João V. Vitola, MD, PhD
Cardiologist and Nuclear Medicine Physician Quanta Diagnostico Nuclear
Curitiba - Brazil
Pharmacological stress agents and protocols
DISCLOSURES
Honorarium – Research and Conferences in Nuclear Cardiology
BMS, CVT, Astellas, Pgx Health/Forest laboratories, Lantheus Medical ImagingInternational Atomic Energy Agency
Royalties – Publications in Nuclear Cardiology
Springer-Verlag-Nuclear Cardiology and Correlative Imaging: a teaching file, NY, 2004
Lippincott Williams & Wilkins, - Nuclear Medicine teaching File, 2009
1- Collect data – medical historyTalk to the patient – define the ideal stress protocol for that patientEstimation of pre test probability based on age, symptoms, risk factorsWhy pharm stress ? Any contraindication ? COPD/ AVB/ LV arr?
2- Rest ECG and Stress data
LBBB ? PM ? Previous infarct ?Any ECG changes induced by stress ?
3- Imaging analysis
4 –Final report (1+2+ 3)
Consider info from history , ECG and stress data for image interpretation
Stress Protocols
Exercise (“ max” )Bruce, Ellestad, Modified Bruce, Kattus, NaughtonBike
Pharm stress
Regadenoson and padenoson
Combined or hybrid : exercise + vasodilator - DipEx, AdenoEx, RegExDipyridamole / AdenosineDobutamine
Mieres J et al. in Vitola and Delbeke: Nuclear Cardiology and Correlative Imaging, Springer 2004Chapter 12, page 333
Selecting Patients for Pharm Stress – before and after nucs
http://www-pub.iaea.org/MTCD/Publications/PDF/Pub1566_web.pdf
Selecting Patients for Pharm Stress
Goal: To Test Coronary Reserve
Reserve coronary flow
Baseline flow
hyperemia
% Stenosis
20 40 60 80 100
Cor
onar
y flo
w (m
l.min
.g-1
)5
4
3
2
1
0
Gould, L 1974
• Exercíse– Increase Oxygen Demand
• Adenosine– A2 , AMPc, decrease intracelular calcium, relax SMC – decrease R2 resistance
• Dipyridamole– inhibits adenosine deaminase and adenosine reuptake– increase endogenous adenosine
• Dobutamine– B1, contractility, HR– Increase Oxygen Demand
MECHANISMS OF ACTIONThe goal is hyperemia
http://www-pub.iaea.org/MTCD/Publications/PDF/Pub1566_web.pdf
ml/m
in/g
AdenDipExerc Dobut0
1
2
3
4
5
6
BaseIskandrian AS et al. J.Nucl.Cardiol.;27(4):803-9,1994.
Modalities and Hyperemic Flow
Does Higher Flow (MORE HYPEREMIA) Means higher sensitivity ? effects of myocardial extraction plateau
0,10
0,08
0,06
0,00
0,02
0,04
0 3 4Coronary flow (ml.min.g-1)
99mTc-Mibi201Tl
% D
ose.
gram
tiss
ue
1 2
Protocols – inject tracer at peak hyperemia
BERGMANN et al.JACC 1989;14:639-52
Normal VolunteersMBF - H2
15O - PET
Dip 0.56 mg/kg
All patients respond the same ? Why a wide SD ?
Exercise Favored as a Stress Modality
Vitola JV et al (QUANTA Database, n = 41671)
Vitola JV et al (QUANTA Database, n = 41671)
Frequency of Abnormality on SPECT Men vs Women - Exercise vs Pharm Stress
Exercise Below Average
Pharm Above Average
Elderly patients undergoing Pharm Stress have a worse prognosisMortality in a higher risk subset (>75 yo) according to stress
modality : Exercise vs Pharmacologic stress (n=1358)
Vitola J et al. - ASNC presentation 2012; Baltimore/USA
Combined protocol : Vasodilator + low level exercise
Vitola J et al, J Nucl Cardiol 2001, 8 (6):652-9
DipEx since 1998
JNC 2009
Vasodilator ExerciseIMAGE QUALITY
Exercise vs VasodilatorBLOOD FLOW distribution
heart/ liver
Dip Exercise(46%)
1.3 0.3 1.9 0.5*
Taillefer et al
Dip Exer + Dip(23%)
1.3 0.5 1.6 0.6*
Vitola et al
*p<0.05
Vitola J et al, J Nucl Cardiol 2001, 8 (6):652-9
200 1 2 3 4 5 6 min
…Holly 2003Crossover trialn=35Exercise=variable
Adenosine
Exercise, Bruce Protocol (treadmill)
Tc-99m
Samady 2002Crossover trialn=41
Exercise, Modified Bruce Protocol (treadmill)
Adenosine
Tc-99m
Thomas 2000Parallel trialn=507
Exercise to tolerance (treadmill)
Adenosine
Tc-99m
Hashimoto 1999Parallel trial designn=462
Exercise, 0.5-1.7 mph @ 0% grade (treadmill)
Adenosine
Tc-99m
Elliot 2000Crossover trialn=19Exercise=6 min
Courtesy: R Thompson, MD
Adenosine + exercise
Dip DipEx
Isch Patients 30 39*Isch Segts/pt (multivessel) 1.3 1.5 2.5 2.2*Extent (% polar map) 16.8 12.9 26.4 18.5*Lung Uptake 5 16*TID 4 10*
Stein et al., Am J Cardiol, 75:568-72, 1995 *p<0.001
Increased Sensitivity of MPIDipEx(n=54)
AdAd
AdAd
Short AxisShort Axis
Vertical Long AxisVertical Long Axis
Ad-ExAd-Ex
Rest Rest
RestRest
Ad-EXAd-EX
Horizontal Long AxisHorizontal Long Axis
CF
Tc-99m-sestamibi
Samady H et al, J Nucl Cardiol 2002;9:188-196
0 1 2 3 54 6 7 8
Tc-99m
Thomas, Thompson et al. 2008RCT trialn=60
Exercise 1.7 mph at 0% grade
Regadenoson + exercise
Reg
Thomas,Thompson, et al. J Nucl Cardiol 2009;16:63–72
Eixo Curto
Eixo Longo Vertical
Eixo Longo Horizontal
Cortes Tomográficos-Referência
Potential for “ on the fly ” protocol
• 30 secs from peak hyperemia•Pts on meds•Depressed chronotropic response
5%7%
17%
0%
5%
10%
15%
20%
2001 2002 2003 2004 2005
Adapted from imv Nuclear Medicine Census Market Summary Reports 11-02, 12-03, 7-06
% of Vasodilator Stress Studies Performed with Exercise (US)
G Thomas
Indication– Incapacity to exercise (consider adding low workload
exercise)– LBBB, PM (vasodilator alone)– On Medications
Limitations compared to exercise– Side effects– Sensitivity of the ECG ( < 6 %)– Information from exercise not available– Liver uptake – inferior artifacts– Non-responders
VASODILATORS
LBBB or RV pacing
• O’Keefe AHJ 1992;124:614-21
O’Keefe AHJ 1992;124:614-21
Indication– Incapacity to exercise – COPD
Protocol– 10 / 20 / 30 / 40 microgramas/kg/min (push to max
HR)
DOBUTAMINE
ATROPINE up to 2 mg in 4 boluses (0.5 + 0.5 + 0.5 + 0.5)* *careful Glaucoma and BPH
• HR response variable• BP response variable• Hyperemia variable• Arrythmias/other side effects• Fragile patient (Elderly COPD)• VT (4%)
DOBUTAMINELimitations
Side effect Adenosine Dipyridamole Dobutamine
Any 81% 47% 75%
Flushing 37% 43% 14%Dyspnea 35% 3% 14%Chest Pain 35% 20% 31%STdepression 6% 8% 30%GI disconfort 15% 6% -Headache 14% 12% 14%AV Block 8% 0% 0%Arrythmia 3% 5% 50%
Adenosine/Dipyridamole Dobutamine
Hypotension HipertensionCOPD (steroids/hospit) Frequent Ventr EctopyAV Block > 1 Uncontrolled AF/Flutter
Obstruction LV outflow Aortic Aneurysm
General ContraindicationsAMI within 24 horasACSUncontrolled CHF
Specific Contraindications
Stress testingConclusions
• Understand the population you are studying ~ choose wisely the right stress for the right patient
• Try to understand and answer the clinical question being asked
• Build a strong cooperation with clinicians by providing good quality comprehensive NC work ~ go beyond reading images !
• Prefer exercise. If exercise is not possible, good pharmacologic stress alternatives are available
• www.iaea.org – recommendations for a successful NC practice
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