|Year : 2014 | Volume
| Issue : 4 | Page : 480-484
Hatem Said, Amr Sobhi
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
|Date of Submission||21-Sep-2014|
|Date of Acceptance||12-Oct-2014|
|Date of Web Publication||28-Nov-2014|
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, 11566
Source of Support: None, Conflict of Interest: None
Peripartum cardiomyopathy (PPCM) is a rare disorder of dilated cardiomyopathy in which no other cause of heart dysfunction can be identified within the final trimester of pregnancy or within 5 months after delivery. It is relatively rare but can be life threatening. The National Hospital Discharge Survey (1990-2002) estimated that it occurs in one in every 2289 live births in the USA. The disease appears to be more common in African-American women. So this study aims to summarize the most recent management plans in the face of this serious and, relatively not uncommon, complication.
Keywords: heart failure, obstetric anesthesia, peripartum cardiomyopathy
|How to cite this article:|
Said H, Sobhi A. Peripartum cardiomyopathy
. Ain-Shams J Anaesthesiol 2014;7:480-4
| Introduction|| |
Peripartum cardiomyopathy (PPCM) is a rare disorder of dilated cardiomyopathy in which no other cause of heart dysfunction can be identified within the final trimester of pregnancy or within 5 months after delivery. Heart failure during pregnancy was recognized as early as 1849, but it was first described as a distinctive form of cardiomyopathy only in the 1930s . In 1971, Demakis et al.  described 27 patients who presented during the puerperium with cardiomegaly, abnormal ECG findings, and congestive heart failure, and they named the syndrome PPCM. PPCM is relatively rare but can be life threatening. The National Hospital Discharge Survey (1990-2002) estimated that it occurs in one in every 2289 live births in the USA. The disease appears to be more common in African-American women. The rate varies in other populations; it is highest in Haiti, with one case in 300 live births, which is nearly 10 times higher than in the USA. The reason for such a variation remains unclear .
| Pathophysiology|| |
(1) Several etiologic mechanisms have been suggested; none of them is definite.
(a) Myocarditis has been found on endomyocardial biopsy of the right ventricle in patients with PPCM, with a dense lymphocytic infiltrate and variable amounts of myocyte edema, necrosis, and fibrosis. The prevalence of myocarditis in patients with PPCM ranged from 8.8 to 78% in different studies  ([Figure 1] and [Figure 2]).
|Figure 1: Most histologic specimens demonstrate nonspecific changes of myocyte hypertrophy, cell loss, and fi brosis.|
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|Figure 2: Postmortem gross morphology showing dilated heart in peripartum cardiomyopathy.|
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(b) After cardiotropic viral infections, a pathologic immune response occurs that is directed against native cardiac tissue proteins, leading to ventricular dysfunction. Bultmann et al.  found parvovirus B19, human herpesvirus 6, Epstein-Barr virus, or cytomegalovirus DNA in endomyocardial biopsy specimens from eight (31%) of 26 patients with PPCM. Kühl et al.  found that left ventricular ejection fraction improved in those in whom the virus was cleared (from 50.2% before to 58.1% afterward), whereas it decreased in those in whom the virus persisted (from 54.3% before to 51.4% afterward).
(c) Chimerism, in which cells from the fetus take up residence in the mother (or vice versa), sometimes provoking an immune response. As reviewed by Ansari and colleagues, the serum from patients with PPCM has been found to contain autoantibodies in high titers. Most of these antibodies are against normal human cardiac tissue proteins. The peripheral blood in these patients has a high level of fetal microchimerism in mononuclear cells, an abnormal cytokine profile .
(d) Apoptosis and inflammation (programmed cell death) of cardiac myocytes occurs in heart failure and may contribute to progressive myocardial dysfunction. Fas and Fas ligand are cell surface proteins that play a key role in apoptosis. Sliwa and colleagues followed patients with PPCM for 6 months, and those who died had significantly higher plasma levels of Fas/Apo-1. In the same study, plasma levels of C-reactive protein and tumor necrosis factor-α and interleukin 6 (markers of inflammation) were elevated and correlated with higher left ventricular dimensions and lower left ventricular ejection fractions .
(e) Nutritional factors: Many nutritional disorders have been suggested as causes. Lower levels of selenium have been found in patients with PPCM. Lyden and Huber  study found it in 62% of 44 women with PPCM; the finding did not correlate with survival.
(f) Other possible factors: Other possible etiologic factors include prolactin [10,11], relaxin , immune complexes , cardiac nitric oxide synthase , immature dendritic cells , cardiac dystrophin , and toll-like receptors .
(1) Demakis Diagnostic Criteria :
(a) Development of heart failure in the last month of pregnancy or within 5 months of delivery.
(b) Absence of recognizable heart disease before the last month of pregnancy.
(c ) Absence of identifiable causes for the heart failure.
(d) Left ventricular systolic dysfunction demonstrated by classic echocardiographic findings, such as depressed shortening fraction or ejection fraction.
(2) 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.
(3) The differential diagnosis includes the following: aortic stenosis, mitral stenosis, cardiomyopathy such as alcoholic, cocaine, dilated, hypertrophic, and restrictive, coronary artery atherosclerosis, and hypertension.
(4) Maternal and fetal complications.
Maternal complications may include the following:
(a) Thromboembolism: Small series have reported the incidence to be as high as 50%.
(b) Progressive cardiac failure.
Fetal complications may include the following:
(a) Distress due to maternal hypoxia, placental hypoperfusion as a result of poor cardiac output, maternal hypovolemia due to excessive diuresis, or hypotension from aggressive afterload reduction.
Creatinine phosphokinase (CPK) levels can be elevated after normal delivery due to release from the uterus and may be elevated after cesarean section due to release from the uterus and/or skeletal muscle. An elevated CPK level is not diagnostic of PPCM. The CPK from the placenta routinely has a CPK-MB fraction of 6% or more .
One study found that a cardiac troponin T level greater than 0.04 ng/ml, measured within 2 weeks of diagnosis, was 60% sensitive at identifying women more likely to have persistent ventricular dysfunction at 6 months after the diagnosis .
As a result of elevated left ventricular end-diastolic pressure due to systolic dysfunction, patients with PPCM commonly have an increased plasma concentration of B-type natriuretic peptide or N-terminal pro-BNP [20,21].
Chest radiography: Rapid diagnosis must be established. When evaluating new-onset dyspnea, tachycardia, or hypoxia, immediately obtain a chest radiograph to detect pulmonary edema. This should be performed to evaluate the etiology of hypoxia and to exclude pneumonia ([Figure 3]).
|Figure 3: Chest radiography for PPCM: It shows cardiomegaly, bilateral mild pleural effusions, and patchy infi ltrates in the lower lung fi elds. PPCM, peripartum cardiomyopathy.|
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ECG: ECGs evaluate for conduction abnormalities. Results may be normal, show sinus tachycardia, or, rarely, atrial fibrillation if the cardiomyopathy is severe. Other nonspecific findings include low voltage, left ventricular hypertrophy, and nonspecific ST-segment and T-wave abnormalities; PR and QRS intervals may be prolonged .
Echocardiography: It shows a dilated left ventricle with marked impairment of overall systolic performance, left ventricular ejection fraction of less than 45%, fractional shortening of less than 30%, and left ventricular end-diastolic dimension of more than 2.7 cm/m 2 of body surface area. Echocardiography should be repeated before patient discharge and at 6 weeks, 6 months, and annually to evaluate the efficacy of medical treatment. If available, cardiac MRI can also be repeated at 6 months and 1 year to get a more accurate assessment of changes in cardiac function [23-26] ([Figure 4] and [Figure 5]).
|Figure 4: Echocardiography for PPCM patient showing four chambers dilatation. PPCM, peripartum cardiomyopathy.|
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|Figure 5: Echocardiography for PPCM patient showing left ventricular mural thrombus. PPCM, peripartum cardiomyopathy.|
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| Management|| |
Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers 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, renal tubular dysplasia, and death. However, a recent study suggested a risk for malformations even after first trimester exposure to angiotensin-converting enzyme inhibitors [27-29].
Patients with systolic dysfunction during pregnancy are treated the same as patients who are not pregnant. The mainstays of medical therapy are digoxin, loop diuretics, K-sparing diuretics, afterload reduction with hydralazine and nitrates, and β-adrenergic blockade with carvedilol or metoprolol succinate as they have been shown to decrease all-cause mortality and hospitalization in those with systolic dysfunction [30,31]. As there is a high risk for venous and arterial thrombosis, anticoagulation with heparin should be instituted when the ejection fraction is less than 30%, with deep venous thrombosis, atrial fibrillation, ventricular thrombi, or embolic events [32,33]. Warfarin can cause spontaneous fetal cerebral hemorrhage in the second and third trimesters, and therefore is generally contraindicated during pregnancy [34,35]. However, guidelines from the American College of Cardiology and the American Heart Association on the management of patients with heart valve disease say that 'warfarin is probably safe during the first 6 weeks of gestation, but there is a risk for embryopathy if the warfarin is taken between 6 and 12 weeks of gestation '.
Inotropic agents should be considered in patients with a low output state, indicated by signs of hypoperfusion (cold, clammy skin, vasoconstriction, acidosis, renal impairment, liver dysfunction, and impaired mentation) and in those with congestion, which persists, despite administration of vasodilators and/or diuretics. When needed, inotropic agents (dobutamine, levosimendan, milrinone) should be administered without unnecessary delay and withdrawn as soon as adequate organ perfusion is restored and/or congestion is reduced [37,38].
If a patient is dependent on inotropes or intra-aortic balloon pump counterpulsation, despite optimal medical therapy, implantation of a mechanical assist device or cardiac transplantation should be considered. As the prognosis in PPCM is different from dilated cardiomyopathy with a significant proportion of patients normalizing their left ventricular function within the first 6 months postpartum, an left ventricle-assisted device may be considered before listing the patient for cardiac transplantation. Select patients may eventually benefit from cardiac resynchronization therapy, internal defibrillators, or cardiac transplantation [39,40].
Antiplatelet agents: A clinical trial assessed pentoxifylline 400 mg three times daily in a group of women with PPCM who were treated with diuretics, digoxin, enalapril, and carvedilol. A small randomized trial (n=39) on pentoxifylline has shown that it may improve symptoms, left ventricular function (by 5%), and lower levels of inflammatory cytokines such as tumor necrosis factor-α. However, not all studies found a beneficial effect .
Intravenous immunoglobulin improved the ejection fraction in several studies [42,43] and also markedly reduced the levels of inflammatory cytokines, namely thioredoxin .
Bromocriptine: On the basis of enhanced oxidative stress-mediated cleavage of prolactin hormone into an antiangiogenic and proapoptotic form that may be responsible for the development of PPCM, Sliwa and colleagues attempted the use of bromocriptine, a prolactin blocker, in the treatment of PPCM. The drug was given after diagnosis at a dose of 2.5 mg twice daily for 2 weeks, followed by 2.5 mg/day for 6 weeks, and resulted in a significantly larger rate of left ventricular recovery at 6 months compared with the control group with PPCM treated with standard therapy alone (31 vs. 9%). In addition, there was a lower rate of mortality in the treatment group (one vs. four patients) [4,45].
| Prognosis|| |
It is dependent on recovery of left ventricular function. Thirty percent of patients return to baseline ventricular function within 6 months, and 50% of patients have significant improvement in symptoms and ventricular function. The usual causes of death in patients with PPCM are progressive heart failure, arrhythmia, or thromboembolism. The mortality rate related to embolic events has been reported to be as much as 30% [24,25].
| Prospects for future pregnancies|| |
In women with persistent ventricular dysfunction, future pregnancy is not recommended because of concern about the ability of the dysfunctional heart to handle the increased cardiovascular workload. Regarding subsequent pregnancies, survey found that 78% of women with fully recovered left ventricular function had a normal outcome, compared with only 37% of those with persistent ventricular dysfunction [46-48].
| Conclusion|| |
PPCM is a rare cardiomyopathy of unknown cause, which is a serious threat to life. PPCM remains a diagnosis of exclusion and echocardiography provides clues to diagnosis in a symptomatic patient. Decompensated PPCM needs a multidisciplinary approach, and hence is a serious challenge.
| Acknowledgements|| |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]