Peripartum Cardiomyopathy

Contributor Information and Disclosures

Author
Michael P Carson, MD Clinical Associate Professor, Department of Medicine, Clinical
Associate Professor, Department of Obstetrics/Gynecology and Reproductive Sciences,
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School;
Director of Research/Outcomes, Department of Medicine, Jersey Shore University Medical
Center

Michael P Carson, MD is a member of the following medical societies: American College of
Physicians, Society of General Internal Medicine, and Society of Obstetric Medicine

Disclosure: Nothing to disclose.
Coauthor(s)
David Evan Jacob, MD, FACC Acting Chief, Section of Cardiology, St Peter's University
Hospital

David Evan Jacob, MD, FACC is a member of the following medical societies: American
College of Cardiology and American Medical Association

Disclosure: Nothing to disclose.
Specialty Editor Board
Gary Edward Sander, MD, PhD, FACC, FAHA, FACP, FASH Professor of Medicine,
Director of CME Programs, Team Leader, Root Cause Analysis, Tulane University Heart and
Vascular Institute; Director of In-Patient Cardiology, Tulane Service, University Hospital;
Visiting Physician, Medical Center of Louisiana at New Orleans; Faculty, Pennington
Biomedical Research Institute, Louisiana State University; Professor, Tulane University
School of Medicine

Gary Edward Sander, MD, PhD, FACC, FAHA, FACP, FASH is a member of the following
medical societies: Alpha Omega Alpha, American Chemical Society, American College of
Cardiology, American College of Chest Physicians, American College of Physicians,
American Federation for Clinical Research, American Federation for Medical Research,
American Heart Association, American Society for Pharmacology and Experimental
Therapeutics, American Society of Hypertension, American Thoracic Society, Heart Failure
Society of America, Louisiana State Medical Society, National Lipid Association, and
Southern Society for Clinical Investigation

Disclosure: Forest Labs Honoraria Speaking and teaching
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska
Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment
Chief Editor
Henry H Ooi, MB, MRCPI Director, Advanced Heart Failure and Cardiac Transplant
Program, Nashville Veterans Affairs Medical Center; Assistant Professor of Medicine,
Vanderbilt University School of Medicine

Disclosure: Nothing to disclose.
Overview
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.
[1]

By this definition, PPCM is an idiopathic cardiomyopathy that presents with heart failure
secondary to left ventricular systolic dysfunction toward the end of pregnancy or in the
months after delivery, in the absence of any other cause of heart failure. PPCM is a diagnosis
of exclusion. Although the left ventricle may not be dilated, the ejection fraction is nearly
always reduced below 45%.
[1]

In contrast to other definitions, the Heart Failure Associations definition specifically
excludes women who develop PPCM early in their pregnancy and explicitly notes that not all
cases of PPCM present with left ventricular dilation.
[2]
Thus, it helps avoid misdiagnosis of
other conditions that present with pulmonary edema in pregnancy, such as diastolic
dysfunction from preeclampsia and other disorders (see Diagnosis).
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.
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
Pathophysiology and Etiology
The exact cause of peripartum cardiomyopathy (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
epidemiologic 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, 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.
Lower levels of selenium have been found in patients with PPCM. Autoantibodies against
myocardial proteins have been identified in patients with PPCM but not in those with
idiopathic cardiomyopathy.
[3]

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.
[4]

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.
[5]

Other findings that are associated with PPCM but are not clearly causal include increased
levels of inflammation and oxidative stress markers, increased levels of cathepsin D, and
oxidized low-density lipoprotein.
Two studies have suggested that a subset of cases of PPCM result from a genetic cause.
[6, 7]
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 physiologic changes of pregnancy.
[6]

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.
Epidemiology
United States statistics
Reports estimating the incidence of peripartum cardiomyopathy (PPCM) in the United States
vary widely, ranging from 1 case per 15,000 live births to 1 case per 4000 live births to 1 case
per 1300 live births. Approximately 75% of cases are diagnosed within the first month post
partum, and 45% present in the first week. When PPCM is suspected, one must establish the
diagnosis rapidly.
[8]

International statistics
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 post partum. The high salt intake leads to volume overload.
Age-, sex-, and race-related demographics
PPCM is unique to pregnant women of all reproductive ages. Initially thought to be more
common in women older than 30 years, PPCM has since 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.
PPCM has been reported in white, Chinese, Korean, and Japanese women. Case series
indicate that 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 PPCM.
[9]

Clinical Presentation
Patient history
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. Mild dyspnea upon exertion is particularly common in a
normal pregnancy. 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.
Early, rapid diagnosis of peripartum cardiomyopathy (PPCM) 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.
[10]
Often, patients do not show any indication of the
syndrome until after delivery. If a patient makes it through laboressentially natures stress
testwithout symptoms, the onsite clinician might not consider PPCM as the first cause
when a woman decompensates.
Many PPCM patients present with heart failure or a major adverse event (eg, 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.
[8]
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
Abdominal pain
Physical examination
In a normal pregnancy, as a result of the increase in 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.
[11]
This pulmonic arterial flow murmur tends to
become quieter during inspiration. Diastolic murmurs warrant further evaluation.
The first heart sound (S
1
) may be exaggerated, and the second heart sound (S
2
) split may be
more prominent due to increased right-sided flow. Whereas a third heart sound (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 womens 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.
In a patient with PPCM, signs of heart failure are the same as in patients with systolic
dysfunction who are not pregnant. Tachycardia and decreased pulse oximetry (should be
97% at sea level) are present. Blood pressure may be normal. Elevated blood pressures
(systolic >140 mm Hg and/or diastolic >90 mm Hg) and hyperreflexia with clonus suggest
preeclampsia.
Physical findings of PPCM include elevated jugular venous pressure, cardiomegaly, third
heart sound, loud pulmonic component of the second heart sound, mitral or tricuspid
regurgitation, pulmonary rales, worsening of peripheral edema, ascites, arrhythmias, embolic
phenomenon, and hepatomegaly.
Maternal and fetal complications
Maternal complications may include the following:
Hypoxia
Thromboembolism - Small series have reported the incidence to be as high as 50%, but
these results have obvious selection bias
Progressive cardiac failure
Arrhythmias
Misinterpretation of hemodynamic data obtained from right-heart catheterization as a
result of failure to consider the normal physiologic alterations of pregnancy (see Invasive
Hemodynamic Monitoring)
Inadequate treatment or testing because of exaggerated concern about the effect on the
fetus
Misdiagnosis of preeclampsia - Patients with preeclampsia experience depletion of
intravascular volume and should receive low doses of diuretics only when they have
pulmonary edema
Fetal complications may include the following:
Distress due to maternal hypoxia
Distress due to placental hypoperfusion as a result of poor cardiac output, maternal
hypovolemia due to excessive diuresis, or hypotension from aggressive afterload reduction
Diagnosis
The differential diagnosis includes the following:
Aortic Stenosis
Cardiomyopathy, Alcoholic
Cardiomyopathy, Cocaine
Cardiomyopathy, Dilated
Cardiomyopathy, Hypertrophic
Cardiomyopathy, Restrictive
Cardiovascular Disease and Pregnancy
Coronary Artery Atherosclerosis
Hypertension
Hypertension and Pregnancy
Hypertension, Malignant
Mitral Stenosis
Noncardiogenic pulmonary edema during pregnancy: Pregnancy is a state of low oncotic
pressure reflected in decreased serum albumin (expected values, ~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
Preeclampsia (toxemia of pregnancy)
Pulmonary Disease and Pregnancy
Pulmonary Edema, Cardiogenic
Pulmonary Edema, Neurogenic
Other problems to be considered include the following:
Arrhythmogenic right ventricular dysplasia
Cardiomyopathy, diabetic heart disease
Infectious, toxic, or metabolic disorders
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. An elevated CPK level is not diagnostic of peripartum
cardiomyopathy (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.
[12]
Therefore,
without an obvious clinical presentation and electrocardiographic (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 is
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; these women should be placed on maximal medical
therapy and undergo serial echocardiographic assessments regardless of the troponin
result.
[13]

Preeclampsia should be excluded on the basis of the history, the physical examination, and
blood work. New headaches, visual disturbances, right-side abdominal pain, and new
swelling of the hands or face may be present. Retinal vasospasm, a fourth heart sound (S
4
)
heard on cardiac auscultation, hyperreflexia/clonus, right upper quadrant tenderness, and face
or hand edema may be present. Abnormalities found with preeclampsia include the
following:
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)
More than 300 mg of proteinuria evident on a 24-hour collection
On urinalysis, trace or 1+ proteinuria can be normal. Proteinuria 2+ or higher suggests
preeclampsia. Exclude infection; urine culture is helpful in this regard.
Measure pulse oximetry. Determine thyroid-stimulating hormone levels. Keep the potassium
level above 4 mEq/L and the magnesium level above 2 mEq/L.
Serologic 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.
Electrocardiography
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
Consider calling a cardiologist for an immediate echocardiogram. Echocardiography should
be performed in all women in whom the diagnosis of PPCM is considered in order to assess
ventricular function, valve structure, chamber size, and wall motion. 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
Rapid diagnosis must be established. When evaluating new onset dyspnea, tachycardia, or
hypoxia, immediately obtain a chest radiograph to detect pulmonary edema. This should be
performed with abdominal shielding to evaluate the etiology of hypoxia and exclude
pneumonia.
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.
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.
Bilateral lower lobe infiltrates without vascular redistribution suggest either an atypical
pneumonia or noncardiogenic pulmonary edema (see the image below) resulting from the low
oncotic state of pregnancy combined with various stressors.
Noncardiogenic pulmonary edema in patient with preeclampsia,
due to capillary leak that can be primary component of preeclampsia. Radiograph reveals diffuse
increase in lung markings without cephalization or vascular redistribution seen in patients with
pulmonary edema from systolic dysfunction. Patient had rapid clinical improvement after only 10 mg
of intravenous furosemide.
Stress Testing
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.
Stress echocardiography is the test of choice to look for coronary artery disease during
pregnancy. 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.
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 5 rads. Thus, a single stress test
represents only 1/50th of the safe dose, or 1 out of the 50 stress tests that can theoretically be
performed safely during pregnancy. Organogenesis is complete after the first trimester (13th
week of gestation); therefore, testing in the second or third trimester will not cause any gross
physical deformities.
Invasive Hemodynamic Monitoring
Right-side 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 medical therapy (see General Treatment Approach).
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/sec/cm
-5
, and heart rate increases by approximately 10-20% above the prepregnant
value in a singleton gestation.
Preeclampsia is associated with diastolic left ventricular dysfunction, increased systemic
vascular resistance, and intravascular volume depletion despite total-body volume overload.
Empiric use of pulmonary artery catheters in critically ill patients has come under question;
this particularly is true for pregnant women. Use of a pulmonary artery catheter 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
Overview).
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 patients unique physiology rather than a standard response to a
single number.
Other Studies
Magnetic resonance imaging
A report of 2 cases found no magnetic resonance imaging (MRI) abnormalities in one of the
patients and areas of delayed myocardial enhancement in the other.
[14]
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.
Another series of 8 patients with PPCM did not detect any abnormalities on cardiac MRI.
[15]

A single 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.
Tissue Analysis and Histologic Findings
Endomyocardial biopsy is controversial, in that it has not yet been demonstrated to offer
information that can significantly alter the plan of care.
A series of 18 American women
[16]
and 11 African women
[17]
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.
Whereas some small cohort studies suggest that the finding of myocarditis on biopsy could
provide prognostic information, others have not found it to provide any such information.
Accordingly, the use of this invasive procedure in this population is not clear.
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 with endomyocardial biopsy, there is no convincing evidence to support
immunosuppressive therapy if this result is obtained.
[16]

General Treatment Approach
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 US Food and Drug Administration (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.
Medications should be used when the benefit to the mother is clear. To quote the FDA
descriptions, any medication in class A through D may be used when the potential benefit
justifies the potential risk. 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. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-
receptor blockers (ARBs) are contraindicated in pregnancy because of fetal renal dysgenesis
and death.
Patients with systolic dysfunction during pregnancy are treated the same as patients who are
not pregnant. The mainstays of medical therapy are digoxin, loop diuretics, afterload
reduction with hydralazine and nitrates, and beta-adrenergic blockad with carvedilol or
metoprolol succinate as they have been shown to decrease all-cause mortality and
hospitalization in those with systolic dysnfuction. Because there is a high risk of venous and
arterial thrombosis, anticoagulation with heparin should be instituted when the ejection
fraction is less than 30%.
Consider rapid transfer to an intensive care unit (ICU) for monitoring of maternal status.
Consider transfer to a center that offers tertiary care services for both the mother and the
fetus. If the mother is less than 37 weeks gestation, transfer her to a center with a neonatal
ICU.
Route of delivery
Delivering the fetus decreases the metabolic demands on the mother, but afterload increases
due to the loss of the low-resistance placental bed.
Vaginal deliveries are preferred because they are associated with much lower rates of
complications, such as endometritis and pulmonary embolism, 75% of which occur in
association with cesarean delivery. 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.
Unless the mother is decompensating, managing her medically and waiting for a spontaneous
vaginal delivery is reasonable. 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.
Pain control
Early and effective control of maternal pain during delivery is paramount. Regional
anesthesia, such as epidural or spinal, is not associated with the myocardial depression
observed with inhaled anesthetics. Ideally, the laboring patient will receive early epidural
anesthesia, and labor will be augmented with oxytocin, when necessary.
The patient should not be allowed to push; the uterus can expel the fetus without maternal
pushing. The obstetrician may apply a low-forceps or a vacuum device to assist with the final
stage of the delivery.
Analgesics reduce pain, which decreases sympathetic stress, in addition to providing some
preload reduction.
Surgical therapy
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.
Diet and activity
The patient should follow a low-sodium (2 g/day sodium chloride) diet. 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 patients symptoms. In severe cases of true
PPCM, bedrest may promote better uteroplacental perfusion.
Consultations
Many internists do not have extensive exposure to diagnosing and treating medical disorders
during pregnancy and therefore feel uncomfortable doing so. The best way to address this is
consultation with an obstetric internist, a perinatologist, or a medical subspecialist. Their
experience allows them to quickly help assess which treatments offer the best risk-to-benefit
ratio. In most situations, the benefit of maximizing maternal well-being with the usual
therapies outweighs the potential effects on the fetus, which make some feel uneasy.
Consultations depend on which specialties are available locally and may include the
following:
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, low-molecular-weight
heparin should be used with caution.
Pharmacologic Therapy
In the treatment of systolic dysfunction in peripartum cardiomyopathy (PPCM), data prove
the benefits of many medications, such as digoxin, vasodilators in combination with nitrates,
beta-adrenergic blocking agents (metoprolol succinate and carvedilolmetoprolol tartrate is
reasonable if the succinate form is not available), calcium channel blockers (amlodipine),
loop diuretics (furosemide), and potassium-sparing diuretics (spironolactone).
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.
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.
Digoxin and inotropes
Initiate therapy with digoxin in women with an abnormal ejection fraction. Digoxin is the
drug of choice during pregnancy. Intravenous (IV) dobutamine should be used when
indicated. Improving cardiac output ensures adequate uteroplacental perfusion. Consider
invasive hemodynamic monitoring to gauge the response to therapy. These agents are
compatible with breastfeeding.
Diuretics
Diuretics should be used very cautiously in women with preeclampsia because intravascular
volume depletion is a hallmark of that syndrome.
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 glomerular filtration rate
(GFR) that facilitates secretion of the drug into the loop of Henle.
Spironolactone has been shown to decrease morbidity and improve survival when
administered to nonpregnant outpatients with systolic dysfunction. However, clinical
experience with potassium-sparing diuretics such as spironolactone in pregnancy is limited in
comparison to that accumulated with furosemide. Bumetanide may be used when clinically
indicated, and a thiazide may be added cautiously to a loop diuretic for a synergistic effect in
diuretic-resistant patients.
Hydralazine and nitrates
Nitrates may be used to decrease maternal preload when indicated; they are safe for the
mother and fetus and are compatible with breastfeeding. As with any medication that alters
maternal hemodynamics, a drop in blood pressure can result in fetal hypoperfusion and
distress. IV drips should be titrated very slowly, and maternal intravascular euvolemia should
be maintained.
Hydralazine, in combination with nitrates, is the first choice for afterload reduction and
vasodilatation during pregnancy. A Veterans Affairs study of nonpregnant patients with
congestive heart failure showed a 36% mortality risk reduction in the group treated with
preload and afterload reducers such as hydralazine and oral nitrates.
Although hydralazine in combination with nitrates is the preferred regimen during pregnancy,
women should be switched to an angiotensin-converting enzyme inhibitor (ACEI) after
delivery.
Beta-blockers
Carvedilol and amlodipine have been shown to benefit patients with systolic function who are
not pregnant. These drugs may be used safely as second-line agents during pregnancy when
clinically indicated. Vasodilators should be started at a low initial dose, but recognize that
hepatic and renal clearance of medications is accelerated during pregnancy. All are
compatible with breastfeeding. More data are available on the use of metoprolol during
pregnancy, but carvedilol is a reasonable option.
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.
Calcium channel blockers
In specialized conducting and automatic cells in the heart, calcium is involved in the
generation of the action potential. The calcium channel blockers inhibit movement of calcium
ions across the cell membrane, depressing both impulse formation (automaticity) and
conduction velocity.
Anticoagulants
PPCM is associated with a high rate of thromboembolic complications. Cases of arterial or
venous thrombosis have been reported in as many as 50% of women with PPCM; 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, prophylactic anticoagulation should be considered during pregnancy.
Full-dose/therapeutic anticoagulation should be initiated ante partum for women with deep
venous thrombosis, atrial fibrillation, ventricular thrombi, or embolic events, and possibly for
those with an ejection fraction of less than 30%. Treatment should be continued until at least
6 weeks post partum.
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 subcutaneously 2 or 3 times daily in the first trimester, 7,500 units in the second
trimester, and 10,000 units twice daily in the third trimester. Enoxaparin 40 mg daily or twice
daily is also reasonable.
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 on the basis of obstetric issues and the severity
of the disease (see above).
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. The LMWH is not predictably reversed with protamine. Fresh
frozen plasma should be used to definitively neutralize it. If cesarean delivery is required,
these patients may receive an inhaled anesthetic that can further depress myocardial
contractility.
Warfarin is the drug of choice post partum. Consider it for use in pregnant women with
mechanical heart valves. Warfarin crosses into breast milk, but studies show that it does not
affect the newborn coagulation system; therefore, it is compatible with breastfeeding. It does
carry a risk of spontaneous fetal cerebral hemorrhage in the second and third trimesters.
Women may prefer oral warfarin to 1-2 heparin injections a day.
Antiplatelet agents
In an open-label clinical trial assessing pentoxifylline 400 mg 3 times daily in a group of
women with PPCM who were treated with diuretics, digoxin, enalapril, and carvedilol, a
combined end-point of poor outcomedefined as death, failure to improve the left
ventricular ejection fraction more than 10 absolute points, or functional class III or IV at
latest follow-upoccurred in 27% of patients treated with pentoxifylline and in 52% of those
on usual therapy.
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 tumor
necrosis factor alpha. However, not all studies found a beneficial effect.
Given the poor prognosis of persistent cardiac dysfunction, and on the assumption 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 both the clinician and the patient
understand that the available data were obtained from underpowered studies.
Other agents
Oxytocin is used to augment labor and may increase pulmonary arterial pressures. It also can
control postpartum bleeding or hemorrhage. The pressor effect of sympathomimetics may
increase when used concomitantly with oxytocic drugs, causing postpartum hypertension.
Oxytocin has an intrinsic antidiuretic effect that, when administered by continuous infusion
to a patient receiving fluids by mouth, can cause water intoxication.
Morphine sulfate can be used to decrease preload and decrease dyspnea.
Immunosuppression should not be used empirically, and current evidence does not support
the routine use of immunosuppressive agents for myocarditis.
On the basis of inferences from an animal model of PPCM,
[18]
a pilot study reported
randomizing women to bromocriptine therapy after the diagnosis of PPCM
[19]
. 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.
[20]

Further Inpatient/Outpatient Care
Consider the following for hemodynamic changes during labor and delivery.
During the second stage of labor, cardiac output can increase by 15-20% with each
contraction and as high as 45% from baseline. Immediately after delivery, the contracted
uterus squeezes 300-500 mL of blood into the systemic circulation. This autotransfusion,
along with the release of inferior vena cava compression by the gravid uterus, leads to an
increase in cardiac output as high as 10-20% over predelivery levels. Most of the stress
related to the autotransfused blood may be offset by typical blood loss of 300-500 mL during
delivery.
Additionally, cardiac output may increase by as much as 65% in the subsequent postpartum
period due to the loss of the low-resistance placental bed and a decrease in the vascular
compliance that was maintained by the hormonal changes of pregnancy. Most of the
subsequent return of blood volume and cardiac output to normal prepregnancy levels occurs
by approximately 2 weeks post partum.
Importantly, when pulmonary edema resolves within 1-2 days, a noncardiogenic etiology
should be considered.
An echocardiogram should be ordered as indicated by new clinical findings or by a decline in
function. If an echocardiogram reveals abnormal systolic function during pregnancy, a repeat
study should be obtained approximately 2 months after delivery. If the results of that study
show that systolic function has improved but has not returned to normal levels, another study
should be obtained within the year to determine the patients new baseline.
After delivery, patients on hydralazine/nitrates should be placed on an angiotensin-converting
enzyme inhibitor (ACEI), and the dose should be maximized. These medications are felt to be
compatible with breastfeeding.
For women considering pregnancy or those who desire an evaluation to estimate the risk of a
future pregnancy, recovery of systolic function is a prime concern (see Prognosis). If
recovery of systolic function is complete, the prognosis is excellent. Those women with
persistent systolic dysfunction should be maintained on vasodilators, nitrates, and diuretics as
tolerated and indicated.
Prognosis
Prognosis seems dependent on recovery of left ventricular function. Thirty percent of patients
return to baseline ventricular function within 6 months, and 50% of patients have significant
improvement in symptoms and ventricular function.
The usual causes of death in patients with peripartum cardiomyopathy (PPCM) are
progressive heart failure, arrhythmia, or thromboembolism. The mortality rate related to
embolic events has been reported to be as much as 30%.
Historically, mortality figures from multiple small series have ranged from 7-50%, with half
of the deaths occurring within 3 months of delivery. Subsequent case series have found the
following mortalities
[21, 22, 23, 24, 25, 26]
:
In the United States, a 15.9% 2-year mortality rate among African American women
In other US series, a mortality of 3.3-9.6%
In South Africa, a mortality of 10-27% at 6 months and 28% at 2 years
In Haiti, a mortality of 15% at 2 years
As with any cardiomyopathy, mortality is directly related to recovery of ejection fraction.
Patients may not understand this. Women with persistently abnormal ejection fractions are at
high risk of developing heart failure and worsening cardiac function if they become pregnant
again. If an abnormal ejection fraction declines further, it will predict a shorter lifespan to
spend with any children already born, as well as with family members.
Contractile reserve, as demonstrated on dobutamine stress testing, is correlated with clinical
outcome. However, women who have had PPCM and have recovered ventricular function
according to transthoracic echocardiography may have decreased contractile reserve during
dobutamine stress testing. Women demonstrated to have this abnormality might not tolerate
the increased hemodynamic stress of a subsequent pregnancy. To date, appropriate follow-up
studies have not been performed.
A cohort of 29 cases available for follow-up reported 4 deaths (14%) and 7 complications
(pulmonary embolism, 1 case; hemiplegia, 1 case; subsequent deterioration of heart function,
5 cases).
A 10-year retrospective comparative cohort study included patients if cardiomyopathy was
diagnosed before pregnancy (DCM group, n = 8) or if it developed during pregnancy or
within 5 months post partum (PPCM group, n = 23) and follow-up data was available. In the
PPCM group, there were 3 maternal deaths and 4 heart transplants. In the DCM group, 1
woman with a prepregnancy ejection fraction of 16% underwent transplantation after
termination of pregnancy for genetic indications; none of the others had a significant decline
in cardiac status.
Patient Education
Patients have the expectation that their pregnancy and delivery will involve nothing but
happiness. When severe complications occur, patients feel scared, angry, and helpless. The
best approach is to discuss any and all issues with your patient. Do as much as you can to
help her and her family understand what is happening.
The author begins the discussion by telling them what the diagnosis is and that we do not
know why it happens. Then, he reassures her that this was not due to anything that she did or
did not do. That is followed by the plans for evaluation and treatment, with an opportunity for
her to ask questions. He repeats this pattern each day. This empowers the patient by involving
her in the decision-making process.
Patients today ask very good questions. One should feel comfortable being honest and telling
patients and family when one does not have all of the answers, while letting them know that
the physician will work to find them. This honesty, combined with an effort to obtain the
answer, will solidify your relationship as a caring and competent physician. Consultation with
experienced clinicians will help the physician care for the patient and help the patient be sure
that all avenues of treatment are being explored.
Many reference texts and articles are available on the treatment of this disorder during
pregnancy. Becoming educated about the topic will help one feel more comfortable treating
and counseling patients.
A case series from Haiti involving 16 pregnancies in 15 women who became pregnant after
an index pregnancy during which they were diagnosed with PPCM showed that during the
subsequent pregnancy, 8 women (50%) suffered a worsening of left ventricular function.
[27]
Of those 8, none developed preeclampsia, 1 died 10 months after delivery, and only 1 had a
full recovery of left ventricular function. The authors observed that improvement of left
ventricular function may continue for more than 12 months after the index pregnancy.
A report by the same authors found that relapse in a subsequent pregnancy occurred in 46%
of those with an ejection fraction less than 55%, but only 17% of those with an ejection
fraction greater than 55%.
[28]

Prospects for future pregnancy
In women with persistent ventricular dysfunction, future pregnancy is not recommended,
because of concern about the ability of the dysfunctional heart to handle the increased
cardiovascular workload.
Regarding subsequent pregnancies, a survey found that 78% of women with fully recovered
left ventricular function had a normal outcome, compared to only 37% of those with
persistent ventricular dysfunction. The complications in the normal group and in the group
with residual dysfunction were maternal death (2% and 8%, respectively), live birth (93%
and 83%), elective abortions (5% and 17%), and stillbirth (2% and 0%).
In a study involving 44 women who had had PPCM and a total of 60 subsequent
pregnancies28 with normal left ventricular function (group 1) and 16 with ventricular
dysfunction (group 2)the ejection fraction decreased slightly in group 1, but not
significantly in group 2. Group 2 had the following complications respective to group 1: heart
failure symptoms (44% vs 21%) and mortality (19% vs 0%). Therapeutic abortions were
performed more often in group 2 (25% vs 4%).
From a cohort of 29 cases available for follow-up, 4 of 5 women (80%) who became
pregnant after the index pregnancy developed recurrent congestive heart failure.
Before a subsequent pregnancy, the following recommendations are appropriate:
Women should undergo echocardiography and, if findings are normal, dobutamine stress
echocardiography
Pregnancy should not be recommended to women with persistent left ventricular
dysfunction
Patients with normal findings upon echocardiography but decreased contractile reserve
should be warned that they might not tolerate the increased hemodynamic stresses of
pregnancy
Patients with full recovery should be told that although a chance of recurrence exists, the
mortality is low and the majority of such women have normal pregnancies
Patients often avoid situations because they dread a particular outcome. The drive to become
pregnant and bear children is a strong, and not necessarily rational, one that can often
overshadow a patients sense of dread. The patient may be willing to accept the risk of an
adverse outcome, but the physician should make an objective recommendation, document it,
and not compromise his or her best medical judgment because of a patients emotional
desires.