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Stress Techniques
Eliana Reyes, MD Dipl. Cardiology
National Heart and Lung Institute, Imperial College London
Royal Brompton Hospital
London, United Kingdom
Nice, May 2010
Royal Brompton& Harefield
Learning Outcomes
By the end of this presentation, you should be able to:
• Understand the concept of coronary hyperaemia
• Identify the several forms of stress techniques available
• Appreciate the differences and similarities between the different stress techniques
Europe Survey 2007
Underwood, Wiener. Eur J Nucl Med Mol Imaging
2009;36:260
Reyes. Underwood. Wiener. 2010; under review
exercise
43%
adenosine
25%
dipyridamole
28%
dobutamine
4%
58% of
vasodilators are
combined with
exercise
Austria, Belgium, Czech Republic,
Denmark, Finland
France, Germany,
Greece,Hungary, Italy,
Netherlands, Norway
Portugal, Slovenia,
Spain, Sweden
Switzerland, United
Kingdom
Resting Perfusion
0
1
2
3
4
0 20 40 60 80 100
MBF ml/min/gr
% Diameter narrowing
rest
Myocardial distribution of tracer at rest
VLA SAHLA
RCA
LAD
Hyperaemia
0
1
2
3
4
0 20 40 60 80 100
MBF ml/min/gr
% Diameter narrowing
rest
hyperaemia
Myocardial distribution of tracer following stress
VLA VLA
coronary flow
reserve
RCA
LAD
Dynamic Exercise
• Widely validated
• Exercise indices and prognostic scores
• Familiarity
• Improved image quality
• Cheap
Submaximal exercise and MPS
0
20
40
60
80
100
1 VD 3VD All
52
797374
98
88 Submaximal
Adequate
P < 0.05
P < 0.002
Iskandrian et al. JACC 1989; 14:1477
sens
itiv
ity
%
n = 461 pts
LBBB and stress MPS
5660
16
28
12
10
20
30
40
50
60
70
LAD RCA LCx
Exercise
Adenosine
% false positive studies
O’Keefe et al. JACC 1993;21:1332Vascular territories
n = 173 patients
Pharmacological Stress
Indications for adenosine stress
• Contraindication to exercise or unable to exercise
adequately
• LBBB or paced rhythm on resting ECG
• Convenience
Adenosine
• Natural purine nucleotide
• Half life < 10 sec
• IV infusion
0
1
2
3
4
5
6
Baseline Ex Aden Dipy Dob
Myocardial perfusion in ml/min/gr
Haemodynamic response
Cerqueira et al. JACC 1994;23:384
n = 6921 patients
Time (minutes)
50
70
90
110
130
150
60
80
90
100
110
120
70
Systolic BP
Diastolic BP
Heart rate
Baseline 1 2 3 4 5 6
P<0.0001
Adenosine receptor
cell membrane
Intracellular space
Adenosine
Adenosine deaminase
A2A Receptor
G-protein
AMP - ADP - ATP
S-adenosyl homocysteineUric acid
cAMP Ca++
Facilitatedtransport
Vasodilation
Caffeine
theophylline
Adenosine
Steal phenomenon
Adenosine IV
Abbott JNC 2003;10:9
Patient preparation
• Caffeine abstention 24 hr prior to test
• Discontinue aminophylline/ theophylline 24 hr before test
• Stop dipyridamole for 24-48 hrs
• Discontinue beta-blockers for 24-48 hours
Contraindications
• Hx of severe asthma / wheeze on auscultation
• 2/3 HB without a pacemaker
• SBP < 90 mmHg
• Dipyridamole in the last 24 hrs
• Sick sinus syndrome
• Caffeine intake in the last 12 hrs
• ? Asthma / COPDModified protocol
IV infusion
140 mcg/kg/min0 642 minutes3
tracer
Adenosine protocol
Monitor HR, BP and ECG
40 2 minutes3
Treuth MG. J Nucl Cardiol 2001; 8:548
Asthma/COPD: modified protocol
120
2 64 min
140
30
Adenosine
Starting at 70 or 100 mcg/kg/min
100
15-10 min
2-receptor agonist
Reyes et al. J Nucl Cardiol 2007; 14:827-34
Caffeine: modified protocol
64 min
Adenosine
210 mcg/kg/min
0 3
Reyes et al. JACC 2008; 52:2013
Early termination
• Symptomatic hypotension (SBP <90 mmHg)
• Persistent / symptomatic 2° or complete HB
• Bronchospasm
Resolves spontaneously soon after termination
IV aminophylline
Adenosine Receptors
adenosine
A2A
A3
A1
A2B
Modulate sympathetic activity
Anti-inflammatory effect
A-V conductionPreconditioningChest pain
Peripheral vasodilationMast cell degranulationBronchoconstriction ?
Coronary arteriolar dilation
Bronchoconstriction?Peripheral vasodilation? Preconditioning?
Side effects
Cerqueira. JACC 1994;23:384
0
10
20
30
40
50
35 35 37
14
8
%
n = 9256 pts
Side effects in 81% pts
CP HBHeadacheFlushingSoB
Severity of side effects
0%
20%
40%
60%
80%
100%
mild moderate severe
Nurse
Doctor
n = 1261 patients
Reyes. Nucl Med Commun 2002;23:380
test completed
Response to Vasodilator Stress
• Blunted heart rate response (peak stress to baseline HR ratio)
• Marked hypotension
• Ischaemic ECG changes
Poor prognosis
Multivessel disease or LMS disease
Mathur. JNC Published online May 2010
Exercise?
Really?
Why to bother?
Image quality
Improves image quality
Raw data Adenosine alone Adenosine + Exercise
Background/Heart ratio =
P=0.01
P=0.03
P=NS
Thomas G. JNC 2000;7:439
Backg
rou
nd
to
targ
et
rati
os
Role of exercise during adenosine stress
0%
10%
20%
30%
40%
50%
faint flushing headache nausea anxiety
Adenosine Aden + ex
Pennell DJ...Underwood SR.JACC 1995;25:1300
n = 500 patients
Courtesy of Prof. SR Underwood
Protocol
tracer
0 7 - 8 min4 min
dynamic exercise
140 mcg/kg/min
IV aminophylline available - monitor ECG, HR and BP
Dipyridamole IV infusion
Regadenoson
• Selective adenosine A2A receptor agonist
• Onset of action within 30-60 seconds
• Duration < 5 minutes
• Bolus injection
• Non-weight adjusted single IV dose (400 mcg)
Regadenoson vs. Adenosine
Time (minutes)241680
Regadenoson
AdenosineCoro
nary
Conducta
nce
(ml/m
in/m
mH
g)
0.1
0.15
0.2
0.25
Adapted from Gao Z et al J Pharmacol Exp Ther 2001;291:209
Adenosine
Regadenoson
Rest
Regadenoson Protocol
0 1 2 // 30 min
Radiotracer
Lexiscan (0.4 mg/5ml)
Saline flush (10-20 ml)
Monitor HR, BP and ECG
Lexican Brochure
Adverse Events
AE with an incidence ≥ 5% are shown
Iskandrian JNC 2007; 14:645
Cerqueira JACC Img 2008;1:307
Dobutamine
• Synthetic analogue of dopamine
• Half-life = 2 min
• Potent -1 agonist,
weak -2 / -1
• Dose-dependent effect:0
1
2
3
4
5
6
Baseline Ex Aden Dipy Dob
Direct arteriolar vasodilator
5 10 20 30 400
inotropy chronotropy
mcg/kg/min IV
Protocol
10
4030
5
1520
mcg/kg/min IV
tracer
3-5 min intervals
Short acting IV B-B available (esmolol)
Monitor ECG, HR and BP
250 mg/20 ml vial
2 mg/ml
Atropine
50 mcg/kg/min
Exercise
Endpoints
Peak dose = 40 mcg/kg/min
Peak HR = 85-100% MPHR
Symptoms of ischaemia + ST depression 2 mm
Symptomatic hypotension
Arrhythmia
Radiopharmaceutical injection prior to test termination
Safety profile
Event (%)ExerciseN = 0.5 M
Dobutaminen = 3011
Dipyridamolen = 73806
Adenosinen = 9256
Fatal MI/cardiac death
1/20 000 0 1/10 000 0
Non-fatal MI 1/3000 1/3000 1/5000 1/10 000
Thank you
Beta-blockade and Adenosine MPS
Reyes et al. 2009; under review
Beta-blockade and Adenosine MPS
Reyes et al. 2009; under review
n=45 patients
Bicycle ergometer
– Workload in watts or kilopond-meter/min
– Non-weight-bearing
Protocol
– 2-1 min warm-up phase
– Progressive workload 25W - 50W every 2 min
– Workload dependent on pedalling speed
– Discomfort of quadriceps muscles
Dynamic exercise
Pros
• physiological
• related to everyday activity
• objective assessment of symptoms
• widely validated and accepted
• prognostic information
Cons
• frequently inadequate
• labour intensive
• slow
Contraindications to exercise testing
Absolute
• acute MI (4-5 days)
• unstable angina
• active myo(peri-)carditis
• severe aortic stenosis
• systemic infection
• deep venous thrombosis
Relative
• severe CAD (e.g. LMS)
• moderate aortic stenosis
• significant arrhythmia
• exercise syncope
• cardiomyopathy
– dilated
– hypertrophic
• uncontrolled systemic or
pulmonary hypertension
• severe LV dysfunction
Adenosine in asthma/COPD
0
20
40
60
80
100
Protocol adherence Dyspnoea Bronchospasm
Control
Asthma/COPD%
p=0.03
p=0.04
p=NSn = 144 patients
4 cases of bronchospasm, aminophylline was not required in any case
Reyes. J Nucl Cardiol 2007;14:827
Reyes et al. J Nucl Cardiol 2007; 14:827-34
Reyes et al. JACC 2008; 52:2013
Inotropic drugs: dobutamine
Regadenoson
Dipyridamole
Adenosine
Vasodilators:
NICE guidelines: Assessment of Stable Chest PainApril 2010
www.noonelikesmeanymore.co.uk
Gatekeeper
0
20
40
60
80
100
0 0.1 - 0.9 1 - 1.9 2 - 4.9 > 5
12-hr
24-hr
serum caffeine mg/L
% pa
tient
s
Reyes. Eur Heart J 2006;27:180(abstract)
Jacobson. Eur JNM 1994;21:23
Abstinence
Caffeine abstention: 12 vs. 24 hours
0
50
100
150
200
250
300
350
400
USA Scandinavian countries UK World
Coffee
Tea
Other
Food and Agriculture Organisation report 1989
Adverse events
Adverse Events Nurse
n = 467
Doctor
n = 794
p value
Fatal MI/Death 0% 0% NS
Bronchospasm 1.1% 0.7% NS
CP + ST 2.3% 1.4% NS
Transient heart block
1.3% 1.8% NS
Reyes. Nucl Med Commun 2002;23:380
PP P
12-hr
serum caffeine mg/L
% pa
tient
s
Reyes. Eur Heart J 2006;27:180(abstract)
Abstinence
Caffeine abstention: 12 vs. 24 hours
serum caffeine threshold = 2 mg/L