2. • Pregnancy-associated cardiomyopathy.
• A rare cause of heart failure (HF) that affects
women late in pregnancy or in the early
puerperium .
• >50% of cases occur in women >30 years of age.
3.
4. Definition (ESC 2010)
• An idiopathic cardiomyopathy presenting with heart
failure secondary to left ventricular systolic
dysfunction towards the end of pregnancy or in the
months following delivery, where no other cause of
heart failure is found.
• It is a diagnosis of exclusion.
• The left ventricle may/may not be dilated.
• The ejection fraction is nearly always reduced below
45%
5.
6. Epidemiology
• 1:20,000 live births in Japan
• 1:10,149 in Denmark
• 1:968 to 1:4000 in the United States
• 1:2400 in Canada
• 1:1000 in South Africa
• 1:300 in Haiti
• 1:100 in Zaria, Nigeria
7. Nigerian story of PPCM
• Related to a local Hausa custom of eating kanwa,
a dry lake salt for forty days after delivery.
• Development of PPCM in these patients may be
related in part to hypervolemia and possibly
hypertension.
• Genetic predisposition.
8. Risk factors
• Age greater than 30 years.
• African descent .
• Pregnancy with multiple fetuses.
• A history of preeclampsia, eclampsia, or postpartum
hypertension.
• Maternal cocaine abuse
• smoking
• Long-term (>4 weeks) oral tocolytic therapy with
beta adrenergic agonists such as terbutaline.
• Diabetes
• Selenium deficiency
• Multiparity
9. Pathogenesis
• Multi-factorial
• Genetic Predisposition
• Proposed mechanism: a common final pathway with
enhanced oxidative stress
cleavage of prolactin to an angiostatic N-terminal 16 kDA
prolactin fragment
impaired vascular endothelial growth factor (VEGF)
signaling because of upregulated soluble fms-like
tyrosine kinase (sFLT1)
10. Genetic predisposition:
• DCM-associated mutations have been identified
in some patients with PPCM.
• Genes that encode the sarcomeric proteins titin,
myosin, and troponin.
• Sequencing of 43 genes associated with DCM in
172 women with PPCM detected 26 truncating
variants, 65% of which occurred in TTN, the
gene that encodes titin.
11. TTN mutations
• Were a/w lower LVEF at 6 and 12 months
• Were seen in 13% of black women and 8% of white
women with PPCM.
• Studies have reported that women with a family
history of DCM have poor recovery.
12. Prolactin
• Altered prolactin processing.
• Mice with a knockout in the cardiac tissue-specific signal
transduction and activator of transcription 3 (STAT3)
develop PPCM.
• Reduction in STAT3 leads to increased cleavage of
prolactin into an antiangiogenic and proapoptotic 16kDa
isoform by cathepsin D.
• The 16 kDa prolactin fragment (16K PRL) also causes
endothelial damage and myocardial dysfunction.
13. • STAT3 protects the heart from pregnancy-
induced oxidative stress in part by up-regulation
of a powerful reactive oxygen species, by a
scavenging mitochondrial enzyme named
manganese superoxide dismutase (MnSOD)
14. • High expression of 16-kDa prolactin fragment
Destroys cardiac microvasculature, reduces in vivo
cardiac function, promotes ventricular dilatation.
inhibits vascular endothelial growth factor-induced
proliferation of endothelial cells and migration
induces apoptosis
dissociation of capillary structures
impairs nitric oxide-mediated vasorelaxation
cardiomyocyte function
15. • 16K PRL induces microRNA-146a expression in
endothelial cells, which leads to most of the anti-
angiogenic effects of 16K PRL.
• Women with PPCM have elevated levels of
microRNA-146a compared with healthy
postpartum women or women with other
cardiomyopathies
16.
17. Placental angiogenic factors
• Soluble fms-like tyrosine kinase receptor 1 (sFlt-1)
an anti-angiogenic protein secreted by the placenta
exponentially increased amounts towards the end of
pregnancy.
sequesters circulating vascular endothelial growth
factor (VEGF) and placental growth factor (PlGF)
18.
19. Other putative pathophysiological
mechanisms
• Inflammation
• Serum markers of inflammation [including the
soluble death receptor sFas/Apo‐1, C‐reactive
protein, interferon gamma (IFN‐γ), and IL‐6]
are elevated in patients with PPCM
20. • Viruses
• Viral infection of the heart is another possible
cause of peripartum inflammation, although
clinical data are far from conclusive.
21. • Autoimmune mechanism
• High titres of auto‐antibodies against selected
cardiac tissue proteins have been found in the
majority of women with PPCM.
• titres correlated with clinical presentation and
with New York Heart Association (NYHA)
functional class.
23. Clinical features
• Mimic normal physiological findings of
pregnancy.
• Dyspnea, cough, orthopnea, paroxysmal
nocturnal dyspnea, pedal edema, Hemoptysis.
• Tachycardia, arrythmias, elevated jugular
venous pressure, a displaced apical impulse, a
third heart sound and a murmur of mitral
regurgitation.
24. • Left ventricular thrombosis (LVEF < 35%).
• Peripheral embolic episodes, including cerebral
embolism, with serious neurological
consequences, coronary and mesenteric
embolism.
27. ECG
• No pathognomic changes.
• LVH with strain pattern.
• Biventricular and biatrial dilatation
• Complications such as atrial fibrillation and flutter,
prolonged PR and QRS intervals, and bundle branch
blocks.
• Helps to distinguish PPCM from other causes of
symptoms.
28. 2DECHO
• Reduced LV wall motion is generalized or global
rather than regional
• LVEF
• Dilatation of all chambers (particularly left
ventricle)
• Left ventricular end diastolic dimension ( normal 36
to 52mm)
• LV thrombus
29. Magnetic Resonance Imaging
• Cardiac MRI using T2-weighted spin echo
sequences enables the precise diagnosis of
myocarditis, necrosis, and LV thrombi, and it
yields accurate measurements of ventricular
volumes.
• Injection of gadolinium as the contrast agent is
best avoided prepartum, because gadolinium
can cross the placenta.
30. Biomarkers:
• NT pro BNP ( not specific, but sensitive)
• CRP (prognosis of disease)
31. • Cardiac troponin- High cardiac troponin T levels
(>0.4 ng/mL) within 2 weeks of peripartum
cardiomyopathy onset significantly predicted
smaller LVEF and persistent LV dysfunction at
6-month follow-up.
34. Diuretics
• Diuretics reduce preload and treat pulmonary
congestion or peripheral edema.
• Hydrochlorothiazide and furosemide are safe during
pregnancy and lactation.
• Diuretic-induced dehydration can cause uterine
hypoperfusion and maternal metabolic acidosis, so
bicarbonate monitoring and management with
acetazolamide are needed.
• Potassium-sparing diuretic spironolactone should
be cautiously administered.
35. Vasodilators
• Hydralazine is safe during pregnancy and is the
primary vasodilator drug antepartum.
• More severe cases warrant the use of
intravenous nitroglycerin starting at 10 to 20
µg/min and continuing up to 200 µg/min.
• Nitroprusside is not recommended because of
the potential for cyanide toxicity
37. Inotropic Agents
• Dopamine, dobutamine, and milrinone is warranted
only in cases of severe low output, and the patient
should be weaned from them as soon as she is
hemodynamically stable.
• Levosimendan should be avoided antepartum and
lactation should be held while using levosimendan.
• Digoxin, an inotropic and dromotropic agent, is safe
to use during pregnancy
38. β-Blockers
• Safe during pregnancy
• β1-selective blockers are preferred over
nonselective β-blockers to avoid anti-tocolytic
action induced by β2-receptor blockade.
• Carvedilol combined with a blockade to restrict
peripheral vasoconstriction has been shown to
be effective in peripartum cardiomyopathy.
months.
39.
40. Anticoagulation
• Heart failure and pregnancy are independent
risk factors for thromboembolism.
• The administration of low-molecular-weight
heparin (LMWH) antepartum or
heparin/LMWH and warfarin postpartum is
recommended when the LVEF is <30%.
44. • In a pilot study in peripartum cardiomyopathy
(South Africa)
10 patients were administered the prolactin inhibitor
bromocriptine at a dose of 2.5 mg twice daily for 2 weeks and
then 2.5 mg once daily for 4 weeks, in addition to receiving
standard care
10 control patients received only standard care.
• The bromocriptine group had
better survival (1 vs 4 deaths)
greater LVEF recovery (from 0.27 at baseline [both groups] to
0.58 [bromocriptine] vs 0.36 [control] at 6 mo).
45.
46.
47. • Multicenter trial performed in Germany
• enrolled 63 women with PPCM with LVEF ≤35
percent who were randomly assigned to
short-term bromocriptine (one week of 2.5 mg
daily)
long-term bromocriptine (eight weeks: 5 mg for
two weeks followed by 2.5 mg for six weeks) in
addition to standard HF therapy .
48. • Improvement in LVEF as assessed by cardiac
magnetic resonance imaging at six months was
similar in the two groups (28 to 49 percent in
the one-week group and 27 to 51 percent in the
eight-week group).
• The frequency of full recovery (LVEF ≥50
percent) was not significantly higher in the
eight-week group compared with the one-week
group (68 versus 52 percent).
49. At present available data is insufficient to
recommend routine use of bromocriptine
treatment for PPCM.
50. Other therapies
• Intravenous Immunoglobulin
• Pentoxifylline
• Serelaxin
• Antisense therapy against microRNA-146a
• VEGF agonism and removal of anti-angiogenic
proteins
51. Mechanical Circulatory Support and
Transplantation
• Mechanical circulatory support and even heart
transplantation may be needed.
• Peripartum cardiomyopathy has resolved in
some patients so treated with LVADs.
• Because peripartum cardiomyopathy can resolve
within 3 to 6 months postpartum, LVADs can
also serve as a bridge to recovery in cases of
fulminant peripartum cardiomyopathy.
52. Timing and mode of delivery
• Timing and mode of delivery :- limited data ( need
multidisciplinary approach)
• PPCM with compensated HF: normal vaginal delivery
preferred
• Caesarean is generally reserved for obstretic indications
• Epidural anasthesia preferred
• Early delivery not reqiured if maternal and fetal
conditions are stable (2010 ESC)
53. Natural course and prognosis
• 50% patients - complete recovery (occurs usually
with in 3 to 6 monts)
• 25% patients – persistent symptoms
• 25% patients – develops complication
(progressive heart failue, arrythmia,
thromboembolism)
• Mortality- 3% to 9.6%
54. Poor outcome is a/w
• higher NYHA functional class
• black ethnicity
• LV thrombus
• Multiparity
• LVEF <30 %
• Delayed diagnosis,
• High troponin levels at baseline
55. Subsequent pregnancy and counselling
• Because of the sparse knowledge in this field, it is difficult to
give individual counselling, but with a LVEF of <25% at
diagnosis or where the LVEF has not normalized, the patient
should be advised against a subsequent pregnancy.
• All patients should be informed that pregnancy can have a
negative effect on cardiac function and development of HF
and death may occur.
• Women with PPCM need careful counselling about
contraception because, as they have a high risk of relapse in
subsequent pregnancies and terminating pregnancy may not
prevent the onset of PPCM.
