Pharmacological stress agents and protocols

Transcription

1 Pharmacological stress agents and protocols João V. Vitola, MD, PhD Cardiologist and Nuclear Medicine Physician Quanta Diagnostico Nuclear Curitiba - Brazil DISCLOSURES Honorarium Research and Conferences in Nuclear Cardiology BMS, CVT, Astellas, Pgx Health/Forest laboratories, Lantheus Medical Imaging International 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

2 1- Collect data medical history Talk to the patient define the ideal stress protocol for that patient Estimation of pre test probability based on age, symptoms, risk factors Why 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 Consider info from history, ECG and stress data for image interpretation 4 Final report (1+2+ 3)

3 Stress Protocols Exercise ( max ) Bruce, Ellestad, Modified Bruce, Kattus, Naughton Bike Pharm stress Regadenoson and padenoson Combined or hybrid : exercise + vasodilator - DipEx, AdenoEx, RegEx Dipyridamole / Adenosine Dobutamine

4 Selecting Patients for Pharm Stress before and after nucs Mieres J et al. in Vitola and Delbeke: Nuclear Cardiology and Correlative Imaging, Springer 2004 Chapter 12, page 333

5 Selecting Patients for Pharm Stress

6 Goal: To Test Coronary Reserve Coronary flow (ml.min.g-1) 5 hyperemia 4 3 Reserve coronary flow 2 Baseline flow % Stenosis Gould, L

7 MECHANISMS OF ACTION The goal is hyperemia 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

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9 Modalities and Hyperemic Flow 6 ml/min/g Base Exerc Dobut Dip Aden Iskandrian AS et al. J.Nucl.Cardiol.;27(4):803-9,1994.

10 Does Higher Flow (MORE HYPEREMIA) Means higher sensitivity? effects of myocardial extraction plateau 0,10 % Dose.gram tissue 0,08 0,06 99mTc-Mibi 201Tl 0,04 0,02 0, Coronary flow 3-1 (ml.min.g ) 4

11 Protocols inject tracer at peak hyperemia

12 All patients respond the same? Why a wide SD? Normal Volunteers MBF - H215O - PET Dip 0.56 mg/kg BERGMANN et al. JACC 1989;14:639-52

13 Exercise Favored as a Stress Modality Vitola JV et al (QUANTA Database, n = 41671)

14 Frequency of Abnormality on SPECT Men vs Women - Exercise vs Pharm Stress Exercise Below Average Pharm Above Average Vitola JV et al (QUANTA Database, n = 41671)

15 Elderly patients undergoing Pharm Stress have a worse prognosis Mortality 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

16 Combined protocol : Vasodilator + low level exercise DipEx since 1998 Vitola J et al, J Nucl Cardiol 2001, 8 (6):652-9

17 JNC 2009

18 Vasodilator Exercise IMAGE QUALITY Exercise vs Vasodilator BLOOD FLOW distribution

19 heart/ liver Dip Exercise (46%) * Taillefer et al Dip Exer + Dip (23%) * Vitola et al *p<0.05 Vitola J et al, J Nucl Cardiol 2001, 8 (6):652-9

20 Adenosine + exercise Tc-99m Hashimoto 1999 Parallel trial design n=462 Exercise, % grade (treadmill) Adenosine Tc-99m Thomas 2000 Parallel trial n=507 Exercise to tolerance (treadmill) Adenosine Tc-99m Samady 2002 Crossover trial n=41 Exercise, Modified Bruce Protocol (treadmill) Adenosine Tc-99m Elliot 2000 Crossover trial n=19 Exercise=6 min 20 Holly 2003 Crossover trial n=35 Exercise=variable Exercise, Bruce Protocol (treadmill) Adenosine min Courtesy: R Thompson, MD

21 Increased Sensitivity of MPI DipEx (n=54) Dip Isch Patients Isch Segts/pt (multivessel) Extent (% polar map) Lung Uptake TID DipEx 30 39* * * 5 16* 4 10* Stein et al., Am J Cardiol, 75:568-72, 1995 *p<0.001

22 Tc-99m-sestamibi Ad-Ex Ad-Ex Ad Ad Rest Rest Short Short Axis Axis Horizontal Horizontal Long Long Axis Axis Vertical Vertical Long Long Axis Axis Ad-EX Ad-EX Ad Ad Rest Rest CF Samady H et al, J Nucl Cardiol 2002;9:

23 Regadenoson + exercise Thomas, Thompson et al RCT trial n=60 Exercise 1.7 mph at 0% grade Tc-99m Reg Thomas,Thompson, et al. J Nucl Cardiol 2009;16:63 72

24 Cortes Tomográficos-Referência Potential for on the fly protocol Eixo Curto Eixo Longo Vertical 30 secs from peak hyperemia Pts on meds Depressed chronotropic response Eixo Longo Horizontal

25 % of Vasodilator Stress Studies Performed with Exercise (US) 20% 17% 15% 10% 5% 7% 5% 0% 2001 G Thomas Adapted from imv Nuclear Medicine Census Market Summary Reports 11-02, 12-03, 7-06

26 VASODILATORS 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

27 LBBB or RV pacing O Keefe AHJ 1992;124: O Keefe AHJ 1992;124:614-21

28 DOBUTAMINE Indication Incapacity to exercise COPD Protocol 10 / 20 / 30 / 40 microgramas/kg/min (push to max HR) ATROPINE up to 2 mg in 4 boluses ( )* *careful Glaucoma and BPH

29 DOBUTAMINE Limitations HR response variable BP response variable Hyperemia variable Arrythmias/other side effects Fragile patient (Elderly COPD) VT (4%)

30 Side effect Adenosine Dipyridamole Dobutamine Any 81% 47% 75% Flushing Dyspnea Chest Pain ST depression GI disconfort Headache AV Block Arrythmia 37% 35% 35% 6% 15% 14% 8% 3% 43% 3% 20% 8% 6% 12% 0% 5% 14% 14% 31% 30% 14% 0% 50%

31 General Contraindications AMI within 24 horas ACS Uncontrolled CHF Specific Contraindications Adenosine/Dipyridamole Hypotension COPD (steroids/hospit) AV Block > 1 Dobutamine Hipertension Frequent Ventr Ectopy Uncontrolled AF/Flutter Obstruction LV outflow Aortic Aneurysm

32 Stress testing Conclusions 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 recommendations for a successful NC practice

33 Join us - international membership Fee reduced from 250 to U$ 75 / year for members from developing countries Our mission : strenghten NC worldwide Wide range of information for a successful NC practice (JNC online, guidelines, clinical cases, practical information, )

34 Thank you CURITIBA - BRASIL