Peripartum Cardiomyopathy: A Case Report and Literature Review
By Harald Lausen, DO, FACOFP
Abstract: Peripartum cardiomyopathy is a rare and potentially fatal form of heart failure. The true incidence of peripartum cardiomyopathy is unknown secondary to diagnostic difficulty and the lack of population-based estimates. An exact cause of peripartum cardiomyopathy is yet to be identified. Possible causes include physiologic stress, idiopathic events, autoimmune responses, and infectious diseases. Risk factors for peripartum cardiomyopathy include multiparity, advanced maternal age, multifetal pregnancy, preeclampsia, use of tocolytics, gestational hypertension, and African-American race.
The research definition of peripartum cardiomyopathy has four criteria.
The diagnosis of peripartum cardiomyopathy may be challenging in the last month of pregnancy since normal pregnant patients experience dyspnea, fatigue, and pedal edema. Currently, the treatment of peripartum cardiomyopathy is the standard therapy for heart failure. Primary therapy consists of bed rest, sodium and fluid restriction, vasodilators, digoxin, and diuretics. The overall prognosis is generally reported to be poor, with a high incidence of death or refractory heart failure. Reported mortality rates have ranged from 18 to 56 percent. Survivors may not recover completely and may require heart transplantation.
Patients with peripartum cardiomyopathy tend to have a better prognosis than those with other forms of cardiomyopathy. Only patients with a normalized ventricular function during resting and stress/dobutamine tests should be considered candidates for repeat pregnancy without risk of increased maternal mortality. Subsequent pregnancy after peripartum cardiomyopathy in women with recovery of left ventricular function may result in recurrence of peripartum cardiomyopathy and possible permanent decrease in left ventricular function or even death. The exact risk of reccurrence is unknown and the risk of irreversible cardiac damage likely increases with each subsequent pregnancy. There is currently no consensus statement regarding recommendations for future pregnancy after peripartum cardiomyopathy.
Case Report
A 21 year-old gravida two para one African-American female presented to the emergency room five days postpartum with a chief complaint of chest congestion. The patient had a normal prenatal course. The only identified complications were an abnormal Pap smear (LGSIL) and treatment for bacterial vaginosis and a chlamydia infection. All other prenatal labs, studies, and vital statistics including blood pressure were normal. The patient had a previous elective abortion at eight weeks, two years prior to this pregnancy. Medical, surgical, social, and family histories were otherwise unremarkable. The patient delivered at forty weeks gestation via normal spontaneous vaginal delivery without complication. The patient and her child were discharged two days after delivery.
The patient noted chest tightness, shortness of breath, and cough since the day of discharge. These symptoms were exacerbated by lying down. The patient denied fever, chills, nausea, vomiting, or productive cough. Additionally, the patient noted that her legs and ankles were more swollen than on the day of discharge. The patient noted shortness of breath that required her to stand up during the night prior to admission.
On physical exam, the patient appeared well-nourished, well-developed and in mild distress. She was found to have a blood pressure of 159/108 and a pulse of 63. Otherwise, the patient was afebrile and comfortable in the seated position with a 99 percent pulse oximetry on room air. Jugular veins were distended and visible three centimeters above the clavicle. The cardiac PMI was mildly displaced laterally to the mid-clavicular line. An apical S4, a 1-2 / 6 apical holosystolic murmur, and a 1 / 6 right upper sternal border murmur were heard on auscultation. Scattered bibasilar crackles were auscultated on lung exam. There was 2+ edema noted in the bilateral lower extremities to the knees.
Electrocardiography revealed normal sinus rhythm at 65 beats per minute. Chest x-ray showed pulmonary congestion with mild enlargement of the left ventricle. CT scan of the chest showed small bilateral pleural effusions and interstitial edema without evidence of pulmonary embolism. Echocardiogram demonstrated an ejection fraction of 42 percent, mildly dilated left ventricle with mild global hypokinesis, severe diastolic dysfunction, mild pulmonary hypertension, and mild mitral and aortic valve regurgitation.
Initial laboratory evaluation revealed a white blood cell count of 8,000/mm3 with normal differential; hemoglobin 9.6 g/dL; and hematocrit 29 percent. Complete metabolic panel was normal except for AST 45 U/L; LDH 227 IU/L; and albumin 2.7 g/dL. Thyroid, B-12, and folate studies were normal. Urinalysis was normal with no evidence of proteinuria. A CPK of 255 U/L and CPKMB of 4.8 ng/ml were noted to be mildly elevated. Sedimentation rate was 48 mm/hr. B-natriuretic peptide was elevated at 460 pg/ml with an elevated troponin-I of 0.155 ng/ml.
The patient was hospitalized and cardiac consultation was obtained. The admitting diagnosis was peripartum cardiomyopathy. Treatment included fluid restriction, sodium restriction, bed rest, furosemide, lisinopril, carvedilol, digoxin, pentoxifylline, and subcutaneous enoxeparin. The patient’s blood pressure responded quickly to medical management.
Further history and laboratory evaluation essentially ruled out preeclampsia, gestational hypertension, familial peripartum cardiomyopathy, congenital heart disease, myocarditis, prolonged tocolysis, recent infection, and malnutrition. Serial cardiac enzymes, electrolytes, B natriuretic peptide, and cardiac function tests were followed during hospitalization. The patient was discharged home after five days in stable condition.
The patient’s left ventricular systolic function normalized with an ejection fraction of 54 percent within two months after discharge. She was slowly weaned from cardiac medication. Six months after discharge the patient completed a cardiopulmonary stress test which revealed moderate cardiopulmonary limitation and was designated as New York Heart Association Functional Class II. It was recommended that the patient avoid any future pregnancies.
Definition
The research definition of peripartum cardiomyopathy has four criteria. The patient must develop cardiac failure, specifically dilated cardiomyopathy, due to decreased systolic dysfunction of the left ventricle in the last month of pregnancy or within five months of delivery. There must be an absence of an identifiable cause for the cardiac failure. There must be an absence of recognizable heart disease prior to the last month of pregnancy. Additionally, left ventricular systolic dysfunction should be demonstrated by classic echocardiographic criteria, such as depressed shortening fraction (less than 30 percent) or decreased ejection fraction (less than 45 percent).1,2,3,4,5,6,7
Incidence and Risk Factors
The true incidence of peripartum cardiomyopathy is unknown secondary to diagnostic difficulty and the lack of population-based estimates.1,2,3,5 Reported incidence ranges from 1 per 1,300 to 1 per 15,000 deliveries.1,2,3,5 The currently accepted estimate of incidence is approximately 1 per 3,000 to 1 per 4,000 live births in the United States.1,2,5,7,8 This translates to 250 to 1,300 women each year in the US.1,3,5
During 1979-1984, 3 percent of reported pregnancy-related deaths were caused by cardiomyopathy; this percentage increased to 7.7 percent in 1991-1997.6 Cardiomyopathy is one of the few causes of pregnancy-related death that has risen since 1970.6 Of the 245 cardiomyopathy deaths during 1991-1997, 171 (70 percent) were due to peripartum cardiomyopathy.6 Less than one percent of all cardiovascular events related to pregnancy are due to peripartum cardiomyopathy.7
Risk factors for peripartum cardiomyopathy include obesity1, previous peripartum cardiomyopathy, multiparity, advanced maternal age, multifetal pregnancy, preeclampsia, gestational hypertension, use of tocolytics, and African-American race.2,3,4,5,6,7,8
Etiology
An exact cause of peripartum cardiomyopathy has yet to be identified.1,2,3,4,5 The hypothetical causes of peripartum cardiomyopathy include myocarditis, a maladaptive response to the hemodynamic stresses of pregnancy, hypertension, an abnormal immune response to pregnancy, stress-activated inflammatory cytokines, cardiac myocyte apoptosis1,4, prolonged tocolysis, viral infection, a relaxin abnormality3, selenium deficiency, malnutrition3,4, unmasked familial dilated cardiomyopathy, and familial peripartum cardiomyopathy.1,2,3,4,5
Peripartum cardiomyopathy is believed to be a distinct entity, as opposed to being an underlying cardiomyopathy unmasked by the hemodynamic stresses of pregnancy.1,5 The reported incidence of peripartum cardiomyopathy is higher than the incidence of idiopathic cardiomyopathy.5 Peripartum cardiomyopathy also has a better prognosis than does idiopathic cardiomyopathy, infiltrative myocardial disease, ischemic heart disease, and all other identified causes of cardiomyopathy.2,9 A high prevalence of biopsy proven myocarditis (76 percent) in peripartum cardiomyopathy would not be expected in a population presenting with decompensation of preexisting heart disease due to hemodynamic stress.1,5,9,10 The reported incidence of myocarditis as diagnosed by biopsy in peripartum cardiomyopathy varies from 8.8 to 76 percent according to multiple studies.1,5,7,9,10 There is no difference in clinical outcome between myocarditis and non-myocarditis peripartum cardiomyopathy.2 The prognosis was significantly better in peripartum cardiomyopathy than cardiomyopathy due to myocarditis.9
The maximal hemodynamic burden of pregnancy occurs in the second trimester of pregnancy.7,8 Important physiologic changes that peak during the second trimester of pregnancy are blood volume expansion, relative anemia, alterations in vascular resistance, ventricular dilatation, an increase in metabolic demands and cardiac output, and increases in preload and heart rate.7,8 Most patients with previously diagnosed cardiac disease develop symptoms of heart failure in this period.7,8 Peripartum cardiomyopathy must be strongly considered when these hemodynamic stressors lead to decompensated heart failure.10 The differential may include infectious, metabolic, and toxic causes of cardiomyopathy. One must also consider systemic disorders, valvular heart disease, and myocardial infarction.7,10 The late complications of pregnancy such as massive pulmonary embolism, amniotic fluid embolism, and severe toxemia which may simulate heart failure should also be ruled out.7,10
Diagnosis
The diagnosis requires satisfaction of the research definition for peripartum cardiomyopathy and exclusion of other causes of cardiomyopathy with confirmation by standard echocardiographic assessment of new left ventricular systolic dysfunction during a limited period surrounding parturition.1,5 Most patients (78 percent) present with symptoms in the first four months postpartum.7 Fewer patients (9 percent) present in the last month before delivery and others (13 percent) present either more than one month antepartum or more than four months postpartum.7 Another report found that over 90 percent of patients presented in the first two months postpartum and only 3.5 percent presented in the antepartum period.7
Signs/Symptoms
The diagnosis of peripartum cardiomyopathy may be challenging in the last month of pregnancy since normal pregnant patients experience dyspnea, fatigue, and pedal edema.1,2,3,4,5,10 Peripartum cardiomyopathy may go unrecognized leading to an under-estimation of incidence.2,5 Symptoms that may raise suspicion include paroxysmal nocturnal dyspnea, chest pain, tachycardia, arrhythmias, tachypnea, cough, neck vein distention, third heart sound, new murmurs consistent with AV valve regurgitation, pulmonary crackles, hemoptysis, hepatomegaly, ascites, and embolic events.1,2,4,5,7
Electrocardiography may demonstrate no abnormalities or may show sinus tachycardia, atrial fibrillation, nonspecific ST segment and T wave changes, evidence of left ventricular hypertrophy, prolongation of the PR or QRS intervals, low voltage, and occasionally left bundle branch block.1,2,4 Chest films reveal typical signs of CHF which include interstitial edema, pulmonary venous congestion, cardiomegaly, and occasionally pleural effusion.2 Echocardiography may demonstrate dilated cardiomyopathy involving all four chambers of the heart, with the left heart being most affected.4 Normal wall thickness with diffuse symmetric hypokinesis and high intracardiac pressure with low cardiac output are very characteristic.4 A common finding is left atrial enlargement with mitral regurgitation along with a high incidence of mural thrombi and/or a left ventricular thrombus.4 A small pericardial effusion may be present.7 Pulmonary hypertension is common.7
Treatment
Currently the treatment of peripartum cardiomyopathy is the standard therapy for heart failure.1,2,3,4 Treatment aims to reduce afterload and preload, and to increase contractility.10 Primary therapy consists of bed rest, sodium and fluid restriction, vasodilators, digoxin, and diuretics.1,2,7 Cesarean section is reserved for obstetric indications only.5 Vaginal delivery is recommended.5
Care should be taken when deciding which medications to use during the prepartum period and postpartum period, especially with breastfeeding.
In the prepartum period, afterload reduction is accomplished with a combination of medications. Most of these medicines are considered pregnancy class C. The drug of choice during pregnancy is hydralazine which dilates peripheral vessels and decreases afterload.1,5 Cardiac afterload may be further reduced by using beta-blockers. Carvedilol and Metoprolol are preferred due to evidence that they improve cardiac function and prolong survival in patients with CHF and decreased contractility.2,5,10 Nitrates may add to the overall effect by decreasing afterload and preload.3 Diuretics are used to reduce preload and circulating volume.1,2,3 Spironolactone may be used since it also improves the prognosis of patients with CHF.10 Additional preload reduction and positive inotropy are achieved using Digoxin.2,5
In the postpartum period, ACE inhibitors are the drug of choice to reduce afterload.1,4,5 ACE inhibitors are absolutely contraindicated in pregnancy.1,2 Patients intolerant of ACE inhibitors should be placed on ARBs.10 Both beta-blockers and ACE inhibitors have been shown to improve overall survival in patients with non-specific cardiomyopathy.1,3 Long-term use of beta-blockers during pregnancy may associated with low-birth-weight babies.1,3 Amlodipine is considered the calcium channel blocker of choice because it has been shown to improve survival in patients with nonischemic cardiomyopathy.3,5,7 Patient education, dietary consultation, early ambulation to prevent DVT, and exercise rehabilitation should be an integral part of the treatment regimen.3,10
Critical patients may be treated with IV inotropic therapy, right-sided heart catheterization and IV pressor or after-load reducing therapy, intra-aortic balloon pump counterpulsation, and left ventricular or biventricular assist device.1,2,7 An endomyocardial biopsy to diagnose myocarditis should be performed on patients who fail to improve within two weeks.3 A trial of immunosuppressive agents such as prednisone, azathioprine, or cyclosporine may be administered to patients with biopsy-proven myocarditis who fail to improve with standard heart failure therapy.7 Studies with these agents have shown mixed results.4 Recent studies have shown that pentoxifylline inhibits inflammatory cytokines and markers of apoptosis while improving ejection fractions in patients with left ventricular dysfunction.3,4,10 Improved ejection fraction in women with peripartum cardiomyopathy has also been shown with the use of intravenous immune globulin.1,3,10 Heart transplantation is an option for those who do not respond to medical treatment3 or have persistent cardiomegaly.3,10
Patients with significant ventricular dysfunction also require anticoagulation to prevent thrombosis and emboli. These patients typically have an ejection fraction of less than 25-35 percent or a previous history of emboli.2,4,7 Enoxaparin (low molecular weight heparin) should be used during pregnancy to avoid unnecessary volume loading.3 Warfarin should only be used in the post-partum period or possibly during the second trimester.1,7 The most important complication of peripartum cardiomyopathy is thromboembolism.7 The incidence of pulmonary and systemic embolism has been reported to be as high as 50 percent and may be the presenting problem.7 The tendency for thromboembolism is likely caused by the hypercoagulant state of late pregnancy in combination with stasis and turbulent flow in the dilated heart.7 This high rate may also reflect prolonged bed rest.7
Treatment should continue up to one year in patients who respond to standard therapy.4,10 A dobutamine stress echo should be performed to determine whether or not the patient has impaired myocardial reserve and if there is complete resolution of left ventricular dysfunction at three and six months.2,4,10 Therapy can be tapered gradually in patients with normal heart size and function at rest and normal cardiac enhancement with dobutamine or exercise.10
Prognosis
Prognosis depends on normalization of left ventricular size and function within six months after delivery.1,2,5,7 About 30-50 percent of patients with peripartum cardiomyopathy are reported to recover baseline ventricular function within 6 months of delivery.1,2,10 A fractional shortening value less than 20 percent and a left ventricular end diastolic dimension 6 cm or greater at the time of diagnosis are associated with a more than 3-fold higher risk for persistent left ventricular dysfunction.1,2 Persistent left ventricular dysfunction may result in mortality as high as 85 percent over five years.2,5,7,10 Mortality has slowly increased since 19716, but new medications have helped survivors significantly improve left ventricular function.5 The five year survival rate increases to 94 percent when using the strict definition of peripartum cardiomyopathy.2,9 At eight years, the survival was estimated to be 91-93 percent with only 7-14 percent requiring heart transplantation.1,2,3,10 Survivors tend to have a higher baseline ejection fraction and smaller mean left ventricular cavity size at presentation.3 Baseline ejection fraction at presentation appears to be the strongest predictor of outcome.3,4,10 Decreased left ventricular stroke work index7, lower left ventricular ejection fraction at 6 months after delivery, larger left ventricular end diastolic dimension, and clinical presentation greater than 2 weeks postpartum were associated with worse outcomes.10 Patients with persistent or abnormal ventricular dysfunction should not become pregnant and should be treated using the guidelines for heart failure.2,5 Patients who have normalized systolic function are more difficult to counsel. There is currently no consensus statement regarding recommendations for future pregnancy after peripartum cardiomyopathy.1,5,7
Subsequent pregnancy after peripartum cardiomyopathy in women with recovery of left ventricular function may result in recurrence of peripartum cardiomyopathy and possible permanent decrease in left ventricular function or even death.4,8 The exact risk of reccurrence is unknown and the risk of irreversible cardiac damage likely increases with each subsequent pregnancy.5 There is some evidence that contractile reserve is impaired after peripartum cardiomyopathy.1,2,3,5,7 This has been shown using dobutamine stress testing which increases heart and cardiac output similar to stresses experienced in pregnancy.1,2 Contractile reserve in patients with recovered ventricular function was reduced compared to nonpregnant matched controls.1,2 Patients with what appears to be normal function at rest have impairment in contractile reserve following an episode of peripartum cardiomyopathy.1,2 Subsequent pregnancies following peripartum cardiomyopathy have an increased risk of maternal and fetal morbidity and mortality.1,3,5 Women with persistent left ventricular dysfunction have an even greater risk of cardiac failure with subsequent pregnancy.3,5 Only patients with a normalized ventricular function during resting and stress/dobutamine tests should be considered candidates for repeat pregnancy without risk of increased maternal mortality.2
Discussion
The diagnosis of peripartum cardiomyopathy is difficult due to the complexities of pregnancy and the challenge of eliminating other etiologies. Vigilance is necessary to reduce the number of possible causes. The question is whether the clinician can ever exclude some of the possibilities such as unmasked dilated cardiomyopathy, infectious cardiomyopathy, or coincidental cardiomyopathy. Additionally, family history is only as reliable as its provider. There is likely an influence of genetic predisposition when considering the prevalence of familial cardiomyopathy. While these questions exist, the research definition of peripartum cardiomyopathy may never truly be satisfied.
The patient in the case study only had one of the seven identified risk factors. However, she did meet the accepted criteria of the research definition. Medical history, family history, physical exam, laboratory results, and cardiac studies essentially eliminated the other possibilities of cardiomyopathy in our patient. Yet, the lack of pathophysiologic data and absence of specific genetic testing leave some doubt in our diagnosis. This uncertainty also undermines our prognostic estimates and recommendations for future pregnancies even with the findings of persistent exercise-induced moderate cardiopulmonary limitation.
The need for an international registry was outlined in the workshop recommendations and review on peripartum cardiomyopathy by the National Heart, Lung, and Blood Institute.1,5 The key points were to develop better incidence and prevalence estimates, determine risk factors and prognostic variables, ascertain cardiovascular risks for subsequent pregnancies, establish a central serum and tissue bank, and evaluate therapeutic interventions.5 Seven years later, these excellent goals are yet to be achieved.1
Dr. Lausen is a 2000 graduate of the Chicago College of Osteopathic Medicine. He received his certification in Osteopathic Family Medicine in 2004. He currently serves as the Osteopathic Residency Program Director and Institutional Director of Osteopathic Medical Education for the Southern Illinois University School of Medicine in Springfield, Illinois.
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