Stress test

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Activity OverviewPrimary healthcare professionals are responsible for identifying patients with or at risk of developing coronary artery disease (CAD). They are also

ibl f idi th f ll f h lthresponsible for providing the full range of health-related needs for these patients, as well as issuing appropriate referrals for cardiac testing in patients with suspected CAD and in at-risk preoperative patients. This 60-minute, discussion-based Webcast addresses specific gaps in appropriate testing techniques and the treatment f CAD i h h l f h l i iof CAD with the goal of helping primary care

clinicians integrate the latest research on CAD risk assessment with cardiac testing, and thereby optimizing patient outcomes.

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This Webcast is intended for primary healthcare

Target Audience

This Webcast is intended for primary healthcare professionals in family practice and internal medicine.

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Continuing Medical Education to provide continuing medical education for physicians.

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The content of this activity has been peer reviewed and has been approved for compliance. The facultyand has been approved for compliance. The faculty and contributors have indicated the following financial relationships, which have been resolved through an established COI resolution process, and have stated that these reported relationships will not have any impact on their ability to give an unbiased presentation.

Disclosure Statements

Ronald G. Schwartz, MD, MS, FACC, FAHA, ABNM, FASNCConsulting fees/advisory boards: Astellas Pharma US, Inc.Fees received for promotional/non-CME activities: Abbott Laboratories, Astellas Pharma US, Inc., Merck & Co., Inc.

Corey Evans, MD, MPH, has indicated no real or apparent conflicts.

The Med-IQ activity planner, Robert Miller Geist IV, has no financial relationships to disclose.

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Statement of NeedMany cardiovascular illnesses are encountered in the primary care setting, and cardiac stress testing and imaging have become routine in the diagnostic workup of patients with suspected CAD. It is difficult, however for primary healthcare professionals to remain up to date onhowever, for primary healthcare professionals to remain up-to-date on recent research regarding the benefits and risks of different testing and imaging methods in this rapidly evolving and highly technical field. Substantial innovations in technology have enhanced diagnostic accuracy. The use of noninvasive procedures such as stress electrocardiography, computed tomography, magnetic resonance imaging, echocardiography, nuclear imaging, and positron emission tomography is only slightly more familiar to the community of referring primary care physicians than more invasive techniques, such asprimary care physicians than more invasive techniques, such as coronary arteriography. Although there are benefits to patient diagnosis and management with cardiovascular stress testing and imaging modalities, these benefits must be balanced with an awareness of the economic cost and potential health risks that accompany these tools.

Statement of Evidence-Based ContentEducational activities that assist physicians in carrying out their professional responsibilities more effectively and efficiently are consistent with the ACCME definition of CME. As an ACCME-

dit d id f CME it i th li f M d IQ t i daccredited provider of CME, it is the policy of Med-IQ to review and ensure that all the content and any recommendations, treatments, and manners of practicing medicine in CME activities are scientifically based, valid, and relevant to the practice of medicine. Med-IQ is responsible for validating the content of the CME activities it provides. Specifically, (1) all recommendations addressing the medical care of patients must be based on evidence that is scientifically sound and recognized as such within the profession; (2) all scientific research referred to, reported or used in CME in support or justification of a patient care recommendation must conform to generally acceptedpatient care recommendation must conform to generally accepted standards of experimental design, data collection and analysis.

Med-IQ is not liable for any decision made or action taken in reliance upon the information provided through this activity.

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Acknowledgment of Commercial Support

This activity is supported by an educational grant fromThis activity is supported by an educational grant from Astellas Pharma US, Inc.

Copyright© 2012 Med-IQ. All rights reserved.

Ronald G. Schwartz, MD, MS, FACC, FAHAProfessor of Medicine and Imaging SciencesAttending in Cardiovascular Medicine, Imaging and PreventionDirector of Nuclear Cardiology and Cardiac PET CT

Faculty

Director of Nuclear Cardiology and Cardiac PET CTUniversity of Rochester Medical CenterRochester, NY

Corey Evans, MD, MPHDirector of Medical Education St. Anthony’s HospitalSt Petersburg FLSt. Petersburg, FL

Activity PlannerRobert Miller Geist IV, MDClinical Content ManagerMed-IQBaltimore, MD

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• Discuss the relative clinical usefulness of risk algorithms such as Framingham, PROCAM, SCORE, UKPDS, Reynolds, and HealthDecision.org for evaluating baseline risk of CAD

Learning Objectives

g g• Compare the relative risks and benefits of standard exercise

ECG “stress” tests, nuclear exercise stress tests, pharmacologic stress tests, and imaging modalities such as echocardiography, SPECT, MPI, and PET for detecting CAD in different types of patients

• Identify appropriate preoperative cardiac risk assessment testing for high-risk patients with comorbidities such as CAD, PAD, cerebrovascular disease, hypertension, congestive heart , , yp , gfailure, diabetes, and renal insufficiency

• Identify gender differences in presenting symptoms and cardiac testing results between men and women with CAD, and explain how those differences may affect differential diagnosis and primary care plans

Contributions to Change in Life ExpectancyUS 1970-2000

CV Disease

Increase due to CVD: 3.9 years

CV Disease

Perinatal Disease

Injuries

Cancer

COPDNet increase: 6.0 years

CHDStrokeOther CVD

Change in Life Expectancy (Years)

HIV / AIDS

Other Causes

Net increase: 6.0 years

Shurin SB. NHLBI Podium Session. May 2008; Lenfant C. N Engl J Med. 2003;349:868-74.

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Approach to CHD Risk Assessment

• Clinical CAD risk assessment begins with a careful history – Coronary risk factors: age, gender, FH, dyslipidemia, HTN, DM, smoking – Four types of chest pain: non-cardiac, atypical CP, atypical angina,Four types of chest pain: non cardiac, atypical CP, atypical angina,

typical angina– Snoring, interrupted breathing at night, daytime sleepiness, palpitations?

• Consider OSA and need for formal sleep study, CPAP • Association of OSA, AF, and stroke risk

• Physical examination can enhance risk assessment – Weight, height, BMI – BP, funduscopic exam – Smell of cigarette smoke arcus senilis xanthelasma gallop apicalSmell of cigarette smoke, arcus senilis, xanthelasma, gallop, apical

heave • Calculate baseline CAD risk• Limitations of FRS • UKPDS is better risk predictor than FRS for DM • SCORE system adds precision to risk estimates

Redberg RF, et al. J Am Coll Cardiol. 2009;54:1364-405; Conroy RM, et al. Eur Heart J. 2003;24:987-1003; Guzder RN, et al. Diab Med. 2005;22:554-62; Other background statements provided by R. Schwartz, MD.

Case 1• 50-year-old asymptomatic postmenopausal woman

arrives for discussion of recent lab work • Noted lab values: TC = 228; HDL-C = 65; TG = 140• She wonders if she should be treated for her

cholesterol• Medical history: no known heart disease• Social history: non-smoker• Medications: none• Physical examination: height = 5 ft 5 in; weight = 140

lbs; BP = 125/75; waist circumference = 32 in;lbs; BP 125/75; waist circumference 32 in; remainder of physical examination is unremarkable

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Case 1 (cont.)

• How would you analyze her risk?• Is further testing indicated?

Assessment of Suspected CAD

Suspected CAD

No CAD Low-RiskCAD

High-RiskCAD

Ri kS iti it RiskStratification

SensitivitySpecificity

No Rx Med Rx Intervention

Diagram courtesy of R. Schwartz, MD.

10

Risk of CVD According to Serum Cholesterol at Specified Levels of Other Risk Factors

Epidemiologic Profile of HDL-C

60,000

)60.2

0

10203040

5060

18338-Ye

ar P

roba

bilit

y (p

er 1

,

3.9

23.2

34.6

Kannel WB. Am J Cardiol. 1983;52:9B-12B..Kannel WB, et al. Am Heart J. 2004;148:16-26.*Framingham study, 18-year follow-up (Monograph No. 28); 35-year-old men.

185 185 185 185335 335 335 335Cholesterol

8

Glucose Intolerance 0 + + +

++

+105

00

00 0

195 195 195SBPCigarettesECG-LVH

Comparison of a Sample of Global Coronary and CV Risk ScoresFramingham SCORE PROCAM

(Men)Reynolds (Women)

Reynolds (Men)

Sample size 5,345 205,178 5,389 24,558 10,724

Age (y) 30 to 74; M: 49 19 to 80; M: 46 35 to 65; M: 47 > 45; M: 52 > 50; M: 63

Mean follow-up (y) 12 13 10 10.2 10.8

Risk factors considered

Age, sex, cholesterol,

HDL-C, smoking,

systolic BP,

Age, sex, total/HDL-C ratio,

smoking, systolic BP

Age, LDL-C, HDL-C,

smoking, systolic BP,

family history

Age, HbA1C (with DM),

smoking, systolic BP, total

cholesterol, HDL-C hsCRP

Age, systolic BP, total cholesterol, HDL-C, smoking, hsCRP, parental

antihypertensive medications

systolic BP family history, DM, TG

C, hsCRP, parental history

of MI < 60

history of MI < 60

Endpoints CHD (MI and CHD death) Fatal CHD

Fatal/nonfatal MI or sudden

cardiac death

MI, ischemic stroke, coronary

revascularization, CV death

MI, stroke, coronary

revascularization, CV death

Greenland P, et al. Circulation. 2010;122:e584-636.

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FRS Assessment – ATP III

http://hin.nhlbi.nih.gov/atpiii/calculator.asp

Limitations of FRS System

• Population specific – Variability by country – Underestimates risk in special populations in

the US • Women • + family history; primary relative with CVD • Metabolic syndrome• Metabolic syndrome • Renal insufficiency • DM

Taylor AJ, et al. In: Kramer CM. Multimodality Imaging in Cardiovascular Medicine. 2010; Michos ED, et al. Atherosclerosis. 2006;184:201-6; Chang A, et al. Nephron Clin Pract. 2011;119:c171-7;

Zarich S, et al. Diab Vasc Dis Res. 2006;3:103-7; Stevens RJ, et al. Diabet Med. 2005;22:228.

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SCORE Project

Reprinted with permission from Conroy RM, et al. Eur Heart J. 2003;24:987-1003.

www.healthdecision.org

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www.healthdecision.org

www.healthdecision.org

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Case 1:Conclusions

• Very–low-risk patient with some risk factors • Calculated 0.8% HCE (CD + NFMI) per decade is very low( ) p y• Conclusions:

– Treat risk factors according to NCEP guidelines; because global risk is very low, consider lifestyle interventions

– Further diagnostic testing is unlikely to reveal CAD and should be avoided

Note: Elevated hsCRP may be a useful risk factor—consider selective use if it would make a difference in the decision for treatment compared with ATP III guidelines

Ridker PM, et al. N Engl J Med. 2008;359:2195-207.http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Coll_Cardio.pdf

Case 2

• 55-year-old asymptomatic man with DM arrives for a review of recent lab work and consultationfor a review of recent lab work and consultation

• Medical history: HTN, obesity• Family history: brother had heart attack at age 50• Social history: currently smokes 1 pack of

cigarettes daily, 40 pack-year history • Medications: lisinopril (10 mg daily), HCTZ (12.5

mg daily)mg daily)• Physical examination: BP = 160/100; height = 5 ft

9 in; BMI = 34; waist circumference = 39 in; otherwise within normal limits

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• Lab work: TC = 260; HDL-C = 34; TG = 182

Case 2 (cont.)

• HbA1C = 6.8%• Patient wonders aloud if he should be on

medication for his cholesterol • FRS = 30% / decade = 3%/yr • What further workup is needed? • Would you consider CRP?• Would you consider CRP?• Would you consider stress testing? • Would you consider imaging?

Approach to CHD Risk Assessment

• Risk assessments are population specificE i ECG D k T d ill S• Exercise ECG: Duke Treadmill Score

• Cardiac imaging risk stratifies patients beyond the level achieved by undergoing exercise ECG with Duke Treadmill Score

• At any level of CAD, patients with DM have greater risk than those who do not have these conditionsconditions

Breen DP. J Fam Pract. 2007;56:287-93.

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Evidence of Imaging Asymptomatic Patients

• Start with FRS Cl III l i t di t littl l t t ti• Class III low intermediate—little value to any testing

• CAC Greenland Guidelines• IIA FRS 10-20 "reasonable"• IIB FRS 6-10 “may be considered” • III FRS < 6% “inappropriate” • CTA—Class III (inappropriate) • Very few Class I recommendations

– AAA in older men with a sibling or parent with AAA; relatively few with asymptomatic status

Greenland P, et al. Circulation. 2010;122:2748-64.Hirsch AT, et al. Circulation. 2006;113:e463-654.

Gibbons RJ. ACCEL Interview. April 2012.

Evidence of Imaging Asymptomatic Patients (cont.)

• MPI• IIB for DM, elevated CAC (400 or greater), “may

be considered" • Million Hearts ABCS• Do not overburden healthcare system

Gibbons RJ. ACCEL Interview. April 2012.http://millionhearts.hhs.gov/index.html.

Greenland P, et al. Circulation. 2010;122:2748-64.Personal opinion, R. Schwartz.

http://choosingwisely.org/wp-content/uploads/2012/03/033012_Choosing-Wisely-National-Press-Rls-FINAL.pdf.

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Risk Stratification in Uncomplicated Type 2 DM:Prospective Evaluation of the Combined Use of CAC

Imaging and Selective MPS

1.0CAC

0.8

0.6

0.4Sens

itivi

ty

CAC AUC: 0.92 (0.87-0.96); P < 0.0001UKPDS score AUC: 0.74 (0.65-0.83); P < 0.0001FRS AUC: 0.60 (0.48-0.73); P = 0.13

UKPDS

FRS

Anand DV, et al. Eur Heart J. 2006;27:713-21. ROC analysis comparing the value of Framingham risk function, UKPDS risk engine, and the CAC score for predicting CV events.

0.2

0.00.0 0.2 0.4 0.6 0.8 1.0

1-Specificity

Noninvasive Imaging Selection After Inconclusive Exercise Test

• Identify why stress test was initially orderedWh t t i l i ?• Why was test inconclusive?

• Will patient benefit from further testing?• For high-risk patients or individuals who already have

CAD, the objective should be to quantify the presence and magnitude of ischemia to define the potential role of coronary revascularization

MPI cardiac MRI– MPI, cardiac MRI• Consider patient factors that influence test accuracy• Consider local expertise and availability of options

Koh AS, et al. Curr Treat Options Cardiovasc Med. 2012;14:8-23.

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Case 2: Conclusions

• 55-year-old asymptomatic man with DM arrives for a review of recent lab work and consultation

• Global risk is high: 3% per year; similar to the risk level of a g p ypatient with angina

• Guidelines indicate that it would be “reasonable” to consider CAC for this patient (Class II)

• We have no data to indicate whether revascularizing an asymptomatic high-risk patient will improve the health of the individual; this remains an exciting hypothesis for future investigation

• The physician has the dual responsibility of providing careThe physician has the dual responsibility of providing care for the patient without doing harm to the individual or the limited resources of society

• Conservative approach suggests the value of treating risk factors aggressively and watching for symptoms in this individual with a high-risk profile

Greenland P, et al. Circulation. 2010;122:2748-64; Personal opinion, R. Schwartz, MD.

Case 3

• 64-year-old woman presents for assessment of chest painchest pain

• She reports that the pain began 2 days ago while she was walking on the beach; she had chest pressure at the end of her 2-mile walk

• She also reports that, yesterday, the pressure began after she walked a half mile; as soon as she stopped, the pain subsided

• Today, she reported experiencing similar chest pressure while getting dressed

• Physical examination: within normal limits• ECG: within normal limits

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Acute Chest Pain

Spectrum of patients with acute chest pain• Cardiac causes:

– Acute ST-segment elevation MI– Non-ST-segment elevation MI– UA

• Other CV causes:– Acute dissection of the aorta– Acute pericarditis/myocarditis

A t l b li– Acute pulmonary embolism• Non-cardiac causes:

– Pulmonary: pneumonia, pneumothorax– Musculoskeletal, radicular– GI causes: hiatal hernia, GERD, cholecystitis

Fruergaard P, et al. Eur Heart J. 1996;17:1028-34.

TLC, Medical Therapy, and/or Revascularization Treatment

• How do we best match the level of intervention with the level of risk to optimize clinical outcomes?

• How can we use cardiac imaging to identify the proper roles for medical therapy and revascularization?revascularization?

20

Risk Stratification by MPI

• Depends on ability of perfusion tracer to define the extent and severity of perfusion abnormalities

• Outcome predictions driven by these parameters• Similar sensitivity and specificity for detecting CAD

may not translate into similar risk stratification ability

• ECG-gated SPECT MPS: fixed and transientECG gated SPECT MPS: fixed and transient (stress induced) LV dilation and reduced EF further amplify prognostic impact of perfusion abnormalities

Gibbons RJ. Heart. 2000;83:355-60.Marcassa C, et al. Eur Heart J. 2008;29:557-63.

RNI:Potential Applications for Chest Pain

ISCHEMIC EQUIVALENTAcute Chronic

ACSPretest

probability?

ECG interpretable AND able to exercise?

Inappropriate

Possible

Low

Definite Intermediate/High

Hendel RC, et al. Circulation. 2009;119:e561-87

Appropriate Appropriate AppropriateInappropriate

Yes No

21

RNI:Potential Applications for Asymptomatic Patients

CHD RISK(FRS-ATP III)( )

Low CHD Risk Intermediate CHD Risk High CHD Risk†

ECG interpretable?

Hendel RC, et al. Circulation. 2009;119:e561-87.

AppropriateInappropriateInappropriate Uncertain

†Includes DM or the presence of other clinical atherosclerotic disease, including peripheral arterial disease, abdominalaortic aneurysm, carotid artery disease, and other likely forms of clinical disease (eg, renal artery disease).

NoYes

Cardiac SPECT Provides Incremental Coronary Event Risk Identification Compared to Exercise Testing With ECG

7 0 5 012.0

26 vs. 4.3Hi/Lo HR 22.3 vs. 2.9 2.8 vs. 2.6Nuc vs. Echo Scan Results

10 0*

0.7

1.8

3.0

2.4

3.7

7.0

4.6

5.0 NL

MILDSEV

Even

t Rat

e (%

)

1.8

7.8*

0 4

6.4

8.9*

3.6

9.110.0

Hachamovitch R, et al. Circulation. 1996;93:905-14.*Marwick TH, et al. Circulation. 2001;103:2566-71.

*Stress Echo Data Marwick Circulation 2001 (Table 4, annual mortality based on 5-year data 0, 1 or MV )

N = 762 113 51 834 185 168 28 22 40High

(7.7%)Intermediate

(2.5%)Low

(0.9%)

Duke TM Score

0.3 0.4

22

MPI: Pharmacologic Stress Agent Selection

• Some patients are not candidates for exercise testing, including those with large AAA, pacemaker, or left bundle branch block

• Age and neurologic and orthopaedic limitations are a consideration

• Factors such as poor fitness level, patient comorbidities, and certain medications may keep patients from achieving sufficient workload through exercise

• For these patients, consider pharmacologic stress testing• Contraindications:Contraindications:

– Hypotension, ACS within 24 hours– Critical aortic stenosis, severe left main stenosis– Severe LV outflow obstruction, decompensated HF– Hypersensitivity to stress agent

Hendel RC. Reports in Medical Imaging. 2009;2:13-23.

Pharmacologic Stress Testing:Vasodilators

• Adenosine (nonselective vasodilator)• Dipyridamole (nonselective vasodilator)py ( )• Nonselective vasodilators:

– High incidence of side effects such as chest pain, flushing, headache, dyspnea

– Risk of bronchoconstriction or sinoatrial node or atrioventricular block

– Contraindications: bronchoconstrictive/bronchospastic lung disease second- or third-degree atrioventricularlung disease, second- or third-degree atrioventricular block, allergy to aminophylline, ingestion of caffeine within 12 hours, use of dipyridamole within 24 hours (for adenosine)

• Regadenoson (selective A2A vasodilator): similar side-effect profile, but milder

Hendel RC. Reports in Medical Imaging. 2009;2:13-23.

23

Pharmacologic Stress Testing: Catecholamine

• Dobutamine may be considered as a second-line h l i tpharmacologic stressor

• Cardiac inotrope and chronotrope• Consider use in patients who cannot perform

exercise stress testing and who have a contraindication to vasodilator stress testing

• Side-effects: chest pain, arrhythmiasy• Contraindications: Uncontrolled HTN, uncontrolled

AF/flutter, serious ventricular ectopy, large aortic aneurysm, beta blocker use within 24 hours

Hendel RC. Reports in Medical Imaging. 2009;2:13-23.

Effects of Age, Gender, Obesity, and Diabetes on the Efficacy and Safety of the Selective A2A

Agonist Regadenoson vs. Adenosine in MPI:Integrated ADVANCE-MPI Trial Results

• Study designed using a database of 2,015 patients• Authors’ conclusion: regadenoson can be safely administered as a

fixed-unit bolus and is as efficacious as adenosine in detecting ischemia, regardless of age, gender, BMI, or diabetes

• Patients taking regadenoson reported feeling more comfortable (1.7 +/- 0.02 vs. 1.9 +/- 0.03, P < 0.001)

• Limitations– Trials excluded patients who had contraindications to

adenosine and patients who had significant symptoms on initial adenosine scan

– No formal evaluation of the reduction of dosing errors and improved lab efficiency associated with fixed, bolus dosing

– It is possible that quantitative analysis will decrease variability

Cerqueira MD, et al. JACC Cardiovasc Imaging. 2008;1:307-16.

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New Populations to Consider for Vasodilator Stress Testing

• Recent trials have addressed the safety of regadenoson pharmacologic stress testing for patients with renal and respiratory comorbidities In both studies side effects were shown to be more common with• In both studies, side effects were shown to be more common with regadenoson (P < 0.0001)

• Ananthasubramaniam et al studied 504 patients with stage 3 or 4 CKD and found that no serious adverse events or deaths were reported over the 24-h post-dose period (primary outcome measure) – Only 14% of randomized patients had stage 4 CKD, none were

on dialysis; no pharmacokinetic data were collected• Prenner et al found no statistically significant difference in the

percent of subjects who experienced a >15% decrease in FEV1from baseline to 24-h post-baseline between regadenoson and placebo groups for asthma or COPD – Could not rule out severe bronchoconstriction with adenosine

receptor agonists or extrapolate results for patients with acute exacerbation of underlying illness

Ananthasubramaniam K, et al. J Nucl Cardiol. 2012;19:319-29; Prenner BM, et al. J Nucl Cardiol. 2012; Epub ahead of print.

Probability of a Coronary Event Within 10 Years Calculated on the Basis of the Results of Electron-Beam

CT or of Exercise Electrocardiography

Pretest Probability of a Coronary Event

Within 10 Yrs

Probability Within 10 Yrs According to Results of Electron-Beam CT

Probability Within 10 Yrs According to Results of Exercise Electrocardiography

Calcium Score ≥ 30 Calcium Score < 80 Abnormal Normal

Percent

1.0 3.0 0.2 4.0 0.4

2.0 6.5 0.4 3.0 0.9

3.0 9.5 0.6 12.0 1.3

4.0 12.5 0.9 15.0 1.9

5.0 15.0 1.0 19.0 2.3

Greenland P, et al. N Engl J Med. 2003;349:465-73.

6.0 18.0 1.2 22.0 2.8

7.0 20.0 1.4 25.0 3.3

10.0 27.0 2.2 33.0 4.8

15.0 38.0 3.4 44.0 7.4

20.0 46.0 4.8 52.0 10.0

25

Cardiac Survival for 3 Separate Subgroups:Patients With Normal Perfusion Scans

80

100 99.4

97.089.0

20

40

60

80Su

rviv

al (%

)

Normal scan/normal size (N = 3,463)Near-normal scan/normal size (N = 357)

P < 0.001

Gibbons RJ, et al. Circulation. 1999;100:2140.

0 1 2 3 4 5 6 7Years

0

20 ( )Cardiac enlargement (N = 167)

Women at Greater Risk

Women HCE Women ACMMI Women HCE Women ACMMI Women HCE Women ACMMI

0.1

0.2

0.3

0.4

0.5

0.6

Pred

icte

d Ev

ent R

ate

A B C

0.1

0.2

0.3

0.4

0.5

Pred

icte

d Ev

ent R

ate

0.1

0.2

0.3

0.4

Pred

icte

d Ev

ent R

ate

Men ACMMIMen HCE Men ACMMIMen HCE Men ACMMIMen HCE

Wexler O, et al. J Nucl Cardiol. 2009;16:28-37.

A-C: Risk-adjusted HCE and all-cause mortality rates by ESVI, EDVI, and LVEF, by gender. ESVI and EDVI > 300 mL/m2 were excluded. Predicted event rate is defined as 1-predicted survival based on gender-specific Cox models with adjustment for clinical variables. Graphs display the best fit with a 3rd order polynomial.

0 50 100 150 200ESVI mL/m2

00 50 100 150 200 250

EDVI mL/m2

0 00 50

LVEF (%)10 20 30 40 60 70 80

26

Nuclear Cardiology Testing With SPECT or PET:Comparing Proven Clinical Value vs. Potential

Radiation Risk

• Proven clinical value – 25-fold increase in risk assessment compared in

intermediate-risk Duke treadmill exercise scores patients – 10-fold increased risk assessment compared with stress

wall-motion studies – Up to twice risk assessment compared with coronary

angiography • Theoretical cancer radiation riskTheoretical cancer radiation risk

– 10 mSv radiation annually from 40 to age 80 tracks baseline risk associated with background radiation exposure in the US

Hachamovitch R, et al. Circulation. 1996;93:905-14; Marwick TH, et al. Circulation. 2001;103:2566-71; Iskandrian AS, et al. J Am Coll Cardiol. 1993;22:665-70; Pancholy SB,et al. J Nucl Cardiol. 1995;2:110-6; Gerber TC, et al. J Am Coll Cardiol Img. 2010;3:528-35; Sadeghi MM, et al. J Nucl Med. 2011;52:1162-4.

40,00045,00050,000

cide

nce Sestamibi 40 mCi (annually from age 40-80 yrs)

Background Radiation (3 mSv/yr)Natural Cancer Incidence (SEER)

Cumulative Cancer Incidence Comparison

5,00010,00015,00020,00025,00030,00035,000

0Cum

ulat

ive

Can

cer I

nc

Gerber TC, et al. J Am Coll Cardiol Img. 2010;3:528-35.

Cumulative cancer incidence (expressed as cases per 100,000 women) that can be attributed to background radiation (3 mSv), an annual dose of 40 mCi of technetium-99m sestamibi from age 40 to 80 years, and naturally occurring cancer. Data are based on the excess absolute risk model from the Biologic Effects of Ionizing Radiation VII report. Figure courtesy of Michael O’Connor, PhD.

0C

0 10 20 30 40 50 60 70 80 90Age (years)

27

Predicting Response to Treatment: TLC, Medical, and/or Revascularization Therapy

• Measure the extent/severity of ischemia and scar as risk surrogate• Treat any level of ischemia with TLC and medical therapy • Consider adding revascularization to OMT when ischemic burdenConsider adding revascularization to OMT when ischemic burden

is > 10% and scar is < 10% • Consider TID (with ischemic defect) • Quantify the hibernation and viability in apparent scar; consider

revascularization if extent of hibernating, viable exceeds pure scar • Caution:

– CMR by CE does not identify hibernation; get SPECT or PET If ESVI is > 100 mL/m2 re asc lari ation ma not impro e HF– If ESVI is > 100 mL/m2, revascularization may not improve HF outcome

– Women have higher event rates then men at any given ESVI, EF; would a lower threshold for revascularization of women improve their outcomes?

Hachamovitch R, et al. Eur Heart J. 2011;32:1012-24; Thomas GS, et al. J Am Coll Cardiol. 2004;43:213-23; Roes SD, et al. Eur J Nucl Med Mol Imaging. 2009;36:594-601;

Yamaguchi A, et al. Ann Thorac Surg 1998;65:434-8; Wexler O, et al. J Nucl Cardiol. 2009;16:28-37.

1.5

Medical therapy

Log Hazard Ratio: Revascularization vs. Medical Therapy

1.0

0.5

Log

Haz

ard

Rat

io

0.0Early revascularization

Log hazard ratio for revascularization vs. medical therapy as a function of % myocardium ischemic in patients with < 10% ischemic myocardium. Graphic representation based on Cox proportional hazards model. Interaction P < 0.001.

-0.5

0 12.5% 25% 37.5% 50%

% Total Myocardium Ischemic

Hachamovitch R, et al. Eur Heart J. 2011;32:1012-24.

28

SPECT Identifies Revascularization Benefit

> 10%

Risk Benefit

Ischemic myocardium

Scarred myocardium

Risk Greater

Benefit Greater< 10%

Adapted from P Soman, UPMC.Hachamovitch R, et al. Eur Heart J. 2011;32:1012-24.

If cardiac testing is needed for a symptomatic patient, why not just go

directly to coronary angiography?

I i i k• Invasive risks • Costly • SPECT MPI is proven more cost effective

– Cost effectiveness of SPECT MPS as a gatekeeper for coronary arteriography has been established by the Economics of yNoninvasive Diagnosis study

Shaw LJ, et al. J Am Coll Cardiol. 1999;33:661-9.

29

END Study: Diagnostic Yield by Screening Strategy in Women

MPI + Cath(N = 539)

Cath

No CAD1 VD2+ VD

42.1%

24.6%33.3%

22.6%

20.4%56.9%

Shaw LJ, et al. J Nucl Cardiol. 1999;6:559-69..

Distribution of coronary angiographic findings in women with chest pain who initially underwent stress MPI followed by coronary angiography (MPI + Cath) compared with patients proceeding directly to coronary angiography (Cath).

0 10 20 30 40 50%

60

Cost-Effectiveness of MPS Risk Assessment (N = 11,249)

$4.2$4.8

6.0

5.0

($)

Diagnostic CostFollow-up Cost

P < 0.000001

L I t Hi h

$2.9

$2.0$2.4

$2.8

4.0

3.0

2.0

1.0

0.0

Thou

sand

s

Low Int High813 2,928 1,682

Pretest Clinical RiskDirect Cath(N = 5,423)

Low Int High816 3,379 1,631

Pretest Clinical RiskMPI + Selective Catheterization

(N = 5,826)

Shaw LJ, et al. J Am Coll Cardiol .1999; 33:661-9.

N =

Study limitations included use of nonrandomized comparisons; quality of life comparisons between stable angina patients were not available.

30

PET: Cardiac Risk Assessment

• In this study, 2,783 consecutive patients referred for rest-stress PET assessment were followed up for 1.4 years to determine whether noninvasive assessment of coronary vasodilator function in patients with suspected or known CAD carries incrementalin patients with suspected or known CAD carries incremental prognostic significance

• Incorporation of coronary flow reserve into cardiac death risk-assessment models resulted in correct reclassification of 34.8% of intermediate-risk patients

• Corresponding improvements in risk assessment for all-cause mortality were shown

• Authors concluded that noninvasive quantitative assessment of dil t f ti ith PET i f l i d d tcoronary vasodilator function with PET is a powerful, independent

predictor of cardiac mortality in patients with known/suspected CAD

• Incremental risk stratification over clinical and gated MPI variables• Limitations: single-center, non-randomized observational study;

broad inclusion criteria may have led to an understatement of previously validated measures

Murthy VL, et al. Circulation. 2011;124:2215-24.

Stress Echocardiography for the Detection of CAD / Risk Assessment:

Asymptomatic (Without Ischemic Equivalent)Asymptomatic

General Patient Populations

Low global CAD riskIntermediate global

CAD riskHigh global

CAD risk

ECG interpretable?

Douglas PS, et al. J Am Soc Echocardiogr. 2011;24:229-67.

Inappropriate(124)

Uncertain(126)

Inappropriate(125)

Uncertain(127)

Yes No

p

31

Stress Echocardiography for the Detection of CAD / Risk Assessment:

Symptomatic or Ischemic Equivalent

Ischemic Eq i alent

Acute Chronic

Low Intermediate or high

Ischemic Equivalent

ACS Pretest probability?

ECG

Douglas PS, et al. J Am Soc Echocardiogr. 2011;24:229-67.

Inappropriate(123)

Appropriate(119, 120,121, 122)

Inappropriate(114)

Appropriate(115)

Appropriate(116, 117, 118)

Yes No

DefinitePossible

ECG interpretable and able to exercise?

Clinical Presentation, Diagnosis, and Prognosis of CAD in Women

• Improvements in case-fatality rates for women are not on par with those of men

• The authors report that for women presenting for CAD evaluation, traditional disease management approaches that focus ontraditional disease management approaches that focus on detection of occlusive angiographic disease often fail to serve those at risk of significant cardiac events

• Symptoms rarely helpful in differential diagnosis of chest pain in women, contributing to under-diagnosis, misdiagnosis– Prodromal symptoms include fatigue, sleep disturbance,

shortness of breath, indigestion, anxiety; fewer than 1/3 of women report warning signs involving chest pain or discomfort

i t MIprior to MI– Less than half report attack symptoms of chest pressure, pain,

or tightness• The authors state that in 50% of cases, non-obstructive CAD at

coronary angiography, due to “noncardiac chest pain” or coronary microvascular dysfunction is frequently reported

Leuzzi C, et al. Nutr Metab Cardiovasc Dis. 2010;20:426-35.McSweeney JC, et al. Circulation. 2003;108:2619-23.

32

Results From the WOMEN Trial

• In this study, 824 symptomatic women with suspected CAD, an interpretable ECG and > 5 metabolic equivalents on thean interpretable ECG, and > 5 metabolic equivalents on the Duke Activity Status Index were randomized to ETT or exercise MPI1

• In low-risk, exercising women, the diagnostic use of ETT versus exercise MPI yielded similar 2-year posttest outcomes (98.0 vs. 97.7%, P = 0.59)while providing significant diagnostic cost savings (P < 0.001)1

• Study noted to have limited power to detect outcomeStudy noted to have limited power to detect outcome differences2

• Study results may not be applicable to intermediate- or high-risk women (population actually enrolled was low risk)2

1Shaw LJ, et al. Circulation. 2011;124:1239-49.2Chaitman BR, et al. Circulation. 2011;124:1207-9.

Anatomic vs. Functional Testing

• Cost-effectiveness trials that compared i i i k t tifi ti ith t inoninvasive risk stratification with anatomic or

functional testing– PROMISE – RESCUE

• Potential prognostic benefit of reducing ischemia or noninvasive testing g– ISCHEMIA

Chaitman BR, et al. Circulation. 2011;124:1207-9.

33

Case 4

• You are asked to medically clear a 70-year-old man for elective hip replacementman for elective hip replacement

• Medical history: HTN, hyperlipidemia, type 2 DM, osteoarthritis

• Physical examination: within normal limits• Resting ECG: within normal limits• Lab work: TC = 240; HbA1C = 8.5%; CMP

normal; CBC normal; urinalysis normalnormal; CBC normal; urinalysis normal

Case 4 (cont.)

• Would you recommend further testing?• What if the patient was being admitted for an

emergency appendectomy?• What if he was being considered for elective

aortofemoral bypass?• What if the patient was noted to have significant

renal impairment?

34

Stress Echocardiography for Risk Assessment: Perioperative Evaluation for Noncardiac Surgery Without

Active Cardiac Conditions

Perioperative Evaluation for Noncardiac Surgery

Yes No

Low-risk surgery Intermediate-risk or vascular surgery

Asymptomatic < 1 year post normal catheterization,

noninvasive test, i

Moderate-to-good functional capacity (≥ 4 METs) or no clinical risk factors

Douglas PS, et al. J Am Soc Echocardiogr. 2011;24:229-67.

Inappropriate(154)

Inappropriate(155, 156, 159, 160)

Inappropriate(153, 162)

Appropriate(161)

Uncertain(157)

or previous revascularizationType of surgery?

Vascular surgeryIntermediate-risk surgery

RNI:Perioperative Evaluation

PERI-OP EVALUATION: S G

Low-risk surgery

No risk factors OR moderate/good

Intermediate-risk surgery OR

vascular surgery

1 or more risk factors* AND

SURGERY TYPE

Hendel RC, et al. Circulation. 2009;119:e561-87.

Inappropriate Inappropriate Appropriate

moderate/good functional capacity

risk factors* AND poor functional

capacity

*History of ischemic heart disease, compensated or prior heart failure, CV disease, DM (requiring insulin), or renal insufficiency (creatinine > 2.0).

35

Perioperative Risk Assessment: RCRI

Each risk factor is assigned 1 point: 1. High-risk surgical procedures: intraperitoneal, intrathoracic, suprainguinal

vascular2 History of ischemic heart disease2. History of ischemic heart disease

– History of MI– History of positive exercise test– Current complaint of chest pain considered secondary to myocardial

ischemia– Use of nitrate therapy; ECG with pathologic Q waves

3. History of congestive heart failure– History of congestive heart failure– Pulmonary edema– Paroxysmal nocturnal dyspnea– Bilateral rales or S3 gallop; chest radiograph showing pulmonary vascular

redistribution4. History of cerebrovascular disease

– History of transient ischemic attack or stroke5. Preoperative treatment with insulin6. Preoperative serum creatinine > 2.0 mg/dL

Lee TH, et al. Circulation. 1999;100:1043-9.

Risk of Major Cardiac Event

Perioperative Risk Assessment 2: RCRI

• Points, class, risk– 0, I, 0.4%– 1, II, 0.9%– 2, III, 6.6%– 3 or more, IV, 11%"Major cardiac event" includes MI pulmonary• "Major cardiac event" includes MI, pulmonary edema, ventricular fibrillation, primary cardiac arrest, and complete heart block

Lee TH, et al. Circulation. 1999;100:1043-9.

36

Caveats

• Beware of a negative imaging study in a patient ith di i k f t b t i t t t th i kwith cardiac risk factors; be certain to treat the risk

factors perioperatively • Consider perioperative beta blocker and statin

therapy when indicated by guidelines (potential for withdrawal)

• ACEIs and ARBs intensify hypotensive effects of anesthesia

Burrell S, et al. J Nucl Med Technol. 2006;34:193-211.Fleischmann KE, et al. J Am Coll Cardiol. 2009;54:2102-28.

Whinney C. Cleve Clin J Med. 2009;76:S126-S32.

Summary1. Asymptomatic low-intermediate–risk patients:

– “Imaging for prevention” is not recommended– TLC– Consider risk factors, and treat if warranted based on global risk

scores > 5% per decadescores > 5% per decade – Consider lifetime attributable risk of CV event – hsCRP may be considered if it would alter treatment plan

2. High-risk asymptomatic patient: you can feel comfortable with aggressive medical therapy

3. Symptomatic patients: – Stable low risk (outpatient) or unstable intermediate-high risk

(inpatient)? – > low risk: consider ETT and imaging to define CV risk precisely

4 Pre-operative risk:4. Pre-operative risk: – RCRI – Image selectively if risk of ischemia is > low and surgery can be safely

deferred– Emergency operation in vascular patient: treat with statin and beta

blocker continuously perioperatively

37

Evidence-Based Assessment and Treatment of CHD Risk

• Asymptomatic patients with multiple coronary risk factors: risk assessment

FRS ATP III H lthD i i t b li d CAD– FRS ATP III, HealthDecision.org, metabolic syndrome, CAD risk equivalent, SCORE, PROCAM

– DM: UKPDS – Controversial role of imaging for prevention: cost vs. benefit

• Lessons from DIAD: limitations of study design • Clinician’s dilemma: how to prioritize the effective use of

limited healthcare dollars – AHA Million Hearts Program: screen and treat risk factors– AHA Million Hearts Program: screen and treat risk factors

(ABCs) considering lifetime attributable risk – Prevalence of high-risk individuals is too low and cost is too

high to justify imaging to screen asymptomatic patients with risk factors

Turner RC, et al. BMJ. 1998;316:823-8; Cooney MT, et al. J Am Coll Cardiol. 2009;54:1209-27; www.healthdecision.org; Young LH, et al. JAMA. 2009;301:1547-55;

Shaw LJ, et al. J Nucl Cardiol. 2005;12:131-42; http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Coll_Cardio.pdf.

• Symptomatic patients:– Characterize presenting symptoms that suggest a risk of CHD clinical

events

Evidence-Based Assessment and Treatment of CHD Risk

events• UA, ST deviation; admit for workup• Stable angina, atypical chest pain with low to intermediate

probability of CAD: consider outpatient workup with imaging – Diagnosis vs. prognosis: define and manage clinical event risk of CHD – Incremental value of SPECT exercise ECG using the Duke TES – Clinical and cost effectiveness of using SPECT as gatekeeper for

coronary arteriography (END Study) – Purposes of imaging: diagnosis, prognosis, monitoring treatment p g g g , p g , g

effectiveness • Radionuclide SPECT and PET: END, COURAGE, and proven

incremental effectiveness vs. potential radiation risk • When to revascularize? Measure LV ischemia, scar, LV volume

indices, and EF with SPECT/PET • Wall-motion studies: strengths and limitations

Shaw LJ, et al. J Nucl Cardiol. 1999;6:559-69; Shaw LJ, et al. Circulation. 2008;117:1283-91; Personal opinion R. Schwartz, MD.

38

The Symptomatic Patient

• Consider ETT as first-line evaluation • Substantial incremental risk stratification with SPECT

and quantitative PET • Stress echo is helpful when positive; beware of a

negative wall-motion study in intermediate-risk patient • Pharmacologic stress testing:

– A2A selective coronary vasodilators (eg, regadenoson) provide new safety standard for

i i h COPD h d l dipatients with COPD, asthma, and renal disease – Can be safely given to patient with a history of AF

(avoid dobutamine)

Gibbons RJ, et al. Circulation. 2002;106:1883-92; Di Carli M, et al. Circulation. 2010;122:A12921; Marwick TH. Heart. 2003;89:113-8; Prenner BM. J Nucl Cardiol. 2012;Epub ahead of print;

Ananthasubramaniam K, et al. J Nucl Cardiol. 2012;19:319-29; Hendel RC. Reports in Medical Imaging. 2009;2:13-23.

References for Consideration

Ellestad MH. Stress Testing: Principles and Practice, 5e;Evans CH, White RD, eds. Exercise Testing for Primary Care and Sports Medicine Physicians

Froelicher VF, Myers J, eds. Exercise and the Heart, 5e.

39

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Abbreviation/Acronym List AAA = abdominal aortic aneurysm ACEI = angiotensin converting enzyme inhibitor ACO = accountable care organization ACS = acute coronary syndrome AF = atrial fibrillation AHA = American Heart Association ARB = angiotensin receptor blocker ATP = adult treatment panel AUC = area under the curve BMI = body mass index BP = blood pressure CAC = coronary-artery calcium CAD = coronary artery disease CBC = complete blood count CE = clinical evaluation CHD = coronary heart disease CMP = comprehensive metabolic panel CMR = cardiac magnetic resonance COPD = chronic obstructive pulmonary disorder COURAGE = Clinical outcomes utilizing revascularization aggressive drug evaluation CP = chest pain CPAP = continuous positive airway pressure CRP = C-reactive protein CTA = coronary CT angiography CV = cardiovascular CVD = cardiovascular disease DIAD = detection of ischemia in asymptomatic diabetics DM = diabetes mellitus ECG = electrocardiogram ECG-LVH = electrocardiography-left ventricular hypertrophy EDVI = end-diastolic volume index EF = ejection fraction END = Economics of Noninvasive Diagnosis Study ESVI = end-systolic volume index ETT = exercise treadmill test FEV1 = forced expository volume in 1 second FRS = Framingham Risk Score ft = feet GERD = gastroesophageal reflux disease HbA1C = hemoglobin A1C HCE = hard cardiac event HCTZ = hydrochlorothiazide HDL-C= high-density lipoprotein cholesterol HF = heart failure

HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome hsCRP = high-sensitivity C-reactive protein HTN = hypertension in = inches ISCHEMIA = International Study of Comparative Health Effectiveness with Medical and Invasive Approaches lbs = pounds LDL-C = low-density lipoprotein cholesterol LV = left ventricle LVEF = left ventricular ejection fraction mCi = millicurie MET = metabolic equivalent MI = myocardial infarction MPI = myocardial perfusion imaging MPS = myocardial perfusion scintigraphy MRI = magnetic resonance imaging mSv = millisievert NCEP = National Cholesterol Education Program NFMI = non-fatal myocardial infarction NL = normal limits OSA = obstructive sleep apnea OMT = optimal medical therapy PAD = peripheral artery disease PET = positron emission tomography PMI = private medical insurance PROCAM = Prospective Cardiovascular Munster Heart Study PROMISE = Prospective Multicenter Imaging Study for Evaluation of Chest Pain RCRI = revised cardiac risk index RESCUE = Randomized Evaluation of Patients with Stable Angina Comparing Diagnostic Examinations RNI = radionuclide imaging ROC = receiver operator characteristic RRS = Reynolds Risk Score SCORE = strategies concentrating on risk evaluation SBP = systolic blood pressure SEER = surveillance, epidemiology, and end results SEV = severe SPECT = single-photon emission computerized tomography TC = total cholesterol TES = treadmill exercise score TG = triglycerides TID = transient ischemic dilation TLC = therapeutic lifestyle choices UA = unstable angina UKPDS = United Kingdom Prospective Diabetes Study US = United States

VD = vasodilator WOMEN (trial) = What Is the Optimal Method for Ischemia Evaluation in Women