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Long-term treatment of recurrent neurocardiogenic
syncope (NCS) is still matter of dispute1. However, pharmacological therapy has proven ineffective
in most instances, while available data support a promising role for cardiac pacing in the long-term
treatment of such condition2. As a matter of fact, the clinical efficacy of cardiac pacing in recurrent
NCS seems to depend critically upon the pacing modality, as shown in preliminary experiences3,4.
In fact, conventional pacing therapies (VVI, DDD, DVI, DDI with rate hysteresis) are limited by a
hemodynamically inappropriate and delayed intervention, which cannot effectively contrast the
vasovagal reflex. The recent introduction of DDD pacing with a new function, the rate-drop response
algorithm (RDR), has significantly changed the clinical outcome of paced patients with NCS5. The RDR
algorithm has two main features: 1) a diagnostic function, which allows the recognition of the initial
heart rate drop during the vasovagal reflex, 2) a therapeutic function, triggered by the diagnostic
function, which provides early high rate pacing following the diagnostic phase4. As a matter of fact,
constant cardiac pacing is not necessary in NCS, while a proper physiological pacing intervention has
to be delivered for incipient syncopal spells. To prevent NCS, the ideal pacing device should sense
the initial hemodynamic modifications and subsequently pace early in the episode at a relative high
rate. Such pacing support, inducing a relative tachycardia, is expected to provide a sufficient cardiac
output to overcome bradycardia and vasodepression, which are both somehow always present
during a vasovagal reflex6. Actually, the positive effect of DDD-RDR pacing on the vasovagal reflex
has been confirmed by an early clinical investigation showing that such pacing modality is more
effective than the conventional approach of DDI pacing with rate hysteresis4.
After preliminary experiences, the North American Vasovagal Pacemaker Study was the first
randomized trial showing the possible efficacy of pacing treatment in patients with recurrent
NCS5. In this study, 54 patients with frequent syncope and a positive head-up tilt test, were
enrolled and randomized to a DDD-RDR pacemaker or no pacing treatment. The primary outcome
was the first syncopal recurrence. Syncope recurred in 19/27 control patients and in 6/27 paced
patients (relative risk reduction of 85%) during follow-up. The authors concluded that DDD-RDR
pacing is effective in reducing the likelihood of syncope in patients with recurrent NCS. A limitation
of such clinical experience was represented by the absence of a true control group using
conventional treatment for NCS.
In order to further clarify the specific role of cardiac pacing in recurrent NCS a new trial has been
designed and undertaken: the SYDIT study (SYncope DIagnosis and Treatment). This study differs
from previous experiences as it has been planned to compare the efficacy of the best available
pacing therapy (DDD-RDR), with conventional pharmacological treatment (beta-blockers or
alpha-agonists), in patients with recurrent NCS. The population of the SYDIT study includes
patients with recurrent syncope and a positive response to head-up tilt testing. After informed
consent, included patients are randomized to pacing treatment (DDD-RDR) or to oral pharmacological
therapy with atenolol (up to 100 mg/die). RDR function programming is performed on the basis of the
heart rate behavior during the diagnostic head-up tilt testing. In case of intolerance to beta-blockade
or syncope recurrence, patients included in the pharmacological arm are switched to treatment with
oral etilefrine (up to 50 mg/die). In case of syncope recurrence in patients included in the pacemaker
arm of the study, the device is reprogrammed according to the heart rate behavior recorded by the
solid state memory of the pacemaker during the spontaneous spell. The endpoints of the study are
represented by: time to first recurrence, time to second recurrence after either pharmacological or
pacing therapy modification. After the randomization of 69 patients, with a mean follow-up of 13
months, preliminary data support a trend in favor of pacing treatment.
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