©2015 MFMER | slide-1
Stress Testing in Women
Todd D. Miller, M.D.Mayo ClinicRochester, MN
E-mail: [email protected]: 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