Vasovagal Syncope: Vasovagal Syncope: Current Management and Role of Current Management and Role of Cardiac PacingCardiac PacingAntonio Raviele, MD, FESC, FHRSAntonio Raviele, MD, FESC, FHRS
ALFA – Alliance to Fight Atrial fibrillation, Mestre – Venice, ItalyALFA – Alliance to Fight Atrial fibrillation, Mestre – Venice, Italy
Curso de Actualizaciòn en Arritmias, Mexico City, Mexico - 16-18 November, 2016
Treatment of VVS
Only rarely necessary
Vasovagal Syncope
•Is a begnin condition
•Is not a threat to life
•Does not impair quality of life
Majority of casesMajority of cases
Patient Reassurance
• Benign nature of VVS
Patient Counseling
• Recognition premonitory symptoms
• Avoidance of precipitating conditions
• Prolonged Sitting - Standing
• Crowded - Hot Places
• Strenuous Exercise in Warm Enviroment
• Dehydration - Volume Depletion
• Potentially Hypotensive Drugs
• Venipuncture – Emotional/Stressful Situations
VVS - Triggering factors
Treatment - VVS
• Frequent syncopal episodes
• No predictable circumst. / warning sympt.
• Important physical injury
• Potential occupational hazard
IndicatedIndicated
Therapeutical Options
NON PHARMACOLOGICAL
• alpha-agonists• betablockers• fludrocortisone • serotonin inhibitors• disopyramide• scopolamine• teophylline/clonidine• ACE-I
PHARMACOLOGICAL ELECTRICAL
• pacemaker• ablation
• reassurance • counseling • high salt diet• water intake• support stockings• counter-maneuvers• tilt training
Therapeutical Options
NON PHARMACOLOGICAL
• reassurance • counseling • high salt diet• water intake• support stockings• counter-maneuvers• tilt training
Leg Crossing Leg Crossing & &
Muscle Muscle TensingTensing
HandgripHandgrip Arm muscle Arm muscle tensingtensing
Counter-Pressure Maneuvers
SquattingSquatting Bending Bending forwardforward
Crash Crash positionposition
Mechanism of action
• Venous Return
• Cardiac Output
• Blood Pressure
• Interruption of VV Reaction
J Am Coll Cardiol 2006; 48: 1652-7
Van Dijk N et al.J Am Coll Cardiol. 2006;48:1652-1657
Kaplan-Meier syncope-free survival curve of time to first syncopal recurrence
31.6%31.6%
50.9%50.9%
FU = 14 mthsFU = 14 mths
Comparison between Kaplan–Meier curves of freedom from syncope recurrence in patients who performed PCM training and control untreated group of patients.
Tomaino M et al. Europace 2014;16:1515-1520
PCM
No Therapy
ISSUE-3 trial subanalysis
PACE 1998;21:193-196PACE 1998;21:193-196
HUTT / Tilt Training
• 5 in-hospital head-up tilt sessions for a planned duration of 10-50 minutes at 60° (once a day for 5 days)
• daily tilt training at home by standing against a wall for a planned duration of up to 40 minutes (twice a day)
Tilt TrainingTilt Training
In the literature there are discordant results
regarding the real efficacy of this measure
Vyas A, et al. Int J Cardiol 2012; 167: 1906-1911
• However, the effect is lost if only randomized studies are included.• Moreover, tilt training is hampered by the low compliance of the patients to
continue the treatment for a long period of time.
A recent metanalysis of all studies performed with tilt training has shown that this therapy is effective in preventing recurrences of VVS with 70% decrease
HUTT / HUTT / Tilt TrainingTilt Training
• Tilt training, at best, and if really effective,
may be recommended only in a very selected
group of highly motivated patients.
Therapeutical Options
• alpha-agonists• betablockers• fludrocortisone • serotonin inhibitors• disopyramide• scopolamine• teophylline/clonidine• ACE-I
PHARMACOLOGICAL
VVS Open Studies – Drug EfficacyVVS Open Studies – Drug Efficacy
• alpha-agonists 73% 86% 12
• betablockers 74% 81% 15
• fludrocortisone 47% 68% 13
• serotonin inhibitors 55% 92% 13
• disopyramide 87% 91% 24
• scopolamine 44% 93% 14
• teophylline 33% 50% 11
Drug Acute Chronic FU
In all these studies, with only few exceptions, no difference was found in the recurrence rate of syncope during follow-up between pts treated with drugs and those treated with placebo
Placebo – Controlled Trials
Ammirati F et al. In: Alboni P, Furlan R (eds), Vasovagal Syncope, Springer 2015; 237-245
Liao Y, et al. Acta Paediatrica 2009; 98: 1194-1200
Midodrine
This drug has given positive results in 4 studies, with a consistent risk reduction of syncopal recurrences of more than 60%,
• These studies are not placebo-controlled
• Studied children or extraordinarily symptomatic pts
• Used tilt test outcomes as the main measure
• Regarded a limited number of patients
• Had a short period of follow-up
Midodrine & VVS / Positive results
Europace 2011; 13: 1639-1647
Metanalysis of prespecified, prestratified substudy of POST I and a large earlier observational study showed evidence of benefit of metoprolol in pts older than 42
yearsSheldon RS et al. Circ Arrhythm Electrophysiol. 2012;5:920-926
(Metoprolol) (Metoprolol)
Metoprolol
• However, these data need to be confirmed by an ongoing prospective, multicenter, randomized trial (POST 5) with results expected in 2017, before they can be largely applied in daily clinical practice.
Metoprolol & VVS / Positive results
Sheldon R. et al.J Am Coll Cardiol. 2016; 68: 1-9
49%
Fludrocortisone
Fludrocortisone, at a dose of 0.2 mg daily, significantly reduced by 49% the syncopal recurrence rate after the initial 2 weeks of dose stabilization.
However, the study did not meet its primary objective of demonstrating that fludrocortisone reduces the likelihood of vasovagal syncope by the specified risk reduction of 40%. Indeed the reduction was more modest, only 31%
31%
Drug Therapy for Vasovagal SyncopeDrug Therapy for Vasovagal Syncope
“To date there are not sufficient data to
support the use of any pharmacological
therapy for vasovagal syncope”
ESC Guidelines on Management of SyncopeBrignole et al. Eur Heart J 2001; 22: 1256-1306
Therapeutical OptionsTherapeutical Options
ELECTRICAL
• pacemaker• ablation
VVS / Rationale for pacingVVS / Rationale for pacing
To counteract
the cardioinhibitory component
of the pathological reflex
Pacing for VVS / StudiesPacing for VVS / Studies
• Randomized open-label controlled
• Randomized double-blind placebo-controlled
VPS VASIS SYDIT Pts no. 54 42 93 Mean age 43 60 58 Median no. of syncopes 14-35 5.5 7-8 Tilt test + + +
Control arm no pm no pm atenol
Recurrence (Pm arm) 22% 5% 4%
Recurrence (control arm) 70% 61% 25%
p value 0.000 0.000 0.004
Pacemaker RDR DDI 45-80
RDR
Randomized open-label controlled studies
VPS. J Am Coll Cardiol 1999; 33: 16-20VASIS. Circulation 2000; 102: 294-299 SYDIT. Circulation 2001;104:52-57
Risk Risk
83%83%
92%92%
Mean FU: few mo – 3.7 yrs
VPS II SYNPACE
Pts no. 100 29 Mean age 49 53 Median no. of syncopes 16 14-10 Tilt test + / - +
Control arm pm off pm off
Recurrence (Pm arm) 33% 50%
Recurrence (control arm) 42% 38%
p value ns ns
Pacemaker RDR RDR
Randomized double-blind placebo-controlled trials
Risk Risk
-21%-21%
+32%+32%
VPS II. JAMA 2003; 289: 2224-2229 SYNPACE. Eur Heart J 2004; 25: 1741-8
a substantial placebo effect
of pacemaker implantation
Randomized double-blind placebo-controlled trials
VVS / Limitation of pacingVVS / Limitation of pacing
The vasodepressor component
is not affected by pacing and may be
responsible for the LoC at the time
the pathological reflex develops
It has been suggested that selecting patients
with vasovagal syncope for PM implantation
on the basis of the results of implantable loop
recorder may give better results
Pacing for VVSPacing for VVS
Eur Heart J 2006; 27: 1085-92
Brignole M et al. Eur Heart J 2006; 27: 1085-92
90%
59%1 year
Patients with documentation of asystole by ILR at the time of
spontaneous syncope
PM
Time to first recurrence of syncope according to the intention-to-treat analysis (ISSUE III)
Brignole M et al. Circulation. 2012;125:2566-2571
75%
43%
PM
2 years
Patients who seem to benefit mostly from pacemaker implantation are those with tilt test negative.
Brignole M et al. Circ Arrhythm Electrophysiol. 2014;7:10-16
This is because a positive tilt test might identify patients who are likely to also have a vasodepressor response during VVS, and therefore not respond as well to permanent pacing
Eur Heart J 2009; 30: 2631-2671
VVS / Pacing indication
Class IIa recommendation
Cardiac pacing is recommended in patients 40 years of
age or older, with frequently recurrent and unpredictable
syncope, and with documented spontaneous pauses during
electrocardiographic monitoring (≥3 sec if symptomatic
and ≥6 sec if asymptomatic).
Moya A et al. Eur Heart J 2009; 30: 2631-2671
VVS / Pacing indication
However, owing to the risk of complications following
pacemaker implantation and the fact that electrical
therapy may be ineffective in a significant percentage of
patients considered to be appropriate candidate (25% at 2
years in ISSUE III trial), pacing should be considered
only in highly selected patients, especially those with
repeated injury and limited or absent prodromes.
Sheldon RS et al. Heart Rhythm 2015; 12(6): e41-e63
Therapeutical OptionsTherapeutical Options
ELECTRICAL
• pacemaker• ablation
Europace 2005; 7: 1-13
J Cardiovasc Electropysiol 2009; 20: 558-563
It consists in performing a transcatheter endocardial ablation of the parasympathetic post-ganglionic neurons located inside the atrial wall that allows selective vagal denervation and elimination or
attenuation of the cardioinhibitory reflex of the vasovagal syncope
Pachon JCM et al. Europace 2011;13:1231-1242
Pachon JCM et al. Europace 2011;13:1231-1242
Cardioneuroablation was performed in 43 patients with recurrent VVS and important cardioinhibition at tilt testing
93% of syncopal recurrence during a mean follow-up of 41 months
Considerations
• It is clear that these results, although interesting, need to
be confirmed by future randomized, multicenter trials
before considering cardioneuroablation a consolidated
therapy for vasovagal syncope