Pharmacologic Stress Testing for SPECT Myocardial Perfusion Imaging g (MPI): Preferred Over Exercise Stress?

Size: px

Start display at page:

Download "Pharmacologic Stress Testing for SPECT Myocardial Perfusion Imaging g (MPI): Preferred Over Exercise Stress?"

Marvin Bryant
5 years ago
Views:

2 Pharmacologic Stress Testing for SPECT Myocardial Perfusion Imaging g (MPI): Preferred Over Exercise Stress? John J. Mahmarian, MD, FACC, FASNC Professor of Medicine, Department of Medicine, Weill Cornell Medical College Medical Director, Nuclear Cardiology and CT Services, Methodist DeBakey Heart and Vascular Center, The Methodist t Hospital, Houston, Texas

3 Faculty Disclosure The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: John J. Mahmarian, MD, FACC, FASNC Consulting Fees: Astellas Fees for Non-CME/CE Services Received Directly From a Commercial Interest or Their Agents: Astellas

4 Exercise is the Preferred Stressor When Performing Myocardial Perfusion Imaging Exercise is the preferred method to induce hyperemia in patients who are able to adequately exercise Achieve at least 85% of the maximal predicted heart rate for age Five metabolic equivalents Provides additional diagnostic and prognostic information Heart rate, blood pressure, ECG changes, exercise-induced i d symptoms, functional capacity, ventricular ectopy, heart rate recovery Better SPECT image quality (heart-to-background ratio) in patients who exercise adequately Henzlova MJ et al. J Nucl Cardiol. 2006;13:e80-e90. Anagnostopoulos C et al. Heart. 2004;90(suppl 1):i1-i10. Verna E et al. J Nucl Cardiol. 2007;14:

5 e Surviving Percentag Perce entage Surv viving Exercise Capacity and Mortality in Male Patients With and Without CVD METS Achieved Normal Subjects >8 MET 5-8 MET <5 MET Percentage e Surviving 75 Target Heart Rate (%Predicted) Normal Subjects Subjects with Cardiovascular Disease >8 MET 5-8 MET <5 MET Perc centage Surv viving >100% % 50-74% <50% Subjects with Cardiovascular Disease <50% >100% % 50-74% Independent of Risk Factors For CAD OR Framingham Risk Score Myers J et al. N Engl J Med. 2002;346:

6 Exercise Capacity and Mortality in Women 2.5 Meta analysis: 8715 Asymptomatic and 8214 Symptomatic ti Women Annua l Death Rate (% / year) or higher or higher Pharm Stress Mieres JH et al. Circulation. 2005;111: Asymptomatic Women Symptomatic Women METs

7 Duke Treadmill Score Calculation Duke Treadmill Score = Exercise time (min) - (5 x ST depression) - (4 x angina index) High Moderate Low Risk

8 Duke Treadmill Score Predicting Mortality Based on Gender Survival Estimates for Men (n=2249) 1 1 Survival Estimates for Women (n=976) ty of Surviva al Probabili High (12%) Moderate (54%) Low (34%) 72% CAD>75% 2yr. Mortality: 4.9% ty of Surviva al Probabili High (4%) 32% CAD>75% 2 year Mortality 1.9% Moderate (63%) Low (33%) Years Years Alexander KP et al. J Am Coll Cardiol. 1998;32:

9 Integration of Duke Treadmill Score and Exercise SPECT Results th/ ar) rdiac Dea ate (%/ye nnual Car I Event Ra An MI Normal Mildly Abnormal Mod-sev Abnormal Low Intermediate High Duke Treadmill Score Hachamovitch R et al. Circulation. 2002;105:

10 Gender and Exercise SPECT Incremental Predictive Value of MPI 150 Clinical Variables Clinical + Exercise Variables Clinical + Exercise + Nuclear Variables 120* * 50 *p < Men Women Hachamovitch R et al. J Am Coll Cardiol. 1996;28:34-44.

11 DARKAM Exercise SPECT 52 year old asymptomatic man without a previous cardiac history referred for exercise SPECT due to an abnormal rest ECG (non-specific ST-T wave changes) Risk factors for CAD included his age, gender, hyperlipidemia and DM Patient exercised for 6:30 seconds (Bruce protocol) and stopped due to fatigue Max BP 195/97 mmhg Max HR 160 beats/minute (95% predicted) ST shift -3.0 mm inferolateral leads Duke treadmill score -8.5 (intermediate)

12 DARKAM SPECT Results

13 DARKAM LAD/LM Stenosis CTA vs ICA LAD STENOSIS LEFT MAIN STENOSIS

14 DARKAM CIRCUMFLEX CTA vs ICA Cx Stenosis

15 MPI SPECT The Rise of Pharmacologic Stressors Number of Proce edures 9,000,000 8,000,000 7,000,000 6,000,000 5,000,000 4,000,000 3,000, M MPI Nuclear MPI scans Pharm Stress scans 7.5 M MPI 46% Pharm 2,000,000 1,000, % Pharm * *2008 data includes actual scans through August and averages for the remainder of the year.

16 The Clinical Need for Pharmacologic Stressors: Exercise Limitations 50% of patients t are unable to perform adequate exercise stress due to non-cardiac limitations Submaximal exercise can reduce sensitivity for detecting the presence and extent of ischemia in patients with known or suspected significant CAD Botvinick EH. J Nucl Med Technol. 2009;37: Duvall WL et al. J Nucl Cardiol. 2006;13: Hashimoto A et al. J Nucl Cardiol. 1999;6: Wenger NK. Cardiovasc Res. 2002;53:

17 Influence of Exercise Intensity on PDS Thall ium-201 SPECT Sc core (%) Incremental Exercise Protocol Submaximal Heller GV et al. Am Heart J. 1992;123(4 Pt 1):

18 When to Consider Pharmacologic Stress Agents Patients who may not be able to achieve an adequate heart rate 1 and blood pressure response due to non-cardiac limitations 1 : Pulmonary diseases Orthopedic and other physical limitations Limited capacity Lack of motivation Paced rhythm Some patient groups are more likely than others to require pharmacologic stress agents Elderly 2 Obese 3 Women 4 1. Henzlova MJ et al. J Nucl Cardiol. 2006;13:e80-e Hashimoto A et al. J Nucl Cardiol. 1999;6: Duvall WL et al. J Nucl Cardiol. 2006;13: Wenger NK. Cardiovasc Res. 2002;53:

When to Consider Pharmacologic Stress Agents (cont d) 60

branch block (LBBB) 40 Paced rhythm due to MPI septal 30

2006;13:e80-e90. 2. Vaduganathan P et al. J Am Coll Cardiol.

20 10 0 False Positive Rate for Septal Defects (%) 2 46%

19 When to Consider Pharmacologic Stress Agents (cont d) 60 Exercise is a suboptimal stressor in 1 : 50 Left bundle branch block (LBBB) 40 Paced rhythm due to MPI septal 30 artifacts 1. Henzlova MJ et al. J Nucl Cardiol. 2006;13:e80-e Vaduganathan P et al. J Am Coll Cardiol. 1996;28: False Positive Rate for Septal Defects (%) 2 46% Peak HR 141+/-22 p<0.001 P< % p=ns 8% Peak HR 88+/-17 Peak HR 115+/-23 Exercise Adenosine Dobutamine (26/57) (4/35) (1/13)

20 Meta-Analysis of SPECT Results Similar CAD Detection With Stressors Exercise 33 studies in 4480 patients Sensitivity: 89% Specificity: 73%* Vasodilator Stress 24 Studies in 2492 patients Sensitivity: 89% Specificity: 75%* Dobutamine Stress 24 studies in 1208 patients Sensitivity: 85% Specificity: 72%* *Improves to >90% with AC and gating Klocke FJ et al. ACC/AHA/ASNC Guidelines. Circulation. 2003;108:

21 Stress MPI SPECT For Predicting Outcome: Patient Subgroups and Stressor Modality Gender and Diabetes Stressor Modality Death or (%/year) Cardiac MI Rate Low Risk High Risk Women Men Diabetics Non- Diabetics Diabetic Women Diabetic Men Cardiac Death or MI Rate (%/year) 9 8.3% % Pharmacologic Stress Low Risk High Risk 5.6% 0.7% Exercise Shaw LJ, Iskandrian AE. J Nucl Cardiol. 2004;11;

22 Adenosine SPECT MPI Predicts Outcome Impact of Perfusion Defect Size and Severity ate, %/ye ear Event R Myocardial infarction Cardiac death Normal Mildly Abnormal Moderately Abnormal 9 13 Summed stress score (SSS) Severely Abnormal >13 Hachamovitch R et al. Circulation. 1998;97:

23 Dobutamine Tc-99m SPECT Long-Term Prognostic Results 532 consecutive patients: mean age 61 yrs 44% prior MI 58% men 35% prior 15% diabetic revascularization Mean follow-up 8.0+/-1.5 yrs: 67 cardiac deaths 49 late revascularizations 34 NFMI (1.5% event rate/year) Event-F Free Surv vival Cardiac Death All Events normal 0.9 reversible both P= fixed 0.7 P= Follow-up (Years) Follow-up (Years) normal reversible both fixed Schinkel AF et al. Radiology. 2002;225:

24 Stress SPECT for Predicting Death/MI ACS Studies Follow Scan Scan Up Event Abnormal Normal +Ischemia -Ischemia Study Stressor N (mos) Rate Predictor PPA NPA PPA NPA Brown Ex Tl ±11 7 (13%) RD 7/37 (19%) 15/15 (100%) 6/23 (26%) 28/29 (96%) Madsen Ex Tl (6%) RD 8/61 (13%) 95/97 (98%) 6/29 (21%) 125/129 (97%) Strattman Ex Tc-99m ±7 11 (9%) RD 10/74 51/52 10/40 85/86 (14%) (98%) (25%) (99%) Younis DIP Tl (15%) RD 10/54 (19%) 14/14 (100%) 4/21 (19%) 41/47 (87%) Miller DIP Tc-99m ±5 20 (15%) RD, FD 20/110 27/27 13/66 64/71 (18%) (100%) (20%) (90%) Strattman DIP Tc-99m ±11 32 (25%) RD, FD 30/99 (30%) 27/29 (93%) 17/47 (36%) 66/81 (82%) Total (13%) 85/435 (20%) 229/234 (98%) 56/226 (25%) 409/443 (92%)

ients Ima % Pat 30 25 20 15 10 5 28% USA sites

9 (median 2) days 5% 11% 18%18% 13% 23% 7% 16%

to Imaging 0 Day 0/1 Day 2 Day 3 Day 4 Day 5

25 Safe Imaging Early After ACS/MI AdenosineTc-99m SPECT % Patients Imag ged ged ients Ima % Pat % USA sites 26% 2.7 +/-1.9 (median 2) days 5% 11% 18%18% 13% 23% 7% 16% non-usa sites 4.5+/-2.4 (median 4) days Overall p< (USA vs non-usa sites) 2% 13% 6% 14% Days to Imaging 0 Day 0/1 Day 2 Day 3 Day 4 Day 5 Day 6 >Day 6 USA N= Non-USA N= Mahmarian JJ et al. J Am Coll Cardiol. 2006; 48:

26 Reinfarction Following Thrombolytic Rx For AMI TIMI Experience in 20,101 Pts: Evidence Against Watchful Waiting Recurrent MI during index hospitalization = 4.2% Timing of Recurrent MI = 2.2 days 1 No early reinfarction % Surviv val 0.75 Log-rank p < Early reinfarction Gibson CM et al. J Am Coll Cardiol. 2003;42:7-16. Years

27 Adenosine Tc-99m Sestamibi SPECT Results Objective 1: Cardiac Events Death/AMI Total Cardiac Events p=0.007 tients % Pa p=0.009 % Pat tients Low Risk (N=242) Randomized (N=205) Intermediate Risk (N=213) High Risk (N=68) Low Risk (N=242) Randomized (N=205) Intermediate Risk (N=213) High Risk (N=68) Follow-up Time (Year) Follow-up Time (Year)

28 Predicted Event Rates Based on Adenosine Induced Perfusion Defects Total Perfusion Defect Size (%LV) Ischemic Perfusion Defect Size (%LV) ts (% pati ients) Card diac Even Total Cardiac Events Cardiac Death and Reinfarction N

29 Monitoring Medical Therapy with SPECT Author Study Design Patient Population Therapy Stressor Tracer Time Interval Beta Blockers Shehata et al, 1997 (N=17) open label, SB RD, ischemia propranolol IV DOB Tc 8±3 days Murthy et al, 2000 (N=22) RN, DB, PC RD metoprolol l IV DOB Tc 34±25 days Taillefer et al, 2003 (N=21) RN, DB, PC CAD >70% metoprolol IV DIP Tc <30 days Nitrates Stegaru et al, 1988 (N=40) RN, DB CAD >50%, RD Nifedipine; ISDN EX TL 1 month Aoki et al, 1991 (N=7) open label CAD, collaterals sublingual NTG EX TL 1 week Mahmarian et al, 1994 (N=40) RN, DB, PC CAD, >5% RD NTG patch EX TL 6±2 days Lewin et al, 2000 (N=40) open label CAD, RD ISMN EX Tc 5 days; 6 wks Lifestyle Modification/Lipid Rx Schuler et al, 1992 (N=38) open label CAD >50% exer; low fat diet EX TL 1 year Eichstadt et al, 1995 (N=22) open label RD, hyperlipidemia fluvastatin EX TL 12 wks Mahmarian et al, 1997 (N=36) open label, SB smoking, CAD > 50%, >5% RD nicotine patch; smkng cesstn EX TL 1 week 2 wks Mostaza et al, 1999 (N=20) RN, DB, PC CAD, RD pravastatin DIP TL 16 wks Hosokawa et al, 2000 (N=40) open label CAD >50%, RD simvastatin EX TL 1 year Schwartz et al, 2003 (N=25) SB, open label CAD >50%, hyperlipidemia pravastatin EX; AD Tc 6 wks; 6 mos Manfrini et al, 2004 (N=74) RN, SB, PC RD, CAD >50%, PTCA pravastatin EX Tc 2 wks; 6 mos Combination Anti-Ischemic Rx Parisi et al, 1997 (N=270) RN, DB CAD >50%, RD PTCA; comb med EX TL 6 mos Rx Sharir et al, 1998 (N=26) open label RD comb med Rx DIP TL 11±6 days Dakik et al, 1998 (N=44) RN, SB post MI, >20% PDS, comb Rx; PTCA AD TL 43±26 days >10% IPDS Angiogenesis Factors Hendel et al, 2000 (N=14) open label, SB NR CAD; RD rhvegf EX, DIP; DOB TL, Tc 30, 60 days Udelson et al, 2000 (N=59) open label, SB NR CAD, RD rfgf-2 EX; DIP TL, Tc 30, 60, 180 days Henry et al, 2001 (N=15) open label, SB NR CAD, RD rhvegf EX; DIP; DOB TL, Tc 30, 60 days Grines et al, 2003 (N=52) RN, DB, PC NR CAD, >9% RD Ad5FGF-4 AD Tc 30, 60 days

30 Serial Vasodilator Stress SPECT Assessing Therapy INTENSIVE MEDICAL THERAPY (N=101) Adenosine SPECT #1 PDS >20% Ischemia >10% LVEF>35% CORONARY REVASCULARIZATION (N=104) Adenosine SPECT #2 (1-2 months after SPECT #1) Follow-up: 12 months Mahmarian JJ et al. J Am Coll Cardiol. 2006;48:

31 Objective 2: Randomized Patients Gated SPECT Results: Medical vs Revascularization Strategy 33.1 (8.9)%LV 22.0 (7.1)%LV Strategy 1 Strategy 2 Medical Therapy Revascularization p (N=83) (N=86) Value Total PDS ( change) -16.2± ± Ischemic PDS ( change) -15.0±9-16.2± Scar PDS ( change) -1.2±8 12±8-1.6±7 16± % patients >9% decrease Total PDS Ischemic PDS LVEF ( change) 4.7±7 4.6±8 0.93

32 Change in PDS From SPECT 1 to SPECT 2 in Both Strategies 30 Total PDS Ischemic PDS Strategy 1 Strategy 2 Strategy 1 Strategy 2 (Medical Therapy) (Revascularization Therapy) (Medical Therapy) (Revascularization Therapy) ) DS (%LV) Study 2 ute PD udy 1 to S Absol Stu

33 Randomized Patients Cardiac Events Death/AMI Total Cardiac Events p=0.96 p= ients 0.90 ients 0.90 % Pat 0.85 % Pat Revascularization Medical Therapy 0.80 Revascularization Medical Therapy Time to Follow-up (Year) Time to Follow-up (Year)

34 Anti-Ischemic Therapy After AMI Tracking Risk With Sequential Adenosine SPECT 100 N=24 Surviva l (%) Eve ent-free N=17 >9% Perfusion Defect Size 60 <9% Perfusion Defect Size p= Months Dakik HA et al. Circulation. 1998;98:

35 Case #1 : Intensive Medical Therapy for Treating Ischemia SPECT 1 : Pre-Therapy SPECT 2 : Post -Therapy

36 Case #2 : Intensive Medical Therapy for Treating Ischemia When Revascularization is Not Feasible SPECT : Pre-Therapy SPECT : Post-Therapy

37 Pharmacologic Vasodilator Stress Advantages Over Exercise SPECT Optimal in patients who have non-cardiac limitations for performing maximal exercise stress Expands the accessibility of SPECT to patients who otherwise would not be candidates for MPI Provides similar diagnostic and prognostic information as exercise SPECT Optimal for use in patients with LBBB or paced rhythms Optimal for use in ACS/post AMI patients for very early and safe risk stratification and in assessing therapy The introduction of specific A2A Agonists may allow safe assessment in COPD/Asthma patients thereby supplanting dobutamine as a stressor agent

IAEA International Conference on Integrated Medical Imaging in CV Disease 2013

IAEA International Conference on Integrated Medical Imaging in CV Disease 2013 How to Stress My Patient Choosing the Proper Stress Test Consultant and Advisory Board for Astellas John J. Mahmarian, MD,