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 !