SHA24/012004

Device Therapy for Neurocardiogenic Syncope Amir AbdelWahab, MD Director of EP and Pacing Service Cardiology Department Cairo University Feb 2013

Syncope: Definition 

a syndrome in which loss of consciousness is:  relatively

sudden,

 temporary,  self-terminating  usually

rapid recovery



due to inadequate cerebral perfusion



most often triggered by a fall in systemic arterial pressure

Syncope: Epidemiological Data 

40% of population, presumed syncope at least once1



1-6% of hospital admissions2



1% of ED visits per year3,4



10% of falls by elderly 5

Kenny RA, et al. eds. The Evaluation and Treatment of Syncope.

Futura;2003:23-27.

1

Kapoor W. Medicine. 1990;69:160-175.

2

Brignole M, et al. Europace. 2003;5:293-298.

Blanc J-J, et al. Eur Heart J. 2002;23:815-820.

5 Campbell A, et al. Age and Ageing. 1981;10:264-270.

3 4

Causes of Syncope

Masqueda-Garcia et al. Circulation 2000;102:2898

Pathophysiology of NCS

Exagerated Sympathetic Activation

Hypovolemia

Sympathetic Withdrawal

↑ Vagal Tone

Vasodilation

Bradycardia

Hypotension

Masqueda-Garcia et al. Circulation 2000;102:2898

Syncope

BP and HR responses in NCS

Evaluation of NCS: History • Nausea before or after syncope • Palpitations: nonspecific • Pallor: neurocardiogenic • Long hx of many episodes: neurocardiogenic or hysterical

Evaluation of Syncope: ECG Monitoring • 24-hour Holter monitor – low yield (0.5%)

• External loop recorder/Extended Holter – Useful if syncope at least once per month

• Implantable loop recorder – Easy to implant – Battery lasts 1-1.5 years – Automatic recordings of arrhythmias – Also patient-activated

Tilt Table Testing • False positives & false negatives common • Not needed if history is classic • Not useful for evaluating drug therapy • Typical symptoms must be reproduced

Treatment Options • Counseling: avoiding triggers, hydration, head down ASAP • Salt & fludrocortisone • Drugs: β-blockers, disopyramide, SSRI’s • Alpha-agonist: midodrine • Tilt training, muscle tensing • Interventional Options – Dual chamber pacing – Catheter ablation

Pacing Therapy for NCS •

VPS I, VASIS, SYDIT – Control patients did not receive pacemakers (PM) – Pacing benefit in patients with PM vs. unpaced controls

•

VPS II, Synpace – Both test group (PM on) and control group (PM off) had pacemakers implanted – Pacing benefit not apparent

•

ISSUE-3

ISSUE 3

ILR screening phase

SYNCOP E

• Clinical history consistent with NMS

If YES, continue

• Age ≥40 years

If YES, continue

• ≥3 syncope during last 2 years

If YES, continue

• So severe presentation (high risk or high frequency setting) to warrant specific treatment

If YES, continue

• Non-syncopal loss of consciousness

If NO, continue

• Symptomatic orthostatic hypotension

If NO, continue

• Cardiac abnormalities which suggested cardiac syncope

If NO, continue

• Carotid sinus syncope

If NO, continue ILR screening phase

Based on ESC Guidelines on Syncope, Eur Heart J, 2004

ISSUE 3

Study design

SYNCOP E

ILR screening phase

Neurally-mediated syncopes ILR implantation (Reveal DX/XT) ILR follow-up (max 2 yrs)

ISSUE 3 study phase

ILR eligibility criteria: • Asystolic syncope ≥3 s, or • Non-syncopal asystole ≥6 s

R Pm ON

Pm OFF

Screening phase

511 met inclusion criteria and received an ILR

ISSUE 3

SYNCOP E

Study phase

89 had ECG documentation of: - syncopal recurrence with asystole of 12Âą10 s (#72) or - non-syncopal asystole of 10Âą6 s (#17)

77 randomized 38 assigned and received Pm ON

12

39 assigned and received Pm OFF 8 had Pm reprogrammed DDD/VVI in absence of primary end-point

38 analysed

refused randomization

39 analysed

3 lost to follow-up 9

followed-up (registry): 6 implanted Pm 3 no therapy 9 analysed

ISSU E 3

SYNCO PE

ISSUE 3 population

Asystole = 12 s

#8_4, 30/01/2009

ISSUE 3 population

ISSU E 3

SYNCO PE

PP

P P

P

P P

P P

P P

PP

P

P P

P

Asystole = 43 s Total pause: 44 s P

P

KM, m, 01/31/2010

P

P

P P

ISSUE 3

Patient characteristics (I)

SY NCOP E

Characteristics Age, mean Men Syncope events: - Total events, median - Events last 2 years, median - Events last 2 years without prodrome, median - Age at first syncope, mean - Interval between first and last episode, median - History of presyncope - Hospitalization for syncope - Injuries related to fainting: - Major (fractures, concussion) - Minor (bruises, contusion, hematoma) - Typical vasovagal/situational presentation - Atypical presentation (uncertain)

Pm ON n=38

Pm OFF Registry n=39 n=12

63 53%

63 41%

63 58%

7 4 3 48 8

8 5 3 45 8

7 4 1 41 17

50% 63%

56% 64%

75% 58%

5% 39% 47%

10% 46% 41%

53%

59%

17% 50% 58% 42%

ISSUE 3

Patient characteristics (II)

SY NCOP E

Characteristics ILR documentation (eligibility criteria): - Syncope and asystole ≼3 s - Non-syncopal pause ≼6 s - Mean length of asystole, s Tilt testing: performed - Positive of those performed Medical history - Structural heart disease - Hypertension - Diabetes Concomitant medications - Anti-hypertensive - Psychiatric - Any other drugs

Pm ON n=38

Pm OFF n=39

Registry n=12.

79% 21% 10 87% 42%

82% 18% 12 82% 72%

77% 17% 12 83% 50%

13% 50% 11%

10% 49% 10%

0% 33% 8%

47% 11% 26%

31% 5% 25%

25% 0% 25%

First syncope recurrence

ISSUE 3

(intention-to-treat)

SYNCOPE

Kaplan-Meier survival estimates Freedom from syncopal recurrence

1 .9

25%

25%

.8

Pm ON

.7 .6 37%

.5

Pm OFF

.4

57%

.3

log rank: p=0.039 RRR at 2 yrs: 57%

.2 .1 0

Number at risk Pm OFF Pm ON

0

3

6

9

12 Months

15

18

21

24

39 38

31 32

25 27

21 22

21 16

18 14

15 13

12 13

8 11

ISSUE 3

Procedure-related complications

SYNCOP E

• RA lead dislodgment: 2 pts • RV lead dislodgment: 2 pts • Subclavian vein thrombosis: 1 pt

ISSUE 3 SYNCOP E

ISSUE 3 in perspective

Who gets an ILR and (eventually) a PM ?

• 9% of patients affected by NMS referred to Syncope Clinic will receive an ILR • 18% of pts receiving an ILR will be candidates for pacemaker therapy within 1 year and approximately 40% within 4 years • 1 out of 3 pacemaker patients will benefit from pacing therapy within the subsequent 2 years (NNT=3)

Palmisano et al, Europace 2012

Catheter Ablation for NCS

• 43 patients (Mean age 33y) – Pauses (mean=13s) during HUT

• Spectral mapping to identify GPs • Mean FU: 45 months Pachon et al, Europace 2011

Pachon et al, Europace 2011

Outcome

Pachon et al, Europace 2011

• 10 consecutive patients (Mean age 50y) • HFS to identify LA GPs • Endpoint: inhibition of vagal response at target sites • No complications

Yao et al, Circ Arrhythm Electrophysiol 2012

Yao et al, Circ Arrhythm Electrophysiol 2012

Follow-up (Mean 30 months)

Yao et al, Circ Arrhythm Electrophysiol 2012

Conclusions • Pacing can be beneficial in a selective group of NCS patients • CLS may be superior to other rate drop algorithms in preventing NCS • Catheter ablation of Cardiac GPs is a promising tool in treating resistant NCS

Thank You !