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