Credit: Slides Based on Presentation Credit: Slides Based on Presentation from Dr. Jennifer Mieresfrom Dr. Jennifer Mieres

New York University School of MedicineNew York University School of Medicine

Img Source: http://www.flickr.com/photos/yourdon/2683324564/

• 65 y/o female • Presents to local ER• Sudden onset of SSCP,

8/10, pressure like, radiating to the jaw

• Intense nausea / vomiting x2.

• Soon became SOB and lightheaded.

• BP 80/45.

PMHx: HTN, DM, Hyperlipidemia PSHx: None SoHx: No Tobacco Social drinker No Hx of drug use Retired, married lives with husband FHx: No Hx of CAD, MI, SCD. Meds: Lipitor 10mg Daily Atenolol 25mg Daily Metformin 500mg Twice Daily

T: 98.9 HR: 110 BP: 78/43 RR: 32 93% 2L HEENT: Atraumatic, PERRL, mmm Neck: Supple, No JVD, No bruit Chest: Bibasilar crackles CVS: Tachy, S1, S2- no gallops or rub, II/VI

holosystolic murmur LSB Abd: Soft, Tender in epigastric area, ND, NO

BS Ext: No edema

Image: Lisa F Young, Flickr

137 109 18 3.9 22 1.0 244 8.6

2.1 1.0

11.7

14.834.3

390

CPK: 152MB: 13.6Trop: 1.9

AST:29 TP: 6.1ALT: 24 Alb: 3.0Bili: 1.1/0.4

Started on 5mcg dopamine Became more hypotensive,

developed pink frothy sputum. Intubated, STEMI alert called. Given 300mg plavix via NG tube, half dose lytics Transferred to HUH

SOME FACTS DIAGNOSTICS TREATMENT ACTION

410

289

69 6134

461

269

64 42 39

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Leading Causes of Death for All Leading Causes of Death for All Males and Females US 2004 Males and Females US 2004

A Total CVD (Preliminary)B CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimer’s Disease

Source: CDC/NCHS/AHASource: CDC/NCHS/AHA

Dea

ths

in th

ousa

nds

*2004 statistics are preliminary ; NCEP, National Cholesterol Education Programhttp://www.americanheart.org/presenter.jhtml?identifier=3018163. Accessed July 31, 2006Thom T, et al. Circulation. 2007;113:e85-151

Year

400

420

440

460

480

500

520

1980 1985 1990 1995 2000 2004

Dea

ths

in th

ousa

nds

Males

Females

NCEP INCEP I NCEP IINCEP II NCEP IIINCEP III

Leading cause death US women ~½ million CVD annually ~220,000 Coronary heart disease in 2004

CHD symptoms appear ~10 years later in women

CHD/MI can occur premenopausal

Wenger N,Wenger N, Prog Cardiovasc Disease, Prog Cardiovasc Disease, 2003;46:199-2292003;46:199-229AHA. Heart Disease and Stroke Statistics – 2006 Update, Dallas: AHA AHA. Heart Disease and Stroke Statistics – 2006 Update, Dallas: AHA

20062006

More co-morbidities in women with CHD› Hypertension› Diabetes› Heart failure

CHD substantial cause of disability in women. Since 1984 women > men CV mortality

Wenger N,Wenger N, Prog Cardiovasc Disease, Prog Cardiovasc Disease, 2003;46:199-2292003;46:199-229AHA. Heart Disease and Stroke Statistics – 2006 Update, Dallas: AHA AHA. Heart Disease and Stroke Statistics – 2006 Update, Dallas: AHA

20062006

SmokingDiabetes

HTN

Obesity

Sedentary lifestyleHyperlipidemia

Family Hx/genetics

“Conventional” Risk Factors

Psychosocial factorsDepressionEnvironmental stress

Oxidative stress

HomocysteineInflammation CRP, Collagen

vascular Dz

Thrombotic factorsFibrinogen,TpA, PAI-1

Infection

Vitamin deficiency

Iron load

“Nonconventional” Risk MarkersCourtesy :Dr Sharonne Hayes Mayo ClinicCourtesy :Dr Sharonne Hayes Mayo Clinic

65% of diabetics die from heart disease or stroke 4.2 million American women have diabetes

› Diabetes increases CAD risk 3-fold to 7-fold in women vs 2-fold to 3-fold in men

› Diabetes doubles the risk of a second heart attack in women but not in men

Far more powerful coronary risk factor for women than men, negating much of the protective effects of the female sex.

Manson JE et al, Manson JE et al, Prevention of Myocardial InfarctionPrevention of Myocardial Infarction , 1996:241-273., 1996:241-273.American Heart Association.American Heart Association.

Centers for Disease Control and Prevention.Centers for Disease Control and Prevention.

Increasing Public Awareness of Heart Disease Increasing Public Awareness of Heart Disease in Women: NHLBI, AHA and Womenheartin Women: NHLBI, AHA and Womenheart

The National Coalition for Women with Heart Disease. www.womenheart.orgThe National Coalition for Women with Heart Disease. www.womenheart.org

Gaps in knowledge of heart disease in women:

• Underestimation of risks by healthcare professionals

• Disparities in women’s knowledge of heart disease

Age Plaque morphology

Coronary artery

stenosis

Associated risk factor

< 50 years

plaque erosion minimal cigarette smoking

> 50 years

vulnerable plaque rupture

severe hypercholesterolemia

CAD, coronary artery diseaseCAD, coronary artery diseaseBurke AP, et al. Burke AP, et al. CirculationCirculation. 1998;97:2110-2116.. 1998;97:2110-2116.

Typical in both sexes Pain, pressure, squeezing, or

stabbing pain in the chest Pain radiating to neck,

shoulder, back, arm, or jaw Pounding heart, change in

rhythm Difficulty breathing Heartburn, nausea, vomiting,

abdominal pain Cold sweats or clammy skin Dizziness

Source: AHA &: WISE data JACC 2006

Typical in both sexes Pain, pressure, squeezing,

or stabbing pain in the chest

Pain radiating to neck, shoulder, back, arm, or jaw

Pounding heart, change in rhythm

Difficulty breathing Heartburn, nausea,

vomiting, abdominal pain Cold sweats or clammy

skin Dizziness

Can be Seen more commonly in women

Milder symptoms (without chest pain)

Sudden onset of weakness, shortness of breath, fatigue, body aches, or overall feeling of illness (without chest pain)

Unusual feeling or mild discomfort in the back, chest, arm, neck, or jaw (without chest pain)

Source: AHA &: WISE data JACC 2006

0

20

40

60

Milner et al: Am J Cardiol, 1999Milner et al: Am J Cardiol, 1999

%

WomenMen

DyspneaDyspnea Nausea Nausea Indigestion Dizziness Indigestion Dizziness Fatigue Fatigue Sweating Sweating Arm/ Arm/ Vomiting Vomiting Fainting Fainting Shoulder/pain Shoulder/pain

Fewer women than men presented with ST elevation MI › 27.2% in women vs 37% in men› GUSTO IIb 12,142 (30% women)

Women less likely to have angiography 53% vs 59%, however

Women in all subgroups were less likely to have severe stenoses

Hochman et al NEJM341:4:276,1999Hochman et al NEJM341:4:276,1999

Gender differences in mortality› 57% of women who die suddenly from

CAD had no prior typical warning symptoms

› 38% of women vs 25% of men will die within 1 year post-MI

Early recognition of symptoms, accurate diagnosis and proper treatment of CAD are of great importance.

Albert CM et al. Circulation 2003;107:2096-101; Women and Heart Disease Fact Sheet. http://www.womenheart.org/information/WH_fact_sheet_print.html. Accessed June 12, 2006

Heart Attack Symptoms and Warning Signs. http://www.americanheart.org/presenter.jhtml?identifier=4595. Accessed June 15, 2006

ASNC Patient Management Strategy for CT ASNC Patient Management Strategy for CT Imaging & SPECT In Asymptomatic, Int-High Imaging & SPECT In Asymptomatic, Int-High Framingham RiskFramingham Risk

Low FRS

Int-HighFRS

SPECTCCS >400 or 90th %ile

CCS <100or <75th %ile

CCS >100<400 or >75th<90th %ile

Cath - ? CTA

PrimaryPrevention

EBT-CT

Mod-Severe Abnml

Low Risk

Mildly Abnml

Primary Prevention

Consider Re-Testing 3-5 Yrs

Secondary Prevention

Consider Re-Testing 2-3 Yrs

Medical Rx

Consider Re-Testing 1-2 Yrs

Highlighted box indicates patients treated to secondary prevention goals

Source: Shaw LJ, Berman DS, Bax JJ, Brown KA, Cohen MC, Hendel RC, Mahmarian JJ, Williams KA, Ziffer JA. The complementary roles of nuclear cardiology and cardiac CT in the current healthcare environment. J Nuc Cardiol 2005;12:131-142.

Sensitivity Specificity Stress ECG 61% 70% Stress Echo 86% 90% Nuclear (Gated SPECT) 84% 90%

Source: Kwok AJC 1999, klocke et al JACC,, Shaw Source: Kwok AJC 1999, klocke et al JACC,, Shaw Eur Heart JEur Heart J 2005 Mar;26(5):447-56. 2005 Mar;26(5):447-56.

Improved CAD Detection & Improved CAD Detection & Prognostication through Visualization of Prognostication through Visualization of Wall Motion, Perfusion, & FunctionWall Motion, Perfusion, & Function

SPECT Imaging: Visualize Wall Motion, Perfusion, &

Function

Echo Imaging: Visualize Wall Motion &

Function

Exertional Symptoms - Low Predictive Value

Shorter Exercise Duration - Affects diagnostic accuracy

High Rate of “False Positives” Reported Exercise Electrocardiogram Testing:

Beyond the ST Segment:› ST/HR index,› QRS duration and amplitude,› QT and T wave changes.

Source: Shaw et al JACC 2006; Kligfield and Lauer .Circ. Vol 114. Nov 06Source: Shaw et al JACC 2006; Kligfield and Lauer .Circ. Vol 114. Nov 06Image: http://farm2.static.flickr.com/1247/3171917389_c96c5970de.jpg?Image: http://farm2.static.flickr.com/1247/3171917389_c96c5970de.jpg?v=0v=0

Follow-up (Years)3.02.52.01.51.0.50.0

Cum

ulat

ive

Surv

ival

1.00

.95

.90

.85

.80

NondiabeticsDiabetics

p<0.00001

Source:Source: Giri S, et al. Circulation. 2002;105:32-40. Giri S, et al. Circulation. 2002;105:32-40.

Re-Test@ ~1-1.5 years

39 y/o AAF

Multiple Risk Factors

Chest Pain

Stress Perfusion

Arterial Wall Atherosclerosis

Symptomatic Luminal Obstruction

Courtesy LJ Shaw, PhD; Cedars-Sinai Medical Center

Approximately 50% of women referred for evaluation of ischemia do not have obstructive coronary disease

Intermediate risk – future cardiac events and persistent symptoms

Impact for practitioners› Can no longer ignore non-

obstructive coronary angiograms in women

› Can no longer assume a positive troponin or an abnormal stress perfusion test is falsely positive just because a woman’s angiogram shows no obstruction

Lerman A, Sopko G. J Am Coll Cardiol. 2006;47(3 Suppl):S59-S62.

Noninvasive

Coronary anatomy: evaluation of coronary stenosis

( calcified and non-calcified plaque and the vessel wall)

CTA LM/LAD

CATH LM/LAD

Similar benefit in men and women for › Statins› Antiplatelet

therapy› Beta Blockers› Nitroglycerin› Thrombolytics› ACE- inhibitors

Img Source: Flickr, 2588342742_8634700f43.jpg

NOT for prevention of heart Disease Postmenopausal Hormone Therapy is

FDA approved for: Treatment of postmenopausal

symptoms Prevention of osteoporosis Black Box warning (3/03) Use lowest dose for shortest duration

Intermediate- risk Women ( 10-20% risk)› Class I Recommendations

Smoking Cessation Physical Activity Heart Healthy Diet Weight Maintenance / Reduction Blood Pressure Control Lipid Control

› Class IIa Recommendations Aspirin Therapy ( women >65 YO)

Lower- risk Women ( <10% risk)› Class I Recommendations

Smoking Cessation Physical Activity Heart Healthy Diet Weight Maintenance / Reduction Treat Individual CVD Risk Factors as

Indicated

Recent improved outcomes for women following PCI

Women are older , more DM,HTN,CHF,USA,and single vessel disease

One year mortality higher in women 6.5% than men 4.3% post PCI

In-hospital mortality for women is higher › 50 < y/o and have 3.4% operative

mortality vs. 1.1% in men. Differences have persisted for > 20 yrs Less like to get LIMA grafts Women have increased Angina

symptoms post CABG Women have better long term survivalVaccarino V et al. Circ

2002

RHC: RA: 3 PAP: 28/7/15 CO: 4.2 RV: 28/4 PCW: 8 CI: 2.3 PA Sat: 64%

LHC: AO: 70/43 LM: NL LAD:Mid/distal

bridge, LI’s LCX: Non-dominant,

LI’s

RCA: Dominant, LI’s

LV gram: Apical ballooning 3+ MR Dopamine D/Ced,

norepinephrine started at 200mcg.

LV 192/15 pull back 160/91

NL LV size, Proximal septum is thickened

Late peaking LVOT gradient measuring 80mm

Basal ventricle is hyperdynamic Apex and distal ventricle are

akinetic with ballooning appearance

H/H stable Decreased O2 requirement on the vent Cardiac enzymes CPK 146 187 179 195 MB 13.0 14.2 11.2 10.4 Trop 1.9 3.07 2.442.00

Stress-induced Cardiomyopathy Stress-induced Cardiomyopathy / Apical Ballooning Syndrome / / Apical Ballooning Syndrome / Broken Heart Syndrome:Broken Heart Syndrome:› Increasingly reported Increasingly reported › Characterized by transient systolic Characterized by transient systolic

dysfunction of the apical and/or dysfunction of the apical and/or mid segments of the left ventricle mid segments of the left ventricle

› Mimics myocardial infarction (MI) Mimics myocardial infarction (MI) › BUT in the absence of significant BUT in the absence of significant

coronary artery disease coronary artery disease

““Typical" stress-induced Typical" stress-induced cardiomyopathy: cardiomyopathy: › Contractile function of the mid and Contractile function of the mid and

apical segments of LV are depressedapical segments of LV are depressed› Compensatory hyperkinesis of the Compensatory hyperkinesis of the

basal wallsbasal walls› Ballooning of the apex with systole. Ballooning of the apex with systole. › In a minority of cases (40 percent in In a minority of cases (40 percent in

one report), the ventricular one report), the ventricular hypokinesis is restricted to the hypokinesis is restricted to the midventricle ("atypical") with midventricle ("atypical") with relative sparing of the apex relative sparing of the apex

http://www.flickr.com/photos/yourdon/2683324564/

Women present with milder and more atypical symptoms

Imaging is critical for early diagnosis

Aggressive approach to management

WISE Study:› Can no longer ignore non-

obstructive coronary angiograms in women

› Can no longer assume a positive troponin or an abnormal stress perfusion test is falsely positive just because a woman’s angiogram shows no obstruction

http://www.flickr.com/photos/yourdon/2683324564/

http://www.flickr.com/photos/yourdon/2683324564/

Gender Differences in Pathophysiology of CAD and Clinical Recognition of CAD in Women

Risk factors for CAD in Women and Prevention

Gender Differences in the Diagnostic Evaluation of Coronary Heart Disease

Percentage of Men with one vessel, two vessel, three vessel left main or no CAD on coronary angiography

Reference: JACC 2003;41:158-68

N indicates Normal or <50% stenosis; one-vessel, two-vessel, three-vessel disease; LM: Left N indicates Normal or <50% stenosis; one-vessel, two-vessel, three-vessel disease; LM: Left main diseasemain disease

Percentage of Women with one vessel, two vessel, three vessel left main or no CAD on coronary angiography

Reference: JACC 2003;41:158-68

N indicates Normal or <50% stenosis; one-vessel, two-vessel, three-vessel disease; LM: Left N indicates Normal or <50% stenosis; one-vessel, two-vessel, three-vessel disease; LM: Left main diseasemain disease

Epidemiological data – CAD uncommon in premenopausal women

Observational data› 30-50 studies, overwhelmingly

positive Physiologic benefits – cholesterol

lowering, etc.

Randomized control trial(PEPI): intermediate outcome was positive

Studies: Clinical or angiographic endpoints all negative – HERS, ERA, WHI› No benefit of Hormone Therapy in

primary or secondary prevention

• CVD kills 2X American Women than from all cancers combined.

• ~ 500,000 women die from CVD vs. ~ 41,500 by breast cancer.

• CVD declining but rate of decline for Women < Men; • African-American < Caucasian Women

• Women develop CHD ~10 yr later than Men• Men have a greater risk of MI & at earlier ages • Ave 1st MI 65.8 yr Men vs. 70.4 yr Women• Strokes more common in Women than Men &

associated with atrial fibrillation

Type II Diabetic Women 3-4X more likely to develop CHD2X risk of a 2nd heart attack have lower E2 & loose “estrogen’s protective effect”experience reproductive problems2-4X more likely to be African American, Hispanic, American Indian, or Asian Pacific Islander than Caucasian

Diabetes associated with low total testosterone in Men high levels of bioavailable testosterone in Women

Lower estrogen levels may account for the same rate of kidney and CV disease-related conditions.

Cardiac arrest ~ 3x > in Men than Women, but lower recovery and survival rates in Women

Pathophysiology: Cardiovascular II

Cardiac arrhythmias, drug-induced torsades de pointes, and long QT syndrome more prevalent in WomenAt younger ages, prevalence of CHF > Men; after 75

reversesWomen with CHF more likely to have co-morbid diabetes

and hypertension than Men.

1. Chest discomfort or uncomfortable pressure,fullness, squeezing or pain in the center of thechest that lasts longer than a few minutes, orcomes and goes.

2. Spreading pain to one or both arms, back, jaw, orstomach.

3. Cold sweats and nausea.

Women often don’t experience the “hallmarks” (only 30%), instead: shortness of breath, nausea, vomiting sleeplessness back pain or jaw pain, and a feeling of generalized weakness, fatigue in weeks prior to Acute MI!

Consequently treatment delayed, inappropriate, or wrong leading to preventable deaths.