Cardiomyopathy, Peripartum

Introduction

Background

Peripartum cardiomyopathy (PPCM) has a number of definitions, but the authors prefer to use the one put forth by
the Heart Failure Association of the European society of Cardiology Working Group on PPCM 2010: "Peripartum
cardiomyopathy is an idiopathic cardiomyopathy presenting with HF secondary to left ventricular (LV) systolic
dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of HF is
found. It is a diagnosis of exclusion. The LV may not be dilated but the ejection fraction (EF) is nearly always
reduced below 45%."1

As opposed to other definitions, this one specifically excludes women who develop PPCM early in their pregnancy
and says that not all cases of PPCM present with left ventricular dilation. 2 This documentation helps avoid
misdiagnosing other conditions that present with pulmonary edema in pregnancy, such as diastolic dysfunction
from preeclampsia and other disorders listed in Differentials.

PPCM is more common in multiparous women. It has been reported more often in twin gestations and in women
with preeclampsia, but both of these conditions are associated with a lower serum oncotic pressure that can
predispose to noncardiogenic pulmonary edema in the setting of other stressors.

Pathophysiology

The exact cause is unknown. Proposed etiologies including low selenium levels, various viral infections, and
autoantibodies have been implicated. More recent evidence makes myocarditis less likely.

Two studies have suggested that a subset of cases of peripartum cardiomyopathy result from a genetic cause. 3,4

Frequency

United States

Reports estimating incidence in the United States vary and include 1 case per 1300, 4000, and up to 15,000 live
births.

75% are diagnosed within the first month postpartum and 45% present in the first week. When suspected, one
must establish the diagnosis rapidly. 5

International

The prevalence is reported to be 1 case per 6000 live births in Japan, 1 case per 1000 live births in South Africa, and
1 case per 350-400 live births in Haiti. A high prevalence in Nigeria is caused by the tradition of ingesting kanwa
(dried lake salt) while lying on heated mud beds twice a day for 40 days postpartum. The high salt intake leads to
volume overload.

Mortality/Morbidity
Historically, mortality figures from multiple small series have ranged from 7-50%, with half of the deaths occurring
within 3 months of delivery. More recent case series have found the following mortality rates: 6,7,8,9,10,11

 The 2-year mortality rate among African American women in the United States is 15.9%.
 Other series in the United States show mortality at 3.3-9.6%.

 Mortality in South Africa is 10-27% at 6 months and 28% at 2 years.

 Mortality rate in Haiti is 15% at 2 years.

The usual causes of death are progressive heart failure, arrhythmia, or thromboembolism. The mortality rate
related to embolic events has been reported to be as much as 30%.

 Acutely, maternal hypoxia can cause fetal distress.

 Thromboembolic phenomenon may complicate PPCM due to the hypercoagulability of pregnancy and
either a low-flow state predisposing to venous thrombosis or arterial embolism originating from a severely
dilated left ventricle or fibrillating left atrium. When PPCM is diagnosed, antepartum anticoagulation with
subcutaneous heparin should be instituted and continued until 6 weeks postpartum. For reasons
described in the Treatment and Medication sections, unfractionated heparin offers some advantages over
low molecular weight heparin during the antepartum period.

Race

PPCM has been reported in white, Chinese, Korean, and Japanese women. Based on case series, many cases occur
in African American women from the southern United States.

A case control study in the United States found that, when compared to non-African Americans, African American
women had a 15.7-fold higher relative risk of peripartum cardiomyopathy (OR, 15.7; 95% CI, 3.5-70.6). 12

Sex

PPCM is unique to pregnant women of all reproductive ages.

Age

Initially thought to be more common in women older than 30 years, PPCM has been reported across a wide range
of age groups. The past bias toward older women may be related to the fact that this group has a higher prevalence
of undiagnosed conditions, such as thyrotoxicosis, mitral stenosis, or hypertension, which, in combination with
some complication of pregnancy and the physiologic alterations of pregnancy, leads to pulmonary edema.

Clinical

History

Presenting symptoms in peripartum cardiomyopathy


Early, rapid diagnosis of this syndrome is not the norm. It took 7 or more days to establish the diagnosis in
48% of women, and half of those had major adverse events before the diagnosis was made. 13 Often,
patients do not show any indication of the syndrome until after delivery. If a patient makes it through
labor, essentially nature's stress test, without symptoms, the onsite clinician might not consider PPCM as
the first cause when a woman decompensates.
 
Many patients present with heart failure or a major adverse event such as a stroke or respiratory failure
without any previous signs or symptoms to alert the clinician that a cardiomyopathy was going to develop;
19% of patients may present with the syndrome before the last gestational month. 5

Symptoms are the same as in patients with systolic dysfunction who are not pregnant.

New or rapid onset of the following symptoms requires prompt evaluation: cough, orthopnea, paroxysmal
nocturnal dyspnea, fatigue, palpitations, hemoptysis, chest pain, and abdominal pain.

Normal pregnancy

 Mild dyspnea upon exertion is common.

 Many presenting complaints observed in patients with cardiac disease occur during a normal pregnancy.

 Dyspnea, dizziness, orthopnea, and decreased exercise capacity often are normal symptoms in pregnant
women.

 The classic dyspnea of pregnancy is often described as the woman feeling as if she is unable to get enough
air in, to get a good deep breath, or both, and it is thought to be due to the progesterone-mediated
hyperventilation.

Physical

Normal pregnancy

 Due to the increase of endogenous progestins, respiratory tidal volume is increased and patients have a
tendency to hyperventilate. However, the rate of respiration should be normal.
 Normal pregnancy is characterized by an exaggerated X and Y descent of the jugular venous waveform,
but the jugular venous pressure should be normal.

 Cardiac auscultation reveals a systolic ejection murmur at the lower left sternal edge, over the pulmonary
area, or both in 96% of women.14 This pulmonic arterial flow murmur tends to become quieter during
inspiration. Diastolic murmurs warrant further evaluation. The S 1 may be exaggerated, and the S2 split may
be more prominent due to increased right-sided flow. While an S 3 has been described as a normal finding
in pregnancy, the authors have not found that to be the case in busy clinical practices at women's hospitals
that see approximately 14,000 deliveries a year.

 Peripheral edema occurs in approximately one third of healthy gravid women. However, be alert to sudden
changes in swelling late in pregnancy, which can be abnormal and should be investigated.

Peripartum cardiomyopathy

 Signs of heart failure are the same as in patients with systolic dysfunction who are not pregnant.
 Tachycardia

 Decreased pulse oximetry (should be ≥ 97% at sea level)

 Blood pressure may be normal. Physical findings of PPCM include elevated jugular venous pressure,
cardiomegaly, third heart sound, loud pulmonic component of the second heart sound, mitral and/or
tricuspid regurgitation, pulmonary rales, worsening of peripheral edema, ascites, arrhythmias, embolic
phenomenon, and hepatomegaly.
Elevated blood pressures (systolic >140 mm Hg and/or diastolic >90 mm Hg) and hyperreflexia with clonus suggest
preeclampsia.

Causes


The cause of PPCM is unknown, but the usual causes of systolic dysfunction and pulmonary edema should
be excluded.

Many nutritional disorders have been suggested as causes, but other than salt overload, none has been
validated by epidemiological studies.

An increased prevalence of myocarditis has been found in case series and in a small case-control study.
Abnormal myocardial biopsy findings were associated with a worse long-term prognosis for recovery.
More recent data have found a similar incidence of myocarditis in women with PPCM, when compared to
those with the idiopathic type. However, a study that found myocarditis in 62% of 44 women with PPCM
found that the finding did not correlate with survival.

Recent studies have found lower levels of selenium in patients with PPCM.

Autoantibodies against myocardial proteins have been identified in patients with PPCM but not in those
with idiopathic cardiomyopathy.

Case reports and anecdotal experience have documented ejection fractions as low as 10-15% in patients
with severe preeclampsia, with subsequent normalization of echocardiograms within 3-6 months.
Preeclampsia has been listed as a risk factor, but it may be the cause in some cases. Noncardiogenic
pulmonary edema has many causes, all of which must be considered. 15

A study in 2005 found that 8 of 26 patients had parvovirus B19, human herpes virus 6, Epstein-Barr virus,
and human cytomegalovirus detected after molecular analysis of myocardial biopsy specimens. 16

Other findings that are associated with PPCM, but not clearly causal, include increased levels of
inflammation and oxidative stress markers, increased levels of cathepsin D, and oxidized low-density
lipoprotein.

Case reports of women from the same family who developed PPCM suggest a possible familial/genetic
risk, but it seems that some of these women may have familial dilated cardiomyopathy that is unmasked
by the normal physiological changes of pregnancy. 17

Some have hypothesized that microchimerism, or fetal cells present in the maternal system that elicit an
inflammatory response, could be a potential contributing factor to the development of PPCM.

Differential Diagnoses

Aortic Stenosis Hypertension

Cardiomyopathy, Alcoholic Hypertension and Pregnancy
Cardiomyopathy, Cocaine Hypertension, Malignant
Cardiomyopathy, Diabetic Heart Disease Mitral Stenosis
Cardiomyopathy, Dilated Preeclampsia (Toxemia of Pregnancy)
Cardiomyopathy, Hypertrophic Pulmonary Disease and Pregnancy
Cardiomyopathy, Restrictive Pulmonary Edema, Cardiogenic
Cardiovascular Disease and Pregnancy Pulmonary Edema, Neurogenic
Coronary Artery Atherosclerosis
Other Problems to Be Considered

 Arrhythmogenic right ventricular dysplasia

 Noncardiogenic pulmonary edema during pregnancy: Pregnancy is a state of low oncotic pressure that is
reflected in decreased serum albumin (expect to see values of approximately 3.2 mg/dL). Consequently,
when other stressors are present, pulmonary edema can occur with normal cardiac filling pressures. The
most common triggers include pyelonephritis and other infections, corticosteroids, and tocolytics such as
beta agonists and magnesium sulfate.

 Infectious, toxic, or metabolic disorders

Workup

Laboratory Studies


Creatinine phosphokinase (CPK) levels can be elevated after normal delivery due to release from the
uterus and may be elevated after cesarean section due to release from the uterus and/or skeletal muscle.
Elevation of this enzyme is not diagnostic of PPCM because it can be elevated for many other reasons,
including normal delivery, skeletal muscle disorders, and viral myocarditis. The CPK from the placenta
routinely has a CPK-MB fraction of 6% or more.18 Therefore, without an obvious clinical presentation and
ECG findings to suggest myocardial infarction, the use of this test in the puerperium is very limited.

Troponin-I elevations are more likely to indicate true myocardial disease whether it be inflammatory or
due to infarction. They are certainly useful in diagnosing acute myocardial infarction. One study found that
a cardiac troponin T level greater than 0.04 ng/mL, measured within 2 weeks of diagnosis, was 60%
sensitive at identifying women more likely to have persistent ventricular dysfunction at 6 months after the
diagnosis. Given the poor sensitivity, the clinical use of this test is not entirely clear as these women
should be placed on maximal medical therapy and have serial echocardiographic assessments regardless
of the troponin result.19

Preeclampsia should be excluded based on history, physical examination, and blood work.

o History: New headaches, visual disturbances, right-sided abdominal pain, and new swelling of the
hands or face may be present.

o Examination: Retinal vasospasm, an S4 heard on cardiac auscultation, hyperreflexia/clonus, right

upper quadrant tenderness, and face or hand edema may be present.

o Lab studies: Abnormalities found with preeclampsia include serum creatinine level greater than
0.8 mg/dL, hemoglobin level greater than 13 g/dL (due to leaky capillaries and
hemoconcentration), elevated liver enzymes, thrombocytopenia, urine dipstick test results
indicating more than "1+" protein, decreased 24-hour urine creatinine clearance (normally 150%
above the nonpregnant level or approximately 150 mL/min), and more than 300 mg of
proteinuria evident on a 24-hour collection.

Urinalysis: Trace or 1+ proteinuria can be normal. Proteinuria 2+ or higher suggests preeclampsia. Exclude
infection.

Urine culture helps exclude infection.

Measure pulse oximetry.
 
Determine thyroid-stimulating hormone levels.

Electrolytes: Keep potassium level above 4 mEq/L and magnesium above 2 mEq/L.

Serological testing may help identify known causes of cardiomyopathy, including infections (eg, viral,
rickettsial, HIV, syphilis, Chagas disease, diphtheria toxin).

Exclude toxic etiologies such as ethanol and cocaine.

When indicated, exclude systemic disorders such as collagen vascular diseases, sarcoidosis, thyrotoxicosis,
pheochromocytoma, and acromegaly.

Imaging Studies

 Electrocardiogram (ECG): ECGs evaluate for conduction abnormalities. Results may be normal, show sinus
tachycardia or, rarely, atrial fibrillation if the cardiomyopathy is severe. Other nonspecific findings include
low voltage, left ventricular hypertrophy, and nonspecific ST-segment and T-wave abnormalities.
 Echocardiography
o
Consider calling a cardiologist for a STAT echocardiogram
o
Echocardiography should be performed in all women in whom this diagnosis is considered in
order to assess ventricular function, valve structure, chamber size, and wall motion.
o
Cardiac chambers enlarge slightly during pregnancy, usually within normal limits. Normal function
suggests a lung process or noncardiogenic pulmonary edema, and diastolic dysfunction can be
observed in patients with severe preeclampsia.

 Chest radiography
o
Rapid diagnosis must be established. When evaluating new onset dyspnea, tachycardia, or
hypoxia, obtain a STAT chest radiograph to detect pulmonary edema.
o
This should be performed with abdominal shielding to evaluate the etiology of hypoxia and
exclude pneumonia.
o
Fetal radiation exposure with 2 maternal chest radiographs with abdominal shielding is about
0.00007 rads. The accepted limit of fetal radiation exposure during pregnancy is 5 rads. To
reassure patients about the safety of a single study, note that you are obtaining 1 out of more
than 70,000 maternal chest radiographs that are theoretically permissible.
o
Patchy infiltrates in the lower lung fields, with vascular redistribution/cephalization, cardiomegaly,
and pleural effusions, indicate congestive heart failure. Remember that noncardiogenic
pulmonary edema may occur when a pregnant woman has a concurrent infection. In this setting,
the cardiac pressures may be normal and cephalization of vessels may not be present (see Other
Problems to be Considered).
o
Bilateral lower lobe infiltrates without vascular redistribution suggest either an atypical
pneumonia or noncardiogenic pulmonary edema due to the low oncotic state of pregnancy
combined with the stressors listed in Differentials.

 Magnetic resonance imaging (MRI)

 o
One report of 2 cases found no MRI abnormalities in 1 patient and areas of delayed myocardial
enhancement in the other. One month after presentation the patient with the normal MRI had a
normal ejection fraction. Six months after presentation the patient with MRI abnormalities at
baseline had an ejection fraction of 30% and some persistent areas of abnormality seen on repeat
cardiac MRI.20
o
Another series of 8 patients with PPCM did not detect any abnormalities on cardiac MRI. 21
o
One case report does not justify routine use of cardiac MRI as a prognostic tool when an
echocardiogram is readily available to evaluate the ejection fraction.

Other Tests

 When considering testing or treatment in pregnancy, one must recall that a healthy fetus depends on a
healthy mother.
 Exclude coronary artery disease when the patient presents with symptoms suggestive of cardiac ischemia.
Vasospasm can occur with preeclampsia and cocaine use. Some postmenopausal or perimenopausal
women are conceiving with the assistance of hormone replacement therapy. The prevalence of coronary
artery disease in this population must be considered.

o Stress echocardiography is the test of choice to look for coronary artery disease during
pregnancy.

o If stress echocardiography is desired but not available, nuclear imaging can be performed safely
during pregnancy if one feels that the result will significantly alter maternal management.

o The fetal radiation exposure with a thallium stress test is estimated to be less than 0.1 rads. The
accepted limit of fetal radiation exposure during pregnancy is under 5 rads. One stress test is only
1/50th of the safe dose, or 1 out of the 50 that can theoretically be performed safely during
pregnancy. Organogenesis is complete after the first trimester (13th wk of gestation); therefore,
testing in the second or third trimester will not cause any gross physical deformities.

 Electrocardiograms evaluate for conduction abnormalities. Results may be normal, show sinus tachycardia,
or, rarely, atrial fibrillation if the cardiomyopathy is severe. Other nonspecific findings include low voltage,
left ventricular hypertrophy, and nonspecific ST-segment and T-wave abnormalities.

Procedures

 Endomyocardial biopsy is controversial as reports have not demonstrated that this invasive procedure
offers information that can significantly alter the plan of care. A series of 18 American women 22 and 11
African women23 found myocarditis in 10 and 4 patients, respectively. In the African cohort, 3 of 4 with
myocarditis had persistent heart failure, and 4 of 5 without it improved. In the American cohort, 14 of 18
had myocarditis on biopsy. Of the 14, 10 were treated with immunosuppressive therapy and 9 of them
improved. However, all 4 patients with myocarditis who did not receive immunosuppressive therapy
improved as well. Therefore, while some small cohort studies suggest that the finding of myocarditis on
biopsy could provide prognostic information, it did not offer any such information in others. The use of this
invasive procedure in this population is not clear.
 Invasive hemodynamic monitoring in normal pregnancy: Beginning early in gestation and peaking around
28 weeks, blood volume and cardiac output increase by 50%, systemic vascular resistance falls by more
than 50% to a mean of 850 dynes/s/cm-5, and heart rate raises approximately 10-20% above the
prepregnant value in a singleton gestation.
  Invasive hemodynamic monitoring in preeclampsia: Preeclampsia is associated with diastolic left
ventricular dysfunction, increased systemic vascular resistance, and intravascular volume depletion
despite total-body volume overload.

 Invasive hemodynamic monitoring in peripartum cardiomyopathy

o Right-sided heart catheterization should be performed only with an understanding of the

hemodynamic changes observed during normal pregnancy. Catheterization can be avoided if the
patient responds to the medical regimen listed in Treatment.

o Empiric use of pulmonary artery catheters (PAC) in critically ill patients has come under question;
this particularly is true for pregnant women. Use of a PAC may be helpful during labor and
delivery in a patient who has severe structural cardiac disease or stenotic lesions and in anyone
who is New York Heart Association class III or IV (see Staging).

o Close attention to vital signs, volume status, urine output, and oxygenation is more likely to
detect clinically important changes. These assessments allow treatment decisions to be guided by
the global assessment of a patient's unique physiology rather than a standard response to a
single number.

Histologic Findings

Findings at autopsy have included a dilated heart, pale myocardium, endocardial thickening, and pericardial fluid.
Biopsy specimens may show myofiber hypertrophy or degeneration, fibrosis, edema, or lymphocytic infiltration.
Ventricular thrombi can be seen. Lymphocytic myocarditis was found in some series, but the clinical significance of
this is not clear because, as discussed in the Procedures section discussion regarding endomyocardial biopsy, there
is no convincing evidence to support immunosuppressive therapy if this result is obtained. 24

Staging

The severity of symptoms in patients with PPCM can be classified by the New York Heart Association system as
follows:

 Class I - Disease with no symptoms

 Class II - Mild symptoms/effect on function or symptoms only with extreme exertion

 Class III - Symptoms with minimal exertion

 Class IV - Symptoms at rest

Treatment

Medical Care

One must remember that a healthy fetus depends on a healthy mother.

Formulate the care plan and consider the consequences of not treating the mother before addressing the potential
or theoretical effects of a test/treatment on the fetus. This approach will help clarify the best plan for clinicians
who infrequently address medical issues during pregnancy.

The FDA classification system regarding the use of drugs in pregnancy is grossly oversimplified. Rely on a text
dedicated to the use of medications during pregnancy or an experienced clinician. This information will reassure
the treating physician, and the patient, about the best plan of action. Restricting the use of a medication solely
based on medicolegal concerns still occurs, but should not.

Patients with systolic dysfunction during pregnancy are treated the same as patients who are not pregnant.
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should be avoided. The
mainstays of medical therapy are digoxin, loop diuretics, afterload reduction with hydralazine and nitrates, and
beta-adrenergic blockade. Due to a high risk for venous and arterial thrombosis, anticoagulation with heparin
should be instituted when the ejection fraction is less than 30%.

Careful clinical assessment can render invasive hemodynamic monitoring unnecessary. Nitrates and inotropic
support with dobutamine should be used when clinically indicated.

Vaginal deliveries are preferred because third-spacing of fluid, endometritis, and pulmonary emboli occur much
more often after cesarean deliveries.

Early and effective pain control during delivery is paramount. Regional anesthesia, such as epidural or spinal, is not
associated with the myocardial depression observed with inhaled anesthetics.


Digoxin, diuretics, and afterload reduction

Initiate therapy with digoxin in women with an abnormal EF.

Use inotropic support with dobutamine when indicated. Improving cardiac output ensures adequate
uteroplacental perfusion.

Use diuretics when indicated to manage the maternal volume status, but obviously monitor electrolytes
and avoid maternal volume depletion that could lead to uteroplacental hypoperfusion.

Hydralazine, in combination with nitrates, is the first choice for afterload reduction and vasodilatation
during pregnancy.

Nitrates may be used to decrease maternal preload, when indicated, and are safe to the mother and fetus.
As with any medication that alters maternal hemodynamics, a drop in blood pressure can result in fetal
hypoperfusion and distress. Intravenous drips should be titrated very slowly, and maternal intravascular
euvolemia should be maintained.

Beta-adrenergic blocking agents should be prescribed as they would for a nonpregnant woman with a
cardiomyopathy. More data is available regarding the use of metoprolol during pregnancy, but carvedilol is
a reasonable option.

Anticoagulation

o Cases of arterial or venous thrombosis have been reported in as many as 50% of women with
PPCM, and the risk likely is related to the degree of chamber enlargement, systolic dysfunction,
and the presence of atrial fibrillation. Because pregnancy is a hypercoagulable state, once the
diagnosis of PPCM is established, anticoagulation should be considered and continued until at
least 6 weeks postpartum.

 Full dose/therapeutic anticoagulation should be initiated for women with atrial

fibrillation, LV thrombus, or possibly those with an ejection fraction of less than 30%.
  In the absence of those clear risk factors, the authors recommend at least low-dose
unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Enoxaparin
should not be used in women with artificial valves. In this setting a reasonable choice is
5,000 units of UFH SC bid or tid in the first trimester, 7,500 units in the second trimester,
and 10,000 units bid in the third trimester. Enoxaparin 40 mg daily or bid is also
reasonable.

o UFH has an advantage over LMWH because of the ease with which the level of anticoagulation
with UFH can be assessed by obtaining an activated partial thromboplastin time (aPTT). In
addition, protamine is not as effective at reversing LMWH in the setting of obstetric bleeding. The
decision to use prophylactic dosing versus a high-dose regimen that will elevate the aPTT must be
individualized based on obstetric issues and the severity of the disease. Women with atrial
fibrillation, documented left ventricular thrombus, an ejection fraction 30% or less, or severely
dilated ventricles should receive full-dose subcutaneous heparin to prevent arterial embolism.
Refer to Medications for specific dosing recommendations.

o Warfarin carries a risk of spontaneous fetal cerebral hemorrhage in the second and third
trimesters but is compatible with breastfeeding and is, therefore, the preferred medication
postpartum.

o Due to the occurrence of epidural hematomas, the American Society of Anesthesiology

recommends that women on full-dose LMWH not receive spinal or epidural anesthesia for 24
hours after the last injection. Therefore, if cesarean delivery is required, these patients may
receive an inhaled anesthetic that can further depress myocardial contractility.

Antiplatelet agents

o A recent open-label clinical trial assigned a group of women with PPCM to pentoxifylline 400 mg
tid. All patients were treated with diuretics, digoxin, enalapril, and carvedilol.

o A combined end-point of poor outcome, defined as death, failure to improve the left ventricular
ejection fraction more than 10 absolute points or functional class III or IV at latest follow-up,
occurred in 27% of patients treated with pentoxifylline and in 52% of those on usual therapy (P = .
03)

o A small randomized trial (n=39) of pentoxifylline has shown that it may improve symptoms, left
ventricular function (by 5%), and lower levels of inflammatory cytokines such as TNF-alpha.
However, not all studies found a beneficial effect.

o Given the poor prognosis of persistent cardiac dysfunction, and assuming that the patients do not
experience side effects from the medication, it seems reasonable to consider adding this
medication to the standard regimen, as long as the clinician and the patient understand that the
data is based on underpowered studies.

Other agents: Based in inferences from an animal model of PPCM 25 , a pilot study reported randomizing
women to bromocriptine therapy after the diagnosis of PPCM 26 . One should continue to monitor the
literature for new developments regarding this medication, but until the results of an appropriately
powered study are published, bromocriptine should be used with caution. 27

Pain control

o Maternal pain control is paramount. The uterus can expel the fetus without maternal pushing.
 o Ideally, the laboring patient will receive early epidural anesthesia, and labor will be augmented
with oxytocin, when necessary.

o The patient should not be allowed to push, and the obstetrician may apply a low-forceps or a
vacuum device to assist with the final stage of the delivery.

Route of delivery

o Unless the mother is decompensating, managing her medically and waiting for a spontaneous
vaginal delivery is reasonable.

o If she is not responding to medical therapy or if the fetus must be delivered for obstetric reasons,
the best plan is to induce labor with the goal of a vaginal delivery.

o Vaginal deliveries are associated with much lower rates of complications, such as endometritis
and pulmonary embolism, 75% of which occur in association with cesarean delivery.

o Vaginal deliveries are not associated with the postoperative third-spacing of fluid that occurs
after cesarean deliveries. This third-spaced fluid reverses after approximately 48 hours, leading to
intravascular volume overload and possible maternal decompensation.

o Delivering the fetus decreases the metabolic demands on the mother, but afterload increases due
to the loss of the low-resistance placental bed.

Immunosuppression should not be used empirically, and current evidence does not support the routine
use of immunosuppressive agents for myocarditis.

Surgical Care

 Use intra-aortic balloon pumps when indicated.

 Cardiac transplantation and left ventricular assist devices have been used to treat PPCM. These should be
considered for women with progressive left ventricular dysfunction or deterioration despite medical
therapy. Most centers will need to consider transfer of such patients to a heart-transplant center for such
therapy. However, left ventricular function in most of these patients improves over time, and surgical
therapy should be delayed if possible.

Consultations

Consultations depend on which specialties are available in your area.

 Internist with expertise in medical disorders in pregnancy (obstetric internist, pulmonary/critical care
specialist, cardiologist)
 High-risk obstetrician (maternal fetal medicine/perinatologist)

 Anesthesiologist: Neuraxial anesthesia is preferred to avoid myocardial depression from inhaled

anesthetics. For this reason, as the mother nears delivery, LMWH should be used with caution.

Diet

Low sodium (2 g/d sodium chloride)

Activity
  Strict bedrest may increase the risk of venous thromboembolism and no longer is recommended as a
mainstay of therapy.
 Activity should be limited only by the patient's symptoms. In severe cases of true PPCM, bedrest may
promote better uteroplacental perfusion.

Medication

When pulmonary edema is diagnosed, loop diuretics should be the first-line treatment. Start with 10 mg of
furosemide, as pregnant women have an increased GFR that facilitates secretion of the drug into the loop of Henle.

Other first-line drugs include morphine sulphate (decrease preload and dyspnea) and nitrates (sublingual, IV,
transcutaneous).

Remembering that a healthy fetus depends on a healthy mother is crucial; therefore, medications should be used
when the benefit to the mother is clear. Organogenesis is completed by 13 weeks' gestation. Although some
medications may have direct effects on the fetus, no risk of teratogenesis is present after the first trimester. The US
Food and Drug Administration (FDA) categorization for drug use during pregnancy is overly simplistic and should
not be the only source relied upon to decide if the medication should be used during pregnancy. To quote the FDA
descriptions, any medication in class A through D may be used when the potential benefit justifies the potential
risk. Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) are
contraindicated in pregnancy because of fetal renal dysgenesis and death. ARBs are contraindicated in pregnancy
because of their similarity to ACEIs.

In the treatment of systolic dysfunction, data prove the benefits of many medications such as vasodilators in
combination with nitrates, beta-adrenergic blocking agents (metoprolol succinate and carvedilol—metoprolol
tartrate is reasonable if the succinate form is not available), calcium blockers (amlodipine), and potassium-sparing
diuretics (spironolactone). Just as in patients who are not pregnant, medication administration to the pregnant
patient must be based on the clinical picture. If the patient has the chance to benefit from one or more of those
medications, then its use should be considered. Historically, hydralazine and nitrates are effective agents for
reducing preload and afterload and have been the medications of choice during pregnancy, but the critical role of
beta-adrenergic blockers in improving survival in patients with systolic heart failure has now been well established.

Loop diuretics

More experience has been gathered on the use of loop diuretics during pregnancy than with potassium-sparing
diuretics. Diuretics should be used very cautiously in women with preeclampsia because intravascular volume
depletion is a hallmark of that syndrome.

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium
and chloride reabsorption in ascending loop of Henle and distal renal tubule. Diuretic of choice during pregnancy.
Used to effect diuresis and correct intravascular volume overload. Furosemide has been around longer and
therefore is preferred. Can cross the placenta and may affect fetal electrolytes; therefore, the lowest effective dose
should be used.

Adult

10 mg PO/IV initially; dose range is 10-240 mg PO/IV once or more daily; titrate to desired response
Pediatric

Not established

Nitrates

In combination with vasodilators such as hydralazine, nitrates are the drug of choice for cardiomyopathy in
pregnant women. Refer to Hydralazine.

Isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate)

Has been used safely in pregnancy to treat coronary disease and decrease preload. Relaxes vascular smooth muscle
by stimulating intracellular cyclic GMP. Decreases left ventricular pressure (preload) and arterial resistance
(afterload). By decreasing left ventricular pressure and dilating arteries, reduces cardiac oxygen demand.
Compatible with breastfeeding.

Adult

5-40 mg PO tid with meals

Pediatric

Not established

Coadministration with alcohol may cause severe hypotension and cardiovascular collapse; aspirin may increase
serum concentrations of isosorbide and actions; coadministration with channel blockers may increase symptomatic
orthostatic hypotension (adjust dose of either agent); may decrease effects of heparin

Documented hypersensitivity; severe anemia, closed-angle glaucoma, postural hypotension, head trauma, and
cerebral hemorrhage

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions

Avoid maternal hypotension; tolerance to vascular and antianginal effects of nitrates may develop; minimize
tolerance by using smallest effective dose, pulse therapy (intermittent dosing), or by alternating with other
coronary vasodilators

Nitroglycerin IV (Nitrol)

Avoid maternal hypotension. Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic
guanosine monophosphate production. The result is a decrease in blood pressure.

Adult

5 mcg/min IV infusion, titrate to desired response

Mix 50 mg in 250 mL D5W (200 mcg/mL)

Pediatric

Not established

Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with
coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)

Documented hypersensitivity, severe anemia, shock, postural hypotension, head trauma, closed-angle glaucoma, or
cerebral hemorrhage

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Avoid maternal hypotension; caution in coronary artery disease and low systolic blood pressure

Inotropic agents

Provide myocardial support in the peridelivery period for patients with heart failure. Several agents are available in
this category.

Digoxin (Lanoxin)

DOC during pregnancy for inotropic support. Clearance of this drug is markedly increased during pregnancy, and
the maternal dose may need to be as high as 1 mg just to maintain a therapeutic serum level. Dose should be
adjusted to maintain the maternal serum level in the reference range for your lab. A lower, effective, safe
therapeutic range of 0.5-1.0 ng/mL for digoxin is used in patients with HF, lower than the standard therapeutic
range.
This drug crosses the placenta and has been used to treat fetal arrhythmias; therefore, obstetrician should monitor
the fetus; however, fetal heart block is not likely to occur. Crosses into breast milk, but no adverse effects have been
reported.
If used to control ventricular response in patients with atrial fibrillation, adjust dose until desired clinical effect is
realized or patient displays sensitivity.

Adult

Loading dose: 0.25 mg PO/IV q6h for 4 doses

Maintenance dose: 0.125-0.25 mg PO qd and should be dictated by serum level if patient is in sinus rhythm
Due to increased renal and hepatic clearance of medications, some pregnant women require doses as high as 1
mg/d to maintain a maternal serum digoxin level in the therapeutic range

Pediatric

Not established

Medications that may increase digoxin levels include alprazolam, benzodiazepines, cyclosporine, propafenone,
propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate,
erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen,
indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine,
neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic
treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin,
cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine,
barbiturates, kaolin/pectin, and aminosalicylic acid

Documented hypersensitivity; beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive
pericarditis, and carotid sinus syndrome; atrial fibrillation with ventricular rate <60 bpm; WPW syndrome with
unknown or antidromic conduction

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Hypokalemia may reduce positive inotropic effect of digitalis (maintain potassium > 4 mEq/L); IV calcium may
produce arrhythmias in digitalized patients; hypercalcemia predisposes patients to digitalis toxicity, hypocalcemia
can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be
instituted in patients with hypomagnesemia to prevent digitalis toxicity and/or blunting of the effect on the
magnesium-dependent NaK ATPase; patients diagnosed with incomplete AV block may progress to complete block
when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis; levels should be
followed closely when used with warfarin
Hydralazine (Apresoline)

Vasodilator of choice for PPCM. Decreases systemic resistance through direct vasodilation of arterioles. Has been
used extensively for hypertension in pregnancy. Despite the FDA classification, benefits outweigh risks. Reports
exist of fetal thrombocytopenia and a lupuslike syndrome. Compatible with breastfeeding.

Adult

10 mg PO tid-qid; not to exceed 100 mg qid; risk of lupus increases at higher doses

Pediatric

Not established

MAOIs and beta-blockers may increase hydralazine toxicity; indomethacin may decrease pharmacologic effects of
hydralazine

Documented hypersensitivity, mitral valve rheumatic heart disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If used too aggressively, maternal hypotension can result in uterine hypoperfusion and fetal distress
Implicated in myocardial infarction; caution in suspected coronary artery disease

Beta-adrenergic blocking agents

In studies of patients who are not pregnant and had congestive heart failure, metoprolol succinate, in addition to
conventional therapies, effected a 34% reduction in the need for heart transplant or the incidence of death. A
similar study of carvedilol showed a 65% reduction in mortality.

Labetalol (Normodyne, Trandate)

Used in trials to treat hypertension in pregnancy. Cardioselective beta-blockers also may be used to treat
hypertension or arrhythmias. They may blunt fetal heart rate response to stress and decrease reliability of fetal
heart rate monitoring, but a healthy fetus depends on a healthy mother. Other beta-blockers used are metoprolol
and carvedilol. While an effective antihypertensive agent, a survival benefit for labetalol in patients with HF has not
been demonstrated in large randomized clinical trials, unlike carvedilol and metoprolol succinate.
Adult

100-800 mg PO bid

Pediatric

Not established

Decreases effect of diuretics and increases toxicity of methotrexate, lithium, and salicylates; may diminish reflex
tachycardia resulting from nitroglycerin use without interfering with hypotensive effects; cimetidine may increase
blood levels; glutethimide may decrease effects by inducing microsomal enzymes

Documented hypersensitivity, cardiogenic shock, pulmonary edema, bradycardia, atrioventricular block,

uncompensated congestive heart failure, reactive airway disease, and severe bradycardia

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Avoid maternal hypotension or bradycardia, watch for worsening of congestive heart failure; use caution in the
presence of other medications that can depress myocardial function or decrease conduction through AV node; use
caution in impaired hepatic function; discontinue therapy if signs of liver dysfunction occur
Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt
withdrawal may exacerbate symptoms of hyperthyroidism; monitor patients closely and withdraw drug slowly;
during an IV, carefully monitor BP, heart rate, and ECG

Metoprolol (Lopressor)

Selective beta1 adrenergic receptor blocker that decreases automaticity of contractions. The Toprol XL dosage form
has been shown to improve survival.

Adult

25-200 mg PO bid; start at low dose and titrate to desired response

Pediatric

Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease
bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects; toxicity may
increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine,
flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine,
prazosin, verapamil, and lidocaine

Documented hypersensitivity, uncompensated congestive heart failure, bradycardia, asthma, cardiogenic shock,
and AV conduction abnormalities

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs
of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm;
monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart
rate, and ECG

Carvedilol (Coreg)

Nonselective beta- and alpha-adrenergic blocker. Also has antioxidant properties. Does not appear to have intrinsic
sympathomimetic activity. May reduce cardiac output and decrease peripheral vascular resistance.
Cardioselective beta-blockers also may be used to treat hypertension or arrhythmias. They may blunt fetal heart
rate response to stress and decrease reliability of fetal heart rate monitoring, but a healthy fetus depends on a
healthy mother.

Adult

3.125-25 mg PO bid; start at low dose and titrate slowly (2-4 weekly intervals) to desired response

Pediatric

Not established

Rifampin, barbiturates, cholestyramine, colestipol, NSAIDs, salicylates, and penicillins may decrease effects;
carvedilol may increase effects of antidiabetic agents, digoxin, and calcium channel blockers; concurrent
administration with clonidine may increase blood pressure and decrease heart rate; carvedilol may decrease effect
of sulfonylureas; cimetidine, fluoxetine, paroxetine, and propafenone may increase carvedilol levels

Documented hypersensitivity, cardiogenic shock, pulmonary edema, bradycardia, atrioventricular block,

uncompensated congestive heart failure, reactive airway disease, and severe bradycardia; symptomatic hepatic
disease
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Avoid maternal hypotension or bradycardia, watch for worsening of congestive heart failure; use caution in
presence of medications that can depress myocardial function or decrease conduction through AV node; caution in
impaired hepatic function; discontinue therapy if signs of liver dysfunction occur
Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt
withdrawal may exacerbate symptoms of hyperthyroidism; monitor patients closely and withdraw drug slowly;
during an IV, carefully monitor BP, heart rate, and ECG

Antiarrhythmics

These agents alter the electrophysiologic mechanisms responsible for arrhythmia.

Amiodarone (Cordarone, Pacerone)

Use as indicated for life-threatening maternal arrhythmias. May have effects on maternal thyroid and the newborn
thyroid status should be evaluated by the pediatric team. Class III antiarrhythmic. Has antiarrhythmic effects that
overlap all 4 Vaughn-Williams antiarrhythmic classes. May inhibit A-V conduction and sinus node function. Prolongs
action potential and refractory period in myocardium and inhibits adrenergic stimulation. Only agent proven to
reduce incidence and risk of cardiac sudden death, with or without obstruction to LV outflow. It is not a very
effective cardioverter of atrial fibrillation and flutter to sinus rhythm, but it is effective in suppressing recurrence of
these arrhythmias.

Has low risk of proarrhythmia effects, and any proarrhythmic reactions are generally delayed. Used in patients with
structural heart disease. Most clinicians are comfortable with inpatient or outpatient loading with 400 mg PO tid
for 1 wk because of low proarrhythmic effect, followed by weekly reductions with goal of lowest dose with desired
therapeutic benefit (usual maintenance dose for AF 200 mg/d). During loading, patients must be monitored for
bradyarrhythmias.
Oral efficacy may take weeks. With exception of disorders of prolonged repolarization (eg, LQTS), may be drug of
choice for life-threatening ventricular arrhythmias refractory to beta-blockade and initial therapy with other agents.

Adult

Loading dose: 800-1600 mg/d PO in 1-2 doses for 1-3 wk, and decrease to 600-800 mg/d in 1-2 doses for 1 mo
Maintenance dose: 200-400 mg/d PO
Alternatively, 150 mg (10 mL) IV over first 10 min, followed by 360 mg (200 mL) over next 6 h and then, 540 mg
over next 18 h
Pediatric

Not established