Heart Failure in Women
Gender differences and similarities
Lynette W. Lissin, MD FACC
Palo Alto Medical Foundation
April 21, 2012
Goals
• Epidemiology and types of heart failure
• Differences in incidence, clinical
characteristics, prognosis in women vs. men
• Myopathies specific to women
– Takotsubo, pregnancy, cancer rx
• Contemporary treatment of heart failure
– Issues in women
CVD is the leading cause of death
in women
500
450
400
350
300
250
200
150
100
50
0
Death/100,000
CVD
Stroke
Breast CA
AHA 2003
Cardiovascular disease in women
• Coronary artery disease
– Heart attacks, angina
• Congestive heart failure
–
–
–
–
Preserved systolic function/Hypertensive
Peri-partum cardiomyopathy
Chemotherapy induced cardiomyopathy
Autoimmune related cardiomyopathy
• Arrhythmia
– Atrial fibrillation
• Valvular heart disease
– Aortic stenosis
– Mitral regurgitation
• Stroke
• Pericardial disease
Sex differences: Physiology
• Compared to Men, Women have:
– Lower LV mass
– Greater contractility
– Preserved mass with aging
– Lower rate of apoptosis
– Small coronary vessels
– Lower blood pressure
– Faster resting HR
– Less catecholamine mediated vasoconstriction
Sex Hormones
• Estrogen
– Receptors on cardiac cells
– Estrogen affects hepatic gene expression
– Improved lipids
– Vascular effects: vasodilation
– Stimluates immune system
• Affects cytokine/inflammatory pathways
• Testosterone
– Increases inflammation/cholesterol
Heart Failure- Sobering Reality
• Common diagnosis
– >5 million pts with CHF in US
– 2.6 million women
– 550,000 new dx per year
• Leading cause of hospitalizations
– > 1 million annually
– > 85% of CHF admissions > 65 years
• High Mortality Rate
– 5-25 % per year
– 53,000 deaths yearly
• Costly
– $ 39.2 Billion spent on direct/indirect costs
– High rates of readmission
• 25% at 30 days; 33% at 90 days; 50% by 6 months
Women vs. Men
•
•
•
•
•
•
•
•
•
More non-ischemic etiology of HF
More HTN, diabetes
Older age at presentation
Lower QOL, more depression
More frequent LBBB
Similar hospitalization/readmission rates
Lower mortality/transplant rate in DCM
Lower representation in HF trials (17-23%)
Less procedures, including ICDs, CRT
Predictors of Mortality
•
•
•
•
•
•
•
•
Acute presentation
Dyspnea at rest
Age >73 yrs
Systolic BP <125 mm Hg
Heart rate >78 beats/min
Sodium 132 mmol/l
BUN >37 mg/dl 2.53
Cr >1.5 mg/dl
ADHERE J Am Coll Cardiol, 2006; 47:76-84
Systolic Dysfunction
•
•
•
•
•
•
•
•
•
•
•
Coronary artery disease
Hypertension
Idiopathic
Familial
Infectious
Infiltrative
Toxic
Endocrine
Collagen vascular disease
Tachycardia-induced
Miscellaneous
Plaque Progression
Ross NEJM 1995
Coronary Heart Disease Mortality in Younger Women
Higher than in Men
30
Death during Hospitalization (%)
25.3
24.2
25
21.8
Men
21.5
Women
19.1
20
18.4
16.6
14.4
15
13.4
11.1
10.7
9.5
10
8.2
7.4
6.1
5.7
4.1
5
2.9
0
< 50
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-89
Figure 1. Rates of death during hospitalization for Myocardial Infarction among women and men, according to age. The interaction between sex and age
was significant (P<0.001).
Vaccarino NEJM 1999;341:217
One year mortality rates post MI
Schmidt,BMJ. 2012 Jan 25;344
Women and CAD
Compared to men…..
Less classical symptoms
More related to diabetes, inactivity, obesity,
depression
2/3 women who die suddenly had no previous
heart attack
2x more likely to die soon after heart attack
Worse outcome after bypass surgery
Incidence of CHD according to
menopausal status
Annual incidence per 1000
4
3.5
3
2.5
Pre-menopausal
2
Post-menopausal
1.5
1
0.5
0
40-44
45-49
50-54
% chance of angiographic CAD
Gender differences in symptoms
90
80
70
60
50
40
30
20
10
0
Women
Men
Typical angina
Women’s Symptoms
• Prodromal
–
–
–
–
–
Unusual fatigue 70%
Sleep disturbance 48%
Shortness of breath 42%
Indigestion 39%
Anxiety 35%
• Acute
–
–
–
–
–
–
Shortness of breath 58%
Weakness 55%
Unusual fatigue 43%
Cold sweat 39%
Dizziness 39%
43% did NOT have chest
pain
Diastolic Dysfunction
• Heart Failure with Preserved Ejection Fraction
“HFPEF”
– Ventricular Hypertrophy
– Constrictive/Restrictive
– Diabetic
• Ischemia
• Dilated Cardiomyopathy
Incidence of Hypertension
80
70
% of population
60
50
Women
40
Men
30
20
10
0
35-44
45-54
55-64
Age
65-74
75+
Adapted from AHA 1999
Hypertension
A Risk Factor for Cardiovascular Disease
Coronary
disease
50
Biennial
ageadjusted
rate per
1000
subjects
Peripheral artery
disease
Stroke
Cardiac
failure
45.4
40
Normotensive
Hypertensive
30
22.7
21.3
20
10
13.9
12.4
9.5
3.3
9.9
6.2
2.4
5.0
7.3
2.0
3.5
6.3
2.1
0
Risk ratio:
Men Women
2.0
2.2
Men Women
3.8
2.6
Men Women
2.0
3.7
Men Women
4.0
3.0
Kannel WB. JAMA. 1996; 275:1571-1576.
V012005
Lifestyle Modifications
Intervention
Goal
Effect on SBP
Weight reduction
BMI 18.5-24.9
DASH diet
Fruits, veggies, K,
Ca, low fat
< 2.4 g Na/day
5-20 mmHg/10 kg
weight loss
8-14 mmHg
Sodium restriction
Physical activity
Moderate alcohol
consumption
At least 30
minutes/day
No more than 1-2
drinks/day
2-8 mmHg
4-9 mmHg
2-4 mmHg
Takotsubo Cardiomyopathy
Takotsubo Cardiomyopathy
•
•
•
•
•
•
•
Reported by Japanese in 1990
“Broken heart”, apical ballooning, stress CM
Octopus trap appearance
Up to 90% women, age > 60
70% with Severe emotional stress
Troponin moderately elevated
Echo resolution within ~ 30 days
Rivera et al. Med Sci Monit, 2011;17(6):RA135-147
Takotsubo Cardiomyopathy
•
•
•
•
•
1-2% of STEMIs
2/3 CP, 1/3 STE, TWI, QT prolonged
Conservative mgmt, IABP, ?anticoagulation
Complications 19%: clot, shock, MR arrhythmia
Higher mortality in age > 75 and lower EF on
admission; 1-12%
• Prognosis better than ACS
• Recurrence is rare 3-15%
• ? Long term treatment undefined
Mayo Clinic Criteria: all 4
• CP/dyspnea and STE or TWI
• Transient hypokinesia or akinesia of mid-apical
regions and hyperkinesia of basal segments
• Normal coronary arteries (< 50%) at onset
• Absence of significant head injury, CNS
hemorrhage, pheo, myocarditis or HCM
Bybee et al. Ann Int Med 2004;141:858
Takotsubo Cardiomyopathy
• Elevated serum catecholamines
• Higher density of Beta receptors in apex- more
vulnerable to sudden, high levels
• High systolic apical wall stress, less elasticity,
distal blood flow “perfusion gradient”
• Atypical, or apical sparing 1/3
• Reduced estrogen after menopause
– ?indirect action on CNS or direct action on heart
• Other conditions
– SAH , thyrotoxicosis, CVA, pheo, dobutamine stress
TCC Mechanism—Stunning??
• CNS
– High catecholamines (>> than MI with CHF):
primary or secondary? Direct toxicity?
– Density of receptors higher in males-?protective
or less resistant (?Less survival to recovery phase),
but more catechol production to stress, more
catechol-mediated vasoconstriction, or better
repair in females (ie, survive)?
TTC: Mechanisms
• Metabolic
– ?glucose or fatty acid metabolism
– ?mitochondrial dysfunction
• Vascular
– Abnormal vasoreactivity, spasm?, but why
regional
– Endothelial /microvascular dysfunction
• Endocrine
– Striking sex difference, reduced estrogen levels
CMR in TTC
•
•
•
•
•
Typical pattern of LV dysfunction
Edema
Myocardial necrosis with contraction bands
Little LGE (< MI, myocarditis)
+LGE more cardiogenic shock, longer recovery
of EKG, echo
CMR in TTC
Eitel et al. JAMA 2011;306(3):277-286
Stress management
Post-partum Cardiomyopathy
• 1/4000 live US births
• 1 month pre or 5 months post-partum
• Increased maternal age, multiparity, multiple
gestations, preeclampsia/HTN
• 2.9x more likely in AA women
• ?viral, immune, stress, prolactin, tocolysis,
hereditary
• Usual HF therapy, until resolved
• 4% need transplant
• Future pregnancies NOT recommended
Risk in Pregnancy
Adult Congenital Heart Disease and
Pregnancy
• Women with CHD reaching child-bearing age
• Contraindications of pulmonary hypertension,
severe LV failure, aortopathy, left sided
obstruction
• Risk of HF, arrhythmia, fetal complications
• Affected offspring
Heart Failure and Chemotherapy
• Breast cancer most common malignancy
• Adriamycin
– Dose dependent cardiotoxicity (>450 mg/m2)
– Clinical HF in 2-7% of pts; increases over time
• Herceptin
– Reduces recurrence rate up to 50%
– CHF in 2-4%; up to 3-27% after combination
– Esp in pts with elevated troponin/BNP
• Cyclophosphamide, XRT
Monitoring for LV dysfunction
•
•
•
•
•
•
Labs
Biopsy
Exercise testing
MUGA
**Echo
MRI
Pulmonary Hypertension
• Primary vs. Secondary
– Left heart disease, shunts, PE, drugs
• Work up
– Echo, RHC, sleep study, hypercoagulable eval
• Treatment
– Vasodilators, Sildenafil,
– Endothelin receptor antagonists
– Ca Channel blockers
• Transplant
– Heart-lung
Shunts: ASD, VSD
Right ventricle
Autoimmune Heart disease
• 80% of AD occurs in women
• RA, SLE, Scleroderma, Myositis, Sjogrens,
Antiphospholipid syndrome
• Inflammation via Abs and cytokines
• RF + associated with mortality
• Induced by infections
• SLE associated with CAD, thrombosis
• RA associated with MI, CHF, CVA
Heart Failure Management
• Identify and treat underlying etiology
– Ischemia, valvular disorder, arrhythmia
• Non-pharmacologic therapy
– Diet, exercise, follow up
• Drugs
– Diuretics, digoxin, vasodilators, disease-modifying, anticoagulants
• Devices
– IABP, PM, AICD, LVAD
• Transplant
sympatholytics
Angiotensinogen + renin
digoxin
ACE inhibitors
Angiotensin I
converting enzyme
bradykinin breakdown
Angiotensin II
AT II receptor
antagonists
receptor
vasoconstriction
Aldosterone
antagonists
aldosterone
cell hypertrophy
receptor
Efficacy of beta
blockers
Greater benefit in
women vs men
Pharmacologic therapy
• Ace inhibitors
– Mortality benefit in symptomatic women
• ARB
– Similar effect on women and men
• Digoxin
– Increased mortality in women
• Aldosterone antagonists
– Reduced mortality in women
ICD
Trial data
• SCD-HEFT
– No mortality benefit seen (23% women)
• MADIT-II
– Benefit for women (16% enrolled)
• 5 trial metaanalysis
– HR 1.01
• Including COMPANION
– HR 0.78 (p=ns)
• Sudden death less common
Cardiac Resynchronization Therapy
CRT
•
•
•
•
•
•
•
NYHA Class II, III and IV
LV systolic dysfunction
QRS wide
Improves survival
Lower hospitalizations
Reduces symptoms
More LV volume
– reduction, increase EF
Barsheshet et al. Nat Rev Cardiol. 2012;online
Summary
• Heart failure types more common in women
– Diastolic HF, Takotsubo CM, pregnancy
• Compared to men, women have differences
in cardiovascular:
– Physiology
– Etiology of disease, heart failure
– Response to therapy