What to do When the Perfusion is Abnormal and the …The Yentl Syndrome is Alive and Well in 2011...

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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

[email protected]

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

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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



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,


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,


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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→Men > women with



coronaryangiography

→Men > women receive

guidelines Rx



→Men > women with



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


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Model of Microvascular Angina in WomenModel of Microvascular Angina in Women


Model of Microvascular Angina in Women: Model of Microvascular Angina in Women: DetectionDetection


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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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Following guidelineimplementation, mortality for womenmortality for womenimproves andthe sex gap narrows(RED)

+



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


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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


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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: [email protected]

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