Post on 27-Aug-2020
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What to do When the Perfusion is What to do When the Perfusion is Abnormal and the Arteries are Open?Abnormal and the Arteries are Open?
in the symposium in the symposium
Advance in Nuclear CardiologyAdvance in Nuclear Cardiologygygyand Cardiac CTand Cardiac CT
CedarsCedars--Sinai Medical Center 2012Sinai Medical Center 2012
C. Noel Bairey Merz, M.D., F.A.C.C, F.A.H.AWomen’s Guild Endowed Chair in Women’s Health
Barbra Streisand Women’s Heart CenterPreventive and Rehabilitative Cardiac CenterPreventive and Rehabilitative Cardiac Center
Cedars-Sinai Heart InstituteLos Angeles, California USA
merz@cshs.org
Presenter Disclosure InformationWhat to do When the Perfusion is Abnormal and the
Arteries are Open?C. Noel Bairey Merz MDC. Noel Bairey Merz MD
DISCLOSURE INFORMATION:The following relationships exist related to this presentation (*paid to CSMC):Grant support*: NHLBI, SWHR, GileadConsulting*: Abbott Vascular, Amarin, Pozen, Medscape BMSMedscape, BMSHonorarium*: Gilead, Allegheny, Brigham and Women’s, CV Institute San Diego, El Camino Hosp, Expert Exchange, Mayo, Montefiore, SCS, Slocum-Dickson, Women’s Health Congress, Los Robles Med Ctr, U PennStocks: None
2
Female-pattern Ischemic Heart DiseaseMicrovascular Coronary Disease (MCD)
Angina
Abnormal SPECT
No obstructive CAD
Abnormal coronary flow reserve and elevated LVEDPand elevated LVEDP
Diffuse atherosclerosisby IVUS
NCDR estimate 3 million women in the US – a largerproblem than breast cancer.
Circulation. 1999;99:1774
Euro Heart Survey of Stable Angina:Euro Heart Survey of Stable Angina:Increased Risk of Death in WomenIncreased Risk of Death in Women
0.15
Cumulative Probability of Death or MI(Patients With Confirmed Coronary Disease)
Patients with clinical diagnosis of angina on initial assessment by a cardiologist (n=3779)
W ( 276)
0 05
0.1
tive
Eve
nt
Pro
bab
ility
y g ( )
Hazard ratio for death or MI (females versus males)
− Overall: 2.07 (1.16-3.72; P=0.01)
− Similar significant results when adjusted for
• Age diabetes LV
Women (n=276) Men (n=718)
P=0.02
4
0
0.05
Cu
mu
lat
0 3 6 9 12 15 18
Time Since Entry (months)
• Age, diabetes, LV function, severity of coronary disease
• Age and use of statin and antiplatelet therapy
• Age and revascularization
Daly C, et al. Circulation. 2006;113:490-498.
3
Women have Women have Less Less Obstructive CAD on Obstructive CAD on Elective Diagnostic Angiography for SIHDElective Diagnostic Angiography for SIHD
12
10 110.5Women
Patients With >50% Stenosis
4
6
8
10
Inci
den
ce10
00 p
erso
n-y
ears
)
4.03.1
5.6 5.3
10.110.5
5.0
7.6
4.2
Men
5
0
2(per
Age (years)45-54 55-64 65-74 75-84 85-94
Rogers VL, et al. Circulation. 2011;123:e1-e192.
0.9
Angina: uncomplicated based physician interview of patient.Rate for women 45-54 years of age considered unreliable.
Outcomes Stratified by Diagnostic Outcomes Stratified by Diagnostic CathCath ((SedlakSedlak et al JACC abstract et al JACC abstract 2012; 2012; manumanu submitted)submitted)
6
4
Women with Women with nonnon--obstructiveobstructive have have elevatedelevated risk compared risk compared to men to men ((SedlakSedlak et al JACC abstract 2012; et al JACC abstract 2012; manumanu submitted)submitted)
7
, per
cen
t
10
20
30
Mechanisms: Stress ischemia in patients with SIHD with and without CAD
PC
r/A
TP
du
rin
g s
tres
s,
-20
-10
0
p < 0.025,compared to normals
2 sd
1615PC
81615PC Bairey-Merz/Slide #
Ch
ang
e in
-50
-40
-30
>70% StenosisWomen with Chest Pain
but normal Angio
ReferencePopulation
NEJM 2001
5
, per
cen
t
10
20
30
Mechanisms: Stress ischemia is prevalent in patients with SIHD and normal angiography
PC
r/A
TP
du
rin
g s
tres
s,
-20
-10
0
p < 0.025,compared to normals
2 sd
1615PC Bairey-Merz/Slide #
91615PC Bairey-Merz/Slide #
Ch
ang
e in
-50
-40
-30
>70% StenosisWomen with Chest Pain
but normal Angio
ReferencePopulation
NEJM 2001
50% of womenhave metabolic ischemia
Documented Stress Ischemia in No Obstructive CAD Predicts Adverse Outcome
MACE = death, nonfatal MI,nonfatal CVA, hospitalizationfor CHF, other vascular events,
1615PC Bairey-Merz/Slide #
101615PC Bairey-Merz/Slide #10
Johnson et al Circulation 2008
, ,unstable angina
Among No CAD/Abnormal MRSevents included: hospitalizationfor angina, other vascular, repeatangiography, PCI
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Stress Ischemia in No Obstructive CAD Predicts Adverse Outcome
Metabolic ischemia similar prognosis as CAD
MACE = death, nonfatal MI,nonfatal CVA, hospitalizationfor CHF, other vascular events,
1615PC Bairey-Merz/Slide #
111615PC Bairey-Merz/Slide #11
Johnson et al Circulation 2008
, ,unstable angina
Among No CAD/Abnormal MRSevents included: hospitalizationfor angina, other vascular, repeatangiography, PCI
HYPOTHESIS:Male and
Female Pattern SIHD?
M l ttMale-patternObstructive CAD
More prevalent >80% men
Female-patternMicrovascular
NY Times
Microvascular Coronary
Disease
More prevalent >25% in women
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The Yentl Syndromeis Alive and Well
in 2011 Bairey Merz, EHJ 2011
→Men > women with
with recognized angina/ACSangina/ACS
The Yentl Syndromeis Alive and Well in 2011 Bairey Merz, EHJ
2011
→Men > women with
with recognizedwith recognized angina/ACS
→Men > women go to
coronaryangiography
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The Yentl Syndromeis Alive and Well
in 2011 Bairey Merz, EHJ 2011
→Men > women with
with recognized angina/ACSangina/ACS
→Men > women go to
coronaryangiography
→Men > women receive
guidelines Rx
The Yentl Syndromeis Alive and Well
in 2011 Bairey Merz, EHJ 2011
→Men > women with
with recognized angina/ACSangina/ACS
→Men > women go to
coronaryangiography
→Men > women
receiveguidelines Rx
→Women > men death
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MicrovascularMicrovascular Coronary Dysfunction and Coronary Dysfunction and IschemiaIschemia
17Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1571.
MicrovascularMicrovascular Coronary Dysfunction and Coronary Dysfunction and IschemiaIschemia
18Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1571.
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Model of Microvascular Angina in WomenModel of Microvascular Angina in Women
19Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1571.
Model of Microvascular Angina in Women: Model of Microvascular Angina in Women: DetectionDetection
20Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1571.
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What Imaging Modality
Can DetectCan Detect Subendocardial
Ischemia?
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What Imaging Modality
Can DetectCan Detect Subendocardial
Ischemia?
CARDIAC
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MAGNETIC RESONANCE
IMAGING
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NHLBINHLBI--sponsored WISE Study: Cardiac sponsored WISE Study: Cardiac Magnetic Resonance Imaging (CMRI)Magnetic Resonance Imaging (CMRI)
<60 min evaluation− Cardiac structure and
functionStress and rest cardiac− Stress and rest cardiac perfusion
− Scar imagingZero radiation
− Adenosine stress− Gadolinium contrast
Cardiac Team− 4 Specialist MRI
technologists
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technologists − 4 Cardiac nurse
practitioners− Cardiac imaging
radiologist and cardiologists
Stress first pass
perfusion-Adenosine
LVRV
Pap muscle
Liver
Stomach
Rest first pass
perfusion
Basal slice Mid- ventricular
13
25
Abnormal adenosine stress first pass perfusion demonstrating regional first pass hypoperfusion in the septum and apex in a patient with very recent LAD stent for acute MI. The patient has microvascular coronary obstruction.
How to Get ResultsHow to Get Results
Re-name it “Ischemic Heart Disease (IHD) rather than “Coronary Artery Disease (CAD)”
Use a simplified approach to IHD management helps to increase adherence to guidelines
This can be achieved using an ABC format toThis can be achieved using an ABC format to present important pharmacologic therapies and lifestyle approaches
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Know Your ABCsKnow Your ABCs
•• A A •• Antiplatelets/anticoagulants*Antiplatelets/anticoagulants*•• AngtiotensinAngtiotensin--converting enzyme (ACE)converting enzyme (ACE)AngtiotensinAngtiotensin converting enzyme (ACE) converting enzyme (ACE)
inhibitors/angiotensininhibitors/angiotensin--receptor blockers receptor blockers (ARBs)*(ARBs)*
•• AntianginalsAntianginals•• BB
•• Blood pressure controlBlood pressure control•• BetaBeta blocker*blocker*•• BetaBeta--blockerblocker
•• CC•• Cholesterol management (statin)*Cholesterol management (statin)*•• Cigarette smoking cessationCigarette smoking cessation
* 4 Magic Pills
What About Women (and Men) with What About Women (and Men) with FemaleFemale--Pattern Ischemic Heart Disease?Pattern Ischemic Heart Disease?
Remember, ACS/angina guidelines are not , g g“cath” based – treat evidence of ischemia and angina, not the cath
Abundant evidence exists documenting lifesaving risk reduction of the 4 magic pills (ASA, ACE, BB, statin)
The power of the prescription pen to implement guidelines therapy preferentially saves women’s lives
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Impact of AHA Get With The GuidelinesImpact of AHA Get With The Guidelines--CAD CAD Program on Quality of CareProgram on Quality of Care
Baseline Q1 Q2 Q3 Q4
93
79
64 6757
95
83
6570 70
9787
6573 76
9687
6775 75
9791
6874
82
30405060708090
100
01020
Aspirin Beta Blocker ACE Inhibitor Lipid Rx SmokingCessation
GWTG-CAD: 123 US Hospitals n=27,825Labresh, Fonarow et al. Circulation 2003;108:IV-722
GuidelineImplementation andACS and the Sex Survival Gap
Novak et al Am J Medicine 2008;121:602.
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GuidelineImplementation andACS and the Sex Survival Gap
Following guidelineimplementation, mortality for womenmortality for womenimproves andthe sex gap narrows(RED)
+
Novak et al Am J Medicine 2008;121:602.
GuidelineImplementation andACS and the Sex Survival Gap
Following guidelineimplementation, mortality for womenmortality for womenimproves andthe sex gap narrows(RED)
Persistent sex gap (BLUE)suggests more workstill needed
+
still neededto understand sex-specific pathophysiologyto improve outcomesfor women and men
Novak et al Am J Medicine 2008;121:602.
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WISEWISE--ISCHEMIA:ISCHEMIA:A Companion Trial to the A Companion Trial to the
NHLBINHLBI--sponsored ISCHEMIAsponsored ISCHEMIAppNoel Bairey Merz MDNoel Bairey Merz MD
Carl Carl PepinePepine MDMDHarmony Reynolds MDHarmony Reynolds MD
LesleeLeslee Shaw PhDShaw PhDEileen Eileen HandbergHandberg PhDPhD
Rhonda CooperRhonda Cooper--DeHoffDeHoff PharmDPharmD
1615PC Bairey-Merz/Slide #
33
Women’s IschemiaSyndrome Evaluation
WISE
John Spertus MDJohn Spertus MDDavid Maron MDDavid Maron MD
Judy Hochman MDJudy Hochman MD
International Study of Comparative Health Effectiveness
with Medical and Invasive ApproachesISCHEMIA
ISCHEMIAEnrolled patients
n=8650
C
C
T
A
Randomized in main trialn=8000
LM
no
excluded
Figure 1. ISCHEMIA-WISE Companion Trial to ISCHEMIA
ISCHEMIA ‐ typePatients sent to
C
No obstructive CAD by ISCHEMIA CCTA
n ~ 250‐400
No obstructive CAD by clinical invasive
coronary angiography
WISE – ISCHEMIARandomized trial
n=2600
no obstructive CAD(US/Canada)
no obstructive CAD
Patients sent to cath lab clinically(evidence of ischemia)
A
T
H
g g p yn= 2200‐2350
Obstructive CAD excluded
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AtherothomboticStrategy
Atorvastatin
Hypertension / Angina Strategy
Step 1
Continued Angina Strategy
Step 1Atorvastatin
40-80 mg daily
Aspirin
81-325mg daily
• Metoprolol 50-400mg or
Verapamil SR 240-480mg if metoprolol
intolerant daily
Step 2
• Add ramipril2.5-20mg daily or
losartan 50-100mg d il f i il
• Isosorbidemononitrate
30-120mg daily
Step 2• Add
ranolazine500-1000mg twice daily
daily for ramiprilintolerant
Step 3• Add HCTZ
12.5-25mg daily
520
Problem: Adverse Mortality Gap Resulting in a New Female CVD Majority (National Center for Health Statistics and American Heart Association)
400
420
440
460
480
500
Dea
ths
in T
ho
usa
nd
s
NHLBI WISE Study And Guidelines Campaigns
38079 80 85 90 95 00 04
Years
Males Females
0
19
520
Problem: Adverse Mortality Gap Resulting in a New Female CVD Majority Solution: Clinical Translational Research and Guidelines
400
420
440
460
480
500
Dea
ths
in T
ho
usa
nd
s
NHLBI WISE Study, NHLBI and AHA Red Dress Awarenessand Guidelines
38079 80 85 90 95 00 04
Years
Males Females
0and Guidelines Campaigns
SummarySummary: What to do When the Perfusion is : What to do When the Perfusion is Abnormal and the Arteries Open?Abnormal and the Arteries Open?
Women face a higher mortality from SIHD likely due to their relatively higher prevalence
f “f l tt ” i h i h t diof “female-pattern” ischemic heart disease (microvascular coronary dysfunction) which is not recognized or treated.
Ongoing research is aimed at detection of microvascular coronary dysfunction with cardiac MRI.cardiac MRI.
Application of guidelines therapy can close adverse gender outcome gaps.
Questions, comments, referrals: merz@cshs.org