Circulation. 2001;104:52-57
doi: 10.1161/hc2601.091708
doi: 10.1161/hc2601.091708
(Circulation. 2001;104:52.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Permanent Cardiac Pacing Versus Medical Treatment for the Prevention of Recurrent Vasovagal Syncope
A Multicenter, Randomized, Controlled Trial
From the Dipartimento di Malattie Cardiovascolari, Ospedale "S. Filippo Neri," Rome, Italy.
Correspondence to Dr Fabrizio Ammirati, Via Attilio Friggeri 95, 00136 Rome, Italy. E-mail fabamm{at}openaccess.it
Background—This clinical investigation was performed to compare the effects of permanent dual-chamber cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope.
Methods and
Results—Patients from 14 centers were
randomized to receive either a DDD pacemaker provided with rate-drop
response function or the ß-blocker atenolol at the dosage of 100 mg
once a day. Inclusion criteria were age >35 years, 
3 syncopal spells
in the preceding 2 years, and positive response to tilt table testing
with syncope occurring in association with relative bradycardia. The
primary outcome was the first recurrence of syncope after
randomization. Enrollment was started in December 1997, and the first
formal interim analysis was performed on July 30, 2000. By that
time, 93 patients (38 men and 55 women; mean age, 58.1±14.3 years) had
been enrolled and randomized, although follow-up data were available
for all patients (46 patients in the pacemaker arm, 47 patients in the
pharmacological arm). The interim analysis showed a significant
effect in favor of permanent cardiac pacing (recurrence of
syncope in 2 patients [4.3%] after a median of 390 days) compared
with medical treatment (recurrence of syncope in 12 patients
[25.5%] after a median of 135 days; OR, 0.133; 95% CI, 0.028 to
0.632; P=0.004). Consequently,
enrollment and follow-up were terminated.
Conclusions—DDD pacing with rate-drop response function is more effective than ß-blockade for the prevention of syncopal recurrences in highly symptomatic vasovagal fainters with relative bradycardia during tilt-induced syncope.
Key Words: syncope • pacing • ß-blockers
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|
|
|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
W. N. Kapoor Current Evaluation and Management of Syncope Circulation, September 24, 2002; 106(13): 1606 - 1609. [Full Text] [PDF]
|
|
|
|
|
|
A. Raviele Tilt-induced asystole: a useful prognostic marker or clinically unrelevant finding? Eur. Heart J., March 2, 2002; 23(6): 433 - 437. [Full Text] [PDF]
|
|
|
|
|
|
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|
|