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Critical Care in
Obstetrics:
An Innovative and Integrated Model for
Learning the Essentials
Peripartum Cardiomyopathy
Leo R. Brancazio, M.D.
Division of Maternal-Fetal Medicine
Department of Obstetrics & Gynecology
Duke University Medical Center
I have no conflicts of interest to disclose
I will be discussing one off-label or
investigational drug: bromocriptine in the
management of peripartum cardiomyopathy
Disclosure
Please go to online video to view lecture
without cases
Some items will not be discussed during this
presentation
Disclosure
Learning Objectives
Background
Etiologies/ Pathophysiology
Diagnosis
Treatment/ Management
Prognosis/ Future Pregnancies
Summary
Evidence
Outline*
* Some parts will be in online version
Review current epidemiology of
peripartum cardiomyopathy (PPCM)
Understand pathophysiology of PPCM
Discuss signs, symptoms, and diagnosis of
PPCM
Discuss management and prognosis of
PPCM
Learning Objectives*
* Some parts will be in online version
True incidence unknown
Wide variation worldwide
Population differences
Estimates 18-333/100,000 births
In the United states: ~ 1/2066-1/4025 live
births
Clinical presentation highly variable
Incidence
33-year-old G5P3104
At 34 weeks, undergoing induction of labor
for preeclampsia with severe features
(blood pressure criteria)
Of note, patient has 3+ BLE edema
Case 1
Obstetrical history
G1 – Preterm induction for preeclampsia
G2 – Cesarean delivery for abnormal
FHT during labor induction for
preeclampsia
G3 – Successful VBAC at term
G4 – Uncomplicated NSVD at term
G5 – Current
Case 1
Medical history
Obesity (BMI = 48 kg/m2)
Blood pressures are “high normal” when
not pregnant
Possible sleep apnea (patient did not
show for sleep study)
Case 1
Medications
Low-dose aspirin
Prenatal vitamins
Increasing doses of Labetalol during this
admission
Magnesium sulfate for prophylaxis
against eclampsia
Case 1
Labor induction started with misoprostol for
24 hours
Oxytocin for next 39 hours
After all this, patient cervix was
1/20%/High/Midposition/Firm
Amended plan – Cesarean delivery for
failed induction
Case 1
Cesarean complicated by prolong OR time
secondary to obesity and adhesive disease
POD # 3 – Patient with several complaints
Shortness of breath – “suffocating”
Palpitations
Case 1
Signs and Symptoms
Symptoms of PPCM
Dyspnea
Peripheral Edema
Fatigue
Orthopnea
Paroxysmal Nocturnal
dyspnea
Palpitations
Chest pain
Decreased exercise
tolerance
Anorexia
Persistent cough
Abdominal discomfort
Signs of PPCM
Pulmonary Rales
Loud P2
Third Heart Sound (S3) or
Gallop Rhythm
New Mitral Murmur
New Tricuspid Murmur
Lateral / Downward
Displacement of PMI
Jugular Venous Distension
Hepatojugular Reflux
Hepatomegaly
Peripheral Edema
Ascites
Blauwet et al
Risk Factors
Blauwet, L A, & Cooper, L T. (2011). Diagnosis and management of peripartum cardiomyopathy. Heart (British Cardiac Society), 97(23),
1970-1981. doi: 10.1136/heartjnl-2011-300349
Probable Risk Factors Proposed Risk Factors
Emerging Risk Factors
PPCM
Twin
Pregnancy
High Parity
High Gravidity
Extremes of
Reproductive Age
Prolonged
Tocolysis Preeclampsia
Genetics
Obesity
Smoking
Hypertension
Malnutrition
Cocaine Abuse
African Ancestry
Socioeconomic
Status
Case 1
Development of heart failure in last month of
pregnancy or up to 6 months postpartum
Absence of preexisting heart disease
Indeterminate cause
Echocardiographic findings
(a, together with b or c; or all 3)
A. LV end-diastolic dimension > 2.7 cm/m2
B. M-mode fractional shortening < 30 %
C. LV ejection fraction < 0.45%
Diagnostic Criteria
Demakis, J. G., & Rahimtoola, S. H. (1971). Peripartum cardiomyopathy. Circulation, 44(5), 964-968.
Manolio, T. A., Baughman, K. L., Rodeheffer, R., et al. (1992). Prevalence and etiology of idiopathic dilated
cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop. Am J Cardiol, 69(17), 1458-1466.
Blauwet et al
Diagnosis - Adjunct Studies Rule out pneumonia & pneumothorax
Assess for
Cardiac MRI
Useful when echo images are non-diagnostic
May provide prognostic information
Right Ventricular Biopsy
Useful with ventricular tachycardia or high grade failure
Patients who fail to respond to optimal medical therapy
Anemia
Thyroid disease
Liver disease
End stage renal disease
Infection
HIV
Electrolytes
NT-proBNP
hs-CRP
Pathophysiology
Blauwet et al
Prolactin
Hilfiker-Kleiner, D., Struman, I., Hoch, M., Podewski, E., & Sliwa, K. (2012). 16-kDa prolactin and bromocriptine in postpartum
cardiomyopathy. Curr Heart Fail Rep, 9(3), 174-182. doi: 10.1007/s11897-012-0095-7
16-kDA
Prolactin
23-kDA
Prolactin
Cathepsin D
(Vasoinhibin)
Prolactin
Hilfiker-Kleiner, D., Struman, I., Hoch, M., Podewski, E., & Sliwa, K. (2012). 16-kDa prolactin and bromocriptine in postpartum
cardiomyopathy. Curr Heart Fail Rep, 9(3), 174-182. doi: 10.1007/s11897-012-0095-7
Apoptosis
Migration
Inhibition
Leukocyte
Adhesion
Vaso-
dilatation
Inhibition
16K PRL
Impaired
Vessel
Maturation
Capase
3/8/9
NF-kB
eNOS
Proliferation
Inhibition
MAPKDelta /Notch
Ras-Tiam-Rac1
ICAM
VCAM
SELE
Treatment-
Compensated
Non-pharmaceutical
therapies
Low-sodium diet
≤ 2 liters fluid per day
Decreased activity
Antepartum
management
Beta-blocker
Carvedilol
Metoprolol extended
release
Vasodilator
Digoxin
Diuretic
LMWH for EF < 35%
Treatment (Compensated)
Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.
Postpartum therapy
Angiotensin-converting enzyme (ACE) inhibitor
Angiotensin-receptor blocker (if ACE inhibitor not tolerated)
± Nitrates or hydralazine
Loop Diuretic
Vasodilator
Aldosterone antagonist
Beta-blocker
Warfarin for EF < 35%
Treatment (Compensated)
Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.
ABCs
Loop diuretic
Vasodilator
Positive inotropic agents
Avoid beta-blockers
Heparin
Consider endomyocardial biopsy
Consider cardiac MRI
Assist devices
ECMO
Transplantation
Treatment (Decompensated)
Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.
Possible novel therapy for patients with
PPCM
Still should be considered experimental
May consider use in patients failing
conventional therapy or who are
severely compromised
Bromocriptine
Pilot study – Open-label randomized 10:10
Open-label randomized 10:10
8 weeks of bromocriptine therapy
Improved EF at 6 months vs. standard care
Decreased risk of composite poor outcomes
Bromocriptine
Sliwa et al
Treatment algorithm
Bachelier-Walenta et al.
Treatment algorithm
Bachelier-Walenta et al.
Treatment algorithm
Bachelier-Walenta et al.
Management
– Labor &
Delivery
If possible, delay until heart failure has
resolved (or is resolving)
Route of delivery- ideally vaginal
Decreased hemodynamic burden
Condition may not tolerated prolonged
induction
Supplemental oxygen
Left tilt
Labor & Delivery
Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.
Anesthesia - early epidural
Avoid tachycardia
Avoid hypotension
Careful fluid management
Continuous ECG
± Arterial catheter
± Pulmonary catheter
Intensive care 48 hours postpartum
Labor & Delivery
Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.
36-year-old African American G4P4004
At 38 weeks, had induction of labor for
chronic hypertension
Vaginal delivery
Medical history
Chronic hypertension for 4 years
Obesity (BMI = 39 kg/m2)
Smoker (20 pack-year history)
Case 2
Risk Factors
Blauwet, L A, & Cooper, L T. (2011). Diagnosis and management of peripartum cardiomyopathy. Heart (British Cardiac Society), 97(23),
1970-1981. doi: 10.1136/heartjnl-2011-300349
Probable Risk Factors Proposed Risk Factors
Emerging Risk Factors
PPCM
Twin
Pregnancy
High Parity
High Gravidity
Extremes of
Reproductive Age
Prolonged
Tocolysis Preeclampsia
Genetics
Obesity
Smoking
Hypertension
Malnutrition
Cocaine Abuse
African Ancestry
Socioeconomic
Status
For 3 weeks before delivery
Complained of “much more swelling”
than she had with her other deliveries
Fatigue
Depressed
Case 2
During admission – “Something is not right”
Told she was older and this was to be
expected
Discharged PPD #1
PPD #3 – Called obstetrician
Fatigue
Sense of doom
Cough
Case 2
Signs and Symptoms
Symptoms of PPCM
Dyspnea
Peripheral Edema
Fatigue
Orthopnea
Paroxysmal Nocturnal
dyspnea
Palpitations
Chest pain
Decreased exercise
tolerance
Anorexia
Persistent cough
Abdominal discomfort
Signs of PPCM
Pulmonary Rales
Loud P2
Third Heart Sound (S3) or
Gallop Rhythm
New Mitral Murmur
New Tricuspid Murmur
Lateral / Downward
Displacement of PMI
Jugular Venous Distension
Hepatojugular Reflux
Hepatomegaly
Peripheral Edema
Ascites
Blauwet et al
Patient seen on PPD # 3 (by nurse)
Vitals done
No other physical exam performed
Diagnosed with depression
Rx of sertaline
Case 2
PPD # 5 – feeling worse
Asked to be seen again
New complaints
Inability to sleep – cannot get comfortable
Persistent swelling
Patient appeared agitated
Still with cough
Again, doctor does not see patient
Case 2
PPD # 7 – Patient tells husband to call
ambulance
“Cannot breathe”
“Severe chest pain”
In route to hospital, patient arrests
30 minute code in ED
Case 2
Autopsy
Cardiomegaly
Severe pulmonary edema
Small thrombus on mitral valve
Postpartum uterus
Case 2
34-year-old G2P2002 for prepregnancy
consultation
4 years ago – peripartum cardiomyopathy
Diagnosed 10 days postpartum
Ejection fraction = 25%
Furosemide, Digoxin, Enalapril, Warfarin
Currently on Furosemide & Enalapril
New partner
Case 3
Older studies
50% recovery
25% stable but reduced cardiac
function
25% deteriorate
Prognosis
Patient reports dyspnea after 2-3 flights
of stairs
Echocardiogram ordered
35-40% EF
Case 3
Higher diagnosis and 6 month EF than other causes for
cardiomyopathy
Trend to greater change in EF in 6 months
PPCM vs. other CM
Cooper, L. T. et al
Greater percentage of PPCM patients with EF>50%
Percentage of patients with EF<30% similar between
etiologies
Distribution of EF in PPCM
Cooper, L. T et al
Felker, G M, Thompson, R E, Hare, J M, Hruban, R H, Clemetson, D E, et al. (2000). Underlying causes and long-term survival in patients
with initially unexplained cardiomyopathy. The New England journal of medicine, 342(15), 1077-1084. doi:
10.1056/NEJM200004133421502
Survival PPCM vs. other CM
Future Pregnancy Inadvisable
Elkayam, U et al.
Future Pregnancy Inadvisable
Future Pregnancy Inadvisable
Elkayam, U et al.
Summary
Summary
Widely variable incidence
Rule out other etiologies first
Better long term outcomes that other CM
etiologies
Future pregnancies are not recommended
regardless of recovery
Summary
Initial treatment includes diuretics, beta-
blockers, and inotropes
Consider Bromocriptine for those that do
not respond to maximum therapy
Consider delivery if fetus mature or
cardiac failure decompensated
Evidence
REFERENCES
• Bachelier-Walenta, Katrin, Hilfiker-Kleiner, Denise, & Sliwa, Karen. (2013). Peripartum
cardiomyopathy. Curr Opin Crit Care, 19(5), 397-403. doi: 10.1097/MCC.0b013e328364d7db
(Level III)
• Blauwet, L A, & Cooper, L T. (2011). Diagnosis and management of peripartum cardiomyopathy.
Heart (British Cardiac Society), 97(23), 1970-1981. doi: 10.1136/heartjnl-2011-300349 (Level
III)
• Cooper, L. T., Mather, P. J., Alexis, J. D., Pauly, D. F., et al. (2012). Myocardial recovery in
peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men
and nonperipartum women. J Card Fail, 18(1), 28-33. doi: 10.1016/j.cardfail.2011.09.009
(Level II-2)
• Demakis, J. G., & Rahimtoola, S. H. (1971). Peripartum cardiomyopathy. Circulation, 44(5), 964-
968. Level III)
• Elkayam, U., Tummala, P. P., Rao, K., Akhter, M. W., Karaalp, I. S., Wani, O. R., et al. (2001).
Maternal and Fetal Outcomes of Subsequent Pregnancies in Women with Peripartum
Cardiomyopathy. The New England journal of medicine, 344(21), 1567–1571.
doi:10.1056/NEJM200105243442101(Level II-2)
• Felker, G M, Thompson, R E, Hare, J M, Hruban, R H, Clemetson, D E, et al. (2000). Underlying
causes and long-term survival in patients with initially unexplained cardiomyopathy. The New
England journal of medicine, 342(15), 1077-1084. doi: 10.1056/NEJM200004133421502 (Level
II-3)
Evidence
REFERENCES – continued
• Habli, Mounira, O'Brien, Thomas, Nowack, Elizabeth, Khoury, Saeb, Barton, John R, &
Sibai, Baha. (2008). Peripartum cardiomyopathy: prognostic factors for long-term maternal
outcome. American journal of obstetrics and gynecology, 199(4), 415.e411-415. doi:
10.1016/j.ajog.2008.06.087 (Level II-3)
• Harper, Margaret A, Meyer, Robert E, & Berg, Cynthia J. (2012). Peripartum cardiomyopathy:
population-based birth prevalence and 7-year mortality. Obstet Gynecol, 120(5), 1013-
1019. doi: 10.1097/AOG.0b013e31826e46a1 (Level II-3)
• Heart Failure Society Of, America. (2006). Executive summary: HFSA 2006 Comprehensive
Heart Failure Practice Guideline. J Card Fail, 12(1), 10-38. doi:
10.1016/j.cardfail.2005.12.001(Level III)
• Hilfiker-Kleiner, D., Struman, I., Hoch, M., Podewski, E., & Sliwa, K. (2012). 16-kDa prolactin
and bromocriptine in postpartum cardiomyopathy. Curr Heart Fail Rep, 9(3), 174-182. doi:
10.1007/s11897-012-0095-7 (Level III)
• Johnson-Coyle, L., Jensen, L., Sobey, A., American College of Cardiology, Foundation, &
American Heart, Association. (2012). Peripartum cardiomyopathy: review and practice
guidelines. Am J Crit Care, 21(2), 89-98. doi: 10.4037/ajcc2012163 (Level III)
• Lata, I., Gupta, R., Sahu, S., & Singh, H. (2009). Emergency management of decompensated
peripartum cardiomyopathy. J Emerg Trauma Shock, 2(2), 124-128. doi: 10.4103/0974-
2700.50748 (Level III)
Evidence
REFERENCES – continued
• Manolio, T. A., Baughman, K. L., Rodeheffer, R., Pearson, T. A., Bristow, J. D., et al. (1992).
Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart,
Lung, and Blood Institute workshop. Am J Cardiol, 69(17), 1458-1466. (Level II-3)
• Natalie Bello, M. D., Iliana S Hurtado Rendon, M. D., & Zoltan Arany, M. P. (2013). Accepted
Manuscript. Journal of the American College of Cardiology, 1–35.
doi:10.1016/j.jacc.2013.08.717 (Level I)
• Patten, Ian S, Rana, Sarosh, Shahul, Sajid, Rowe, Glenn C, Jang, Cholsoon, et al. (2012).
Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature, 485(7398), 333-
338. doi: 10.1038/nature11040 (Level III)
• Sliwa, K, Blauwet, L, Tibazarwa, K, Libhaber, E, Smedema, J P, et al. (2010). Evaluation of
Bromocriptine in the Treatment of Acute Severe Peripartum Cardiomyopathy: A Proof-of-
Concept Pilot Study. Circulation, 121(13), 1465-1473. doi:
10.1161/CIRCULATIONAHA.109.901496 (Level I)
Evidence
Thank You for Your Attention!
Planning Committee
Mike Foley, Director Shad Deering, co-Director
Helen Feltovich, co-Director Bill Goodnight, co-Director
Loralei Thornburg, Content co-Chair Deirdre Lyell, Content co-Chair
Suneet Chauhan, Testing Chair Mary d’Alton
Daniel O’Keeffe Andrew Satin
Barbara Shaw