconsider the value of some ECG criteria
according to gender and age? Europace 2003;5:57–64.
102. Ho YL, Lin LY, Lin JL et al. Usefulness of ST-segment elevation in
lead aVR during tachycardia for determining the mechanism of
narrow QRS complex tachycardia. Am J Cardiol 2003;92:1424–8.
103. Page RL, Wilkinson WE, Clair WK et al. Asymptomatic arrhythmias in
patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation 1994;89:224–7.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
69. Cauchemez B, Lavergne T, Extramiana F et al. Endocavitary
ablation for arrhythmias. New modalities of radiofrequency applications. New energy types. Arch Mal Coeur Vaiss 2002;95(Spec No
5):
31–9.
70. Hood MA, Smith WM. Adenosine versus verapamil in the treatment of
supraventricular tachycardia: a randomized double-crossover trial.
Am Heart J 1992;123:1543–9.
71. Morrison LJ, Allan R, Vermeulen M et al. Conversion rates for
prehospital paroxysmal supraventricular tachycardia (PSVT) with
the addition of adenosine: a before-and-after trial. Prehosp Emerg
Care 2001;5:353–9.
72. Arnold RW. The human heart rate response profiles to five vagal
maneuvers. Yale J Biol Med 1999;72:237–44.
73. Wen ZC, Chen SA, Tai CT et al. Electrophysiological mechanisms and
determinants of vagal maneuvers for termination of paroxysmal
supraventricular tachycardia. Circulation 1998;98:2716–23.
74. Mehta D, Wafa S, Ward DE et al. Relative efficacy of various physical
manoeuvres in the termination of junctional tachycardia. Lancet
1988;1:1181–5.
75. Domanovits H, Laske H, Stark G et al. Adenosine for the management of patients with tachycardias – a new protocol. Eur Heart J
1994; 15:589–93.
76. Martynyuk AE, Seubert CN, Zima A et al. Contribution of I(K, ADO) to
the negative dromotropic effect of adenosine. Basic Res Cardiol
2002;97:286–94.
77. Tai CT, Chen SA, Chiang CE et al. Influence of beta-adrenergic and
vagal activity on the effect of exogenous adenosine on supraventricular tachycardia termination. Am J Cardiol 1997;79(15):
1628–31.
78. Chang KC, Lin YC, Chen JY et al. Interactions of esmolol and
adenosine in atrioventricular nodal-dependent supraventricular
tachycardia: implication for the cellular mechanisms of adenosine.
Cardiology 2002;97:138–46.
79. Martynyuk AE, Zima A, Seubert CN et al. Potentiation of the
negative dromotropic effect of adenosine by rapid heart rates:
possible ionic mechanism. Basic Res Cardiol 2002;97:295–304.
80. Tonkin AM, Aylward PE, Joel SE et al. Verapamil in prophylaxis of
paroxysmal atrioventricular nodal reentrant tachycardia. J Cardiovasc Pharmacol 1980;2:473–86.
81. Prystowsky EN. The effects of slow channel blockers and beta
blockers on atrioventricular nodal conduction. J Clin Pharmacol
1988;28:6–21.
82. Tonkin AM, Shorne L. The prophylaxis of AV nodal re-entry
tachycardia. Clin Exp Pharmacol Physiol Suppl 1982;6:135–43.
83. Iinuma H, Dreifus LS, Price R et al. Influence of the site of
stimulation on atrioventricular nodal refractory periods and the
effect of verapamil. Am J Cardiol 1986;57:1167–74.
84. Stark G, Kasper K, Schulze-Bauer C et al. How to measure AV nodal
refractoriness in the presence of verapamil, amiodarone, digoxin,
and diltiazem. Pacing Clin Electrophysiol 1996;19:157–64.
85. Segawa K. The relationship between refractory period and conduction time of the AV node under various cycle lengths in the canine
heart. The significance of wavelength and excitable gap in reentrant
tachycardia. Jpn Heart J 1996;37:373–82.
1317