Cardiovascular Disease and Pregnancy

Nandita S. Scott MD
Co-Director - MGH Corrigan Women’s Heart Health Program

nsscott@mgh.harvard.edu
@NanditaScott
@MGHHeartHealth

Massachusetts General Hospital

Boston MA

National Press Foundation

January 2020
FINANCIAL DISCLOSURE:
No relevant financial relationship exists
 Data from Pregnancy Mortality Surveillance
System

3
 Pregnancy Related Death: CDC definition

Death of a woman, while pregnant or within 1 year

of the end of a pregnancy
regardless of the pregnancy outcome,
duration or site
from any cause related to or aggravated
by the pregnancy or its management

but not from accidental or incidental

causes.

4
 Maternal Mortality is Rising in the US as it
Declines Elsewhere. NPR Morning Edition 5/12/2017

5
 Leading causes of pregnancy-related deaths from maternal
mortality review committees 2008-2017

6 CDC data
Racial/Ethnic Disparities in Pregnancy-related Mortality

January 2018
Deaths per 100,000
live births

42.8 Black non Hispanic

32.5 American
Indian/Alaskan native

14.2 Asian/Pacific islander

non Hispanic

13.0 White non Hispanic

11.4 Hispanic women

7
 Racial/Ethic Disparities in Maternal Mortality

8
 Why is Maternal Mortality Increasing?

• Women are older, more chronic conditions

• Fertility Therapies greater incidence of multiple

gestation pregnancies
• Lack of access to primary care
• Variability in quality of care

• Lack of national protocols and thus standardized care

• Lack of systemic review of cases

• Rising rate of Caesarian section

• Variable access to birth control – which allow a pregnancy

to be planned and preexisting medication conditions are
optimally managed
9
 35 year old for preconception counseling
Asymptomatic

10
 Normal Hemodynamics of Pregnancy

Yucel E, DeFaria Yeh D. Curr Treat options CardioMed 2017

11
Physiologic Vascular Changes

Hormonal changes increasing the susceptibility to tearing

– Fragmentation of reticular fibers
– Diminished acid mucopolysaccharides
– Loss of normal corrugation of elastic fibers
– Circulating elastase breaks up elastic lamellae and
weakens media
– Relaxin detectable in serum causes reduced collagen
synthesis

Uterine compression can increase outflow resistance of

lower arterial tree
 Symptoms

• Symptoms that often reflect cardiac disease in non

pregnant patients
• Fatigue, dyspnea, dizziness, palpitations, edema and
orthopnea all caused by weight gain, dilutional anemia,
decreased venous return from caval compression
• Edema from increased total body sodium and reduced
colloid osmotic pressure
 Increased Arrhythmias during Pregnancy

Hyperdynamic
State

Atrioventricular Increased
stretch Arrhythmogenesis adrenergic
responsiveness

Higher resting
heart rate

14
 How to Risk Stratify

Risk of Primary Cardiac Event:

0-1 – 5%

2 – 10%

3 – 15%

4 – 22%

Silversides et al. JACC 2018 71 (21): 2419-2430 > 4 – 41%

15
 Modified WHO Classification of Pregnancy Risk
mWHO 1 mWHO II mWHO II-III mWHO III mWHO IV
Diagnosis Mild PS ASD/VSD Mild LV EF Moderate LV PAH
small PDA Repaired ToF impairment systolic dysfunction
MVP Turner with normal HCM Prior PPCM with LV EF < 30%
repaired aorta Native or tissue valve normal LV EF
ASD/VSD/PDA Most arrhythmias disease not WHO 1 or Mechanical valve Prior PPCM with
Ectopy IV Fontan circulation impairment
Marfan without Moderate MS
dilatation Severe AS Severe MS
Aorta < 45 in BAV Moderate Aortic
AVSD dilatation in Marfan Severe symptomatic
Repaired coarctation or BAV AS
VT
Systemic RV Systemic RV with
Unrepaired cyanotic moderate or more
impairment

Severe aortic
dilatation

Vascular EDS

Severe coarctation

Fontan with any

complication
Mortality Risk None Small increase Intermediate Significant increased Extremely high

Morbidity Risk No/mild Moderate Moderate to Severe Severe

severe
Maternal cardiac 2.5 – 5% 5.7-10.5% 10-19% 19-27% 40-100%
event rate
Care During Local Local Referral hospital Expert center Expert center
Pregnancy
Followup
16
Once or twice Once per trimester Bimonthly Monthly or bimonthly Monthly
 35 year old for preconception counseling
Asymptomatic

More
volume
through
smaller
orifice in
less time

CARPREG 2 score
of 3, event rate 15%

mWHO 3, event rate

19-27%

17
 35 year old, 38 weeks gestation
Difficulty Breathing

18 Challenging diagnosis as pregnancy mimics congestive heart failure

Peripartum Cardiomyopathy

• Idiopathic cardiomyopathy presenting with heart failure secondary to left

ventricular systolic dysfunction towards the end of pregnancy or months
following
• Diagnosis of exclusion

• 1:3000-4000 pregnancies
• 1:300 Haiti
• In US 1:2229, higher in African-Americans
lowest in Hispanics (1:9861)

• Incidence rising in US
 Cardiac Biomarkers during Pregnancy
Brain Natriuretic Peptide
• Hormone released from the heart in response to the heart
stretching
• Despite hemodynamic load of pregnancy, should remain
in the normal range
• May increase with preeclampsia, found to be elevated
above 100 in 6.1% of normal pregnancies early post
partum
• Higher in women with congenital heart disease, may
exceed upper limit of normal

20
 Suggestions for Clinical Practice

Clinical Situation Should we measure

BNP
Healthy asymptomatic women
Healthy women with new symptoms or signs suggestive
of heart failure
Women with established cardiovascular disease at
baseline
Serial measurements in women with established
cardiovascular disease or increasing symptoms

A low BNP ( < 20 pg/mL) or NT-proBNP ( 125 pg/mL)

has high negative predictive value and make
cardiovascular disease unlikely

Elevated value should prompt further evaluation

21
Peripartum Cardiomyopathy – subsequent
pregnancies

Stress echo preconception to

evaluate contractile reserve

Elkayam et al. JACC 2011

Peripartum Cardiomyopathy

• Heart failure can develop rapidly

• Prognosis better than dilated cardiomyopathy

• Significant proportion normalizing/improving heart function

over 6 months
• 50 % spontaneous recovery- lower in African Americans
 Mode of Delivery

• Vaginal delivery remains optimal method of delivery

• Caesarian section increases risk of maternal infection, has

greater hemodynamic shifts and blood loss, risk of surgical
injury and greater risk for thrombotic events
• No consensus absolute contra indications to vaginal
delivery, in a few unique situations, can be considered first
– preterm labor in the presence of full oral anticoagulation
– Marfans with aorta over 45 mm

– Acute or chronic aortic dissection

– Intractable heart failure

24
 Multidisciplinary Care

• Managing pregnant women with heart disease implicates

several stakeholders, all with different perspectives but
COMMON goals

• Team should include Cardiologist with expertise, OB

anesthesia, Maternal-Fetal Medicine and Nursing

• Meet regularly to discuss, anticipate and plan for any

potential difficulties

25
 Future Directions:
HOPE for Mom and Baby
(Heart Outcomes in Pregnancy: Expectations for Mom and
Baby)

Dalhousie Univ Wentworth-Douglass Hospital

University of Washington University of Nebraska Rush Northwestern; University of Pittsburgh Halifax, Nova Scotia Dover, NH
Seattle, WA Omaha, NE Mayo Clinic Northwestern; UIC Pittsburgh, PA U Mass
Rochester, MN Chicago, IL Univ of Michigan Worcester, MA
OSHU Ann Arbor, MI
Portland, OR Beth Israel/Harvard/MGH
Harvard Brigham & Women’s
Hospital
University of Colorado Medical Boston Children’s Pediatric
Ctr Cardiology
Brown University
Denver, CO Boston, MARI
Providence,
Stony Brook
Kaiser Stony Brook, NY
SF/UCSF Montefiore
San Francisco, Bronx, NY
CA
Lankenau Medical Center
Stanford Wynnewood, PA
Stanford, CA
Penn Heart & Vascular
Philadelphia, PA
Kaiser So. CA
Anaheim CA University of Kansas Hospital Johns Hopkins
Kansas City, KS Baltimore, MD
Cedars Sinai Medical University of Indiana
Center St. Vincent Heart Center
Saint Luke’s Mid America Heart Institute Barnes Jewish Hospital
USC; UCLA University of Indianapolis, IN
Kansas City, MO St. Louis, MO
Los Angeles, CA Florida
UCI Health Emory University Northside
UT Southwestern Vanderbilt Gainesville, FL Memorial Regional Northside Hospital
Orange County, Dallas, TX Hosp
CA Nashville, TN Atlanta, GA
Hollywood, FL
 Conclusion

• Maternal Mortality in the USA is rising

• Cardiovascular disease is significant cause of maternal
death
• Collaboration and solutions need to be built on many
levels
• State
• National/policy
• Medical – collaboration within disciplines
• Research – data to build the solutions

27
 PREVENTING AND HEALING
HEART DISEASE FROM WITHIN

Malissa J Wood, MD FACC

Co-director Corrigan Women’s Heart
Health Program
Massachusetts General Hospital
Associate Professor of Medicine,
Harvard Medical School

@drmalissawood
• Stress Is a risk factor for
heart disease
• Psychosocial risk factors
affect women more than me
• Stress heart attacks are real!
• Psychosocial stressors
magnify effect of existing CV
risk factors
• Current system ill prepared to
integrate medical and
behavioral health
• Novel community based
models hold promise for
improving overall health of
women (and those around
them!)
 Stress CAN Break Your Heart!

30
Proposed remodeling of mind-heart interactions
leads to progressive increases in neuroimmune
activation in response to stress.

Sitaramesh Emani, and Philip F. Binkley Circ Heart Fail.

2010;3:715-725

Copyright © American Heart Association, Inc. All rights reserved.

Effect of Stress on Cardiovascular Health-Interheart
Study (Lancet 364:953 -962, 2004)

• Case-control study: 11,119 patients with a first MI

• 262 Sites in Asia, Europe, the Middle East, Africa,

Australia, and North and South America.
• Link between psychosocial stress/depression: stress at
work and at home, financial stress, and major life events in
the past year, locus of control and presence of depression.
• Stress (OR 1.45) and depression (OR 1.55) associated
with risk of MI
Rozanski, JACC 2014
 After diagnosis of CAD psychological distress
associated with higher risk of events
compared to men

Greater vulnerability to psychological stress

Psychosocial stress increases risk of CVD
generally

Current system ill-equipt to provide integrated

comprehensive care to women and men with
heart disease

(Pimple JAHA 2019, Rosengren

and Manheim, 2015)
Brain-Heart Connection- Evidence Previously
Lacking
• Volume and quality of studies of mind-heart interventions previously insufficient to
change practice
– Uncontrolled, underpowered, design flaws
– Cardiovascular outcomes lacking in many studies
– Small number of well designed, adequately powered, scientifically stringent
studies
• Data looking at factors associated with cardiac risk are available
• Newly appreciated data linking stress, depression and anxiety to poor cardiac
outcomes supports this interaction
• Plausible etiologies: hypothalamic/pituitary/adrenal axis dysfunction, pro-
inflammatory cytokines, autonomic dysregulation
• Childhood stressors may influence HPA axis functioning (Danese and McEwen,
2012; Rich-Edwards et al., 2012; Bremner and Vaccarino, 2015)
Stress and CVD in Women

Increased inflammation due to stress

Coronary vasomotor dysfunction

SCAD and Takotsubo

Takotsubo Cardiomyopathy

• 90% of cases women 58-75

• Presentation identical to STEMI
– Reduced LVEF
– Heart failure
• 2/3 with acute emotional stressor
– Anesthesia, infection,
chemotherapy, physical
stressor
• 3% risk of death (arrhythmia or
heart failure)
• Nearly full recovery of heart
function by 4 weeks
• 3-10% recurrence
• Microvascular dysfunction,
sympathetic activation, vasospasm
Spontaneous Coronary Artery Dissection
Pathology and Histology of SCAD

Hayes Circulation 2018 Adlam European Heart Journal 2018

 Saw JACC 2017

25% 75% 5%
Epidemiology

• SCAD likely accounts for at

least 1-4% of acute coronary
syndromes
• 88-90% of cases in women
• At least 35% of heart attacks
in women under 50
• 43% of pregnancy-associated
heart attacks
• Most women have few
traditional risk factors

Hayes, Circ 2018, Saw JACC 2017

 Predisposing Conditions and Situations

• Pregnancy/post partum
Precipitating events:
• Fibromuscular dysplasia (FMD)
• Triggers
Adrenaline causes ↑ cardiac and vascular Vascular Vulnerability
shear stress which may lead to increased • Genetically mediated
risk of vascular injury vasculopathies
– Severe emotional stress (40%) – Vascular EDS
– Vigorous physical activity (24%) – Marfan syndrome, Loeys-Dietz
• More common in men (>50%)- • Rheumatologic disorders
MGH
SCAD – SLE, PAN, hypereosinophilia
– Cocaine, energy drinks
• Hormone exposure

Tweet et al Circ 2012, Saw et al. Circ CV Interv 2014, Elkayam et al Circ
2014.
Emotional Stress in SCAD

Most frequently reported sources of stress

included:
Intimate partner conflict
Conflict with close family member or friend
Change in work status or responsibilities
40% rated their stress between a 7 and 10 in the
2 weeks prior to SCAD
121 of respondents reported having engaged in
extreme or unusual physical exertion in two
weeks prior to SCAD
Sharma Am J Cardiol 2019, Duran Cath Cardiovasc Int 2019, Adlam EHJ 2019
Overlap Between SCAD and Takotsubo
(Duran, et al Catheter Cardiovasc. Interv 2019)

• MGH Registry
• 43 SCAD pts with LVG at the time of
coronary angiography

• 24/43 (58%) had findings consistent

with TTS

• Hyperdynamic LV function of the

basal territory and hypokinesis to akinesis to
dyskinesis of the apical territories in the
presence of a patent infarct related artery
Psychological Management

• Team approach • Cardiac Rehab*

• SSRI /anxiolytic • Stress management
• Behavioral health
provider
Mind-Body Medicine and The Heart

• Evidence now supports the mind body interaction and the impact
of Interventions: biofeedback, relaxation therapies, tai chi and
meditation -appear to have effect on the mind-heart interaction
– Impact on the neurohoromonal axis critical to heart failure
cascade
– Modification of psychological stress associated with CVD
• Mind-body and mind-heart interactions:
– Mitigate/modify the significant physical and psychological toll
of CVD
– Reverse the neuroimmune activation operative in both
conditions?
• Potential for preventive effects
Mind Body Therapy- Depression, Stress and
Anxiety
• Tai chi: benefit in obese individuals (Evid Based Complement Alternat Med.).
– Improved QOL in Heart Failure (Yeh, Wood, et al Am J Med 2004)

• Yoga: positive effect on depression, ruminations, stress, anxiety, and health-

related quality of life. Arch Psychiatr Nurs. 2014 Dec;28(6):377-83
• Mind Body Group/Relaxation Response : Reductions in stress, depression
and anxiety Adv Mind Body Med. 2014 Summer;28(3):6-13.
• Meditation: Improved negative mood and depression symptoms
Ideal Intervention for Improving Cardiovascular (and
overall) Health in women

• Cost-Effective

• Precise

• Efficacious

• Scalable
• Affordable

• Sustainable
• Enjoyable
• Origin of the name: HAPPY Heart
– Familiar location, trusted staff, accessibility

• Link between how we think and how our bodies react to making healthy
changes in our life!
• How did we luck out and end up here?
• “If you are committed the universe has a way of making things happen”
• Hypothesis:
– Do lifestyle intervention programs decrease cardiovascular risk among
socioeconomically disadvantaged and minority women?
– Can these women work together w a team of health coaches to improve
their overall (but especially) CV health
Methods: Study Design

HAPPY Heart Design Baseline Testing

Patients are recruited/referred by PCP BP, HR, Height, Weight, Waist/Hip Circ.

↓ Past Medical History

Phone screening, if eligible, appt. made Exercise/Activity Assessment
↓ Depression/Anxiety/Stress Assessment
At appointment, RN confirms eligibility
Lab Testing (BMP, Cholesterol, CRP, BNP)
↓
Echocardiography
IRB consent signed/formal enrollment
Electrocardiography
↓
Intimal Medical Thickness (IMT)
*Baseline Testing
↓ 6 Minute Walk Test

Enrollment in the program Framingham Risk Score

 Study Design
Methods: Study Design

Exercise Nutrition Psychological Smoking

PT Consult Nutrition Consult CESD-10 Offered cessation
↓ ↓ STAI program
Individualized Individual diet PSS
exercise plan - Cost/Family ↓ Officered free
↓ ↓ HAPPY Heart pharmacologic
Regular check in w/ Regular check in w/ Relaxation & options
Health Coach Health Coach Medication Classes
↓
Regular check in w/
*HAPPY Heart *HAPPY Heart Health Coach
Exercise Classes Cooking Classes

Enrollment Year 1 Year 2

Year 0 Follow Up Follow Up
N=64 N=57 N=50

Study
Design
Being Smart at Heart!

• Physical Health • Relationships

• Emotional Health • Communication
• Stress Management • Environment
Exercise
• Mindfulness
• Nutrition
• Modification
Exercise First, then RELAX!

Study
Design
Gilstrap L, J Women’s Health 20132
Obesity Runs Through Social
Networks
(Christakis, et al)

• Framingham Heart Study: highly interconnected

social network

• 12,067 people assessed repeatedly from 1971

to 2003
• They examined whether weight gain in one
person was associated with weight gain in
friends, siblings, spouse, and neighbors.
• Obesity likes company! clusters of obese
persons (BMI>30) at all timepoints
Healthy Choices and It’s Influence on Your Friend and
Family: Good Choices Go Viral!!!!

– A clear relationship exists between

intention and desire to lose weight and
your friends and family
– Friends and family are much more likely
to lose weight when a person close to
them starts exercising, changing their
diet and making positive life choices
– This study is the first to show that social
contacts affect weight loss behavior
– Findings underscore the importance of
targeting social influence in the
treatment and prevention of obesity in
this high-risk age group.
Rozanski, JACC 2014;
64: 100-110
 Organizational Structure
• Institutional IRB
Registry Centers • Data Use
Agreement

Site DATA
$
Institutions PERFUSE •
•
Michael Gibson, MD
PERFUSE staff
Organizati
ons
iSCAD DATA Study Chairperson
• Esther Kim, MD, MPH

Steering Committee
Publications • Malissa Wood, MD
Committee • Katherine Leon
• Sahar Naderi, MD
Steering
Advisory Council
Committee • SCAD Alliance Scientific
Advisory Board
Presentations/
Publications
Conclusions
• Stress Is a risk factor for
heart disease
• Psychosocial risk factors
affect women more than me
• Stress heart attacks are real!
• Psychosocial stressors
magnify effect of existing CV
risk factors
• Current system ill prepared to
integrate medical and
behavioral health
• Novel community based
models hold promise for
improving overall health of
women (and those around
them!)
 mjwood@mgh.harvard.edu
(617) 726-0995

@drmalissawood

SCAD Podcast :
https://empoweredhealthshow.com/