DDD Pacing with Rate Drop Response Function
Versus DDI with Rate Hysteresis Pacing for
Cardioinhihitory Vasovagal Syncope
FABRIZIO AMMIRATI, FURIO COLIVICCHI, SALVATORE TOSCANO,
CLAUDIO PANDOZI, MARIA TERESA LAUDADIO,* FRANCESCO DE SETA,*
and MASSIMO SANTINI
From the Department of Heart Disease, San Filippo Neri Hospital and *Medtronic Italia, Rome, Italy
AMMIRATI, F., ET AL.: DDD Pacing with Rate Drop Response Function Versus DDI with Rate Hysteresis
Pacing for Cardioinhibitory Vasovagal Syncope. Background: The effectiveness of cardiac pacing in preventing vasovagal syncope remains controversial. However, DDI pacing with rate hysteresis has been reported to prevent the recurrence of cardioinhibitory vasovagal syncope in up to 35% of affected subjects
and to reduce the overall incidence of syncopal episodes in the others. Recently, DDD pacing with a new
promising rate drop response function (Medtronic Thera-I model 7960) has become available in clinical
practice. Aim of the study: The aim of the present open trial was to test the effectiveness of this new pacing modality in patients with cardioinhibitory vasovagal syncope. Study population and methods: The
study population included 20 patients (12 males and 8 females; mean age 61.1 ± 14 yrs) with recurrent
syncope (mean number of prior episode = 6.8, range 5-11) and cardioinhibitory responses during two
head-up tilt tests: the first diagnostic and the second during drug therapy with either ^-blockade or etilephrine. The study patients were randomized to receive either DDI pacing with rate hysteresis (8 patients)
or DDD pacing with rate drop response function (11 patients). The head-up tilt test performed 1 month after pacemaker implantation was positive in 3 of 12 patients (25%) with DDD pacing with rate drop response function and in 5 of 8 patients (62.5%) with DDI pacing with rate hysteresis. The mean duration
of follow-up was 17.7 ± 7.4 months. During follow-up no patients with a DDD pacemaker with rate drop
response function had syncope, while 3 of 8 patients with a DDI pacemaker with rate hysteresis had recurrence of syncope (P < 0.05). Conclusions: These data suggest that DDD pacing with rate drop response
function is effective in cardioinhibitory vasovagal syncope and may be preferable to DDI pacing with rate
hysteresis. (PACE 1998; 21[Pt. 111:2178-2181)
vasovagal syncope, pacemaker therapy
Introduction
Neiu-ocardiogenic syncope represents a complex S3nidrome in which a specific treatment rarely
is warranted owing to the sporadic nature of the
disorder. However, in a small percentage of patienfs vasovagal episodes present as a chronic recurring disorder with a distiurbing impact on the
quality of life. Moreover, in certain circumstances
syncope may he life-threatening or cause severe injuries. Therefore a thorough clinical assessment
and proper selection of treatment is necessary in
some cases of recurrent syncope. Since patients
Address for reprints: Fabrizio Ammirati, M.D., Department of
Heart Disease, S. Filippo Neri Hospital, Via A. Friggeri 95,
00136 Rome, Italy.
2178
vdth recurrent neurocardiogenic syncope often are
resistant to medical treatment, permanent cardiac
pacing has been repeatedly proposed as long-term
therapy.^"* When significant bradycardia is noted
during tilt-induced syncopal spells, cardiac pacing
may represent a valuable therapeutic option. Several studies have tested the effectiveness of pacing
in ameliorating symptoms of vasovagal syncope in
the laboratory^"'' and in clinical settings.^'^ Cumulative data suggest that cardiac pacing may significantly reduce symptoms, although the optimal
pacing mode has not been clearly defined. In particular, single chamber W I pacing is unlikely to be
effective,^"^ while dual chamber DDI pacing with
rate hysteresis (RH) is more promising.^ DDD pacing with a new rate drop function (RDR) recently
November 1998, Part II
PACE, Vol. 21
DDD-RDR VS DDI-RH PACING FOR VASOVAGAL SYNGOPE
has become available in clinical practice.^'^" Tbe
aim of this open clinical trial was to test tbe effectiveness of tbis new pacing modality (DDD-RDR)
compared to the best known pacing tberapy (DDI
witb RH) in patients witb recurrent cardioinbibitory vasovagal syncope.
Study Population and Methods
Tbe study population included 20 patients
(12 males and 8 females; mean age 61.1 years,
range 27 to 81 years) witb recurrent unexplained
syncope despite a complete diagnostic evaluation
(mean number of syncopal events before tilt testing = 6.8; range 5 to 11). Nine (45%) patients bad
suffered severe trauma from one or more episodes.
In addition, 5 male patients were engaged in potentially dangerous occupations (2 bus drivers, 2
lorry drivers, 1 taxi driver). To be eligible for inclusion in tbe study all patients bad to fulfill tbe
following criteria: (1) a positive cardioinbibitory
response (VASIS type 2B)" to a first head-up tilt
test performed according to the Westminster protocoF^; (2) a positive cardioinhibitory response to
a second bead-up tilt test performed witbin 1
montb of tbe first test using pbarmacological treatment witb eitber etilepbrine (50 mg/day; 7 patients) or atenolol (100 mg/day; 13 patients). After
tbe second positive bead-up tilt test, tbe patients
were randomized to receive one of two types of
permanent pacemaker. Twelve patients received a
DDD pacemaker witb RDR function (Medtronic
Thera-I model 7960, Medtronic, Inc. Minneapolis,
MN, USA) and eight patients received a DDI pacemaker with RH programmed at 40/80 beats/min
(Biotronik Pbysios TC 01, Biotronik, Lake Oswego, OR, USA). One montb after pacemaker implantation all patients underwent a tbird head-up
tilt test and were followed thereafter.
The RDR Algorithm
Tbe RDR algoritbm offers tbe following programmable parameters: (1) top rate (tbe beart rate
from wbicb tbe pacemaker recognizes tbe onset of
drop in beart rate); (2) bottom rate (tbe beart rate at
wbicb tbe pacemaker recognizes tbat beart rate bas
fallen sufficiently to warrant pacing intervention);
(3) widtb beats (if tbe beart rate falls between top
and bottom rates in fewer tban tbis number of beats
pacing is triggered); (4) confirmation beats (tbe
beats below tbe bottom rate necessary before tbe
need for pacing is confirmed); (5) intervention rate
(pacing rate following confirmation); (6) intervention duration (tbe duration of pacing before gradual return to intrinsic beart rate).
RDR Programming
Because of tbe complexity of eacb pacemaker
parameter, careful individual progranmiing is necessary. We believe tbat a critical assessment of the
individual response to head-up tilt testing is required to optimize the pacing intervention during
an episode. Therefore, the RDR parameters were
programmed on the basis of the heart rate bebavior
during bead-up tilt testing in all patients as follows:
(1) tbe beart rate just before tbe onset of symptoms
was used as tbe top rate; (2) tbe bottom rate was set
at 20 beats/min above tbe beart rate at wbicb tbe
patient lost consciousness, (3) tbe widtb beats were
programmed as tbe number of beats occurring between top rate and bottom rate during tbe vasovagal reflex induced by bead-up tilt testing, (4) to
avoid inappropriate pacemaker interventions two
confirmation beats were programmed; (5) tbe intervention rate \yas programmed at 10 to 20 beats/min
above tbe top rate (at least 110-120 beats/min); (6)
intervention duration was progranuned according
to tbe duration of recovery from symptoms after tilt
table lowering.
Statistical Analysis
Pacemaker Programming
Constant cardiac pacing is not necessary in
patients witb recurrent isolated vasovagal syncope, wbile a proper pacing intervention should
be delivered for incipient syncopal episodes. Consequently, tcjaveid inappropriate pacing botb
pacemakers were programmed witb a lower rate at
40 beats/min and an AV delay of 300 ms, tbereby
favoring spontaneous cardiac rbytbm.
PACE, Voi. 21
Data are expressed as mean ± SD and bave
been analyzed witb Fisber's exact test.
Results
Head-up Tilt Testing after Implantation
Tbree of tbe 12 patients (25%) paced in DDDRDR mode and 5 of tbe 8 patients (62.5%) paced
in DDI-RH mode had syncope during the third
November 1998, Part II
2179
AMMIRATI, ET AL.
head-up tilt test performed after pacemaker implantation. Five DDD-RDR paced patients (41.6%)
had a negative response to head-up tilt due to an
appropriate pacemaker intervention during the
test, while four (33.4%) did not develop a vasovagal reaction during the diagnostic procedure. Two
of the DDI-RH paced patients (25%) had a negative
response to head-up tilt from appropriate pacemaker intervention, while one patient (12.5%)
had no vasovagal reaction. Two of the three DDDRDR paced patients with positive response to
head-up tilt test underwent pacemaker reprogramming and had a negative fourth head-up tilt test, in
one case from appropriate pacemaker intervention
and in the other because of absence of a vasovagal
reaction. Tbe tbird patient refused to undergo furtber bead-up tilt testing.
Follow-up
Tbe mean duration of follow-up was 17.7 ±
7.4 montbs. During follow-up no DDD-RDR paced
patients bad syncope, wbile tbree of tbe eigbt patients (37.5%) witb DDI-RH pacemaker bad a syncopal episode (P < 0.05).
Discussion
Most clinicians agree tbat benign forms of
neurocardiogenic vasovagal syncope do not need
any specific tberapeutic intervention.^^ However,
recurrent, unberalded, traumatic forms occiurring
in older patients often are considered malignant
and require a careful clinical assessment and a
personalized tberapeutic approacb.^* Several of
studies bave evaluated tbe effects of cardiac pacing in the prevention of vasovagal episodes in tbe
laboratory ^~'' and in clinical settings,^"® altbougb
limited prospective data bave been gatbered.^^
Several studies bave tested tbe effectiveness of
temporary pacing during tilt induced vasovagal
syncope. In a study by Fitzpatrick et al.,^ temporary pacing witb simulated hysteresis did not prevent hypotension and all patients remained symptomatic. However, it prevented syncope in 85.7%
(6/7 patients ) of the cases. In a subsequent paper,
Samoil et al.^ compared two different pacing
strategies in tilt-induced vasovagal syncope. DVI
pacing prevented sjnicope in 50% (3/6 patients )
of tbe cases, wbile prolonging symptoms to syncope in 33.3% (2/6 patients ) of tbe cases. However, W I pacing was ineffective, altbougb a trend
2180
toward a longer prodromal pbase was noted in all
cases. In tbe study by Sra et al.,'' 22 patients underwent two consecutive tilt tests, tbe first witbout pacing and tbe second with demand pacing
available (AV sequential pacing in all but two patients, who received VVI pacing because of concomitant atrial fibrillation). Syncope was noted in
5 patients (5/22, 22.7%) during paced tilt compared witb 18 (18/22, 81.8%) during tbe unpaced
tilt test. Cumulative evidence from tilt-based studies cannot be considered conclusive as too few patients were enrolled and because tilt-induced
vasovagal bypotension is unlikely to be prevented
by tbe pacing modalities used in tbe preliminary
experiences. Witb respect to clinical studies, tbe
outcome of 37 patients paced for cardioinbibitory
vasovagal syncope was retrospectively evaluated
by Petersen et al.^ Dual cbamber pacemakers witb
rate bysteresis were implanted in 84% of tbe
cases, and patients were followed for a mean period of 50.2 montbs. A significant symptom reduction was noted in 89% of patients, and 62% remained syncope-free during follow-up. On tbe
basis of tbese results, DDI pacing witb RH
presently is considered tbe most effective pacing
option for cardioinbibitory forms of vasovagal
syncope.^ However, even if cardiac pacing may
improve tbe clinical outcome of patients witb recurrent cardioinbibitory vasovagal syncope, tbe
correct pacing mode remains controversial.^^ Recently, Benditt et al.^° reported a multicenter clinical experience witb DDD-RDR pacing in 39 patients witb recurrent vasovagal syncope.
Twenty-tbree (58.9%) remained asymptomatic
during a mean follow-up of 204 days, wbile 6
(15.3%) bad recurrences, and 10 (25.6%) bad
presyncope. Tbese encouraging data add support
to tbe role of cardiac pacing in severe recurrent
forms of vasovagal syncope. A critical appraisal of
tbe incomplete effectiveness of previously tested
pacing modalities in preventing tilt induced vasovagal syncope reveals tbat most of tbe pacing failures may be related to delayed pacemaker intervention during tbe episode.^^"^^ Patients witb
vasovagal syncope do not need continuous pacing, but require physiological pacing at the very
moment of the vasovagal reaction. Pacemaker intervention should always consider the temporal
relation between tbe development of bypotension
and bradycardia. To prevent syncope, the ideal
device should sense the initial heart rate drop and
November 1998, Part II
PAGE, Vol. 21
DDD-RDR VS DDI-RH PACING FOR VASOVAGAL SYNCOPE
pace early in the episode at a relatively high rate.
Such relative tachycardia is expected to provide a
sufficient cardiac output to overcome the effects of
vasodepression. Therefore, the new RDR function
included in a DDD pacemaker may represent a significant improvement in pacing therapy for vasovagal syncope. In this clinical study this new pacing modality was compared with the hest-known
pacing mode (DDI with RH) in a strictly selected
population of patients with a high recurrence rate
of cardioinhibitory vasovagal syncope resistant to
medical treatment eind with a high incidence of
trauma. Approximately 60% of such patients are
expected to have another S5nicopal spell within 1
year of head-up tilt testing^^ and need particular
clinical attention. In such defined patients, pacing
therapy is probahly a promising therapeutic option to reduce the incidence of potentially dangerous syncopal episodes. In our series, DDD-RDR
pacing was fully effective in preventing recurrences over the intermediate term (17.7 months).
Moreover, it proved to be superior to DDI-RH pacing (P < 0.05), previously considered the best pacing mode for these patients. Another point of interest in this study was the absence of a significant
difference between the two tested pacing options
in the assessment of effectiveness during head-up
tilt testing. This finding suggests that, although tilt
testing was necessary for the proper programming
of RDR function, its role in correctly predicting
the effectiveness of any form of therapy may be
overemphasized.*'^^ The only measure of the impact of a specific therapy in recurrent vasovagal
syncope hinges on a sufficiently long clinical follow-up. This experience in carefully selected patients with cardioinhibitory vasovagal syncope
represents a preliminary step before studies in
which the enrollment of subjects with various
forms of the syndrome (mixed and vasodepressor), and a longer follow-up, should be considered.
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