AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Peripartum cardiomyopathy (PPCM) is a dilated cardiomyopathy of uncertain etiology that is defined as (1) development of cardiac failure in the last month of pregnancy or within 5 months after delivery, (2) absence of a demonstrable cause for the cardiac failure, (3) absence of demonstrable heart disease before the last month of pregnancy, and (4) documented systolic dysfunction. 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.

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.¹

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

Mortality figures from multiple small series have ranged from 7-50%, with half of the deaths occurring within 3 months of delivery. The usual causes 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, most cases occur in African American women from the southern United States.

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

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

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 described as an inability 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.

Peripartum cardiomyopathy

• 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.

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. This pulmonic arterial flow murmur tends to become quieter during inspiration. Diastolic murmurs warrant further evaluation. The S₁ may be exaggerated, and the S₂ split may be more prominent due to increased right-sided flow. While an S₃ 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 ³97% 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.²
• 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.³

DIFFERENTIALS

Section 4 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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

Section 5 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
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Lab Studies

• Preeclampsia should be excluded based on history, physical examination, and blood work.
• • History: New headaches, visual disturbances, right-sided abdominal pain, and new swelling of the hands or face may be present.
  • Examination: Retinal vasospasm, an S₄ heard on cardiac auscultation, hyperreflexia/clonus, right upper quadrant tenderness, and face or hand edema may be present.
  • 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 excludes 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)
• Echocardiography
• • Consider calling a cardiologist for a STAT echocardiogram
• • 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.
  • 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, obtain a STAT 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 is about 0.005 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 1 maternal chest radiograph is only 1/1000th of the safe dose, or 1 of 1000 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 (see Other Problems to be Considered).
  • 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.

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.
• • 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.
  • 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.
• 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 rises 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
• • 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.
  • 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).
  • 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.

Staging

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

Section 6 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

One must remember that a healthy fetus depends on a healthy mother. 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 (EF) is <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
• • Arterial or venous thrombosis has 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. Pregnancy is a hypercoagulable state. Once the diagnosis of PPCM is established, anticoagulation should be considered and continued until at least 6 weeks postpartum.
  • Heparin is the drug of choice. Unfractionated heparin (UFH) has an advantage over low molecular weight heparin (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 severely dilated ventricles should receive full-dose subcutaneous heparin to prevent arterial embolism. Refer to Medications for specific dosing recommendations.
  • 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.
  • 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
  • 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.
  • 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).
• Small, published, randomized trials of pentoxifylline have shown that it may improve symptoms, left ventricular function, and lower levels of inflammatory cytokines such as TNF-alpha. However, not all studies found a beneficial effect.

• Pain control
  • Maternal pain control is paramount. The uterus can expel the fetus without maternal pushing.
  • 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, and the obstetrician may apply a low-forceps or a vacuum device to assist with the final stage of the delivery.
• Route of delivery
  • 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.
  • 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.
  • 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.
  • 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

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

When pulmonary edema is diagnosed, loop diuretics should be the first-line treatment.

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 and carvedilol), calcium blockers (amlodipine), and potassium-sparing diuretics (Aldactone). 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 were the medications of choice during pregnancy, but beta-adrenergic blockers have demonstrated benefits that also make them reasonable choices.

Drug Category: 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.

Drug Name	Bumetanide (Bumex)
Description	Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium, potassium, and chloride reabsorption in ascending loop of Henle. These effects increase urinary excretion of sodium, chloride, and water, resulting in profound diuresis. Renal vasodilation occurs following administration, renal vascular resistance decreases, and renal blood flow is enhanced. Individualize dose to patient. Start at 1-2 mg IV; titrate to as high as 10 mg/d. Rarely, doses as high as 24 mg/d are used for edema but generally are not required for treatment of hyperkalemia. One mg of bumetanide is equivalent to approximately 40 mg of furosemide.
Adult Dose	0.5 mg PO/IV initially; titrate to desired response
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; anuria, increasing azotemia, hepatic coma, anuria, or state of severe electrolyte depletion
Interactions	Decreases effects of indomethacin and probenecid; may increase lithium toxicity
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Profound diuresis, with fluid and electrolyte loss may occur; caution in hepatic failure; follow electrolytes and renal function closely; maintain potassium >4 mEq/L and magnesium >2 mEq/L; perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter; maternal volume depletion could lead to uteroplacental hypoperfusion

Drug Category: Potassium-sparing diuretics

Spironolactone should be mentioned because it has been shown to improve outcome in patients who are not pregnant who have congestive heart failure. However, clinical experience regarding use in pregnancy is limited compared to furosemide. Diuretics should be used very cautiously in women with preeclampsia because intravascular volume depletion is a hallmark of that syndrome.

Drug Category: Nitrates

In combination with vasodilators such as hydralazine, nitrates are DOC for cardiomyopathy in pregnant women. Refer to Hydralazine.

Drug Name	Nitroglycerin IV (Nitrol)
Description	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 Dose	5 mcg/min IV infusion, titrate to desired response Mix 50 mg in 250 mL D5W (200 mcg/mL)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, severe anemia, shock, postural hypotension, head trauma, closed-angle glaucoma, or cerebral hemorrhage
Interactions	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)
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

Drug Category: Inotropic agents

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

Drug Name	Dobutamine (Dobutrex)
Description	DOC when other medical therapy is inadequate. Safe in pregnancy if clinically indicated to improve the mother's condition. When a mother is this severely affected, consider induction of labor as soon as possible. Placental hypoperfusion can lead to fetal distress; therefore, this drug can be beneficial if it improves cardiac output and perfusion of the uterus/placenta.
Adult Dose	2-20 mcg/kg/min IV, titrated to desired response Mix 250 mg in 250 mL D5W (1 mg/mL)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, idiopathic hypertrophic subaortic stenosis, atrial fibrillation or flutter
Interactions	Beta-adrenergic blockers antagonize effects; general anesthetics may increase toxicity
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Consider hemodynamic monitoring to determine response to therapy; monitor the fetus, and avoid maternal hypotension from afterload reduction Following a myocardial infarction, use with extreme caution; hypovolemic state should be corrected before using this drug

Drug Category: Analgesics

These agents reduce pain, which decreases sympathetic stress, in addition to providing some preload reduction.

Drug Category: Vasodilators

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. These medications are the drugs of choice for treatment of cardiomyopathy.

Drug Category: Beta-adrenergic blocking agents

In studies of patients who are not pregnant and had congestive heart failure, metoprolol, 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.

Drug Name	Metoprolol (Lopressor)
Description	Selective beta1 adrenergic receptor blocker that decreases automaticity of contractions.
Adult Dose	25-200 mg PO bid; start at low dose and titrate to desired response
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, uncompensated congestive heart failure, bradycardia, asthma, cardiogenic shock, and AV conduction abnormalities
Interactions	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
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

Drug Name	Carvedilol (Coreg)
Description	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 Dose	3.125-25 mg PO bid; start at low dose and titrate to desired response
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, cardiogenic shock, pulmonary edema, bradycardia, atrioventricular block, uncompensated congestive heart failure, reactive airway disease, and severe bradycardia; symptomatic hepatic disease
Interactions	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
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

Drug Name	Atenolol (Tenormin)
Description	Used to treat hypertension. Selectively blocks beta1-receptors with little or no affect on beta 2 types. Beta-adrenergic blocking agents affect blood pressure via multiple mechanisms. Actions include negative chronotropic effect that decreases heart rate at rest and after exercise, negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. Used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure. Beta-adrenergic blockers reduce inotropic state of left ventricle, decrease diastolic dysfunction, and increase LV compliance, thereby reducing pressure gradient across LV outflow tract. Decreases myocardial oxygen consumption, thereby reducing myocardial ischemia potential. Decreases heart rate, thus reducing myocardial oxygen consumption and reducing myocardial ischemia potential. During IV administration, carefully monitor blood pressure, heart rate, and ECG.
Adult Dose	25-100 mg PO qd (may dose bid in pregnancy due to increased renal/hepatic clearance)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; congestive heart failure, pulmonary edema, cardiogenic shock, A-V conduction abnormalities, and heart block (without a pacemaker)
Interactions	Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity of atenolol
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during an IV, carefully monitor BP, heart rate, and ECG

Drug Category: 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.

Drug Category: Anticoagulants

PPCM is associated with a high rate of thromboembolic complications. Prophylactic doses of heparin should be considered during pregnancy. Therapeutic doses must be given to women with deep venous thrombosis, atrial fibrillation, ventricular thrombi, or embolic events. Treatment should be continued until at least 6 weeks postpartum. Because UFH is easily reversed with protamine and the level of anticoagulation is able to be assessed quickly, UFH is preferred over LMWH for antepartum use, especially near term.

LMWH (enoxaparin, dalteparin): Most anesthesiologists do not give neuraxial anesthesia for 24 hours after an injection of full-dose LMWH. It is not predictably reversed with protamine. Fresh frozen plasma should be used to definitively neutralize the heparin.

Warfarin is the DOC postpartum. Consider for use in pregnant women with mechanical heart valves. Crosses into breast milk, but studies show that it does not affect the newborn coagulation system. Therefore, it is compatible with breastfeeding. Women may prefer this to 1-2 heparin injections a day.

Drug Name	Warfarin (Coumadin)
Description	DOC postpartum. Consider for use in pregnant women with mechanical heart valves. Crosses into breast milk, but studies show that it does not affect the newborn coagulation system. Therefore, it is compatible with breastfeeding. Women may prefer this to 1-2 heparin injections a day.
Adult Dose	5 mg PO qd for 2 d; thereafter, adjust dose based on INR
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, severe liver or kidney disease, open wounds or GI ulcers, active bleeding, coagulopathy
Interactions	Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate Medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis

Drug Name	Dalteparin (Fragmin)
Description	Enhances inhibition of Factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of Factor Xa. Except in overdoses, no utility exists in checking PT or aPTT because aPTT does not correlate with anticoagulant effect of fractionated LMWH.
Adult Dose	Low dose: 2500-5000 U SC qd High dose: 120 U/kg, not to exceed 10,000 U SC bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; thrombocytopenia; regional anesthesia; subacute bacterial endocarditis, active bleeding, history of heparin-induced thrombocytopenia, coagulopathy
Interactions	Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	If thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminases may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated low-molecular-weight heparins; protamine sulfate will reverse effect if significant bleeding complications develop; cases of epidural/spinal hematomas have been reported in adults receiving spinal or epidural anesthesia (holding 2 doses prior to LP or surgery is recommended); when using for extended treatment in patients with cancer, if platelet count decrease <100,000/mm3, reduce dose by 2500 IU until platelet count recovers, and discontinue if platelet count <50,000/mm3 (may resume previous dose when platelets recover); reduce dose with impaired renal function (monitor anti-Xa levels)

Drug Name	Enoxaparin (Lovenox)
Description	Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing. LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared to UFH. Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness. Used to treat DVT or PE in conjunction with warfarin for inpatient treatment of acute DVT with or without PE or for outpatient treatment of acute DVT without PE. No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). Average duration of treatment is 7-14 d.
Adult Dose	Low-dose: 40 mg SC bid High-dose: 1 mg/kg SC bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; thrombocytopenia, subacute bacterial endocarditis, active bleeding, history of heparin-induced thrombocytopenia, coagulopathy
Interactions	Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Decrease dose if CrCl <30 mL/min; if thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminases may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated low-molecular-weight heparins; 1.0 mg of protamine sulfate will reverse effect of approximately 1.0 mg of enoxaparin if significant bleeding complications develop; cases of epidural/spinal hematomas have been reported in adults receiving spinal or epidural anesthesia (holding 2 doses prior to LP or surgery is recommended)

Drug Category: Antiarrhythmics

These agents alter the electrophysiologic mechanisms responsible for arrhythmia.

Drug Name	Adenosine (Adenocard)
Description	Used to break or diagnose paroxysmal supraventricular tachycardia. Second-line for stable wide-complex tachycardia. Short duration of action (9 s) makes it an ideal drug for use during pregnancy.
Adult Dose	6 mg rapid IV push, preferably through a central line; if no response after 1-2 min, repeat with 12 mg; a third dose of 12-18 mg may be given prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; second-degree or third-degree AV block, sick sinus syndrome (except in patients with functioning artificial pacemaker), atrial flutter, atrial fibrillation, and ventricular tachycardia
Interactions	Coadministration with carbamazepine may produce higher degrees of heart block; dipyridamole may potentiate effects; methylxanthines may antagonize effects
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	Adenosine-induced bronchoconstriction may occur in patients with asthma; warn patients that they may experience chest pressure or severe but brief shortness of breath

Drug Name	Procainamide (Pronestyl)
Description	Second-line drug for ventricular tachycardia. Used for some supraventricular tachycardias. Class I-A antiarrhythmic used for PVCs. Increases refractory period of the atria and ventricles. Myocardial excitability is reduced by an increase in threshold for excitation and inhibition of ectopic pacemaker activity. Antiarrhythmics should be used when clinically indicated. Use of any antiarrhythmic to stabilize the mother should take precedence over fetal concerns.
Adult Dose	Load 100 mg IV q10-20min, not to exceed 17 mg/kg or 1000 mg, stop the load if QRS widens >50%, dysrhythmia suppressed, or hypotension develops
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; patients diagnosed with complete heart block or second or third degree heart block, if a pacemaker is not in place; torsade de pointes; systemic lupus erythematosus
Interactions	Can expect increased levels of procainamide metabolite NAPA in patients taking cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim and quinidine; procainamide may increase effect of skeletal muscle relaxants, quinidine and lidocaine and neuromuscular blockers; ofloxacin inhibits tubular secretion of procainamide and may increase bioavailability; when taken concurrently with sparfloxacin, may increase risk of cardiotoxicity
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	Monitor for hypotension; plasma concentrations of procainamide and active metabolite, NAPA, may increase in renal failure; high or toxic concentrations may induce AV block or abnormal automaticity; caution in complete AV block, digitalis intoxication, organic heart disease, renal disease and hepatic insufficiency

Drug Category: Antiplatelet agents

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. 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).

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• 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. Additionally, cardiac output may increase by as high 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 postpartum.
  • Most of the stress related to the autotransfused blood may be offset by typical blood loss of 300-500 mL during delivery.
• Importantly, when pulmonary edema resolves within 1-2 days, a noncardiogenic etiology should be considered.

Further Outpatient Care

• Echocardiography
• • 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 improvement but not to normal, another study should be obtained within the year to determine the patient's new baseline.
  • An echocardiogram should be ordered as indicated by new clinical findings or by a decline in function.
• Postpartum follow-up
• • After delivery, patients on hydralazine/nitrates should be placed on an ACEI, and the dose should be maximized. These medications are felt to be compatible with breastfeeding.
  • If recovery of systolic function is complete, the prognosis is excellent. For women considering pregnancy or those who desire an evaluation to estimate the risk of a future pregnancy, see Prognosis. Those women with persistent systolic dysfunction should be maintained on vasodilators, nitrates, and diuretics as tolerated and indicated.

In/Out Patient Meds

• Diuretics: Furosemide is also useful to manage the patient's volume status and is an excellent first-line medication. Spironolactone has been shown to decrease morbidity when administered to non-pregnant outpatients with systolic dysfunction. Bumeta