PPT ON NEUROCARDIOGENIC SYNCOPE AND ITS TREATMENT

1. NEUROCARDIOGENIC SYNCOPE:
CURRENT STATUS WITH EVIDENCE
ON RATE DROP PACING
DR DEVINDER KUMAR

2. SYNCOPE
Defined as brief and self-limited period of loss of
consciousness due to transient global cerebral
hypoperfusion.

4. NEUROCARDIOGENIC SYNCOPE
Refers to heterogeneous group of conditions in
which cardiovascular reflexes that are normally
useful in controlling the circulation become
intermittently inappropriate, in response to a
trigger, resulting in vasodilatation and/or
bradycardia.

5. VVS
• Magnitude of the problem
• Often encountered in young otherwise
healthy patients, but may occur in all age
groups, and is generally unassociated with
cardiovascular or neurologic diseases.

6. VVS
• Common triggers: Unpleasant sights, pain,
extreme emotion, and prolonged standing.
• Autonomic activation (eg, flushing and
sweating) in the premonitory phase strongly
suggests a vasovagal origin.
• Typical presentations occur in about 40% of
presumed vasovagal syncope, but less often in
older patients.

7. PATHOPYSIOLOGY OF VVS
• Incompletely understood.
• Afferent pathway remains uncertain (no
human recordings of baroreceptor signals
during syncope have been made).
• Experimental data from cats.
• It consists of paradoxic impulses from a
hypercontractile, empty left ventricle, which
are conducted by unmyelinated vagal
afferents to the brain stem.

8. • The efferent response is transient vagal
stimulation of the heart and widespread
sympathetic withdrawal.

10. Extrapolating this data to humans?
• Feline reflex, recorded under general anesthesia
and major instrumentation, to the conscious
human, with the knowledge that cats do not faint
• There is evidence to suggest that humans can
have VVS after cardiac transplantation
Fitzpatrick AP, Banner N, Cheng A, et al. J Am Coll Cardiol 1993;21:1132–7
Scherrer U, Vissing S, Morgan BJ, et al. N Engl J Med 1990;322:602–4

11. Extrapolating this data to humans?
• Mechanism when the stimulus is central ? (eg,
blood–injection–injury phobia)
• Echocardiography during tilt

12. DIAGNOSIS
• History
• Physical examination
• ECG
• ECHOCARDIOGRAPHY

14. DIAGNOSIS
• HUTT
• ILRs

15. PHYSIOLOGIC IMPACT
OF UPRIGHT POSTURE
• Initially, as upright posture is achieved, 500 to
800 ml blood is shifted to the lower part of
the body.
• Most of this redistribution occurs in the first
10 seconds.

16. PHYSIOLOGIC IMPACT
OF UPRIGHT POSTURE
• Subsequently, in normal individuals, an
additional 700 ml protein-free fluid is filtered
into the interstitial space in the next 10
minutes.
• The result of these two actions is marked
reduction of venous return and stroke volume.

17. PHYSIOLOGIC IMPACT
OF UPRIGHT POSTURE
• These are compensated by both ↑ HR &
constriction of resistance and capacitance
vessels.
• If compensatory cardiovascular response
maintains MAP atleast 60 mmHg or
more………………..no syncope.

18. PHYSIOLOGIC IMPACT
OF UPRIGHT POSTURE
• In susceptible individuals, an inappropriate set
of neural reflex responses appear to be
triggered - i.e. vasodilatation and bradycardia -
the vasovagal response.
• It is this latter possible outcome that forms
the basis for the use of tilt testing in the
evaluation of patients with suspected
vasovagal syncope.

20. Classification of Positive Response
Response Definition
Type 1
Mixed
HR drops at the time of the syncope, but not to < 40 bpm
If HR drops to <40 bpm, the drop lasts < 10 seconds
The blood pressure (BP) drops before the HR
Type 2A
cardioinhibitory
without asystole
The heart rate drops < 40 bpm for > 10 seconds.
The BP drops before the HR
Type 2B
cardioinhibitory
with asystole
There is asystole that lasts > 3 seconds.
The decrease in BP precedes or coincides with the drop in HR
Type 3
vasodepressor
HR does not drop more than 10% compared to the peak at the
time of syncope

22. HUTT
• Is HUTT indicated in every patient suspected
of VVS?
• Are we better placed after HUTT and if so
how?

23. SENSITIVITY
• No definite evidence based clinical definition
of neurocardiogenic syncope.
• In fact, it is a syndrome defined by a test,
rather than a test that diagnoses a syndrome.
• There is a lack of the validation of tilt table
testing against populations with defined
causes of syncope (hence difficult to know
sensitivity of tilt table tests).

24. SPECIFICITY
• Life time prevalence of VVS 20-40% of general
population.
• It is not known how many control subjects are
simply people who have not yet fainted but will
at some later time (hence difficult to assess true
specificity).
• Also the specificity decreases with
pharmacological provocation.

25. METHODOLOGICAL ROBUSTNESS
• In HUTT, the likelihood of positive tests depends
on whether
Intravenous cannulation is used,
The angle and duration of head-up tilt,
Whether, how and which drug challenge is used,
The number of head-up iterations during the test,
The volume status of the subject,
Subject’s age

26. REPRODUCIBILITY
• Tilt table tests are 70% to 87% reproducible
over periods of days to months.
• The degree of bradycardia and hypotension
during tilt table tests is only modestly
reproducible, suggesting that patients cannot
be classified based on the hemodynamic
changes seen on a single positive tilt table
test.

27. REPRODUCIBILITY
International Study on Syncope of Uncertain
Etiology (ISSUE) investigators concluded that the
degree of bradycardia during a positive tilt table
test does not correlate with the degree of
bradycardia recorded in an ILR during a
subsequent spontaneous syncopal spell in the
community.

28. PROGNOSTIC VALUE
• Tilt table test outcomes do not predict clinical
outcome.
• Patients with negative and positive tests have
similar symptoms, similar symptom burdens,
similar clinical outcomes in the 3 years
following the tilt table test.
Sheldon R, Rose S, Connolly S, et al. Eur Heart J 2006;27:344–50
Sheldon R, Rose S, Koshman ML. Am J Cardiol 1997;80:581–5

29. SELECTING THERAPIES
• The need for isoproterenol to induce syncope
does not predict a clinical response to beta-
blockers.
• Positive during tilt table testing does not
predict a clinical response to pacemakers.
Sheldon R, Connolly S, Rose S, et al. Circulation 2006;113:1164–70
Sud S, Massel D, Klein GJ, et al. Am J Med 2007;120:54–62

30. USEFULLNESS OF HUTT
• Positive test indicates susceptibility to neurally
mediated syncope.
• They have provided the inclusion criteria for
diagnostic and long-term observational studies
and randomized clinical trials.
• Tilt table tests have been used as platforms for
physiologic studies and pilot treatment studies.

31. USEFULLNESS OF HUTT
• Added reassurance.
• For education to early identification of
premonitory symptoms.
• For tilt training.
• For psychogenic syncope.

32. ILRs
• Are small devices implanted subcutaneously in
the left hemithorax.
• Have no intravascular leads, thereby avoiding
most complications caused by pacemakers.
• Last about 3 years.

34. ILRs
ECG findings during syncopal spells within each
patient are highly reproducible, indicating that a
single syncopal spell suffices to provide useable
diagnostic information.

35. ILRs
The overall likelihood of establishing a diagnosis
within the 2- to 3-year lifetime of an ILR is
therefore in the range of 40%, which agrees well
with the likelihood of at least 1 syncope
recurrence in numerous observational and
randomized clinical trials.
Brignole M, Vardas P, Hoffman E, et al. Europace 2009;11:671–87

36. Carotid Sinus Syndrome
• CSS tends to occur most often in older men,
and is especially associated with concomitant
atherosclerotic disease.
• The most common symptoms attributed to
CSH are dizziness (presyncope) and syncope.
• Classical provocative maneuvers: head
turning, shaving, or the wearing of tight neck
collars.

37. PATHOPHYSIOLOGY
Neurodegenerative process in medullary nucleii,
which may in turn be associated with impaired
baroreceptor regulation.

38. CSM
• The procedure should be done with the
patient in both the supine and upright
positions.
• Continuous ECG and BP monitoring.
• Following baseline measurements, CSM is
performed for 5 to 10 seconds at the anterior
margin of the sternocleidomastoid muscle at
the level of the cricoid cartilage.

39. • CICSH is defined as greater than or equal to 3
seconds asystole during carotid massage.
• Vasodepressor CSH is defined as greater than or
equal to 50 mm Hg decrease in blood pressure in
response to carotid sinus massage.
• Mixed CSH is diagnosed by the presence of a
greater than or equal to 3-second pause, along
with a decrease in systolic blood pressure of at
least 50 mm Hg upon rhythm resumption.

40. • If a positive result is not obtained, the
procedure is then repeated on the opposite
side after an interval of 1 to 2 minutes.
• One-third of patients have a positive response
only in the upright position.
• If a cardioinhibitory response is elicited,
atropine may be administered before
repeating massage to determine the degree of
contributory vasodepression.

41. THERAPY FOR
VASOVAGAL SYNCOPE

42. TREATMENT GOALS?
• Prevention of recurrence.
• Prevention of associated injuries.
• Improvement of quality of life.
• Not to prolong survival, as this is a benign
condition.

43. NONPHARMACOLOGICAL
• Education and counselling.
• Salt and water increase.
• Orthostatic training.
• Counterpressure maneuvers.

44. Education and counselling
• Reassurance about benign nature of the
condition.
• Help in identifying prodromal symptoms early (so
as to implement counterpressure maneuvers)
and potential known triggers (venipuncture,
volume depletion, environmental triggers) which
could be avoided.

45. Salt and Water Increase
• Volume expansion: First line therapy and
cornerstone of treatment.
• Improves orthostatic tolerance in patients
with recurrent VVS.
• Beneficial effects are reported in most
subjects within 1 week.

46. Orthostatic Training
• Patients stand with their upper back positioned
against a wall or a corner without moving their
arms or legs.
• Starting at 5 mins twice daily, gradually increased
over a period of 6-8 weeks to 40 mins twice daily.
• Orthostatic training can also be achieved by tilt
training.

48. Orthostatic Training
• Physiologic objective: Reset baroreceptor
reflexes, improving gravitational stress
response by leading to more efficient
vasoconstriction.

49. Orthostatic Training
• Patients with recurrent VVS were randomized
to treatment with propranolol, disopyramide,
or tilt training. On repeat tilt table test,
pharmacologic therapy was not effective at
preventing syncope (32% propranolol, 26%
disopyramide). In contrast, tilt training was
highly efficient and prevented syncope in 92%
of patients.
Abe H, et al. Pacing Clin Electrophysiol 2002;25:1454–8

50. Orthostatic Training
Patients with VVS refractory to standard
medical therapy were randomized to a control
or orthostatic training group.
After a mean follow-up of 18 months,
recurrent syncope was experienced by 56.5% in
the controlled group, compared with no syncope
recurrences in the orthostatic training group.
Di Girolamo E, et al.k. Circulation 1999;100:1798–801

51. Orthostatic Training
• Compliance is poor.
• Three RCTs comparing either orthostatic
training or tilt training have failed to confirm
reductions in long-term syncope recurrence.
1. Reybrouck T, Heidbu¨chel H, Van De Werf F, et al. Pacing
Clin Electrophysiol 2002;25:1441–6
2. Gajek J, Zysko D, Mazurek W. Kardiol Pol 2006;64:602–8
3. Duygu H, Zoghi M, Turk U, et al. Pacing Clin Electrophysiol
2008;31:592–6

52. Orthostatic Training
Progressively prolonged periods of
enforced orthostatic training may reduce
syncope recurrence in highly motivated young
patients when prodromal symptoms are present
and reproducible.

53. Counterpressure Maneuvers (CPMs)
• Younger patients: VVS is preceded by
prodromal symptoms and early recognition
provides enough time to implement CPMs.
• Isometric CPMs of legs (leg crossing) or arms
(hand grip and arm tensing) are able to
induce a significant BP increase during the
phase of impending VVS.

54. Counterpressure Maneuvers (CPMs)

55. Counterpressure Maneuvers (CPMs)
• By increase in sympathetic nerve discharge
and vascular resistance during maneuvers and
by mechanical compression of the venous
vascular bed in the legs and abdomen.

56. Counterpressure Maneuvers (CPMs)
• The Physical Counterpressure Maneuvers Trial
(PC-Trial) was a multicenter, prospective,
randomized clinical trial evaluating the
effectiveness of CPMs in 223 patients with
recurrent VVS and recognizable prodromal
symptoms.

57. During a mean follow-up period of 14
months, the occurrence of syncope was
significantly lower in the group trained in CPMs
(50.9% of the patients receiving conventional
treatment vs 31.6% of those trained in CPMs;
P<.005)

58. CPMs are effective, feasible, safe, and well
accepted by patients in daily life and should be
advised as first-line treatment in younger
patients presenting with VVS and recognizable
prodromal symptoms.

59. PHARMACOLOGICAL TREATMENT
• Beta blockers
• Adrenergic agonists
• Fludrocortisone
• SSRIs
• Experimental therapies

60. Beta blockers
• Based on the initial understanding of the
mechanism of VVS, b-blockers were used as
first-line therapy.
• Early observational studies showed significant
reductions in recurrence of syncope, mostly
assessed by repeated tilt testing.

61. Beta blockers
• RCTs have failed to show beneficial effects of
b-blockers in unselected patients with
recurrent VVS.
• POST(Prevention Of Syncope Trial): large
multicenter, randomized, placebo-controlled,
double-blind study.
• Metoprolol (25 to 200 mg) vs placebo in VVS.

62. Beta blockers
• No differences in the primary outcome (first
recurrence of syncope) were seen between
the groups.
• Subgroup analysis in POST: in patients older
than 42 years, metoprolol may be effective
based on a 48% relative risk reduction (RRR) in
time to first recurrence of syncope.

63. Beta blockers
• The latest ESC guidelines do not recommend
beta-blockers for the routine treatment of
recurrent VVS and might be beneficial in
patients older than 42 years.

64. Alpha agonists
Potent vasoconstrictors that ameliorate
the reduction in peripheral resistance
responsible for venous pooling and
vasodepression, and therefore result in an
increase systolic and diastolic blood pressure.

65. Alpha agonists
• Etilefrine was the first a-agonist tested for
treatment of VVS.
• The Vasovagal Syncope International Study
(VASIS), was a large, multicenter, placebo-
controlled, double-blinded study – no
significant differences in the recurrence of
syncope and time for first syncopal episode
compared with placebo.

66. MIDODRINE
Midodrine, a specific alpha 1-agonist
compared with placebo, provides beneficial
effects in symptom frequency, symptoms during
head-up tilt, and quality of life.

67. A recent meta-analysis of 6 randomized
clinical trials evaluating alpha-agonists for
treatment of VVS included 329 patients. This
meta-analysis reported a large effect favoring
midodrine compared with placebo (odds ratio,
0.21; 95% CI, 0.06–0.77; P = 0.02).
Liao Y, Li X, Zhang Y, et al. Acta Paediatr 2009;98:1194–2000

68. • Midodrine is reasonably well tolerated, but its
use is not recommended in patients with
hypertension or heart failure.
• Midodrine should be administered 3 times per
day and titrated to a maximum dose of 40 mg.

69. FLUDROCORTISONE
• Corticosteroid with marked mineralocorticoid
activity that increases sodium and fluid
retention and, consequently, intravascular
volume expansion.
• It upregulates alpha-adrenergic receptors and
may prevent vasodilatation during neurally
mediated reflex responses.

70. FLUDROCORTISONE
• The second POST trial (POST II) randomized
213 patients to fludrocortisone (0.1 to 0.4 mg
daily) or placebo.
• The primary outcome of the study was time to
the first recurrence of syncope, which was not
significantly reduced by fludrocortisone.

71. FLUDROCORTISONE
• Available evidence does not show a significant
reduction in syncope recurrence with
fludrocortisone in unselected patients with
VVS.
• Further analysis of the POST II population may
identify subgroups that benefit from this
therapy.

72. SSRIs
• Fluoxetine vs propranolol: no differences in
syncope-free period.
• A significant improvement in quality of life
was observed with fluoxetine.
Theodorakis GN, Leftheriotis D, Livanis EG, et al. Europace 2006;8:193–8.

73. SSRIs
• Paroxetine 20 mg/d or placebo.
• After 1 month of treatment, the response
rates (negative tilt) were 61.8% versus 38.2%
(P<.001) in the paroxetine and placebo
groups, respectively.
Di Girolamo E, Di Iorio C, Sabatini P, et al. J Am Coll Cardiol 1999;33:1227–30

74. • Paroxetine significantly improved symptoms
compared with placebo (17.6% vs 52.9,
P<.0001).
• SSRIs are rarely the first choice in the
treatment of neurally mediated reflex syncope

75. Patients in whom standard therapies are
ineffective, poorly tolerated, or contraindicated
might be prescribed SSRIs, which may be
particularly useful in patients with associated
anxiety and panic disorders

76. PACING IN SYNCOPE
• Only treatable component- BRADYCARDIA.
• With the use of tilt testing, several authors
analyzed the role of pacing in preventing
syncope induced during tilt testing.

77. SPECIAL PACING ALGORITHMS
• Rate drop response (RDR) algorithm.
• Closed loop stimulation (CLS).

78. RATE DROP RESPONSE (RDR)
Two detection elements that can be
activated simultaneously and trigger
intervention therapy independently from each
other
Drop-detect method
Low-rate detect method

79. DROP DETECT METHOD

80. LOW RATE DETECTION METHOD

81. CLOSED LOOP STIMULATION (CLS)
• This pacing system tracks the variations in
intracardiac impedance during the systolic
phase of the cardiac cycle on a beat-to-beat
basis.
• Changes in intracardiac impedance are closely
correlated with both right and left ventricular
contractility.

82. Based on that relationship, CLS transfers
the detected changes in myocardial contraction
dynamics into individual pacing rates.

83. In the very first days following programme
implementation, CLS is adjusted to each
individual patient: a reference curve is created
and continuously updated with beat-to-beat
impedance measurements.

84. IMPEDANCE MEASUREMENTS

85. CLS-Reference Vs Load curve
• With each heartbeat, CLS determines the
impedance curve (VIMP) during ventricular
contraction (load curve) and compares it to its
reference curve at rest (rest curve).

86. REFERENCE Vs LOAD CURVE

87. PACING IN RESPONSE TO
CONTRACTION DYNAMICS

88. NONBLINDED STUDIES

89. RANDOMIZED BLINDED STUDIES

90. DISCREPANCIES IN STUDIES
• PLACEBO effect.
• The vasodepressor and cardioinhibitory
components may vary in each patient with
different episodes and 50% to 83% of syncopal
episodes may not have a cardioinhibitory
component ((Sheldon & Connolly, 2003).

91. SUMMARY
• Neurocardiogenic syncope is a common
problem with significant burden.
• Most important for the diagnosis is history.
• Present therapeutic approaches not strongly
supported by randomized clinical trials.

92. SUMMARY
• Pacing in patients with neurocardiogenic syncope is a
difficult decision and requires careful judgement.
• Treatment success is dependent on the underlying
mechanism of neurocardiogenic syncope.
• Use of an ILR can improve identification of patients
with neurocardiogenic syncope, in whom pacemaker
treatment is helpful, esp. those with spontaneous
asystolic episodes.

93. SUMMARY
• Do not expect miracles.
• Patience by both physician and the patient.

94. Status of Pacing in VVS
• Perception of pacing for VVS changing:
– VVS with +HUT and cardioinhibitory response a Class IIb indication1
• Recent clinical studies demonstrated benefits of
pacing in select VVS patients:
– VPS I
– VASIS
– SYDIT
– VPS II –Phase I
– ROME VVS Trial
1Gregoratos G, et al. ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmic Devices. Circulation. 1998; 97:
1325-1335.

95. Status of Pacing in VVS
• Benefits of specific device features evolving:
– Some success with DDD/DDI hysteresis 1
• “False positives” may result in prolonged high rate intervention
• Tied to lower rate intervention
– Rate drop therapies designed for treating VVS
syncope appear to be successful 2-4
1 Sutton R, et al. Circulation. 2000; 102:294-299.
2 Connolly S, et al. J Am Coll Cardiol 1999; 33:16-20.
3 Ammirati F, et al. Circulation. 2002; 104: 52-57.
4 Ammirati F, et al. NASPE Abstract #307. PACE, Vol. 24, April 2002, Part II.

96. VPS-I
Vasovagal Pacemaker Study I
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.
 Study Design:
54 patients randomized, prospective, single center
_ 27 DDD pacemaker with rate drop response (RDR)
_ 27 no pacemaker
 Patient Inclusion Criteria:
6 syncopal events ever (median lifetime history of 35 episodes (no
pacemaker) and 14 episodes (pacemaker).
+HUT
Relative bradycardia*
*a trough heart rate <60/min if no isoproterenol used,
<70/min if up to 2 mcg/min isoproterenol used, or <80/min
if over 2 mcg/min isoproterenol used

98. VPS-I
• Conclusion:
Dual-chamber pacing with rate drop response
reduces the likelihood of syncope in patients
with recurrent VVS.
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.

99. VASIS
Vasovagal Syncope International Study
Sutton, R, et al. Circulation. 2000; 102:294-299.
 Study Design:
 42 patients, randomized, prospective, multicenter
_ 19 DDI pacemaker (80 bpm) with rate hysteresis (45 bpm)
_ 23 no pacemaker
 Patient Inclusion Criteria:
 > 3 syncopal events in 2 years and last event occurring within 6 months of
enrollment and,
 Positive VASIS type 2A or 2B cardioinhibitory response to HUT and,
 Age > 40 years or drug refractory if < 40 years

101. VASIS
• Conclusion:
Dual-chamber pacing (at a rate of 80 bpm ) with
rate hysteresis reduces the likelihood of syncope
in patients with tilt-positive, cardioinhibitory
syncope.
Sutton, R, et al. Circulation. 2000; 102:294-299.

102. SYDIT
Syncope Diagnosis and Treatment Study
• Study Design:
– 93 patients randomized, prospective, multicenter
• 46 DDD pacemaker with rate drop response (RDR)
• 47 Atenolol 100 MG/D
• Patient Inclusion Criteria:
– > 55 yrs
– > 3 syncopal episodes in 2 years
– + HUT with relative bradycardia (trough HR <60 bpm)
Ammirati F, et al. Circulation. 2001; 104:52-57.

104. SYDIT
• Conclusion:
Dual-chamber pacing + RDR is superior to Atenolol
in prevention of recurrent syncope in highly
symptomatic patients with relative bradycardia
during tilt-induced syncope.
Ammirati F, et al. Circulation. 2001; 104:52-57.

105. VPS-II: Phase I
Vasovagal Pacemaker Study-II
• Study Design:
– 100 patients, randomized, prospective, multicenter
• 50 DDD pacemaker with rate drop response (RDR)
• 50 ODO pacemaker (inactive mode)
• Patient Inclusion Criteria:
– > 6 syncope events ever or > 3 syncope events in 2
years or > 1 syncope event in 6 months and,
– Positive HUT with syncope or presyncope and a
heart rate blood pressure product <9000.
Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking
Clinical Trials, May 11, 2002.

107. VPS-II: Phase I
 Conclusions:
 Lower than anticipated syncope event rate in the control
arm.
 Higher than anticipated event rate in the treatment group.
 Consequence: treatment effect was less than VPS-I.
 Results favored pacing but the treatment effect was not
statistically significant.
Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking
Clinical Trials, May 11, 2002.

108. VVS Pacing Trials Conclusions
DDD pacing reduces the risk of syncope
in patients with recurrent, refractory,
highly-symptomatic, cardioinhibitory
vasovagal syncope.

109. SAFE PACE Study Design
• Randomized controlled trial (N=175):
– Pacing (87) vs. No Pacing (88)
• Single center: Royal Victoria Infirmary,
Newcastle, UK
• Recruitment began: April 1998
• 12 month follow-up per patient
• Study concluded: May 2000
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.

110. SAFE PACE Inclusion Criteria
• Consecutive adults attending accident
and emergency department
• > 50 Years
- Experienced non-accidental fall
•Positive response to CSM
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.

111. SAFE PACE Screening Process
Accident and Emergency Attendees > 50 Yrs
Falls or Syncope
Non-accidental Fall
CSM Performed
Cardioinhibitory or Mixed CSH
RCT
Control Pacemaker
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.

112. SAFE PACE Screening Results
RCT (n=175)
Control
(n=88)
Pacemaker
(n=87)
• No pacing intervention • Medtronic Thera DR
(Rate Drop Response
Algorithm)
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.

113. SAFE PACE Results
Number of Falls
Control
n=87
Pacemaker
n=84
% Participants
w/Falls
60% 58%
Total Number of
Falls*
699 216
Mean Number of
Falls**
9.3 4.1
* Falls during 12 months post randomization
** Crude adjustment calculation
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
70%
Reduction
[OR 0.42; 95%
CI: 0.23, 0.75]

114. Control
N=87
Pacemaker
N=84
% Participants
w/Syncopal Events
22% 11%
Total Number of
Syncopal Events
47 22
Mean Number Syncopal
Events
1.14 0.20
SAFE PACE Results
Number of Syncopal Episodes
50%
Reduction
[OR 0.53; 95%
CI 0.23; 1.20 ns]
* Syncopal events 12 months past randomization
** Crude adjustment calculation
Kenny RA, J Am Coll Cardiol 2001; 38:000-000.

115. Control
n= 87
Pacemaker
n= 84
% Participants w/Injurious
Events
41% 35%
Total Number Injury
Events
202 61
-Fractures
-Soft Tissue Injury
4
198
3
58
SAFE PACE Results
Number of Injury Events
70%
Reduction
* Injurious events 12 months post randomization
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.

116. SAFE PACE Conclusions
In patients with unexplained falls and a
diagnosis of Cardioinhibitory CSH, cardiac
pacing reduced the total number of:
• Falls by 70%
• Syncopal events by 53%
• Injurious events by 70%
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.

117. Role of Pacing in CSS --
Syncope Recurrence Rate
Brignole et. Al. Diagnosis, natural history and treatment. Eur JCPE. 1992; 4:247-254
0%
25%
50%
75%
No Pacing Pacing
57%
%6
Class I indication for pacing
(AHA and BPEG)
Limit pacing to CSS that is:
•Cardioinhibitory
•Mixed
DDD/DDI superior to VVI
(Mean follow-up = 6 months)

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124. THANK YOU