Verwendete Distiller 5.0.

x
Joboptions
Intensive Care Med (2003) 29:167–174 ----------------------------
DOI 10.1007/s00134-002-1583-0 REVIEW Adobe Acrobat Distiller 5.0.x
----------------
Joboption Datei
Dieser Report wurde a h
c
is
m
to
u
----------------------------
mit Hilfe der Adobe
----------------
Acrobat Distiller
<<
Erweiterung "Distiller
/ColorSettingsFile
Esther Beus Peripartum cardiomyopathy: Secrets v1.0.5" der
)(
IMPRESSED GmbH
Walther N. K. A. Mook
Graham Ramsay a condition intensivists should be aware of erstellt. Sie koennen
/AntiAliasMonoImages
Jan L. M. Stappers diese Startup-Datei
false
Hans W. H. M. Putten für die Distiller
Versionen
/CannotEmbedFontPo4.0.5 und
5.0.x
/Warning kostenlos unter
http://www.impresse
d.de herunterladen.
/ParseDSCComments
ALLGEMEIN -
false
Dateioptionen:
/DoThumbnails true
Kompatibilität: P
/CompressPages DF
1.2
true
Abstract We use an illustrative case Keywords Peripartum · Für schnelle W
/CalRGBProfile -A
bn
eig (s
z R
GB
Received: 8 September 2002 optimieren: Ja
Accepted: 24 October 2002 of severe peripartum cardiomyopa- Cardiomyopathy · Intensive IEC61966-2.1)
care ·
Published online: 17 January 2003 thy with congestive heart failure to African · Eclampsia · Piktogramme
/MaxSubsetPct einbeten:1
0
© Springer-Verlag 2003 introduce this topic and proceed to Echocardiography Ja
cover its pathophysiology, incidence, Seiten automatisch
/EncodeColorImages
E. Beus · W. N. K. A. Mook (✉) management and outcome. drehen: Nein
G. Ramsay true
Department of Intensive Care Medicine, Seiten von: 1
/GrayImageFilter
University Hospital Maastricht, /DCT
E
e
d
o
c
n Seiten bis: Alle Seitn
P.O. Box 5800, 6202 AZ Maastricht, Bund: Links
/Optimize true
The Netherlands
e-mail: wvm@sint.azm.nl
Auflösung: [ 600 0 6
Tel.: +31-43-3876543 ] dpi
/ParseDSCComments
Fax: +31-43-3874330 Papierformat: [ 595
false
W. N. K. A. Mook 785 ] Punkt
Department of Internal Medicine, KOMPRIMIERUNG -
/EmitDSCWarnings
University Hospital Maastricht, ----------------------------
false
6202 AZ Maastricht, The Netherlands
-----------
/CalGrayProfile ()
J. L. M. Stappers Farbbilder:
/NeverEmbed [ ]
Department of Cardiology,
University Hospital Maastricht, Downsampling: Ja
6202 AZ Maastricht, The Netherlands /GrayImageDownsamp
H. W. H. M. Putten Berechnungsmethode
1.5
Department of Gynecology, Bikubische
/UsePrologue false
University Hospital Maastricht, Neuberechnung
/GrayImageDict <<
6202 AZ Maastricht, The Netherlands Downsample-
/QFactor 0.9 /Blend 1
Auflösung:
/HSamples 150 [ 2 1dpi12]
nancy 10 years previously was complicated by Downsampling
/VSamples
dyspnea [ 2 1 1 2für ]
Case Bilder
>> led über:
and heart failure. Details subsequently obtained to a 225 dpi
At gestational age of 36+1 weeks a 34 year-old African clinical diagnosis of congestive heart failure andKomprimieren:peripar- Ja
woman (gravida 5 para 3) was admitted to hospital with tum (PP) cardiomyopathy (CMP) with a normal ejection Automatische
/AutoFilterColorImages B
m
i
t
s
e m g
n
u
preeclampsia (blood pressure 140/100 mmHg, peripheral fraction 1 month after delivery. Her third pregnancy der
true
edema, and proteinuria of 0.3 g/l). After stimulation with 4 years thereafter was uncomplicated. A fourth Komprimierungsart:
/sRGBProfile (s
pregnan- RG B
Ja8 weeks.
prostaglandin E2 gel a healthy girl weighing 2.66 kg was cy was extrauterine and therefore terminated atIEC61966-2.1)
born 5 days later. Initial postpartum recovery was un- Laboratory investigations revealed a hemoglobin JPEG-Qualität:
lev-
/ColorImageDepth Mitel
eventful, but 4 days after discharge she was readmitted el of 9.0 g/dl with normal leukocyte and thrombocyte -1 Bitanzahl pro Pixel:
with dyspnea (30 shallow breaths/min), a blood pressure counts. Electrolytes, renal function, thyroid Wie function,
Original Bit
of 140/100 mmHg, tachycardia (130 bpm), and pyrexia glucose-6-phosphate dehydrogenase, vitamin/PreserveOverprintSetB12, folic
Graustufenbilder:
(38.2°C) but no peripheral edema. Auscultation of the acid, and iron levels were also normal. Liver trueenzymes
Downsampling: Ja
chest revealed normal breath sounds and a gallop were slightly elevated (although lactate dehydrogenase /AutoRotatePages
rhythm. The patient now reported that her second preg- was 948 U/l), and the total bilirubin level was /N 9.9
e µmol/l.
o
n
Berechnungsmethode
Bikubische
/UCRandBGInfo /Presrve
Neuberechnung
/EmbedAllFonts true
Downsample-
Auflösung: 150 dpi
/CompatibilityLevel
1.2 Downsampling für
Bilder über: 225
/StartPage 1 dpi
Komprimieren: Ja
168
Chest radiography showed an enlarged heart and a dubi-
ous infiltrate in the left lower lobe.
Despite initial treatment with antibiotics her condition
deteriorated with progressive dyspnea. Blood pressure
(175/115 mmHg) and heart rate (145 bpm) remained ele-
vated, bilateral crepitations were now heard on ausculta-
tion, and repeat chest radiography now showed pulmonary
edema. Electrocardiographic ST depression with T wave
inversion was present in the anterior chest leads with flat
ST segments inferiorly. The patient was treated with intra-
venous furosemide, subcutaneous morphine, and continu-
ous positive airway pressure without improvement. After
subsequent intubation and initiation of pressure-regulated
volume controlled mechanical ventilation echocardiogra-
phy revealed an enlarged left ventricle, a global decrease
in contractility with a left ventricular ejection fraction
(LVEF) of 28%, moderate mitral valve insufficiency, and
an estimated stroke volume of 30 ml. Dobutamine and ni-
troglycerin were started. Swan-Ganz catheter measure-
ments subsequently revealed central venous, pulmonary
artery and pulmonary artery wedge pressures of 12, 41/29,
and 20 mmHg, respectively, and a cardiac output of
6.28 l/min (cardiac index 3.27 l min1 m2). After cessa-
tion of the antibiotics bronchoalveolar lavage revealed no
abnormalities and no microbial growth. Serology for res-
piratory viral infections remained negative, serum seleni-
um was normal, and an autoimmune screen (anti-nuclear
factor, anti-neutrophil cytoplasmic antibody, anti-dsDNA,
anti-cardiolipin antibody, and antibodies against cardiac
muscle) also proved negative. A diagnosis of PP-CMP
was thus made.
A continuous furosemide infusion and angiotensin-con-
verting enzyme (ACE) inhibitors were added to the nitrate
and dobutamine therapy. After 6 days the patient was extu-
bated; however, repeat echocardiography showed worsen-
ing of cardiac function (LVEF 17%, mitral insufficiency
grade 2–3, right ventricular pressure 55–60 mmHg). The
patient was transferred to the Coronary Care Unit for intra-
aortic balloon pump counterpulsation. Five days later the
nitrates were stopped. Repeat echocardiography showed a
LVEF of 35%, with grade I mitral insufficiency. Two days
later the intra-aortic balloon pump was removed. Her con-
dition gradually improved, and almost 1 month after ad-
mission she was discharged on bumetanide, carvedilol, and
quinapril. Discharge echocardiography showed a LVEF of
50% and normal electrocardiography. Another pregnancy
was strongly discouraged. In the outpatient clinic
10 months later echocardiography showed further normal-
ization (LVEF of 62%, normal dimensions, and no evi-
dence of valvular insufficiency).
Definition of peripartum cardiomyopathy
PP-CMP is a rare form of cardiac failure occurring late
in pregnancy or in the postpartum period. Heart failure
associated with the peripartum period was first described
in 1849 [1] and was considered a distinct entity from the
1930s [2]. In 1971 Demakis et al. [3] described criteria
for its diagnosis, namely: (a) development of heart fail-
ure in the last month of pregnancy or within 5 months af-
ter delivery, (b) absence of a determinable etiology for
the cardiac failure, and (c) absence of demonstrable heart
disease prior to the last month of pregnancy. Other caus-
es should be carefully excluded, thereby making PP-CMP
a diagnosis of exclusion. Infectious, metabolic, and toxic
causes of CMP, CMP associated with systemic disorders,
valvular heart disease (for example, mitral valve steno-
sis), and myocardial infarction should all be considered.
Other late complications of pregnancy such as massive
pulmonary embolism, amniotic fluid embolism (most of-
ten during labor and delivery), and severe toxemia may
also to some extent simulate heart failure. In the case de-
scribed here blood chemistry, serology, electrocardiogra-
phy, and echocardiography subsequently ruled out these
possibilities. Some consider the disease a subset of idio-
pathic dilated CMP with initial presentation during the
peripartum period [4, 5].
The maximal hemodynamic burden of pregnancy oc-
curs in the second trimester of pregnancy, and most pa-
tients with previously diagnosed cardiac disease develop
symptoms of heart failure in this period [6]. The onset of
symptoms in PP-CMP is, however, most often seen in
the last month of pregnancy or after delivery when the
hemodynamic changes in pregnancy are already resolv-
ing [5, 6]. Nevertheless, others have reported a reversible
decrease in left ventricular systolic dysfunction in the
second and third trimesters of normal pregnancy, persist-
ing into the early postpartum period, and returning to
baseline shortly thereafter [7, 8].
More recently it was suggested that a fourth criterion
should be added, namely, echocardiographic evidence of
diminished left ventricular systolic function [5, 6]. Some
authors use very strict echocardiographic criteria, such
as an ejection fraction less than 45%, or fractional short-
ening less than 30%, or both, and an end–diastolic di-
mension of more than 2.7 cm/m2 [9]. In the case present-
ed here the ejection fraction decreased from 28% to
17%, and fractional shortening decreased from 13% to
8% during the hospital stay. Our patient thereby fulfills
the criteria proposed for PP-CMP. It is possible that
women were previously diagnosed as having PP-CMP
when in fact they had symptoms and signs of other dis-
eases [9] or the high-output state of pregnancy itself [6].
Currently used criteria are summarized in Table 1.
Epidemiology
The reported incidence of PP-CMP varies between 1 in
100 to 1 in 15,000 pregnancies [3, 5, 6, 10, 11, 12, 13,
14, 15, 16]. The currently accepted incidence in the
 169

Table 1 Criteria for peripartum

cardiomyopathy Criteria for peripartum cardiomyopathy (all four of the following) Reference number

1. Cardiac failure occurring in the last month of pregnancy, or within [3]

five months postpartum
2. Absence of an identifiable cause for the cardiac failure [3]
3. Absence of heart disease prior to the last month of pregnancy [3]
4. Left ventricular systolic dysfunction by echographic criteria: [5] [6] [9]
– left ventricular ejection fraction < 45% AND/OR
– decreased fractional shortening < 30%
– end diastolic dimension > 2.7 cm/m2

United States is between 1 in 3000 and 1 per 4000 live Table 2 Peripartum cardiomyopathy reported associations
births [17]. This wide range can be due to regional dif- Reported associated condition Reference number
ferences (possible referral bias) [6, 18], variation in ap-
plication of the criteria for PP-CMP, and differences in Older maternal age (> 30 years) [6]
investigation of underlying diseases [5, 6, 12, 19]. Multiparity [6]
PP-CMP constitutes less than 1% of all cardiovascu- Twin pregnancy [6]
lar events related to pregnancy [5, 12]. Postulated risk Pre-eclampsia/gestational hypertension [4] [12]
Black race [6] [18]
factors are black race, older age (>30 years), multiparity, Living in a tropical or subtropical region [29]
and twin pregnancy [6]. Especially among African pa- Familial occurrence [22] [23]
tients, the incidence is high [18]. In a Nigerian study of Malnutrition [6] [18]
224 patients the occurrence of peripartum cardiac failure Cocaine use by mother [25]
Long-term tocolytic therapy [24]
was hypothesized to be due to the combined pressure Selenium deficiency [27] [28]
load of postpartum hypertension, the volume load from Chlamydia infection [26]
eating the customary sodium-rich kanwa (a dried lake Enterovirus infection [30]
salt), and the cardiovascular demands of heat [11]. The
Hausa-Fulani women in Nigeria eat large quantities of
kanwa up to 40 days postpartum. The syndrome of peri-
partum cardiac failure was more common in the hot Symptoms
rainy season. Furthermore, the first postpartum days are
spent on a bed in a small room, while once or twice daily Most patients present with symptoms in the first
the new mother is given hot baths [20]. In Gambia cul- 4 months postpartum (78%). Only 9% present in the last
tural habits play a less important role [21]. month before delivery, and 13% present either more than
Malnutrition has been reported as a risk factor, but 1 month antepartum or more than 4 months postpartum
many cases have been described among well nourished [6]. Another report found over 90% of patients present-
women, such as our patient [6, 18]. Familial occurrence ing in the first 2 months postpartum, with only 3.5% an-
has been reported [16, 22, 23]. Associations with long- tepartum [31].
term tocolytic therapy [24], maternal cocaine abuse [25], Clinical signs are those of heart failure, most present-
Chlamydia infection [26], selenium deficiency [27, 28], ing with dyspnea, cough and orthopnea [31, 32]. Other
and living in a tropical or subtropical region [29] have common symptoms are hemoptysis, chest pain, and ab-
been reported. No association with enterovirus infection dominal pain [31, 32]. Cardiomegaly, tachycardia, and a
has been found [30]. Preeclampsia, anemia, infection, third heart sound (85%) can be found on physical exami-
and cesarean delivery are often found in patients with PP- nation [6, 31, 32]. Frequently an elevated blood pressure
CMP [4, 12]. Preeclampsia does not cause heart fail- ure (60%) [6, 12], increased jugular venous pressure, hepato-
in healthy young women but may be important in older splenomegaly, peripheral edema, crackles on lung aus-
women with underlying vascular disease [4], or when cultation, a mitral regurgitation murmur, and arrhythmias
multiple compounding factors are present [12]. are also present [5, 6, 31, 32]. Since normal pregnancy
Preeclampsia was present in our patient, which necessi- can cause symptoms similar to heart failure, the NYHA
tated induction of delivery. Moreover, after delivery she classification may not adequately estimate the severity of
was anemic with a hemoglobin level of 5.6 mmol/l. the heart failure [5, 6, 31]. Neurological deficits due to
Table 2 summarizes the reported and postulated associa- thromboembolism can rarely be the presenting symp-
tions and risk factors. toms [5, 12].
Electrocardiography often shows sinus tachycardia or
atrial fibrillation, frequent ectopic beats, and other atrial
arrhythmias, or nonspecific ST and T wave abnormali-
ties. However, it can be completely normal. Occasional-
170
ly, Q waves in the right-sided chest leads are present and
criteria for left ventricular hypertrophy fulfilled [5, 6, 10,
18]. Conduction defects, prolongation of PR and QRS
intervals and (mostly left) bundle branch block can occur
[6, 18]. Chest radiographs invariably show cardiac en-
largement and increased pulmonary vascularity. A vari-
able amount of pulmonary edema can be present [18] as
well as bibasal infiltrates [6].
Echocardiography shows elevated left ventricular end-
diastolic dimensions [33] and reduced fractional shorten-
ing, which is correlated with left ventricular ejection frac-
tion [34]. Atrial dilatation and mitral regurgitation are
also commonly present [5]. A small pericardial effusion
may also be present [6]. Hemodynamic assessment often
shows elevated right and left filling pressures, decreased
cardiac output, and pulmonary hypertension [35]. If the
onset is antepartum, invasive techniques are recommend-
ed for monitoring during delivery [6, 32].
Pathology and etiology
Macroscopic pathological findings include a pale myo-
cardium with dilatation of the heart and often mural
thrombi in the ventricles [35]. Other structural defects
are usually absent. Endocardial thickening and pericar-
dial fluid can be found occasionally [2, 31]. Nonspecific
pathological findings include myocardial cellular hyper-
trophy and myofiber degeneration with areas of fibrosis,
interstitial edema, and, occasionally, lymphocytic infil-
tration [6, 35]. In 1982 Melvin [36] proposed myocardi-
tis as a causal factor, and other reports followed [37, 38,
39, 40, 41]. The reported incidence of myocarditis varies
from 8.8% [39] to 78% [38]. Rizeq et al. [39] found the
incidence of myocarditis to be comparable to that found
in an age- and sex-matched control population undergo-
ing transplantation for idiopathic dilated CMP (8.8 vs.
9.1%), but O’Connell et al. [37] found a much lower in-
cidence in patients with idiopathic dilated CMP (9 vs.
29%). Differences in evaluation and timing of these bi-
opsies are probably the major causes of the noted differ-
ences [17, 38, 39].
It has been postulated that the myocarditis has a viral
[30, 42] or an autoimmune etiology [17, 38, 39, 43], with
pregnancy increasing susceptibility to either [36, 39].
The evidence that PP-CMP is associated with high titers
of autoantibodies against certain cardiac tissue proteins
(adenine nucleotide translocator, branched-chain -keto
acid dehydrogenase) supports abnormal immunological
activity as a possible cause [17, 43]. This autoimmune
reaction may be triggered by fetal cells escaping into the
maternal circulation and are recognized as nonself only
after delivery, when the immunosuppression of pregnan-
cy subsides [17].
Since inflammatory cytokines play an important role
in the pathogenesis and progression of heart failure of
other etiologies (the so-called cytokine hypothesis) [44,
45], Sliwa et al. [46] studied cytokine expression in PP-
CMP. Tumor necrosis factor-, interleukin-6, and
Fas/APO-1 levels were significantly elevated compared
with 20 healthy volunteers. Fas is an apoptosis-signaling
receptor. Furthermore, sFas/APO-1 levels were signifi-
cantly higher in patients who died of PP-CMP than in
survivors. However, the cytokine release in cardiac fail-
ure may also occur secondary to splanchnic hypoperfu-
sion. Other postulated etiological factors include abnor-
malities of relaxin (primarily an ovarian hormone pro-
duced during pregnancy recently found in cardiac atria,
with positive inotropic and chronotropic properties) [47]
and deficiency of selenium [27], which may make the
heart more susceptible to injury from viral infection, hy-
pertension or hypocalcemia [28]. To date no definite
causal relationship has been established, and the cause of
PP-CMP thus remains unknown.
Complications
The most important complication of PP-CMP is throm-
boembolism [34, 48, 49, 50, 51, 52]. The incidence of
pulmonary and systemic embolism has been reported to
be as high as 50% [6, 53, 54] and can even be the pre-
senting problem [50]. On the other hand, the nonspecific
signs of PP-CMP can wrongly lead to an initial diagnosis
of pulmonary embolism [55].
The tendency towards formation of thrombi is proba-
bly caused by the hypercoagulant state of late pregnancy,
in combination with stasis and turbulent flow in the di-
lated heart [6]. The strict bed rest that was advised in
early studies may have also contributed to development
of deep venous thrombosis and subsequent pulmonary
embolism and may in part be an explanation for the high
mortality rates in older studies (see “Prognosis”) [19].
Management
Medical treatment of PP-CMP does not differ from that
for other forms of congestive heart failure [6]. Medica-
tion should be given in close communication with the
gynecologist.
Sodium and fluid restriction are the first measures,
particularly in patients with symptoms and signs of heart
failure. Digoxin, diuretics, inotropics, and afterload-re-
ducing medication may be used [29]. Digoxin concentra-
tions should be monitored since patients with PP-CMP
are more sensitive to this drug [5, 6, 19]. If necessary,
dopamine and dobutamine can be given [18, 32]. After-
load reduction can be accomplished using ACE inhibi-
tors in nonpregnant patients. High-dose ACE inhibitor
therapy has been associated with a significant decrease
in interleukin-6 levels [56], one of the pro–inflammatory

cytokines that may play a role in PP–CMP. During preg-
nancy, ACE inhibitors are contraindicated so hydralazine
is the agent of first choice [5 , 6]. Another safe alterna-
tive during pregnancy are nitrates. Calcium antagonists
have negative inotropic properties that generally pre-
clude their use in the setting of PP-CMP. Amlodipine,
however, has been shown to increase survival in non-
ischemic CMP patients [57]; plasma levels of interleu-
kin-6 are reduced in amlodipine users [58].
Vasodilating -blockers such as carvedilol reduce af-
terload through 1-adrenergic blockade [59]; a mortality
reduction has been suggested in dilated CMP [60] al-
though data on its use in PP-CMP are lacking. A sug-
gested approach is to use -blockers in the postpartum
period in patients with persisting symptoms and echocar-
diographic evidence of left ventricular compromise de-
spite more than 2 weeks of standard heart failure man-
agement [17]. Arrhythmia treatment should be per-
formed using standard guidelines and protocols. When
medical therapy fails, continuous venovenous hemofil-
tration can be used to remove excess fluid until restora-
tion of hemodynamic balance is achieved [61].
Because of the risk of thromboembolic complications
(see “Complications”) low molecular weight heparin
prophylaxis is routinely advised, especially when left
ventricular ejection fraction is 35% or lower [17]. Hepa-
rin is the drug of choice before delivery since oral anti-
coagulants are generally contraindicated in pregnancy
due to teratogenicity [6]. In the postpartum period a
choice can be made between oral anticoagulants and
heparin. Neither heparin nor oral anticoagulants are se-
creted into breast milk, and can be taken safely by
breastfeeding women. Bed rest is no longer advised [19],
and moderate exercise seems beneficial once heart fail-
ure symptoms have been controlled [10, 17].
Immunosuppressive therapy has been used in patients
with PP-CMP with biopsy-confirmed myocarditis result-
ing in improvement in clinical features coinciding with
loss of the inflammatory infiltrate on repeated biopsies
[36]. This has also been associated with improvement in
left ventricular function and prognosis [40]. The use of
immunosuppressive therapy (prednisone and azathio-
prine) will remain controversial until the precise role of
myocarditis is clarified [6]. Its use may be considered in
patients with myocarditis on biopsy who fail to improve
spontaneously within 2 weeks of initiation of standard
heart failure therapy [17]. In a retrospective study of six
patients treated with intravenous immunoglobulins
(2 g/kg) compared to 11 historical control subjects,
Bozkurt et al. [62] found significantly greater improve-
ment in left ventricular ejection in the treatment group
than in controls.
Since cardiac transplantation can be considered for
nonresponders, referral to specialist centers with experi-
ence in treating these rare patients may be considered.
Intra-aortic balloon pumping or insertion of a left ven-
171
tricular (LVAD) or biventricular assist device (BVAD)
can be used as a bridge until transplantation [5, 10].
(Left ventricular assist devices can be used as bridges to
transplantation, and sometimes even recovery in selected
patients [63].) Case reports of the use of left ventricular
or biventricular assist devices in patients with PP-CMP
awaiting transplantation have been published, although
thromboembolism was a major problem [64, 65]. There
are case reports of transplantation for PP-CMP [66, 67,
68], and even successful pregnancies after cardiac trans-
plantation [69, 70]. Some authors state that only myocar-
ditis-negative patients should be offered transplantation
[66]. Actuarial 2-year survival has been reported to be
88% in ten transplanted patients with prior PP-CMP.
They had a 30% higher rate of early rejection than trans-
plant recipients for idiopathic CMP, they tended to have
a greater need for immunosuppressive (cytolytic) thera-
py, and infection rates were consequently higher [68].
The decision as to whether and by what mode early
delivery is necessary, should be assessed in collaboration
with a cardiologist, gynecologist, and anesthetist. It has
been suggested that vaginal delivery is possible with in-
vasive hemodynamic monitoring in patients presenting
antepartum [32]. Neonates do seem not to be adversely
affected, although a premature delivery rate of 21% in 14
women has been reported [37].
Prognosis
In the United States mortality ranges from 25% to 50%,
with nearly 50% of deaths occurring in the first 3 months
postpartum [5, 6, 53, 71]. However, outcome differs
widely between reports [3, 11, 34, 48, 49, 50, 51, 52, 53,
71]. Causes of death include chronic progressive conges-
tive heart failure, fatal arrhythmias, and thromboembolic
complications. In one study approximately half of the 27
patients had resolution of cardiomegaly and left ventric-
ular dysfunction at 6 months after delivery and a favor-
able prognosis with no reported cardiac mortality, where-
as the group with persisting abnormalities at 6 months
after delivery had a mortality rate of 85% over 5 years
and a mean survival of 4.7 years [3, 72]. A more recent
study found similar results [73].
Midei et al. [40] reported that resolution of myocardi-
tis is associated with significant improvement in left
ventricular function, and that immunosuppressive thera-
py may improve both left ventricular function and prog-
nosis. Others, however, have found no relationship be-
tween survival and the presence of myocarditis [41] but
confirmed that a decreased left ventricular stroke work
index is associated with a worse clinical outcome [41].
Women with a history of PP-CMP who have regained
normal resting left ventricular size and performance still
have decreased contractile reserve revealed by the use of
dobutamine challenge testing. The ventricles of these
172

women may respond suboptimally to hemodynamic
stress in spite of evidence of recovery by routine echo-
cardiographic evaluation [74]. Thus the prognosis for
women with PP-CMP depends on normalization of left
ventricular size and function within 6 months after deliv-
ery [17, 72, 73].
Currently there is no consensus regarding recommen-
dations for future pregnancy after PP-CMP [17]. Most
authors agree a subsequent pregnancy can be very dan-
gerous in cases of persisting left ventricular dysfunction,
and that this should be discouraged and avoided. Wheth-
er those recovering normal left ventricular function can
safely undergo a subsequent pregnancy is not clear. Al-
though successful pregnancies without symptoms, or
change in left ventricular diameter of fractional shorten-
ing have been reported [10, 73], recurrence of PP-CMP
despite rapid return of heart size and function in the prior
pregnancy has been reported [75]. A survey carried out
by Veille and Zaccaro [29] reported that 66% of respon-
dents agreed to a future pregnancy if ventricular function
returned to normal. If subsequent pregnancies cannot be
avoided, these should be managed in a high-risk perina-
tal center [17]. Data on neonatal outcome are lacking.
Since PP-CMP has been associated with multiparity in
some studies, the risk of irreversible cardiac damage
may increase with each subsequent pregnancy [17].

References
1. Richie C (1849) Clinical contribution
to the pathology, diagnosis and treat-
ment of certain chronic diseases of the
heart. Edinb Med Surg J 2:333
2. Hull E, Hafkesbring E (1937) “Toxic”
postpartal heart disease. New Orleans
Med Surg J 89:550–557
3. Demakis JG, Rahimtoola SH (1971)
Peripartum cardiomyopathy. Circula-
tion 44:964–968
4. Witlin AG, Mabie WC, Sibai BM
(1997) Peripartum cardiomyopathy: an
ominous diagnosis. Am J Obstet Gyn-
ecol 176:182–188
5. Heider AL, Kuller JA, Strauss RA,
Wells SR (1999) Peripartum cardiomy-
opathy: a review of the literature. Ob-
stet Gynecol Surv 54:526–531
6. Lampert MB, Lang RM (1995) Peri-
partum cardiomyopathy. Am Heart J
130:860–870
7. Geva T, Mauer MB, Striker L, Kirshon
B, Pivarnik JM (1997) Effect of physi-
ologic load of pregnancy on left ven-
tricular contractility and remodelling.
Am Heart J 133:53–59
8. Mone S, Sanders S, Colan S (1996)
Control mechanisms for physiological
hypertrophy of pregnancy. Circulation
94:667–672
9. Hibbard JU, Lindheimer M, Lang RM
(1999) A modified definition for peri-
partum cardiomyopathy and prognosis
based on echocardiography. Obstet
Gynecol 94:311–316
10. Brown CS, Bertolet BD (1998) Peri-
partum cardiomyopathy: a comprehen-
sive review. Am J Obstet Gynecol
178:409–414
11. Davidson NM, Parry EH (1978)
Peri–partum cardiac failure. Q J Med
47:431–461
12. Cunningham FG, Pritchard JA,
Hankins GDV, Anderson PL, Lucas
MJ, Armstrong KF (1986) Peripartum
heart failure: idiopathic cardiomyopa-
thy or compounding cardiovascular
events? Obstet Gynecol 67:157–168
13. Hsieh CC, Chiang CW, Hsieh TT,
Soong YK (1992) Peripartum cardio-
myopathy. Jpn Heart J 33:343–349
14. Seftel H, Susser M (1961) Maternity
and myocardial failure in African
women. Br Heart J 23:43–52
15. Woolford R (1952) Postpartum myo-
carditis. Ohio State Med 48:924–930
16. Pierce J, Brice B, Joyce J (1963) Fa-
milial occurrence of postpartum heart
failure. Arch Intern Med 111:651–656
17. Pearson GD, Veille JC, Rahimtoola S,
Hsia J, Oakley CM, Hosenpud JD,
Ansari A, Baughman KL (2000) Peri-
partum cardiomyopathy: National
Heart, Lung, and Blood Institute and
Office of Rare Diseases (National In-
stitutes of Health) workshop recom-
mendations and review. JAMA
283:1183–1188
18. Julian DG, Szekely P (1985) Peripar-
tum cardiomyopathy. Prog Cardiovasc
Dis 27:223–240
19. Burch G, McDonald C, Walsch J
(1971) The effect of prolonged bed rest
on postpartal cardiomyopathy. Am
Heart J 81:186–201
20. Fillmore SJ, Parry EH (1977) The evo-
lution of peripartal heart failure in
Zaria, Nigeria. Some etiologic factors.
Circulation 56:1058–1061
21. Rolfe M, Tang CM, Walker RW,
Bassey E, George M (1992) Peripartum
cardiac failure in The Gambia. J Trop
Med Hyg 95:192–196
22. Massad LS, Reiss CK, Mutch DG,
Haskel EJ (1993) Familial peripartum
cardiomyopathy after molar pregnancy.
Obstet Gynecol 81:886–888
23. Pearl W (1995) Familial occurrence of
peripartum cardiomyopathy. Am Heart
J 129:421–422
24. Lampert MB, Hibbard J, Weinert L,
Briller J, Lindheimer M, Lang RM
(1993) Peripartum heart failure associ-
ated with prolonged tocolytic therapy.
Am J Obstet Gynecol 168:493–495
25. Mendelson MA, Chandler J (1992)
Postpartum cardiomyopathy associated
with maternal cocaine abuse. Am J
Cardiol 70:1092–1094
26. Cenac A, Djibo A, Sueur JM,
Chaigneau C, Orfila J (2000) [Chla-
mydia infection and peripartum dilated
cardiomyopathy in Niger]. Med Trop
(Madr) 60:137–140
27. Cenac A, Simonoff M, Moretto P,
Djibo A (1992) A low plasma selenium
is a risk factor for peripartum cardio-
myopathy. A comparative study in
Sahelian Africa. Int J Cardiol 36:57–59
28. Kothari SS (1997) Aetiopathogenesis
of peripartum cardiomyopathy: prolac-
tin–selenium interaction? Int J Cardiol
60:111–114
29. Veille JC, Zaccaro D (1999) Peripar-
tum cardiomyopathy: summary of an
international survey on peripartum car-
diomyopathy. Am J Obstet Gynecol
181:315–319
30. Cenac A, Gaultier Y, Devillechabrolle
A, Moulias R (1988) Enterovirus infec-
tion in peripartum cardiomyopathy.
Lancet II:968–969
31. Lee W (1991) Clinical management of
gravid women with peripartum cardio-
myopathy. Obstet Gynecol Clin North
Am 18:257–271
32. Lee W, Cotton DB (1989) Peripartum
cardiomyopathy: current concepts and
clinical management. Clin Obstet Gyn-
ecol 32:54–67

33. Cole P, Cook F, Plappert T, Saltzman
D, St. John Sutton M (1987) Longitu-
dinal changes in left ventricular archi-
tecture and function in peripartum car-
diomyopathy. Am J Cardiol 60:871–
876
34. Aroney C, Khafagi F, Boyle C, Bett N
(1986) Peripartum cardiomyopathy:
echocardiographic features in five
cases. Am J Obstet Gynecol 155:103–
106
35. Homans DC (1985) Peripartum cardio-
myopathy. N Engl J Med 312:1432–
1437
36. Melvin KR, Richardson PJ, Olsen EGJ,
Path FRC, Daly K, Jackson G (1982)
Peripartum cardiomyopathy due to
myocarditis. N Engl J Med 307:731–
734
37. O’Connell JB, Costanzo–Nordin MR,
Subramanian R, Robinson J, Wallis
DE, Scanlon PJ, Gunnar RM (1986)
Peripartum cardiomyopathy: clinical,
haemodynamic, histologic and prog-
nostic characteristics. J Am Coll Car-
diol 8:52–56
38. Sanderson JE, Olsen EG, Gatei D
(1986) Peripartum heart disease: an en-
domyocardial biopsy study. Br Heart J
56:285–291
39. Rizeq MN, Rickenbacher PR, Fowler
MB, Billingham ME (1994) Incidence
of myocarditis in peripartum cardiomy-
opathy. Am J Cardiol 74:474–477
40. Midei MG, DeMent SH, Feldman AM,
Hutchins GM, Baughman KL (1990)
Peripartum myocarditis and cardiomy-
opathy. Circulation 81:922–928
41. Felker GM, Jaeger CJ, Klodas E,
Thiemann DR, Hare JM, Hruban RH,
Kasper EK, Baughman KL (2000)
Myocarditis and long–term survival in
peripartum cardiomyopathy. Am Heart
J 140:785–791
42. Sainani GS, Dekate MP, Rao CP
(1975) Heart disease caused by Cox-
sackie virus B infection. Br Heart J
37:819–823
43. Ansari AA, Neckelmann N, Wang YC,
Gravanis MB, Sell KW, Herskowitz A
(1993) Immunologic dialogue between
cardiac myocytes, endothelial cells,
and mononuclear cells. Clin Immunol
Immunopathol 68:208–214
44. Mann D (1996) Stress activated cyto-
kines and the heart. Cytokine Growth
Factor Rev 7:341–354
45. Seta Y, Shan K, Bozkurt B, Oral H,
Mann DL (1996) Basic mechanisms in
heart failure: the cytokine hypothesis.
J Card Fail 2:243–249
46. Sliwa K, Skudicky D, Bergemann A,
Candy G, Puren A, Sareli P (2000)
Peripartum cardiomyopathy: analysis
of clinical outcome, left ventricular
function, plasma levels of cytokines
and Fas/APO-1. J Am Coll Cardiol
35:701–705
47. Coulson CC, Thorp JM Jr, Mayer DC,
Cefalo RC (1996) Central haemody-
namic effects of recombinant human
relaxin in the isolated, perfused rat
heart model. Obstet Gynecol 87:610–
612
48. Janssens U, Klues HG, Hanrath P
(1997) Successful thrombolysis of
right atrial and ventricle thrombi in a
patient with peripartum cardiomyopa-
thy and extensive thromboembolism.
Heart 78:515–516
49. Bassaw B, Ariyanayagam DC,
Roopnarinesingh S (1992) Peripartum
cardiomyopathy and arterial embolism.
West Indian Med J 41:79–80
50. Hodgman MT, Pessin MS, Homans
DC, Panis W, Prager RJ, Lathi ES,
Criscitiello MG (1982) Cerebral embo-
lism as the initial manifestation of peri-
partum cardiomyopathy. Neurology
32:668–671
51. Chan F, Ngan Kee WD (1999) Idio-
pathic dilated cardiomyopathy present-
ing in pregnancy. Can J Anaesth
46:1146–1149
52. Ford RF, Barton JR, O’Brien JM,
Hollingsworth PW (2000) Demograph-
ics, management, and outcome of peri-
partum cardiomyopathy in a communi-
ty hospital. Am J Obstet Gynecol
182:1036–1038
53. Walsh JJ, Burch GE, Black WC,
Ferrans VJ, Hibbs RG (1965) Idiopath-
ic cardiomyopathy of the puerperium
(postpartal heart disease). Circulation
32:19–31
54. Walsh JJ, Burch G (1961) Postpartal
heart disease. Arch Int Med
108:817–823
55. Chan L, Hill D (1999) ED echocardi-
ography for peripartum cardiomyopa-
thy. Am J Emerg Med 17:578–580
56. Packer M, O’Connor CM, Ghali JK,
Pressler ML, Carson PE, Belkin RN,
Miller AB, Neuberg GW, Frid D, Wer-
theimer JH, Cropp AB, DeMets DL
(1996) Effect of amlodipine on mor-
bidity and mortality in severe chronic
heart failure. Prospective Randomised
Amlodipine Survival Evaluation Study
Group. N Engl J Med 335:1107–1114
57. Mohler ER, Sorensen LC, Ghali JK,
Schocken DD, Willis PW, Bowers JA,
Cropp AB, Pressler ML (1997) Role of
cytokines in the mechanism of action
of amlodipine: the PRAISE Heart Fail-
ure Trial. Prospective Randomised
Amlodipine Survival Evaluation. J Am
Coll Cardiol 30:35–41
58. Frishman WH (1998) Carvedilol.
N Engl J Med 339:1759–1765
173
59. Packer M, Bristow MR, Cohn JN,
Colucci WS, Fowler MB, Gilbert EM,
Shusterman NH (1996) The effect of
carvedilol on morbidity and mortality
in patients with chronic heart failure.
U.S. Carvedilol Heart Failure Study
Group. N Engl J Med 334:1349–1355
60. Beards SC, Freebairn RC, Lipman J
(1993) Successful use of continuous
veno–venous haemofiltration to treat
profound fluid retention in severe peri-
partum cardiomyopathy. Anaesthesia
48:1065–1067
61. Bozkurt B, Villaneuva FS, Holubkov
R, Tokarczyk T, Alvarez RJ,
MacGowan GA, Murali S, Rosenblum
WD, Feldman AM, McNamara DM
(1999) Intravenous immune globulin in
the therapy of peripartum cardiomyop-
athy. J Am Coll Cardiol 34:177–180
62. Aziz TM, Burgess MI, Acladious NN,
Campbell CS, Rahman AN, Yonan N,
Deiraniya AK (1999) Heart transplan-
tation for peripartum cardiomyopathy:
a report of three cases and a literature
review. Cardiovasc Surg 7:565–567
63. Aravot DJ, Banner NR, Dhalla N,
Fitzgerald M, Khaghani A, Radley-
Smith R, Yacoub MH (1987) Heart
transplantation for peripartum cardio-
myopathy. Lancet 2:1024
64. Keogh A, Macdonald P, Spratt P,
Marshman D, Larbalestier R, Kaan A
(1994) Outcome in peripartum cardio-
myopathy after heart transplantation.
J Heart Lung Transplant 13:202–207
65. Kreitmann B, D’Ercole C, Yao JG,
Ambrosi P, Metras D (1997) Success-
ful pregnancy 5 years after cardiac
transplantation for peripartum cardio-
myopathy. Transplant Proc 29:2457
66. Carvalho AC, Almeida D, Cohen M,
Lima V, Moura L, Buffolo E, Martinez
EE (1992) Successful pregnancy, deliv-
ery and puerperium in a heart trans-
plant patient with previous peripartum
cardiomyopathy. Eur Heart J 13:1589–
1591
67. Meadows W (1957) Idiopathic myocar-
dial failure in the last trimester of preg-
nancy and the puerperium. Circulation
15:903–914
68. Demakis JG, Rahimtoola SH, Sutton
GC, Meadows WR, Szanto PB, Tobin
JR, Gunnar RM (1971) Natural course
of peripartum cardiomyopathy. Circu-
lation 44:1053–1061
69. Sutton MS, Cole P, Plappert M,
Saltzman D, Goldhaber S (1991) Ef-
fects of subsequent pregnancy on left
ventricular function in peripartum car-
diomyopathy. Am Heart J 121:1776–
1778
174
70. Lampert MB, Weinert L, Hibbard J,
Korcarz C, Lindheimer M, Lang RM
(1997) Contractile reserve in patients
with peripartum cardiomyopathy and
recovered left ventricular function. Am
J Obstet Gynecol 176:189–195
71. Ceci O, Berardesca C, Caradonna F,
Corsano P, Guglielmi R, Nappi L
(1998) Recurrent peripartum cardiomy-
opathy. Eur J Obstet Gynecol Reprod
Biol 76:29–30
72. Gullestad L, Aukrust P, Ueland T, 75. Tandler R, Schmid C, Weyand M,
Espevik T, Yee G, Vagelos R, Froland Scheld HH (1997) Novacor LVAD
SS, Fowler M (1999) Effect of high- bridge to transplantation in peripartum
versus low-dose angiotensin converting cardiomyopathy. Eur J Cardiothorac
enzyme inhibition on cytokine levels in 11:394–396
chronic heart failure. J Am Coll Car-
diol 34:2061–2067
73. Deng M, Tjan TD, Asfour B, Scheld
HH (1999) Left ventricular assist de-
vices-reasons to be enthusiastic. Eur J
Heart Fail 1:289–291
74. Lewis R, Mabie WC, Burlew B, Sibai
BM (1997) Biventricular assistdevice
as a bridge to cardiac transplantation in
the treatment of peripartum cardiomy-
opathy. South Med J 90:955–958