©2015 MFMER | slide-1

Stress Testing in Women

Todd D. Miller, M.D.Mayo ClinicRochester, MN

E-mail: miller.todd@mayo.eduDisclosures: None

©2015 MFMER | slide-2

Purposes of Stress Testing

•Diagnosis (probability) CAD

•Prognosis (risk stratification)

•Other

©2015 MFMER | slide-3

Factors Affecting Diagnostic Accuracy Exercise ECG

• Prevalence CAD in population (Sp = )

• Exercise performance

• Resting ECG

• Medications

• Gender specific• Hormone status (digoxin)• Abnormal coronary tone• Microvascular disease

TN TN + FP

MI/CD By Age and SexARIC and CHS

35-44 45-54 55-64 65-74 75-84 85+0

20

40

60

80

100

120

140

25

75

125 125120

80

10

35

6070

100110

MenWomen

Mozaffarian D. Circulation 2015;131:e29-e322

New

and

Rec

urre

nt M

I or

Fat

al C

HD

per

1,0

00

Age (Years)

Effect Hormone Therapy Exercise ECG

Sensitivity Specificity0

10

20

30

40

50

60

70

80

90

No HRTERTEPRT

Bokhari S. JACC 2002;40:1092

*

Pe

rce

nta

ge

Meta-Analysis Exercise ECG

Sensitivity Specificity0

20

40

60

80

MenWomen

68%

61%

77%

70%

%

Gianrossi R. Circ 1989;80:87Kwok Y. AJC 1999;83:660

Verification Bias

Verification Bias

Begg CB and Greenes RA: Biometrics 39:207, 1983Diamond GA: AJC 5:1175, 1986

Se =Se =TPTP

TP + FNTP + FN Sp =TN

TN + FP

Cath125

Cath125

No cath735

No cath735

Cath15

Cath15

Nocath125

Nocath125

(–) Test750

(–) Test750

(+) Test250

(+) Test250

1,000 pt1,000 pt

Se =Se = TPTPTPTP + FN+ FN FP

Sp =TN

TN +

Exercise ECGMPI Reference Standard

Sensitivity PV (+) Specificity PV (-) Accuracy0

20

40

60

80

100

MenWomen

42%

30%

70%

34%

78%82%

52%

78%

58%

69%

p<0.001 p<0.001 p=0.002 p<0.001 p<0.001

Miller TD. AJC 2001;87:868

%

Impact of Verification Bias – Women

Roger VL. Circ 1997;95:405Miller TD. AJM 2002;112:290Roger VL. Circ 1997;95:405Miller TD. AJM 2002;112:290

ECHO SPECT

79

97

32

58

SensitivitySensitivity

%%

ECHO SPECT

37

20

86 84

SpecificitySpecificityApparentApparent

AdjustedAdjusted

0

20

40

60

80

100

CAD Prognostic Index

0.1

1.4

2.4

4.2

8.0

0

2

4

6

8

10

No CAD 1-vessel 2-vessel 3-vessel Left main

Annualmortality

(%)

Annualmortality

(%)

Califf RM: JACC 27:964, 1996Califf RM: JACC 27:964, 1996

Prognostic Value Exercise CapacitySt. James WTH Project

<5 MET5-8 MET

>8 MET

0

1

2

3

4

Adjusted for AgeAdjusted for Framingham Risk Score

1.6(1.1-2.4)

Exercise Capacity Categories

Gulati M. Circulation 2003;108;1554

Haz

ards

Rat

io o

f D

eath

2.0(1.3-3.2)

3.1(2.1-4.8)

1.9(1.3-2.9)

1.0

1.0

Duke Treadmill Score

Low Intermediate High0

2

4

6

8

10

0.25

1.3

5.0AnnualCV

mortality(%)

AnnualCV

mortality(%)

Mark DB: NEJM 325:849, 1991

(5)

Score =Duration (min Bruce protocol) –

(5x ST-seg deviation)(mm) –(4x angina index)(0, 1, 2)

Score =Duration (min Bruce protocol) –

(5x ST-seg deviation)(mm) –(4x angina index)(0, 1, 2)

(-10 to +4) (<-10)

CP1197053-2

©2015 MFMER | 3452570-13

0 1 20.5

0.6

0.7

0.8

0.9

1.0

0 1 20.5

0.6

0.7

0.8

0.9

1.0

Duke Treadmill Score

Alexander K. J Am Coll Cardiol1998;32:1657

Women Men

Years Years

Pro

babi

lity

of s

urvi

val

Pro

babi

lity

of s

urvi

val

LowModerateHigh

LowModerateHigh

0123456789

101112131415

Normal Abnormal

ETT MPI

WOMEN Trialn = 824

CostsETT $338MPI $643

% M

AC

E

Shaw LJ. Circ 2011;124:1239

0.4%1.2%

5.1%

13.1%

Test Results

p=0.40

p=0.19

p<0.001

MACE 17 CD 1 MI 3 Hosp 13

©2013 MFMER | 3258712-15

Risk Stratification in the Elderly (Age ≥75)

Cardiac Survival

0 1 2 3 4 5 6 70

20

40

60

80

100

Duke Score

%

Years 59 52 46 39

164 117 104 79

12 7 6 3

0 1 2 3 4 5 6 7

SPECT

Years112 97 89 75

37 30 25 17

83 46 39 26

P=0.4519 P<0.001

LowIntermediateHigh

Kwok JMF. JACC 2002;39:1475 Valeti US. Circ 2005;111:1771

86%

85%

69%

95%

93%

60%

Duke Score SPECT

Kwok JMF. JACC 2002;39:1475 Valeti US. Circ 2005;111:1771

Low25%

Intermediate70%

Intermediate16%

Low49%

High35%

High5%

Duke score SPECTLow 2.0 0.8Intermediate 2.0 1.0High 4.8 5.8

Annual cardiac mortality (%)

0

20

40

60

80

100

0 1 2 3 4 5 6 7

Survival Free of CDSSS Women

At risk (no.)

Low 69 64 60 60 60 57 48 22

Intermediate 15 14 12 12 11 11 8 4

High 19 10 10 10 9 8 7 3

Years

%

Low

High

Intermediate

P=0.012

97%92%

69%

Cancer Incidence in Women

Gerber TC. JACC Cardiovasc Imaging 2010;3:528

©2015 MFMER | 3452570-18

Conclusions

• Standard ETT and stress imaging modest value diagnosis CAD

• Most important role of stress testing risk stratification CAD

• Apply all available information to patient management and not just ischemia

• Approach standard ETT when appropriate as initial test most cost effective

RecommendationsIndividual Stress Modalities

Variable ETT Imaging*

Pre-test prob CAD Intermediate High**

Able to exercise*** Yes No

Interpretable ECG**** Yes No

Prior false (+), indeterminate ETT No Yes

* Pre-menopausal no radiation** Includes elderly (> age 75 yrs)*** 5 METs**** Paced, LBBB, WPW, ≥ 0.5 mm ST ↓

Mieres JH. Circ 2014;130:350