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Baljipally
6/11/2011
Challenges in the Diagnosis and Challenges
in the Diagnosis and
Treatment of Coronary Artery Disease in Women
Gayathri
G
h i Baljepally, M.D.
B lj
ll M D
University Cardiology
University of Tennessee Medical Center
Knoxville, TN.
Myth vs Facts
Baljipally
6/11/2011
Facts about Heart Disease in Women
Courtesy ‐ ASNC
Facts about Heart Disease in Women
Courtesy ‐ ASNC
Baljipally
6/11/2011
Facts about Heart Disease in Women
Courtesy ‐ ASNC
Facts about Heart Disease in Women
Courtesy ‐ ASNC
Baljipally
6/11/2011
Facts about Heart Disease in Women
CAD is the leading cause of death of women in the US
2011 Update of Heart Disease and Stroke per AHA
Facts about Heart Disease in Women
• >250,000 women die
from CAD per year
year.
• There is a decline in
the mortality rate for
CHD, but the rate is
less for women than
men
Heart Disease and Stroke statistics ‐ 2011 update
A report from the American Heart Association Baljipally
6/11/2011
Facts about Heart Disease in Women
Despite aggressive
campaigns like “Go
Red” , only 55% of
women in a survey
were aware that
CVD iis the
h lleading
di
cause of death in
women.
Heart Disease in Women: Lessons From the Past The importance of studying gender‐specific aspects of CAD have helped in the following clinical dilemmas:
l
ldl
–
–
–
–
–
Presentation of CAD: women are older than men
Less specific clinical manifestations of CAD in women
Greater difficulty in diagnosis
More severe consequences of MI when it occurs in women
Gender‐specific differences in treatment and outcomes
d
f d ff
d
Thus, early recognition of symptoms and accurate diagnosis of CAD is of great importance
Baljipally
6/11/2011
Challenges in Diagnosing CAD in Women
• Non Invasive Studies:
‐ Exercise EKG
‐ Myocardial Perfusion Imaging with stress testing
‐ Stress ECHO
‐ Cardiac PET
‐ Cardiac CT
‐ MRI
• Invasive Evaluation:
‐ Coronary Angiogram
Ischemic Cascade
Myocardial Ischemia due to coronary luminal occlusion
Ð
Decreased Myocardial Perfusion
Î
Ð
Metabolic Changes
Ô
Diastolic Dysfunction
Ô
Nuclear Scan
PET Scan
PET Scan
Stress Echo
Ò
Systolic Dysfunction
EKG Changes
Î
EKG
Chest Pain
Î
History
Baljipally
6/11/2011
Pathophysiology of Atherosclerosis in Women
• Symptoms maybe be less related to obstructive stenosis as to the degree of vascular dysfunction or subendocardial
the degree of vascular dysfunction or subendocardial ischemia
• From angiographic literature, women have smaller sized arteries than men
• Microvascular disease is associated with increased risk of CAD events in women, but not in men • Young women have MI from plaque erosion than men who Young women have MI from plaque erosion than men who
have plaque rupture as a cause of AMI
• High prevalence of nonobstructive CAD and single‐vessel disease in women; affects diagnostic accuracy of non‐invasive testing
Regular Treadmill (Exercise EKG Testing) • Despite advances in technology the exercise
technology, the exercise ECG remains an important tool in the diagnosis and prognosis of the women suspected of having CAD
Baljipally
6/11/2011
Utility of Exercise EKG Testing in Women
o Class I Indication: ‐ If they are able achieve necessary workload and have normal baseline EKG
workload and have normal baseline EKG
In men ‐ Sensitivity is 68% ‐ Specificity is 77%
In Women ‐ Sensitivity is 61% ‐ Specificity is 70% o Lower sensitivity and specificity even after adjusting L
ii i
d
ifi i
f
dj i
for posttest bias and pretest prevalence
o Higher false positive rate in women compared to men
Limitations of Exercise Testing in Women in Diagnosing CAD
In Premenopausal women ‐ EEndogenous estrogen ( digoxin like effect)
d
t
( di i lik ff t)
‐ Menstrual cycle variability in ST changes ( midcycle lower estrogen is associated with greater exertional ischemia and frequent symptoms) In postmenopausal women ‐ Increased
Increased prevalence of DM, obesity and other comorbidities
prevalence of DM obesity and other comorbidities
‐ Greater functional decline compared to similarly aged men ( 50% cannot achieve > 5 METS) Baljipally
6/11/2011
Exercise EKG Testing in Women
• Imaging is superior in discriminating risk in women with suspected symptoms
with suspected symptoms
• Prognosis:
‐ Exercise capacity is a strongest prognostic indicator (< 5 METS has fourfold risk of CV event in 5 yrs)
‐ The Duke Treadmill Score works well for both men and women
d
‐ High risk <‐11 with annual CV event >5%
‐ Low risk score >+5 with annual CV event <0.5%
Nuclear Imaging in Women
Myocardial Perfusion Imaging has demonstrated incremental value in risk stratification of women with intermediate pretest likelihood of CAD
Baljipally
6/11/2011
Nuclear Imaging in Women
Technical considerations in Stress MPI for Women • Image quality in women is affected by two major factors
Image quality in women is affected by two major factors
‐ Small heart size and
‐ Breast attenuation
• Robust evidence in women
– Earlier studies reported diminished accuracy of SPECT Thallium scans – Gender‐specific data available for Tl‐201and Tc‐99m tracers
– Tc‐99m tracers is the agent of choice for women due to a 50% reduction in attenuation artifacts from breast tissue Nuclear Imaging in Women
Technical considerations in Stress MPI for Women
Gated‐SPECT Imaging
Gated‐SPECT Imaging – post stress ejection fraction and regional wall motion
– reduce false positives
Tc and TI scan showed same sensitivity, but the Specificity for detecting >70% stenosis was 59% with TI and 82% with Tc and with EKG‐gating improved to 92%
Baljipally
6/11/2011
Diagnostic Accuracy of MPI in Women
• Diagnostic sensitivity: 85% ‐ 90%
• Diagnostic specificity: 65% ‐ 70%
• Methods to improved specificity: 80% – 90%
‐ EKG gated SPECT to assess the LVEF and wall motion ‐ Attenuation‐correction algorithms in obese pts.
‐ Prone imaging to exclude breast artifact
Prone imaging to exclude breast artifact
• Pharmacological stress provides comparable overall accuracy in women and men and is helpful in older and obese women
Prognosis value of MPI in Women
• Exercise MPI provides incremental prognostic value to risk stratify women and to help in CAD management
stratify women and to help in CAD management
• Abnormal Tc99m Sestamibi SPECT findings associated with adverse prognosis in both women and men ‐ Normal scan has <1% annual risk of CV event
‐ Abnormal study has 6% annual risk of CV event
• From END study, extent of perfusion abnormalities was a strong predictor of cardiac mortality
• Severe ischemia associated with decrease in LVEF < 51% had 30% CV event in 3 yrs compared to preserved LVEF with 10‐
15% CV event
Baljipally
6/11/2011
Technetium‐99m SPECT Imaging Predicts Cardiac Mortality in Women ( END) study
Ischemia extent and survival by number of vascular territories
Cardiac survival
C
1.0
0
1
2
0.9
1.0
0 98.5%
1
2
0.9
3
0.8
0.7
0.6
0.8
Women
(n = 3402)
0 0.5 1 1.5 2 2.5 3
Years
80-87%
0.7
3
Men
(n = 4500)
0.6
0
0.5 1
1.5 2
Years
2.5 3
Marwick TH, et al. Am J Med. 1999
Utility of MPI Testing in Women
• Intermediate pretest likelihood with abnormal b li EKG
baseline EKG
• High pretest likelihood women • Diabetic women
• Prior indeterminate exercise EKG
Baljipally
6/11/2011
High risk Female Subsets: Diabetics and Metabolic Syndrome
– Cardiac mortality in Diabetic women exceeds that Cardiac mortality in Diabetic women exceeds that
of Diabetic men or Non‐Diabetic women
– Annual mortality rate 8%
– Reevaluation of risk every 2 years is resonable
y y
– Relative risk threefold higher if risk factors for metabolic syndrome were present as well
3‐Year survival rate for patients with and without Diabetes
Cardiac death or nonfatal MI
No ischemia 1 vessel >/= 2 vessel No
ischemia
1 vessel
>/= 2 vessel
ischemia ischemia
Diabetic women 3.5% 27.5% 40%
Non‐Diabetic women 4.5% 15.0% 23.5%
Diabetic men 3.7% 23.0% 21.0%
Non‐Diabetic men 4.2% 12.0% 15.0%
Giri et al, Circulation 2002
Baljipally
6/11/2011
Algorithm for Evaluation of Symptomatic Women
Risk factor modification
+/or anti‐ischemic Rx
Good exercise
tolerance and normal
rest ECG
Exercise treadmill (TM) testing
Normal/L
ow
post-ETT
likelihood
Intermediate
risk TM
High‐
likelihood Intermediate‐
With Atypical likelihood or Typical With Atypical or Chest Pain
, Typical Chest Pain
Ð
DM, abnormal EKG
Exercise or pharmacologicÐ
stress
gated SPECT imaging
Ex capacity >5 METs
Ex capacity <5 METs
Exercise
stress
gated SPECT
g
Pharmacologic
stress
gated SPECT
g
Normal or mildly
abnormal with
normal LV function
Moderateseverely
abnormal
or reduced EF
Cardiac catheterization
AHA- Consensus Statement on Cardiac Imaging, 2005
Stress Echocardiography
• First‐line diagnostic test in women
• Ultrasound performed both
Ultrasound performed both
at rest and during peak stress • Stress ‐ exercise or pharmacologic • Ischemia defined by development
of new or worsening wall motion abnormalities
Baljipally
6/11/2011
Advantages of Stress Echo
‐ Convenient
‐ Lower cost
‐ No ionizing radiation
‐ Assess cardiac structure and left ventricular function Limitations of Stress Echo •
•
•
•
Preexisting lung disease
Obesity
Limited exercise time
Timely aqcusition of post stress images
Baljipally
6/11/2011
Accuracy of Stress ECHO Testing in Women
Diagnostic Data:
S iti it 84% Sensitivity ‐
84%
Specificity ‐ 76% ‐ Agency for Health‐Related Quality
Prognostic Data of normal stress echo: CV event rate of 0.8% per year in women
CV
event rate of 0 8% per year in women
Compared to 1.2% for men
‐ Metz and colleagues, JACC 2007
Comparative Test Statistics on Diagnostic Accuracy in Women
ECG (n = 3721)
Echo (n = 296)
Nuclear (Tl-201) (n = 842)
Nuclear (Gated tech) (n = 100)
Sensitivity
Specificity
61%
86%
78%
84%
70%
79%
64%
94%
Baljipally
6/11/2011
PET Imaging for Diagnosing CAD in Women
The Role of PET for Evaluating CAD in Women
• Higher resolution than SPECT resulting in better image quality
• Determine absolute coronary flow ( marker of endothelial function)
• Soft‐tissue artifacts encountered in SPECT can be corrected
• Sensitivity and Specificity for diagnosing CAD in women are 93% and 83%
• Lu and co‐workers showed in women with equivocal SPECT,
Lu and co‐workers showed in women with equivocal SPECT
follow ‐ up PET showed normalcy in 77%
• Diagnostic accuracy better in women, obese and those with less extensive CAD
Baljipally
6/11/2011
Prognostic Value of PET in Women
• Similar to SPECT • For normal PET study cardiac events were 1.3% per year • For abnormal PET study cardiac events were 15.2% per year
Cardiac Computed Tomography in
Women
• Detect Coronary
Artery Calcium score
• Coronary CT
angiography for CAD
evaluation
Baljipally
6/11/2011
Cardiac CT in Diagnosing CAD in Women
• Low to Intermediate pretest likelihood of CAD
• Coronary Calcium Scoring: ‐ Marker for atherosclerotic plaque
‐ CAC develops 10 ‐ 15 yrs later in life in women than in men
• CAC is 5 ‐ 7 times lower at any given age
Median score in men is 975 and in women 370
‐ Median score in men is 975 and in women 370
• In Intermediate risk , >400 CAC help reclassify to a higher risk group
Coronary CTA in Women
• Useful
Useful in Low to Intermediate in Low to Intermediate ‐ risk pts with risk pts with
symptoms
• Sensitivity of 85% ‐ 95%
• Specificity of 95% ‐ 98%
• Negative predictive value is high, it is an excellent modality for ruling out CAD
modality for ruling out CAD
Baljipally
6/11/2011
Future Directions in Noninvasive Imaging in Women
• Hybrid imaging ( PET
Hybrid imaging ( PET‐CT
CT, SPECT
SPECT‐CT)
CT) • MRI MRI in Detecting CAD in Women
• Emerging modality
• No ionizing radiation
N i ii
di ti
• Ability to detect subendocardial ischemia, an early manifestation of myocardial ischemia
• MRI spectroscopy can detect anaerobic myocardial shifts indicative of ischemia and microvascular d f
dysfunction per WISE study
i
WISE d
• Stress MRI has sensitivity of 83% ‐ 92% and specificity of 86%
Baljipally
6/11/2011
Coronary Angiography
• Diagnostic angiography is the gold standard f di
for diagnosing CAD
i CAD
• Women have more complications than men after LHC
• Women not as often offered LHC, even after positive noninvasive test
positive noninvasive test
Points to remember…..
1. Order Exercise EKG only if work load is achievable in patients with normal EKG
patients with normal EKG
2. Add Nuclear Imaging or Echo for more diagnostic value
3. Stress Echo can be used as a first line diagnostic test in women
4 PET has improved accuracy in women with less 4.
PET h i
d
i
i hl
extensive CAD or in patients with soft tissue attenuation problems Baljipally
6/11/2011
Points to remember…..
5. MRI useful for detection of subendocardial i h i
ischemia
6. Guidelines support use of cardiac imaging in symptomatic women at intermediate pretest risk with abnormal baseline EKG
7 Consider pharmacologic stress test in patients
7. Consider pharmacologic stress test in patients unable to exercise
8. Diabetic women have higher event rate
Challenges in the Treatment of Coronary Heart Disease in Women
Baljipally
6/11/2011
Gender Differences in Managing Stable CAD and ACS in Women
Symptoms
Treatment
Outcomes
Gender Differences in Symptom Presentation
• CAD presentation lags by ~ 10 yrs. compared to men
• MI and sudden death lag by MI and sudden death lag by ~20yrs
20yrs.
• Women present with similar or higher prevalence of angina rather than MI and SCD • Chest pain is the most commonly reported symptom in both sexes, but women have atypical symptoms more frequently reported as dyspnea, fatigue N/V, indigestion, pain in middle of back and jaw or maybe silent
of back and jaw or maybe silent.
• More comorbidities like DM, obesity, HF, HTN than men
• Less likely to have prior MI or revascularization
Baljipally
6/11/2011
Gender Discrepancies in Treating Women with Stable CAD
• Euro Heart Survey
‐ Less diagnostic testing
‐ Less statin and antiplatelet therapy
‐ Less revascularization
‐ 18 mths f/u showed doubled occurrence of death and nonfatal MI in women
Gender Discrepancies in Treating Women
• Insights from the NHLBI‐Sponsored Women’s
Ischemia Syndrome Evaluation (WISE) Study
• > 50% women with chest pain at noninvasive evaluation had no flow limiting epicardial disease
• 9.4% had absolute risk at of death and MI in 4 9 4% had absolute risk at of death and MI in 4
years
Baljipally
6/11/2011
Medical Therapy for Stable CAD in Women
• ASA, BetaBlockers, Statins and ACEi are underutilized in eligible women
d tili d i li ibl
• Commonly on Calcium channel blockers which have no survival benefit
• Greater utilization of proven therapy needed
The Women’s Health Study (WHS)
Primary Prevention Study
39 876 women
39,876 women
Followed for 10 yrs
100mg every other day ASA vs Placebo
No effect on nonfatal MI or CV death in women > 45 yrs
• Reduction in Ischemic stroke by 24% in women > Reduction in Ischemic stroke by 4% in women
45 yrs of age
• Reduction of nonfatal MI by 26% in women > 65 yrs of age
•
•
•
•
•
Ridker and colleagues, NEJM 2005
Baljipally
6/11/2011
Aspirin Therapy in women
The Women’s Health Study (WHS)
• Primary prevention of stroke in women > 45 yrs of age
• Primary prevention of MI in women > 65 yrs of age
Secondary prevention in both stroke and MI
• Secondary prevention in both stroke and MI Medical Therapy of CAD in Women
• Beta Blockers are beneficial and improve survival ( ISIS I and ISIS II)
( ISIS‐I and ISIS‐II)
• Statins – women benefit more than men from LDL reduction
• In REVERSAL study, women showed reduction in atheroma volume on IVUS compared to men who just showed slowing of disease progression.
• ACEi are beneficial but less than men ( less LVEF reduction after MI)
Baljipally
6/11/2011
Gender Discrepancies in Treating Women with unstable angina and NSTEMI
•
•
•
•
•
Gusto IIB Study:
Women more likely to have unstable angina than EKG changes or enzyme elevation
More delay in presentation to the hospital
Complications were greater, mainly bleeding
Less angiography than men ( 39% vs 53%)
Greater overall mortality
Gender Discrepancies in Treatment
• FRISC II and RITA‐3 early invasive Rx benefitted men only
• TACTICS TIMI 18 showed comparable benefit for both sexes
• In high risk women aggressive therapy is beneficial as it balances the early procedural risk
• 2007 AHA/ACC for unstable angina recommend an 2007 AHA/ACC f
bl
i
d
initial conservative approach for low‐risk women
Baljipally
6/11/2011
Gender Difference in Outcomes
• Women have better outcomes than men in unstable angina
t bl
i
• Comparable outcomes in NSTEMI and
• Worst outcomes than men in STEMI
Acute Myocardial Infarction in Women
Women in Clinical Research
‐ Discordance between representation of women among MI pts. and their representation in clinical trials
‐ Lee PY, et al, JAMA 2001
‐ Women sustain 45% of all MI , but only represent 27% ,
y p
of pts. enrolled in clinical trials of acute myocardial infarction
Baljipally
6/11/2011
Acute Myocardial Infarction in Women
Presentation:
• Besides
Besides Chest Pain, more women described dyspnea, fatigue Chest Pain, more women described dyspnea, fatigue
as well as other atypical symptoms
• Usually have prior stable angina or experience new or different symptoms as compared to men
• 37% of women compared with 27% men did not have CP or discomfort at presentation
• Greater severity of MI and more complications of MI
Acute Myocardial Infarction in Women
Outcomes:
• Atypical Symptoms, late presentation to the ER, lack of rapid ER triage, incorrect Diagnosis – All these result in late and inadequate treatments
• Women, particularly <60 yrs of age have more in‐
hospital, 2 yr mortality and early reinfarction f ll i MI
following MI
• Elderly women have comparable or better survival than men Baljipally
6/11/2011
Compared with Men.....
ƒ 38%
38% of women experiencing a heart attack of women experiencing a heart attack
will die within one year compared to 25% of men.
ƒ 35% of women heart attack survivors will have another heart attack compared to 18% of men
of men. ƒ Women are almost twice as likely as men to die after bypass surgery.
59
Use of Glycoprotein IIb/IIIa inhibitors in Women
• Initial studies showed heterogeneity
• PURSUIT Trial showed men had more benefit and women had increased death or MI
• Subsequent meta analysis showed , treatment benefit extended to both men and women at high risk for adverse outcomes
high risk for adverse outcomes
Baljipally
6/11/2011
Fibrinolytic Therapy in Women with AMI
• Highly effective, but under utilized
• Similar reduction in mortality and successful angiographic reperfusion rates
• Higher bleeding complications particularly hemorrhagic stroke in females > 70 yrs
• Reinfarction twice that of men, suggesting Reinfarction twice that of men suggesting
more aggressive therapy after lytics
Revascularization
• Less likely to to be offered coronary angiography, hence adverse long‐term i
h h
d
l
t
outcomes
• Referred late in the course of the disease
• Little or no difference in use of PCI or CABG, once the anatomy is defined
once the anatomy is defined
Baljipally
6/11/2011
Percutaneous Coronary Intervention in Women
• In the earlier stages of intervention:
‐ PTCA in women had lower angiographic and clinical succcess compared to men ( 56%/ 66%)
‐ Higher procedural complications with sixfold increase in mortality
increase in mortality
PCI in Women
In the present era:
‐ Women continue to have vascular complications compared to men
‐ Increased bleeding
‐ Long term outcomes are similar
‐ Less angiographic restenosis, MI, repeat PCI, or CABG
‐More likely to have residual angina Baljipally
6/11/2011
Coronary Artery Bypass Surgery in Women
• Earlier studies showed greater complications and mortality due to smaller body size
and mortality due to smaller body size, advanced disease at presentation, need for emergent CABG, referral bias
• Coronary Artery Surgery Study (CASS )registry and Bypass Angiography Revascularization Investigation ( BARI) Similar graft patency Investigation ( BARI) ‐
Similar graft patency
and long term survival benefit in women and men
Treatment of CAD in Women
In Summary
‐ All women should receive proven adjuvant medical therapies just like men, according to current ACC/AHA guidelines
‐ Short and long term outcomes of PCI are similar to male patients whether performed electively or emergently for acute MI
‐ ACC/AHA guidelines:
ACC/AHA guidelines:
“CABG should not be delayed or denied to women who have appropriate indications for revascularization”