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