Adenosine testing in syncope Dr Steve W Parry Falls and Syncope Service Royal Victoria Infirmary and...
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Transcript of Adenosine testing in syncope Dr Steve W Parry Falls and Syncope Service Royal Victoria Infirmary and...
![Page 1: Adenosine testing in syncope Dr Steve W Parry Falls and Syncope Service Royal Victoria Infirmary and Institute for Ageing and Health, Newcastle University.](https://reader036.fdocuments.in/reader036/viewer/2022070404/56649f335503460f94c5087c/html5/thumbnails/1.jpg)
Adenosine testing in syncope
Dr Steve W Parry
Falls and Syncope Service
Royal Victoria Infirmary and Institute for Ageing and Health,
Newcastle University
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OutlineOutline
What is it? What does an adenosine test diagnose? What do the guidelines tell us about adenosine
testing? How do you do it? Where are we now?
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Adenosine triphosphate (ATP)
Ubiquitous purinergic amine Rapid catabolism to adenosine
(ATP: some vagal effects) Profound negatively chronotropic and
dromotropic effects on AV node High degree AV block, asystole
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ATP and syncope investigation
Confusion re diagnostic criteria and underlying pathophysiology– VVS
– Sinus node disease
– High degree AV block
– “Adenosine-sensitive syncope”
– “Brady-pacing indications”
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ATP and vasovagal syncope
Supine ATP in Dx of neurally mediated syncope and SND (Brignole PACE 1994)
– 20mg iv ATP, 79 older patients (71 years) v 31 controls (62 years)
– Similar ATP test positivity in both groups, all diagnoses
– More recent results in 175 patients• “ATP no substitute for HUT” (Brignole et al Heart 2000)
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Adenosine and vasovagal Adenosine and vasovagal syncopesyncope
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ATP and syncope investigation:Vasovagal syncope
“Fainting rats” (Waxman et al Circulation 1998)
– VVS rats: isoproterenol and IVC clamp
– Dipyridamole (adenosine inhibitor) caused paradoxic bradycardia at lower iso doses
– ? Adenosine augments sympathoinhibition during vasovagal response
Humans: higher plasma adenosine levels during positive HUT in patients with VVS
(Saadjian, Circulation 2002)
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ATP and vasovagal syncope
Adenosine IV as provocateur during head up tilt table test– Adenosine tilt less
sensitive than isoproterenol tilt(Shen et al JACC 1996, Perez-Paredes et al Rev Espanol Cardiol 1998)
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ATP and vasovagal syncope
Flammang et al (Circulation 1997) ATP 20mg– 10 sec duration of AVB for diagnosis
– Initial studies “cardio-inhibitory VVS”• No proof, diagnostic criteria
– 316 patients with VVS, 51 younger controls
– 130 (41%) patients pauses >10 sec (84% AVB) v only 3 controls
– Increasing positivity with advancing age– Further studies establishing reproducibility (J Cardiovasc
Elect 1998) and response to pacing (Circulation 1999)
– Account for around half of all patients reported
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The Flammang experience.....
Flammang et al (Heart Rhythm, 2006 abstr)
– Multicentre “placebo-controlled” RCT• DDD v AAI @ 30bpm
– Patients with SUO, “mostly vasovagal”• No HUT, no data on why VVS
– 77 patients age 78 years
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Rhythm 2006Europace 1999Circulation 1997
Retrospective study (n=316)
Prospective study (n=20)
Multicenter study (n=77)
The Flammang experience.....
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Adenosine and sinus node Adenosine and sinus node dysfunctiondysfunction
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ATP and sinus node dysfunction
Brignole et al 1994: ATP unhelpful in SND diagnosis, though SND needed for ATP-related sinus arrest
Burnett et al Am Heart J 1999– 10 patients with SND v 67 age matched controls
– 80% sensitivity, 97% specificity Fragakis et al Europace 2007
– Similar results• Editorials: “promising but more work needed”
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Adenosine and atrioventricular Adenosine and atrioventricular blockblock
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ATP and high degree AVB
Brignole et al (Circulation 1997)
– 60 patients (57+/-19 y) v 90 controls
– 15 with AVB and 9 with sinus arrest
– Upper 95th percentile in controls 6000ms
– ATP >6 sec in 53% AVB patients, none of SA
– ? Higher susceptibility of pts with AVB to ATP
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Newcastle pilot study (Parry et al QJM 2009)
Adenosine 20mg iv bolus (Negative HUT, CSM, EP diagnosis excluding
alternative diagnoses) Paced groups
– CSS
– SND
– AVB VVS “Clean” EP controls
ATP and “brady-pacing indications”
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Diagnosis N= Mean age (sd) Adenosine positive
(>6 sec asystole)
Sensitivity
(%)
SSS
AVB
CSS
VVS
EPC
5 (4 F)
7 (1F)
7 (4F)
10(8F)
8 (7F)
77 (5.7)
69 (15.0)
75 (4.9)
57 (19.0)
37 (14.6)
5
7
6
5
1
100
100
85.7
50
163 screened, 37 enrolled (!):
50% unsuitable (contraindications, AF)
40% refusal of CSM, 10% refusal of adenosine
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ATP and ILRs
Donateo et al (JACC 2003)
– 36 ATP positive patients with ILR, 69 yr
– 22 had syncope• 11 (69%) had bradycardia• 50% had long ventricular pause
Deharo et al (JACC 2006)
– 25 patients with tilt +ve VVS, 8 CI, mean 60 yr, all ILR
– No relation between adenosine and CI response during tilt
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ATP and ILRs
ISSUE 2 Brignole et al Eur Heart J 2006
– 392 patients, 343 tilted, 164 (48%) +ve
– 180 ATP, 53 (29%) positive
– Syncope with ILR in 106 (26%) at 3/12
– No relationship between ATP positivity and HUT results
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What do the guidelines say?
ACC/AHA/HRS and ESC pacing guidelines– Adenosine testing not mentioned
ESC syncope guidelines 2009– “Cannot be recommended”; Class III
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If you must.....
• Usual cautions/contraindications
• Counsel your patient....
• Continuous ECG/BP monitoring
• 20 mg IV adenosine with rapid flush
• > 6 sec asystole or > 10 sec high degree AVB abnormal
• No adverse events to date in >1500 patients and control subjects
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Where are we with ATP?
Contradictory evidence base– Some indications of unmasking of conducting
tissue disease
– Predominantly older patients in non-VVS literature
– Increasing positivity with advancing age
– ILR studies show little or no correlation between ATP positivity and real-time ECG/tilt diagnosis
• Difficult patient groups – confusion re underlying diagnoses, many with VVS
– Good evidence from pacing intervention studies of efficacy in ATP positive patients
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Where are we with ATP?
ATP or Adenosine, – Contradictory evidence
– Both used in the literature
– ATP metabolism to adenosine very fast
– Pelleg, Flammang “vagal effect vital”• Dog studies, not replicated in guinea pig or cat
6 sec or 10 sec asystole– 6 sec based on Brignole’s work, 95th centile in 175
controls
– 10 sec based on Flammang’s work, ditto!
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