Terrifying Peripartum Cardiomyopathy - Recent Advances.pdf

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1. TERRIFYING PERIPARTUM
CARDIOMYOPATHY: RECENT ADVANCES
Dr.Narra Lavanya
Consultant Interventional Cardiologist
MD General Medicine, DrNBCardiology, CCK
MSc Heart Failure* (London)
KIMS Hospitals, Kondapur

2. INTRODUCTION
▪Peripartum cardiomyopathy (PPCM) is defined as an idiopathic
cardiomyopathy occurring towards the end of pregnancy or
in the months following delivery, abortion or miscarriage
without other causes for heart failure, and with a left
ventricular (LV) ejection fraction (EF) < 45%. (The 2010 Heart
Failure Association of the European Society of Cardiology
Working Group )

3. EPIDEMIOLOGY
▪The incidence of PPCM varies according to the race, ethnicity
and geographical background of women. The highest risk of
developing PPCM is among Africans and African-Americans.
COUNTRY INCIDENCE
Nigeria 1:100
Haiti 1:299
Japan 1: 346
USA 1:968
India 1:1340
Germany 1:1500
Denmark 1:10,000
Japan 1:20,000

4. PREDISPOSING FACTORS
Maternal age (>30
years)
Multiparity
Multiple
pregnancies
Family history
Ethnicity
Smoking
Diabetes
Hypertension
Pre-eclampsia
Obesity
Malnutrition,
Prolonged use of
tocolytics. (beta-
agonists)

5. •Microchimerism
•Viral Myocarditis

6. PATHOPHYSIOLOGY
▪Pathological response to
hemodynamic stress in
pregnancy:
oUnbalanced oxidative stress
oInduction of antiangiogenic
factors
oStress-activated cytokines
oInflammation and
oAutoimmune reaction
▪Genetic predisposition
▪Low selenium and zinc
levels
▪Viral infections
Systemic
angiogenic
imbalance
Host
susceptib
ility
Two- Hit Model

7. Honigberg MC, Givertz MM. Peripartum cardiomyopathy. BMJ. 2019;364:k5287. Published 2019 Jan 30.

9. Bauersachs J, König T, van der Meer P, et al. Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a
position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum
cardiomyopathy. Eur J Heart Fail. 2019;21(7):827-843.

10. INVESTIGATIONS
•Normal, repolarization abnormalities, LBBB,
tachycardia, Long QTc, ArrhythmiasECG
•LV and right ventricular dilatation and/or dysfunction,
functional mitral and/or tricuspid regurgitation,
pulmonary hypertension, and left atrial or bi-atrial
enlargement and Intracardiac thrombus.
Echo
• Pulmonary venous congestion Chest X-ray
•The most important role of natriuretic peptides
is to rule out heart failure (with a threshold < 100
pg/mL for BNP and < 300 pg/mL for NT-proBNP )
Biomarkers
•Accurate ejection fraction and chamber
measurements , tissue characterization and
differentials
MRI
•It may be used to exclude acute myocarditis after delivery,
reveal significant viral presence, and exclude rare
autoimmune myocarditis, storage or metabolic disease.
Endomyocardial
biopsy

11. ECHOCARDIOGRAM

13. Davis, M, Arany, Z, McNamara, D. et al. Peripartum Cardiomyopathy: JACC State-of-the-Art Review. JACC. 2020 Jan, 75 (2) 207–221.

14. MANAGEMENT

15. MEDICAL MANAGEMENT

16. Medications contra-indicated In Pregnancy

17. NEWER THERAPIES
Pentoxifylline
Xanthine derivative with
anti‐inflammatory properties. Studies
have shown evidence of benefit in
symptoms and systolic function in heart
failure, and a meta‐analysis of six trials
suggested that it reduced mortality.
Antisense therapy against
microRNA-146a
VEGF agonism and
removal of anti-
angiogenic proteins
Serelaxin : A recombinant
form of relaxin‐2
Perhexiline

18. BROMOCRIPTINE
Bromocriptine is a dopamine agonist and inhibits the
release of prolactin.
Originally marketed for lactation suppression, but due to the
association with myocardial infarction, stroke, and seizures it is no
longer approved for this indication.
PPCM is driven by the antiangiogenic and proapoptotic 16-kDa form of
prolactin led to experimentation using bromocriptine to inhibit
prolactin secretion to prevent PPCM in a mouse model.
•Several small scale trials were done on south African women receiving
bromocriptine in addition to standard HF therapy
•Death, New York Heart Association functional class III/IV, or LVEF
<35% at 6 months were lower in those on bromocriptine therapy
compared to controls.

19. ▪The implications of not breastfeeding due to bromocriptine
should be discussed with the patient.
▪The 2018 European Society of Cardiology guidelines
include recommendation Class IIb, Level of Evidence: B
recommendation for the use of bromocriptine.
▪US guidelines consider bromocriptine to be investigational.
▪Due to the association with thrombotic complications,
therapeutic anticoagulation is recommended in conjunction
with bromocriptine.

21. MANAGEMENT OF PPCM

22. SEVERE PPCM
•Intravenous vasodilators, such as
nitroglycerin, may be needed in the setting
of acute decompensated HF during
pregnancy.
•Possible adverse effects of dobutamine
were described in an observational study
of 27 nonrandomized patients with PPCM
and LVEF <25%.
•Recent comparison of milrinone and
levosimendan in 15 women with PPCM
showed comparable hemodynamic
improvement with both drugs.

23. ▪A total of 60% of cases of cardiogenic shock during or shortly
after pregnancy are caused by PPCM.
▪Temporary mechanical circulatory support with intra-aortic
balloon pump, percutaneous ventricular assist device
therapy, and extracorporeal membrane oxygenation have
been used successfully in PPCM and should be considered
early in patients with hemodynamic instability despite
inotropic support.

24. PREVENTION OF SCD
▪Decisions regarding the use of an implantable cardioverter
defibrillator (ICD) in patients with PPCM should consider the
natural history of these diseases, including the potential for the
recovery of ventricular function.
▪Until more date becomes available, it may be reasonable to
consider wearable cardioverter/defibrillators for women
with new onset PPCM and severe LV dysfunction as a
bridge to recovery or until an implantable ICD is indicated.

25. LABOR AND DELIVERY
An attempt to stabilize the mother to avoid potential fetal
complications of prematurity is reasonable.
Stable patients are delivered vaginally unless there are obstetric
reasons for cesarean section.
Unstable patients may benefit from invasive hemodynamic
optimization prior to delivery and monitoring during delivery
and the early postpartum period.
Following delivery, removal of caval compression by the fetus,
autotransfusion due to uterine contractions, and fluid
mobilization and resorption contribute to an increase in venous
return. The post-partum risk of fluid overload and pulmonary
edema must be anticipated.

26. LACTATION
▪The use of pharmacologic prolactin inhibition and cessation of
breast feeding are controversial.
▪Some experts and clinical investigators advocate for
bromocriptine as part of the management of all women with
PPCM, whereas others advise breast feeding for all women who
are stable enough to do so, citing fetal benefit and lack of
evidence of harm to the mother.
▪Until further data are available, it would be reasonable to con‐
sider the use of bromocriptine in women with severe left
ventricular dysfunction (eg, LVEF <25%) or cardiogenic
shock. Other women with less impaired left ventricular
function should be allowed to breast feed if able.
Honigberg MC, Givertz MM. Peripartum cardiomyopathy. BMJ. 2019;364:k5287. Published 2019 Jan 30.

27. CONTRACEPTION
▪Contraception should be discussed at the time of diagnosis or
prior to hospital discharge.
▪In patients with severe LV dysfunction, the increased risk of
thrombo-embolism should dissuade the use of estrogen-
containing contraceptives.
▪Progesterone-releasing subcutaneous implants or the Mirena
intrauterine device are safe and effective choices.
▪Tubal ligation and vasectomy are other options.

28. DURATION OF TREATMENT
•In the presence of persistent cardiac dysfunction, cardiac medications
should be continued indefinitely.
•After LV recovery, optimal duration of treatment is unknown.
•A rationale for continuation of medical therapy is supported by
evidence of subclinical LV systolic dysfunction and anecdotal reports of
late deterioration of LV function.
•If the patient is free from congestive symptoms, diuretic medications
can be stopped.
•Additional HF medications, if stopped, should be weaned in a stepwise
fashion with frequent clinical assessment and echocardiographic
monitoring of LVEF (i.e., every 3 to 6 months).
•Reassessment of LV function is advised after drug discontinuation
followed by annual clinical and echocardiographic assessment.

29. PROGNOSIS
▪The recently completed prospective Investigations of
Pregnancy Associated Cardiomyopathy (IPAC) study
enrolled 100 women from multiple centers throughout the
United States and followed their clinical course for 12 months
with careful clinical evaluations, including repeated
echocardiography.
▪This study found that 71% of the women recovered LVEF to
>50%, whereas only 13% had major events or persistent
cardiomyopathy with EF <35%.
▪Recovery occurred almost uniformly by 6 months, with little
change in EF thereafter, as has been noted by previous stud-
ies.
▪ Recovery of LVEF after 6 months can sometimes occur,
however, and should not be ruled out.
Arany Z, Elkayam U. Peripartum Cardiomyopathy. Circulation. 2016;133(14):1397-1409.

30. PROGNOSIS
▪Favorable Prognostic
Factors
▪Small LV diastolic
dimension (<5.5 cm)
▪LVEF >30% to 35% and
fractioning of shortening
>20% at the time of
diagnosis
▪Absence of troponin
elevation
▪Absence of LV thrombus.
▪Non-African American
ethnicity
▪Poor Prognostic Factors
▪LV diastolic dimension
≥6cm
▪LVEF<35%
▪QRS >120 milliseconds
▪Delayed diagnosis
▪Higher NYHA class
▪Multiparity
▪African descent

31. SUBSEQUENT PREGNANCY
▪The safety of a subsequent pregnancy is a frequent concern for
patients and their families. Appropriate and accurate
counselling is essential.
▪The risks associated with a subsequent pregnancy depend
primarily upon whether the myocardial function has fully
recovered, and the pre-pregnancy LVEF is the strongest
predictor of outcomes.

33. FOLLOW-UP TESTING

34. TAKE HOME MESSAGE
▪PPCM is a pregnancy-related disease which arises in the
peripartum period and is characterised by heart failure with
left ventricular dysfunction.
▪PPCM can occur worldwide but those of black ancestry are at
the greatest risk. (50% of cases).
▪An elevated BNP level should always be followed by an
echocardiogram to assess for systolic dysfunction.
▪Acutely ill women should be managed by specialized
multidisciplinary teams, and may require advanced HF
therapies.
▪Long-term follow-up is important, but the optimal duration of
medications following recovery is unknown.