Peripartum Cardiomyopathy Case File

Peripartum Cardiomyopathy Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 38

A 27-year-old G1P0 Caucasian woman at 35 weeks’ gestation comes into the obstetrical triage unit complaining of increasing shortness of breath, fatigue, and swelling of her legs and feet. She states that these symptoms have begun abruptly over the last 2 days, and seem to be worsening. She denies cough, history of asthma, or fever. She states that she sleeps on three pillows to be comfortable. Her prenatal course has been unremarkable. On examination, her BP is 110/80 mm Hg, HR 120 beats/min (bpm), RR 40 breaths/min and labored, and oxygen saturation 89%. The lung examination reveals rales in the bilateral lung fields, without wheezes. The heart has a rapid heart rate. The abdomen is soft and nontender. The uterus is nontender with a fundal height of 35 cm. The fetal heart tones are in the 170 bpm range. There is 3+ pitting edema of bilateral lower extremities up to the knees. A stat chest radiograph is performed revealing cardiomegaly and bilateral pulmonary infiltrates.

➤ What is the most likely diagnosis?

➤ What is your next therapeutic step?

➤ What would be your diagnostic approach?

ANSWERS TO CASE 38:

Peripartum Cardiomyopathy

Summary: This is a 27-year-old woman G1P0 at 35 weeks’ gestation who presents with dyspnea, orthopnea, and fatigue. She has tachycardia, tachypnea with labored breathing, and hypoxemia. She is not hypertensive. There are no wheezes on chest examination. The chest x-ray reveals marked cardiomegaly and bilateral pulmonary infiltrates.

➤ Most likely diagnosis: Congestive heart failure/possible peripartum cardiomyopathy.

➤ Next therapeutic step: Since the patient is alert on arrival to the hospital and the airway is not obviously compromised the priority at this time is to decrease the work of breathing, the improvement of oxygenation, and maintenance of circulatory status. The first therapeutic interventions would be to provide oxygen by mask with the patient in a Fowler position, obtain IV access, and administration of a diuretic such as furosemide.

➤ Diagnostic approach: CBC, urinalysis, comprehensive metabolic panel, arterial blood gas, ECG, and echocardiogram.

ANALYSIS

Objectives

1. Be able to describe the clinical presentation of peripartum cardiomyopathy (PPCM).
2. Be able to describe the diagnostic approach and differential diagnosis of peripartum cardiomyopathy.
3. Be able to list the treatment of peripartum cardiomyopathy.
4. Be able to describe the counseling of patients including the recurrence of PPCM.

Considerations

Peripartum cardiomyopathy is an infrequent but potentially life-threatening condition of unknown cause that occurs in previously healthy women during the peripartum period. The National Hospital Discharge Survey (1990- 2002) estimated that it occurs in 1 in every 2289 live births in the United States.1

It is characterized by left ventricular dysfunction and symptoms of heart failure that can arise in the last trimester of pregnancy or up to 5 months after delivery. Although the diagnosis can be suspected clinically by the exclusion of other causes of heart failure, it is echocardiographic and a cardiac ultrasound needs to be obtained. As with the patient described in this case, oxygenation and diuresis are important while approaching the diagnostic plan.

APPROACH TO

Peripartum Cardiomyopathy

Clinical Presentation

The diagnosis of PPCM should be considered whenever women present with heart failure during the peripartum period.2

Symptoms of heart failure such as dyspnea, dizziness, pedal edema, and orthopnea can occur even in normal pregnancies, but they always need to be evaluated. Therefore, a pregnant woman in whom peripartum cardiomyopathy is developing may consider her symptoms to be normal. If swelling and other heart failure symptoms develop suddenly in an otherwise normal pregnancy, this should prompt further investigation.3

Symptoms and signs that should raise the suspicion of heart failure include paroxysmal nocturnal dyspnea, chest pain, nocturnal cough, new regurgitant murmurs, pulmonary crackles, elevated jugular venous pressure, and hepatomegaly.2

Pulmonary edema was a presenting symptom in all 106 patients with PPCM in a study conducted in China in 2007.4 The clinical presentation was similar to that of congestive heart failure but was highly variable; 17% of cases were diagnosed antepartum and 83% postpartum. The mean age at diagnosis was 28 ± 6 years.4

Delayed diagnosis may be associated with higher rates of illness and death; therefore physicians should consider peripartum cardiomyopathy in any peripartum patient with unexplained cardiopulmonary symptoms. Although the symptoms of heart failure can be difficult to differentiate from those of late pregnancy, a heightened suspicion can help.5

Diagnostic Approach

The differential diagnosis of PPCM relies on a high index of suspicion in conjunction with timing of symptoms (in respect to pregnancy) and echocardiographic identification of new left ventricular systolic dysfunction.

The diagnostic criteria include (1) development of CHF secondary to deceased left ventricular systolic function in the last month of pregnancy or within 5 months after delivery; (2) absence of preexisting cardiac dysfunction; (3) absence of determinable cause of cardiomyopathy; and (4) left ventricular systolic dysfunction demonstrated by classic echocardiographic criteria: ejection fraction less than 45%, or M-mode fractional shortening less than 30%, or both, and end-diastolic dimension more than 2.7 cm/m2 (Table 38–1).5

Table 38–1 DIAGNOSTIC CRITERIA FOR PERIPARTUM CARDIOMYOPATHY

• Cardiac failure occurring in the last month of pregnancy or within 5 mo of delivery • Absence of identifiable cause for the cardiac failure • Absence of heart disease prior to the last month of pregnancy • LV systolic dysfunction by echocardiographic criteria:     • LVEF < 45 % and/or     • Fractional shortening < 30 %     • End-diastolic dimension > 2.7 cm/m2

 

Data from Pearson GD,Veille JC, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart,

Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations

and review. JAMA. 2000;283:1183-1188; and Demakis JG, Rahimtoola SH, Sutton GC,

et al. Natural course of peripartum cardiomyopathy. Circulation. 1971;44:1053-1061.

The electrocardiogram is nonspecific and may demonstrate normal sinus rhythm or a sinus tachycardia; dysrhythmias may also be present. Left ventricular hypertrophy, inverted T waves, Q waves, and nonspecific ST-segment changes have also been reported.3

The chest x-ray will likely demonstrate pulmonary edema, cephalization of pulmonary flow, cardiomegaly, and occasionally pleural effusions but these changes are nonspecific.

The aims during the diagnosis are to exclude other causes of cardiomyopathy and to confirm left ventricular systolic dysfunction by echocardiography. An endomyocardial biopsy is not routinely necessary for the diagnosis.

The etiology of this disease remains uncertain, but a number of possible causes of PPCM have been proposed, including myocarditis, abnormal immune response to pregnancy, maladaptive response to the hemodynamic stresses of pregnancy, stress activated cytokines, viral infection, and prolonged tocolysis. In addition, there have been a few reports of familial PPCM, raising the possibility that some cases of PPCM are actually familial dilated cardiomyopathy unmasked by pregnancy.2 Risk factors for PPCM are listed in Table 38–2.

Differential Diagnosis

See Table 38–3. In the differential diagnoses of PPCM other causes of acute cardiopulmonary decompensation during pregnancy need to be considered. Such conditions include pulmonary embolism and complications of late pregnancy itself (eg, preeclampsia or amniotic fluid embolism). Other possible causes of decompensation include accelerated hypertension, diastolic dysfunction, systemic infection, and non-cardiogenic pulmonary edema. The history and physical examination and the echocardiogram would be helpful in differentiating among these conditions.

Table 38–2 PPCM RISK FACTORS AND ASSOCIATIONS

• African American ethnic background • Age > 30 years • Multiparity • Twin pregnancy • Preeclampsia • Others:     • Familial     • Malnutrition (selenium and zinc deficiencies)     • Long-term tocolytic Rx     • Cocaine ingestion     • Chlamydia infection     • Living in tropical or subtropical region     • Anemia     • Infection     • Cesarean delivery

 

Preeclampsia is by far the most common of these complications and should be excluded on the basis of history and physical examination.

The incidence of pulmonary thromboembolism which is also increased during pregnancy can be a presenting feature of PPCM.

Table 38–3 DIFFERENTIAL DIAGNOSIS OF PERIPARTUM CARDIOMYOPATHY

Preeclampsia Noncardiogenic pulmonary edema Pulmonary thromboembolism Amniotic fluid embolism Malignant hypertension Aortic stenosis Mitral stenosis Ischemic heart disease Cardiomyopathy:     Alcoholic     Cocaine     Diabetic     Dilated Hypertrophic Restrictive Pulmonary disease

 

Treatment

During pregnancy When considering tests or treatments in pregnancy, the welfare of the fetus is always considered along with that of the mother. Coordinated management with consultants (an obstetrician, maternal-fetal medicine, internal medicine, or cardiology) is essential.

• Digoxin, beta-blockers, loop diuretics, and drugs that reduce afterload such as hydralazine and nitrates have been proven to be safe and are the mainstays of medical therapy of heart failure during pregnancy.5,6
• Beta-blockers have strong evidence of efficacy in patients with heart failure and patients taking these agents prior to diagnosis can continue to use them safely.6,7
• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are contraindicated in pregnancy because they can cause birth defects, although they are the main treatments for postpartum women with heart failure. The teratogenic effects occur particularly in the second and third trimester, with fetopathy characterized by fetal hypotension, oligohydramnios, anuria, and renal tubular dysplasia. However, a recent study suggested a risk of malformations even after first-trimester exposure to ACE inhibitors.8

After delivery After delivery, the treatment is identical to that for nonpregnant women with dilated cardiomyopathy.

• ACE inhibitors and ARBs. The target dose is one-half the maximum antihypertensive dose.6

• Diuretics are given for symptom relief. Spironolactone or digoxin is used in patients who have New York Heart Association class III or IV symptoms (see Table 38–4). The goal with spironolactone is 25 mg/d after the dosing of other drugs is maximized. The goal with digoxin is the lowest daily dose to obtain a detectable serum digoxin level, which should be kept at less than

1.0 ng/mL. In the Digitalis Investigation Group trial,10 serum digoxin levels of 0.5 to 0.8 ng/mL (0.6-1.0 nmol/L) were most beneficial, and levels of 1.1 to 1.5 ng/mL (1.4-1.9 nmol/L) were associated with an increase in deaths related to heart failure.9

• Beta-blockers are recommended for peripartum cardiomyopathy, as they improve symptoms, ejection fraction, and survival.5 Nonselective betablockers such as carvedilol and selective ones such as metoprolol succinate have shown benefit. The goal dosage is carvedilol 25 mg twice a day (50 mg twice a day for larger patients) or metoprolol succinate 100 mg once a day.6
• Anticoagulation treatment. The natural history of PPCM includes a high incidence of thromboembolism. These observations were noted before initiation of mandatory bed rest, which was the standard of care in the past. Cases of arterial, venous, and cardiac thrombosis have been reported in women with peripartum cardiomyopathy, and the risk may be related to the degree of chamber enlargement, systolic dysfunction, and the presence of atrial fibrillation.7 Anticoagulation with subcutaneous heparin (ie, 5000 U heparin subcutaneously twice daily) should be strongly considered in this population. Coumadin, on the other hand, should be avoided during first trimester because it can cause birth defects.2
• Cardiac transplantation. Patients with severe heart failure despite maximal drug therapy need cardiac transplantation to survive and to improve their quality of life. However, fewer than 3000 hearts are available for transplantation worldwide per year. Therefore, ventricular assist devices are indicated as a bridge to transplantation.6
• Patients with symptomatic ventricular arrhythmias should be considered for defibrillator implantation.6
• Other therapies include pentoxifylline (may improve outcomes, left ventricular function, and symptoms when added to conventional therapy), intravenous immunoglobulin (may improve the ejection fraction in several studies and reduce the levels of inflammatory cytokines), immunosuppressive therapy (could be considered in patients with proven myocarditis), calcium channel blockers, statins, monoclonal antibodies, interferon beta, immunoadsorption, therapeutic apheresis, bromocriptine, and cardiomyoplasty.6

How Long to Treat?

Patients with peripartum cardiomyopathy who recover normal left ventricular function at rest or with low-dose dobutamine can be allowed to taper and then discontinue heart failure treatment in 6 to 12 months under the supervision of a cardiologist or internist.6

Counseling

Even after full recovery of left ventricular function, subsequent pregnancies carry a risk of relapse of peripartum cardiomyopathy. A study in Haiti followed

99 patients, 15 of whom became pregnant again. Eight of the women (53%) who became pregnant again experienced worsening heart failure and longterm systolic dysfunction.10

A South African study reported that of six functional class I women (see Table 38-4) who became pregnant after an initial episode of PPCM, two died within 8 weeks of delivery, and the other four continued to have heart failure symptoms.9 In the United States, Elkayam and colleagues11 reported the subsequent outcomes of 44 women with history of PPCM. Of these, 28 had recovered systolic function, with ejection fractions of 50% or higher before becoming pregnant again, and 16 had not. The ejection fraction fell in both groups during pregnancy, but in the first group it fell by more than 20% in only 6 (21%), and none died. In contrast, in the group without recovery it fell by more than 20% in 5 (31%), and 3 (19%) died.11

Patients who recover normal left ventricular function and have normal left ventricular contractile reserve after dobutamine challenge may undertake another pregnancy safely, but they should be warned of the risk of recurrence even with fully recovered left ventricular function.11 Dorbala et al12 performed dobutamine stress echocardiography to measure maximal inotropic contractile reserve in six women presenting with peripartum cardiomyopathy, and it correlated accurately with subsequent recovery of left ventricular function.13

Based on these data, recommendations for further pregnancies are the following:

• If left ventricular function has recovered fully, subsequent pregnancy is not contraindicated, but the patient should be told that, although the recurrence risk is low, it is not absent.
• If left ventricular function has recovered partially, perform dobutamine stress echocardiography. If the left ventricular inotropic response to dobutamine is normal, then patients can be counseled as above; if the left ventricular inotropic response to dobutamine is abnormal, then the risk is moderate and pregnancy is not recommended.
• If left ventricular function has not recovered at all, the risk is high, and subsequent pregnancy is not recommended.6,12

Comprehension Questions

38.1 The diagnosis of PPCM is based on parameters obtained by which of the following?

A. ECG

B. Echocardiogram

C. Arterial blood gas showing hypoxemia and respiratory alkalosis

D. Chest x-ray demonstrating pulmonary edema and cardiomegaly

38.2 The most common cause of pulmonary edema during pregnancy is which of the following?

A. Cocaine induced

B. Arrhythmia

C. Peripartum cardiomyopathy

D. Preeclampsia

38.3 Angiotensin receptor blockers are not used during pregnancy because of which of the following reasons?

A. They are not effective.

B. Their half-life is decreased during pregnancy.

C. They can cause oliguria and occasionally fetal death.

D. They can cause arrhythmias during pregnancy.

ANSWERS

38.1 B. The diagnosis of cardiomyopathy is mainly echocardiographic.

38.2 D. Although the differential diagnosis of all cases of pulmonary edema should include pulmonary edema, during pregnancy the most common cause of pulmonary edema is preeclampsia.

38.3 C. Angiotensin receptor blockers can cause oliguria, anuria, and occasionally fetal death and are contraindicated during pregnancy.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ Suspect peripartum cardiomyopathy in any peripartum patient with unexplained symptoms of heart failure (Level III).

➤ Heightened suspicion is important when a pregnant woman presents with signs of heart failure, because early diagnosis allows proven treatment to be started (Level III).

➤ Pregnant women should not receive angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or warfarin because of potential teratogenic effects (Level II-2).

➤ An initial left ventricular end-systolic dimension less than 5.5 cm, a left ventricular ejection fraction greater than 30%, and a low cardiac troponin level may predict a better outcome (Level II-3).

➤ Subsequent pregnancies carry a high risk of relapse, even in women who have fully recovered left ventricular function (Level II-3).

REFERENCES

1. Mielniczuk LM, Williams K, Davis DR, et al. Frequency of peripartum cardiomyopathy. Am J Cardiol. 2006;97:1765-1768. 

2. Abboud J, Murad Y, Chen-Scarabelli C, et al. Peripartum cardiomyopathy: a comprehensive review. Int J Cardiol. 2007;118:295-303. 

3. Brown CS, Bertolet BD. Peripartum cardiomyopathy: a comprehensive review. Am J Obstet Gynecol. 1998;178:409-414. 

4. Hu CL, Li YB, Zou YG, et al. Troponin T measurement can predict persistent peripartum cardiomyopathy left ventricular dysfunction in peripartum cardiomyopathy. Heart. 2007;93:488-490. 

5. Pearson GD, Veille JC, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA. 2000;283:1183-1188. 

6. Ramaraj R, Sorrell V. Peripartum cardiomyopathy: causes, diagnosis, and treatment. Cleve Clin J Med. 2009 May;76(5):289-296. 

7. Sliwa K, Forster O, Zhanje F, et al. Outcome of subsequent pregnancy in patients with documented peripartum cardiomyopathy. Am J Cardiol. 2004;93:1441-1443, A10. 

8. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354:2443-2451. 

9. Rathore SS, Curtis JP, Wang Y, et al. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289:871-888. 

10. Fett JD, Christie LG, Murphy JG. Brief communication: outcomes of subsequent pregnancy after peripartum cardiomyopathy: a case series from Haiti. Ann Intern Med. 2006;145:30-34. 

11. Elkayam U, Tummala PP, Rao K, et al. Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy. N Engl J Med. 2001;344:1567-1571. 

12. Dorbala S, Brozena S, Zeb S, et al. Risk stratification of women with peripartum cardiomyopathy at initial presentation: a dobutamine stress echocardiography study. J Am Soc Echocardiogr. 2005;18:45-48. 

13. Demakis JG, Rahimtoola SH, Sutton GC, et al. Natural course of peripartum cardiomyopathy. Circulation. 1971;44:1053-1061.

HomeHigh-Risk Obstetrics Case FilePeripartum Cardiomyopathy Case File