European Journal of Heart Failure (2017) 19, 11311141 RESEARCH ARTICLE

doi:10.1002/ejhf.780

Clinical characteristics of patients from the

worldwide registry on peripartum
cardiomyopathy (PPCM)
EURObservational Research Programme in conjunction
with the Heart Failure Association of the European Society
of Cardiology Study Group on PPCM
Karen Sliwa1,2*, Alexandre Mebazaa3, Denise Hilfiker-Kleiner4, Mark C. Petrie5,
Aldo P. Maggioni6,7, Cecile Laroche6, Vera Regitz-Zagrosek8, Maria Schaufelberger9,
Luigi Tavazzi10, Peter van der Meer11, Jolien W. Roos-Hesselink12, Petar Seferovic13,
Karin van Spandonck-Zwarts14, Amam Mbakwem15, Michael Bhm16,
Frederic Mouquet17, Burkert Pieske18, Roger Hall19, Piotre Ponikowski20, and
Johann Bauersachs4
1 Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa; 2 Mary MacKillop Institute for
Health Research, Australian Catholic University, Melbourne, Australia; 3 Hpital Lariboisire, Universit Paris Diderot, Inserm U 942, Paris, France; 4 Department of Cardiology
and Angiology, Medical School Hannover, Hannover, Germany; 5 Golden Jubilee National Hospital, Glasgow, UK; 6 Eurobservational Research Program (EORP), European Society
of Cardiology, Sophie Antipolis, France; 7 ANMCO Research Center, Firenze, Italy; 8 Institute of Gender in Medicine (GiM), CharitUniversittsmedizin, Berlin, Germany;
9 Department of Medicine, Sahlgrenska University Hospital Ostra, Gothenburg, Sweden; 10 Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation,

Cotignola, Italy; 11 University Medical Center Groningen, Groningen, The Netherlands; 12 Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The
Netherlands; 13 Cardiology II, University Medical Center, Belgrade, Serbia; 14 Department of Genetics, Academic Medical Center, University of Amsterdam, The Netherlands;
15 Department of Cardiology, Lagos University Hospital, Lagos; 16 Klinik fr Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universittsklinikum des

Saarlandes, Homburg, Germany; 17 Service de Cardiologie, Ple Cardio-vasculaire et Pulmonaire, Hpital Cardiologique, CHRU Lille, Lille Cedex, France; 18 Department of
Cardiology, CharitUniversittsmedizin, Berlin, Germany; 19 Department of Cardiology, University of East Anglia, UK; and 20 Department of Heart Diseases, Medical University,
Clinical Military Hospital, Poland

Received 3 October 2016; revised 7 December 2016; accepted 8 January 2017 ; online publish-ahead-of-print 8 March 2017

Aims The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic
management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European
Society of Cardiology (ESC) vs. non-ESC countries.
.....................................................................................................................................................................
Methods Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with
and results completed case record forms (from 43 countries) entered into this ongoing registry. There were marked differences
in socio-demographic parameters such as Human Development Index, GINI index on inequality, and Health
Expenditure in PPCM patients from ESC vs. non-ESC countries (P < 0.001 each). Ethnicity was Caucasian (34%),
Black African (25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%). Despite the huge disparities in
socio-demographic factors and ethnic backgrounds, baseline characteristics are remarkably similar. Drug therapy
initiated post-partum included ACE inhibitors/ARBs and mineralocorticoid receptor antagonists with identical
frequencies in ESC vs. non-ESC countries. However, in non-ESC countries, there was significantly less use of

*Corresponding author. Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa. Tel:
+27 21 4066358, Fax: +27 21 447 8789, Email: Karen.Sliwa-Hahnle@uct.ac.za
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European Journal of Heart Failure 2017 European Society of Cardiology
1132 K. Sliwa et al.

beta-blockers (70.3% vs. 91.9%) and ivabradine (1.4% vs. 17.1%), but more use of diuretics (91.3% vs. 68.8%), digoxin
(37.0% vs. 18.0%), and bromocriptine (32.6% vs. 7.1%) (P < 0.001). More patients in non-ESC vs. ESC countries
continued to have symptomatic heart failure after 1 month (92.3% vs. 81.3%, P < 0.001). Venous thrombo-embolic
events, arterial embolizations, and cerebrovascular accidents were documented in 28 of 411 patients (6.8%). Neonatal
death rate was 3.1%.
.....................................................................................................................................................................
Conclusion PPCM occurs in women from different ethnic backgrounds globally. Despite marked differences in socio-economic
background, mode of presentation was largely similar. Embolic events and persistent heart failure were common
within 1 month post-diagnosis and required intensive, multidisciplinary management.
..........................................................................................................
Keywords Peripartum cardiomyopathy Definition Registry Thrombotic events

Introduction Methods

...........................................................................................................................
Peripartum cardiomyopathy (PPCM) is an idiopathic form of car- Study design, patient selection, and data collection have been
diomyopathy, presenting with heart failure secondary to LV dys- published.2 Eligibility criteria for the centres were availability of
function towards the end of pregnancy or in the months following echocardiography, advanced clinical care to make the diagnosis, and
the possibility to follow the patients for at least 6 months and up to 5
delivery, where no other cause of heart failure is identified.1 Data
years. Incident cases of consecutive patients per centre are entered
on suspected or confirmed cases of PPCM from Europe and most
into the database, and only patients diagnosed within 6 months of
other regions of the world are either non-existent or limited.2,3 enrolment can be included. Data can be entered when available and in
It is therefore unknown whether PPCM occurs on all continents stages.
and if ethnicity or heterogeneous accesses to healthcare impacts The case report form (CRF) for this ongoing registry can be
on mode of presentation, management, and short-term (within 1 accessed via the EORP website: www.eorp.org. A dedicated team of
month post-diagnosis) maternal and foetal outcome. data specialists at the ESC Heart House is assisting physicians with
The ongoing prospective, international, multicentre, observa- entering cases and guidance in regulatory approval. The protocol,
tional registry aims to collect information on 1000 patients with patient consent forms and study patient logs are provided on the
website as pdf files. The front page contains mandatory key questions
PPCM, and is part of a rolling programme of surveys of differ-
qualifying the patient as potential PPCM: (i) peripartum stage; (ii) signs
ent aspects of cardiovascular disease, as part of the EURObser-
and/or symptoms of heart failure; (iii) EF <45%; and (iv) other causes
vational Research Programme (EORP) and as an initiative of the of heart failure are excluded. After all these points are checked, the
Study Group on PPCM of the Heart Failure Association. Data are next page opens with the registry data collection. This will ensure that
collected not only in member countries of the ESC, but world- only patients with PPCM will be entered. Follow-up will be requested
wide (Figure 1). The PPCM registrys overall primary objective is at 6 months and, thereafter, 6 monthly for a total duration of a 5-year
to describe the epidemiology, clinical characteristics, and outcome follow-up.
of in- and outpatients with PPCM, the diagnostic and therapeu- Standard management of patients will be the diagnostic and thera-
tic processes applied, and their impact on outcomes. The sec- peutic interventions currently performed in each centre for patients
ondary objective is to evaluate how recommendations of recently presenting with signs and symptoms of PPCM. Drug prescriptions
and indications to perform diagnostic/therapeutic procedures will
published position papers on acute and chronic management of
be completely left up to the participating cardiologists decision.
PPCM2,4 and the ESC Guidelines on cardiovascular disease in
No specific protocols or recommendations for evaluations, manage-
pregnancy as well as acute and chronic heart failure5,6 are cur- ment, or treatment will be put forward during this observational
rently followed. More specifically, information on the reasons for study.
evidence-based treatments not being utilized, or prescribed at
doses less than those recommended by guidelines, is collected. The
Data collected on enrolled patients
registry will help to identify parameters which serve as diagnostic
and prognostic markersthese may be useful for identification and
and their offspring
risk stratification. Furthermore, information on mode of delivery The baseline visit was defined as the first visit to the specialist making
and neonatal outcome will be collected. The project should lead to the diagnosis of suspected PPCM supported by echocardiography. Data
a better understanding of the disease and, subsequently, to practi- were collected, not only on the current visit/admission, but also on a
previous episode of suspected cardiomyopathy/PPCM (one data field).
cal recommendations on how the quality of care for patients with
Data collected include the demographic characteristics, risk factors for
PPCM can be improved.
cardiovascular disease, pregnancy history, breast feeding pattern, data
This first report summarizes the data on the presentation and on familial cardiomyopathy, co-morbidities, clinical signs and symptoms,
initial management of the first 500 patients entered, to obtain infor- and blood tests performed. Mandatory echocardiography parameters
mation that can be used to improve diagnosis, clinical management, include, besides LVEF, parameters of diastolic function, left atrial and
and service provision. LV dimensions, right ventricular function, and valvular abnormalities.

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European Journal of Heart Failure 2017 European Society of Cardiology
PPCM EORP 1133

A
PPCM Participant enrolment in ESC & NON-ESC Countries as of 26 July 2016.
148 registered centres in 61 countries of which, 43 are active countries.

ENROLLMENT 1

ESC countries

NON-ESC Countries

1 5 participants

6 15 participants

> 15 participants

Figure 1 EURObservational Research Programme on peripartum cardiomyopathy (http://www.eorp.org): (A) participant enrolment per
country and (B) representation of ethnic groups in European Society of Cardiology (ESC) and non-ESC regions.

As the diagnosis of PPCM is a diagnosis of exclusion, the final diagnosis Data recording, management, and data
.....................................

could be modified after a more complete work-up was available and

within 6 months of making the diagnosis.
validation
Detailed information on non-pharmacological and pharmacological Information was recorded via an electronic online CRF through a
therapy initiated at the baseline visit/within 6-month follow-up is web-based data entry platform. The electronic CRF was developed by
collected, including the names and doses of all cardiovascular drugs the Executive Committee. Core clinical data such as copy of ECG, copy
used, together with anticoagulation and the use of bromocriptine. of echocardiogram, and information of the foetus were validated via the
central EORP office contacting the sites using a data monitor.
Data collected on participating sites
Key information on each participating site was also collected, including Long-term follow-up
type of hospital, specialization of treating physician, and other parame- Patients will be followed up 6 months after enrolment, at which time
ters characterizing the set up available under which patients with PPCM their symptoms, signs, and medical therapy will be recorded. The
could be assessed. treating physician will be encouraged to perform echocardiography as

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European Journal of Heart Failure 2017 European Society of Cardiology
1134 K. Sliwa et al.

Figure 2 Description of country-level socio-economic data. ESC, European Society of Cardiology; HE, Health Expenditure; HDI, Human
Development Index.

recommended by the current guidelines and the PPCM echo manual. Figure 2 highlights the differences in socio-demographic parame-
............................................................................................

Furthermore, basic data will be collected 6 monthly for up to 5 ters among studied regions, especially when separated between
years if patients and physicians consent to being part of the long-term ESC and non-ESC countries: Human Development Index in PPCM
follow-up arm. patients from ESC (high: 65.5%) vs. non-ESC (high: 12.5%) coun-
tries (P < 0.001), GINI index on inequality in ESC (low: 83.7%) vs.
non-ESC (low: 45.1%) countries (P < 0.001), and Health Expen-
Statistical analysis diture in ESC (low: 0.0%) vs. non-ESC (low: 57.7%) countries
Continuous variables were reported as mean SD or as median and (P < 0.001). A glossary is provided in the Supplementary material
interquartile range. Between-group comparisons were made by using a online, Table S1.
non-parametric test (KruskalWallis test). Categorical variables were Despite the huge differences in socio-demographic factors
reported as percentages. Between-group comparisons were made by among regions of the world, the baseline characteristics of PPCM
using a 2 test or a Fishers exact test if any expected cell count was patients such as obstetric history and clinical presentation were
less than five. For categorical variables with more than two possible remarkably similar (Table 1). The mode of presentation was also
values, exact P-values have been estimated according to the Monte
similar, mean age was 30.7 6.4 years, mean gravidity 3.6 1.9, and
Carlo method.
22.8% had pre-eclampsia while pregnant. A total of 36.6% of PPCM
A two-sided P-value <0.05 was considered statistically significant.
All analyses were performed using SAS statistical software version 9.3
patients were in NYHA functional class III, and 32.2% in class IV;
(SAS Institute, Inc., Cary, NC, USA). mean systolic blood pressure was 118.8 23.5 mmHg, and heart
rate 100.7 21.1 b.p.m. Two-thirds of patients presented after
delivery (mostly within the first month post-partum) and one-third
pre-partum (Figure 3).
Results Differences were, however, seen between ESC and non-ESC
Between 1 August 2012 and 31 March 2016, 500 PPCM patients countries: in the ESC countries, glucose levels were higher and
from 43 countries were entered into the registry (Supplemen- smoking was more prevalent, while more patients were posi-
tary material online, Figure S1). Baseline data on the first 411 tive for HIV in the non-ESC countries. From the patients that
patients with completed CRFs, as entered by 31 March 2016, presented with symptoms pre-partum in the non-ESC countries,
are reported (see Appendix 1). Figure 1 demonstrates partici- 27.7% had a history of a cardiomyopathy diagnosed related to a
pant enrolment per country, whether the country is part of the previous pregnancy/PPCM, but only 10.3% in the ESC countries.
European Society of Cardiology (ECS) and representation of eth- Of the patients that presented pre-partum, 27 patients had a doc-
nic groups of the EORP Research Programme on PPCM (http:// umented cardiomyopathy related to a previous pregnancy, with the
www.eorp.org). Ethnicity was Caucasian (34%), Black African majority having that diagnosis made post-partum (n = 23). Analysis
(25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%). separating patients with a cardiomyopathy diagnosed in a previous

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European Journal of Heart Failure 2017 European Society of Cardiology
PPCM EORP 1135

Table 1 Baseline characteristics: socio-demographic factors, obstetric history, and clinical presentation

All (n = 411) ESC (n = 203) Non-ESC (n = 208) P-value

...........................................................................................................................................
Socio-demographic factors
Age (years) n 411 203 208 0.036
Mean (SD) 30.7 (6.4) 31.4 (6.6) 30.0 (6.2)
Median (Q1Q3) 31.0 (26.035.0) 32.0 (27.036.0) 30.0 (25.034.0)
Family situation Single 22/402 (5.5%) 9/194 (4.6%) 13/208 (6.3%) 0.381a
Married 349/402 (86.8%) 166/194 (85.6%) 183/208 (88.0%)
Living with partner 29/402 (7.2%) 18/194 (9.3%) 11/208 (5.3%)
Single parent 2/402 (0.5%) 1/194 (0.5%) 1/208 (0.5%)
Income (Euros per annum) <1000 137/259 (52.9%) 20/74 (27.0%) 117/185 (63.2%) <0.001*
10009999 89/259 (34.4%) 30/74 (40.5%) 59/185 (31.9%)
10 00030 000 20/259 (7.7%) 15/74 (20.3%) 5/185 (2.7%)
>30 000 13/259 (5.0%) 9/74 (12.2%) 4/185 (2.2%)
Education Primary 104/340 (30.6%) 26/145 (17.9%) 78/195 (40.0%) <0.001*
Secondary 97/340 (28.5%) 37/145 (25.5%) 60/195 (30.8%)
High school 77/340 (22.6%) 43/145 (29.7%) 34/195 (17.4%)
College or University 62/340 (18.2%) 39/145 (26.9%) 23/195 (11.8%)
Obstetric history
Gravidity n 268 119 149 0.526
Mean (SD) 3.6 (1.9) 3.6 (1.9) 3.6 (1.8)
Median (Q1Q3) 3.0 (2.05.0) 3.0 (2.05.0) 3.0 (2.05.0)
Gravida 1 11/268 (4.1%) 5/119 (4.2%) 6/149 (4.0%) 1.000a
Gravida 2 257/268 (95.9%) 114/119 (95.8%) 143/149 (96.0%)
Parity n 267 118 149 0.018*
Mean (SD) 3.1 (1.7) 2.8 (1.6) 3.3 (1.7)
Median (Q1Q3) 3.0 (2.04.0) 2.0 (2.04.0) 3.0 (2.04.0)
Para 0 1/267 (0.4%) 1/118 (0.8%) 0/149 (0.0%) 0.121a
Para 1 40/267 (15.0%) 22/118 (18.6%) 18/149 (12.1%)
Para 2 226/267 (84.6%) 95/118 (80.5%) 131/149 (87.9%)
Hypertension during current pregnancy n/M (%) 120/404 (29.7%) 55/197 (27.9%) 65/207 (31.4%) 0.444
Pre-eclampsia n/M (%) 89/391 (22.8%) 42/195 (21.5%) 47/196 (24.0%) 0.565
Breastfeeding (total, in months) n 199 67 132 <0.001*
Mean (SD) 27.5 (26.7) 15.4 (18.5) 33.7 (28.1)
Median (Q1Q3) 18.0 (6.040.0) 9.0 (5.018.0) 24.5 (12.049.5)
Clinical presentation
Body mass index (kg/m2 ) n 403 195 208 <0.001*
Mean (SD) 26.4 (6.1) 27.2 (5.9) 25.5 (6.3)
Median (Q1Q3) 25.0 (22.429.0) 26.0 (23.230.0) 24.2 (21.727.4)
NYHA class NYHA III 128/410 (31.2%) 57/202 (28.2%) 71/208 (34.1%) 0.418
NYHA III 150/410 (36.6%) 76/202 (37.6%) 74/208 (35.6%)
NYHA IV 132/410 (32.2%) 69/202 (34.2%) 63/208 (30.3%)
Dyspnoea n/M (%) 381/410 (92.9%) 186/202 (92.1%) 195/208 (93.8%) 0.509
S3 gallop n/M (%) 200/409 (48.9%) 83/202 (41.1%) 117/207 (56.5%) 0.002*
Jugular venous pressure (>6 mm) n/M (%) 194/408 (47.5%) 81/201 (40.3%) 113/207 (54.6%) 0.004*
Mitral regurgitation n/M (%) 223/410 (54.4%) 107/202 (53.0%) 116/208 (55.8%) 0.569

ESC, European Society of Cardiology.

a Fishers exact test.
* Significant P-value.

pregnancy and patients with HIV as a co-morbidity (n = 8) showed Table 2 describes the clinical variables and cardiac function at
.................

no difference between the groups (Supplementary material online,
Table S2).
The total number of months breastfeeding in all previous preg-
nancies was significantly different in ESC vs. non-ESC countries
(P < 0.001).
baseline. Mean LVEF was 32.2 9.9% with an end-diastolic diame-
ter of 60.3 8.0 mm and end-systolic diameter of 50.0 8.9 mm,
and no significant differences were seen between studied regions.
Table 3 describes the immediate management and outcome
within 1 month after diagnosis of PPCM; 2.4% died within this

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European Journal of Heart Failure 2017 European Society of Cardiology
1136 K. Sliwa et al.

A B C

Figure 3 Onset of symptoms of peripartum cardiomyopathy (PPCM) in patients in European Society of Cardiology (ESC) and non-ESC
countries (including information on patients having had a cardiomyopathy in a previous pregnancy). (A) Overall, (B) ESC countries, and (C)
non-ESC countries.

period due to heart failure (n = 6), stroke (n = 1), and sudden socio-economic background and ethnicity, the timing and mode

....................................................................................................................
cardiac death (n = 3). Mean stay in the intensive care unit was of presentation were remarkably similar. We found that the
3.4 days, with no significant differences within ESC and non-ESC short-term (1 month post-diagnosis) mortality was lower than
countries. Morbidity is very high, with the large majority of PPCM expected while morbidity, including persistent dyspnoea, need
with symptomatic heart failure after 1 month (92.3% in non-ESC for LVAD, and embolic events were common within 1 month
vs. 81.3% in ESC, P < 0.001). Implantation of a left ventricular assist post-diagnosis and required intensive, multidisciplinary manage-
device (LVAD) was performed in 3.0% of patients in ESC and 1.0% ment.
in non-ESC countries.
Remarkably, venous thrombo-embolic events, arterial emboliza-
tions, as well as cerebrovascular accidents were common and doc- Geographic representation and mode
umented in 28 of 411 cases (6.8%), with no difference between ESC of presentation
and non-ESC countries. A total of 27.9% of patients in ESC coun-
tries received anticoagulant drugs vs. 15.9% in non-ESC countries The epidemiology profile of PPCM is sparse, with most data coming
(P = 0.022; Table 3). from Nigeria and South Africa on the African continent, Haiti, and
Figure 4 describes oral pharmacological management initiated if the USA.7 9 Recently a larger cohort study has been reported
the patient was still pregnant (Figure 4A) or presenting post-partum from Germany,10 Japan,11 and Turkey,12 but reports from other
(Figure 4B). Drug therapy initiated included diuretics (83.6%), European countries, the Middle East, Asia, and Australia remain
ACE inhibitors (78.8%), beta-blockers (79.9%), and bromocrip- absent or are single case reports.7 Our data now reveal that PPCM
tine (21.2%), with significant differences in prescribing pattern of occurs globally. As a large proportion of the cases only present
those medications in ESC vs. non-ESC countries (P < 0.001). While with symptoms and signs of heart failure beyond the standard date
the use of ACE inhibitors/ARBs and mineralocorticoid recep- of reporting of maternal death (<42 days post-partum), PPCM is
tor antagonists (MRAs) was similar in ESC vs. non-ESC coun- likely to be under-reported as a cause of maternal death on a global
tries, beta-blockers and ivabradine were used less frequently in scale.13
non-ESC countries. In contrast, diuretics, digoxin, and bromocrip- Mean age of presentation was relatively high, at 30.7 6.4 years,
tine were applied more frequently in PPCM patients from non-ESC and a parity of 3.1 1.7, with no differences in ESC and non-ESC
countries. countries. Of the one-third of PPCM patients that presented
Only a small minority of patients received a pacemaker, CRT, or pre-partum, 21% had a diagnosis of cardiomyopathy in a previ-
an implantable cardioverter defibrillator in the early phase after ous pregnancy, which was likely to be PPCM as 23 of the 27
diagnosis, with no differences in ESC vs. non-ESC countries. patients presented only in the post-partum period. It is likely that
Of note, neonatal outcome was available for 301 of the 402 cases the diagnosis of a previous PPCM had often been missed. Inter-
who had a live birth (Supplementary material online, Table S3), with estingly, in the non-ESC countries, 28% of these patients had a
a neonatal death of 3.1% (n = 9). history of a previous cardiomyopathy, but only 10% in the ESC
countries, which may be explained by the higher incidence of
PPCM in Africa and some Asian areas. The percentage of previ-
ous cardiomyopathy is probably even higher as milder forms of
Discussion PPCM are commonly missed. Those data demonstrate that women
This large prospective international registry on PPCM thus far with a PPCM need a careful history recording, as pregnancy in
shows that the condition occurs in women from different eth- a women with a previous PPCM has an increased risk of poor
nic backgrounds in all continents. Despite marked differences in outcome.14

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European Journal of Heart Failure 2017 European Society of Cardiology
PPCM EORP 1137

Table 2 Clinical variables, electrocardiogam, and cardiac function at baseline

All (n = 411) ESC (n = 203) Non-ESC (n = 208) P-value

...........................................................................................................................................
Clinical variables
Systolic BP (mmHg) n 394 195 199 0.558
Mean (SD) 118.8 (23.5) 119.7 (25.1) 117.8 (21.8)
Median (Q1Q3) 112.0 (100.0131.0) 115.0 (100.0131.0) 110.0 (100.0130.0)
Diastolic BP (mmHg) n 393 194 199 0.273
Mean (SD) 76.7 (15.8) 76.0 (17.0) 77.4 (14.6)
Median (Q1Q3) 75.0 (65.090.0) 72.5 (60.090.0) 79.0 (70.090.0)
HR (b.p.m.) n 395 197 198 0.130
Mean (SD) 100.7 (21.1) 99.1 (23.2) 102.2 (18.7)
Diabetic n/M (%) 14/407 (3.4%) 10/201 (5.0%) 4/206 (1.9%) 0.093
Smoking (current and former) n/M (%) 48/394 (12.2%) 39/190 (20.5%) 9/204 (4.4%) <0.001*
HIV status n/M (%) 8/230 (3.5%) 0/114 (0.0%) 8/116 (6.9%) 0.007*,a
Glucose (mg/dL) n 204 105 99 0.002*
Mean (SD) 100.6 (42.2) 108.7 (53.1) 92.0 (23.7)
Median (Q1Q3) 89.5 (81.7105.5) 93.3 (83.3110.0) 87.0 (79.098.3)
Haemogoblin (g/dL) n 354 169 185 0.591
Mean (SD) 11.5 (1.9) 11.4 (1.6) 11.6 (2.1)
Median (Q1Q3) 11.4 (10.412.7) 11.3 (10.512.5) 11.6 (10.312.8)
Electrocardiogram
QRS duration n 379 176 203 <0.001*
Mean (SD) 90.1 (21.5) 93.8 (21.7) 86.8 (20.8)
Median (Q1Q3) 82.0 (80.097.0) 90.0 (80.0100.0) 80.0 (80.090.0)
QTc duration n 339 144 195 <0.001*
Mean (SD) 361.3 (58.3) 373.5 (48.9) 352.2 (63.0)
Median (Q1Q3) 360.0 (320.0400.0) 380.0 (345.5400.0) 346.0 (320.0390.0)
LBBB n/M (%) 37/398 (9.3%) 23/194 (11.9%) 14/204 (6.9%) 0.086
LVH n/M (%) 97/397 (24.4%) 14/193 (7.3%) 83/204 (40.7%) <0.001*
Echocardiogram
EF Teichholz (EF1) (%) n 346 150 196 0.253
Mean (SD) 32.2 (9.9) 32.8 (10.1) 31.7 (9.7)
Median (Q1Q3) 32.5 (25.039.0) 34.0 (25.040.0) 32.0 (25.038.0)
Intraventricular septum diastole (mm) n 345 153 192 0.184
Mean (SD) 12.0 (14.2) 13.8 (18.5) 10.6 (9.2)
Median (Q1Q3) 9.0 (8.010.0) 9.0 (8.010.0) 9.0 (8.011.0)
Intraventricular septum systole (mm) n 258 87 171 0.013*
Mean (SD) 12.3 (13.3) 13.0 (16.7) 12.0 (11.2)
Median (Q1Q3) 10.0 (8.012.0) 9.0 (7.012.0) 10.0 (9.012.0)
EDD (mm) n 380 177 203 0.644
Mean (SD) 60.3 (8.0) 60.6 (8.2) 60.1 (7.9)
Median (Q1Q3) 60.0 (55.065.0) 60.0 (55.066.0) 59.0 (55.064.0)
ESD (mm) n 334 135 199 0.698
Mean (SD) 50.0 (8.9) 49.7 (10.0) 50.3 (8.1)
Median (Q1Q3) 49.5 (45.055.0) 49.0 (43.057.0) 50.0 (45.054.0)
Right ventricular function Normal 197/368 (53.5%) 95/171 (55.6%) 102/197 (51.8%) 0.758
Mildly abnormal 134/368 (36.4%) 60/171 (35.1%) 74/197 (37.6%)
Severely abnormal 37/368 (10.1%) 16/171 (9.4%) 21/197 (10.7%)

BP, blood pressure; EDD, end-diastolic diameter; ESC, European Society of Cardiology; ESD, end-systolic diameter; HR, heart rate; LVH, left ventricular hypertrophy.
a Fishers exact test.
* Significant P-value.

Therapeutic management use was higher in non-ESC countries when patients presented
.............

post-partum (P < 0.001). The reason for the significantly lower use
Our data show significant differences in the initial management of of beta-blockers in non-ESC countries is unclear, as patients did
patients with PPCM presenting while still pregnant or post-partum. not differ regarding NYHA class and EF. Beta-blockers are not
Beta-blocker use was higher in ESC countries, whereas diuretic only recommended as a class IA indication in all patients with

2017 The Authors

European Journal of Heart Failure 2017 European Society of Cardiology
1138 K. Sliwa et al.

Table 3 Immediate management and outcome within 1 month post-diagnosis of peripartum cardiomyopathy

All (n = 411) ESC (n = 203) Non-ESC (n = 208) P-value

...........................................................................................................................................
PPCM confirmed n/M (%) 396/411 (96.4%) 193/203 (95.1%) 203/208 (97.6%) 0.173
Vital status Alive 401/411 (97.6%) 196/203 (96.6%) 205/208 (98.6%) 0.216a
Dead 10/411 (2.4%) 7/203 (3.4%) 3/208 (1.4%)
Causes of death Death due to heart failure 6/10 (60.0%) 5/7 (71.4%) 1/3 (33.3%) 0.458a
Death due to stroke 1/10 (10.0%) 1/7 (14.3%) 0/3 (0.0%)
Sudden cardiac death 3/10 (30.0%) 1/7 (14.3%) 2/3 (66.7%)
Time in ICU (days) n 5 4 1 0.114
Mean (SD) 3.4 (1.5) 2.8 (0.5) 6.0
Median (Q1Q3) 3.0 (3.03.0) 3.0 (2.53.0) 6.0 (6.06.0)
Device therapy
PM n/M (%) 3/410 (0.7%) 2/202 (1.0%) 1/208 (0.5%) 0.619a
ICD n/M (%) 5/410 (1.2%) 4/202 (2.0%) 1/208 (0.5%) 0.210a
CRT n/M (%) 1/410 (0.2%) 1/202 (0.5%) 0/208 (0.0%) 0.493a
Assist device n/M (%) 8/410 (2.0%) 6/202 (3.0%) 2/208 (1.0%) 0.170a
Obstetric outcome
Mode of delivery Vaginal 224/410 (54.6%) 98/202 (48.5%) 126/208 (60.6%) 0.008*,a
Primary caesarean section 178/410 (43.4%) 102/202 (50.5%) 76/208 (36.5%)
Abortion 3/410 (0.7%) 0/202 (0.0%) 3/208 (1.4%)
Miscarriage 5/410 (1.2%) 2/202 (1.0%) 3/208 (1.4%)
Tocolytic therapy n/M (%) 8/408 (2.0%) 4/202 (2.0%) 4/206 (1.9%) 1.000a
Massive bleeding during delivery n/M (%) 16/411 (3.9%) 7/203 (3.4%) 9/208 (4.3%) 0.645
Heart failure and embolic events
Cardiac failure 1 month post-diagnosis n/M (%) 357/411 (86.9%) 165/203 (81.3%) 192/208 (92.3%) <0.001
Cerebrovascular haemorrhagic accident n/M (%) 3/411 (0.7%) 3/203 (1.5%) 0/208 (0.0%) 0.120a
Cerebrovascular ischaemic accident n/M (%) 4/411 (1.0%) 3/203 (1.5%) 1/208 (0.5%) 0.367a
Deep venous thrombosis n/M (%) 6/411 (1.5%) 4/203 (2.0%) 2/208 (1.0%) 0.445a
Pulmonary embolism n/M (%) 10/411 (2.4%) 7/203 (3.4%) 3/208 (1.4%) 0.216a
Arterial embolization upper limb n/M (%) 4/411 (1.0%) 2/203 (1.0%) 2/208 (1.0%) 1.000a
Arterial embolization lower limb n/M (%) 1/411 (0.2%) 1/203 (0.5%) 0/208 (0.0%) 0.494a

ESC, European Society of Cardiology; ICD, implantable cardioverter defibrillator; ICU, intensive care unit; PPCM, peripartum cardiomyopathy; PM, pacemaker.
a Fishers exact test.
* Significant P-value.

heart failure with reduced EF,6 but do appear to be of major Embolic events and heart failure
...............................................................

importance for beneficial outcome in PPCM patients when given

Persistent heart failure 1 month after diagnosis was common
in addition to ACE inhibitors, as shown in the German PPCM
(>85%), and embolic events were documented in 6.8% of all
registry.15
patients. A recent transthoracic echocardiographic study from
Bromocriptine was prescribed in 53 of 250 cases that received
Nigeria in patients with PPCM18 demonstrated that 18 of 84
medication post-partum (21.2%), with significantly higher usage in cases (21.4%) had cardiac thrombi, often multiple. This confirmed
non-ESC countries. Bromocriptine is postulated to have a key role previous studies by Sliwa et al. in South Africa19 and Karaye and
of prolonged inhibition of a detrimental 16 kDa prolactin, leading to Sani,20 with >20% showing visible echocardiographic thrombus.
cardiac injury and dysfunction, and has been used in a pilot study in This is likely to be linked to the hypercoagulable peripartum state,
Africa16 and in the majority of patients in the German multicentre venous stasis, and vascular damage.21 However, it is likely that
registry.15 Ivabradine was prescribed for 21 of 249 cases (8.4%), many thrombi are not detected by routine echocardiography as, for
with a significantly higher usage in ESC countries. It is likely that example, left atrial appendage clots can be easily missed. This leads
prescription patterns are influenced by costs, as bromocriptine to the question of whether all patients with PPCM, particularly if
is available as a non-expensive generic in lower income countries EF is <35%, should receive anticoagulation for some time.
whereas ivabradine, which has only recently been reported to be
beneficial in acute PPCM,17 will only be affordable in higher income
countries. Neonatal outcome
Less than 5% of all patients received any form of device therapy The neonatal outcome of women with PPCM is rarely reported, as
in the acute management. Despite those marked differences in patients often presented several months post-partum. Information
therapeutic management, there were no statistical differences in on neonates was available in 301 of the cases, with a reported
lenght of intensive care unit stay and mortality. neonatal death rate of 3.1%.

2017 The Authors

European Journal of Heart Failure 2017 European Society of Cardiology
PPCM EORP 1139

A B

Figure 4 Medication prescribed post-diagnosis in European Society of Cardiology (ESC) and non-ESC countries. (A) Percentage use of ACE
inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists (MRAs). (B) Percentage use of diuretics, digoxin, bromocriptine,
and ivabradine.

Limitations Table S2. HIV status and history of a previous cardiomyopathy.

......................................................................................................

Baseline characteristics by HIV status - Socio-demographic factors,

This is a registry organized and funded by the ESC. We have used
obstetric history and clinical presentation.
the geographical and political definition of ESC vs. non-ESC as a
Table S3. Neonatal outcome.
group definition. This is a clear limitation for this analysis. However,
we have collected and shown the data on ethnicity and income per
patient diagnosed with PPCM in Table 1 and Figure 1. This is an Acknowledgements
ongoing registry. We will analyse the data according to ethnic group The authors would like to acknowledge the expert input and
and per country when we have reached the sample size of 1000. dedication of the EORP Executive and Steering Committee. Data
A further limitation, as in all registries, is that only core infor- collection was conducted by the EORP Department of the Euro-
mation could be validated by monitors. Participation in the EORP pean Society of Cardiology, and overall activities were co-ordinated
registry is voluntary and unpaid. A certain selection bias for cen- by Aldo Maggioni, Scientific co-ordinator EORP, and Thierry Fer-
tres interested in this condition is likely and could explain better reira, Head of Department EORP. Mrs Cecile Laroche conducted
short-term outcome, as previously reported, due to better knowl- the statistical analysis. We also acknowledge the support of Mrs
edge and subsequently multidisciplinary care. Sylvia Dennis, Hatter Institute for Cardiovascular Research, in
preparing the manuscript. The survey could not have been con-
ducted without the generous support of the ESC and spon-
Conclusions sorship of companies supporting the society via unconditional
This ongoing registry highlights the fact that much more data are grants.
needed regarding epidemiology, presentation, and management of
PPCM globally. Much can be learned from such registries. Our
data show that PPCM occurs with similar presentation mode
independent of ethnic and socio-economic backgrounds. It remains Funding
a serious condition with a high rate of patients presenting critically,
Since the start of EORP, the following companies have sup-
remaining in heart failure within 1 month post-diagnosis, and
ported the programme: Abbott Vascular Int. (20112014),
a substantial risk of embolic events. Therapeutic management
Amgen Cardiovascular (20092018), AstraZeneca (20142017),
differed substantially in ESC vs. non-ESC countries.
Bayer (20092018), Boehringer Ingelheim (20092016), Boston
Scientific (20092012), The Bristol Myers Squibb and Pfizer
Alliance (20112016), The Alliance Daiichi Sankyo Europe GmbH
Supplementary Information and Eli Lilly and Company (20112017), Gedeon Richter Plc
Additional Supporting Information may be found in the online (20142017), Menarini Int. Op. (20092012), MSD-Merck &
version of this article: Co. (20112014), Novartis Pharma AG (20142017), ResMed
Figure S1. Recruitment of PPCM patients. (20142016), Sanofi (20092011), and Servier (20102018).
Table S1. Glossary. Confict of interest: none declared.

2017 The Authors

European Journal of Heart Failure 2017 European Society of Cardiology
1140 K. Sliwa et al.

Appendix 1 Colleagues who Dr Anette Sandstrm; Professor J. Gustaf Smith; SWITZER-

........................................................................................................................................................................
LAND Lausanne Dr N. Yarol; TURKEY Eskisehir Professor Y.
entered the first 411 patients Cavusoglu; Professor T. Ulus; Dr S. Eraslan; UGANDA Kampala
ARGENTINA Buenos Aires Dr L. Favaloro; Dr M. Peradejordi Dr E. Okello; Dr B. Kakande; Dr E. Sebatta; UK Cambridge Dr S.
Lastras; Dr R. Ratto; AUSTRALIA Elizabeth Vale Professor M. Pettit; Dr J. Parameshwar; Dr C. Lewis; Glasgow Mrs M. McAdam;
Arstall; Mrs M. Wittwer; Dr Y.Y. Chow; AUSTRIA Salzburg Pro- Mr. N. Walker; Mrs S. McKee; Hull Professor A. Clark; Herts
fessor U. Hoppe; BAHRAIN Manama Dr R. AlBannay; BURK- Dr A. Bakhai; Mrs C. Wick; London Dr G. Amin-Youssef; Mrs J.
INA FASO Ouagadougou Dr N.V. Yameogo; Pr P. Zabsonre; DeCoursey; Mrs K. Martin; Manchester Dr S. Shaw; Manchester Dr
CANADA Sherbrooke, Quebec Dr A. Cumyn; Dr N. Caron; Dr S. Vause; Professor B. Clarke; Dr A. Roberts; Professor B. Keavney;
N. Sauv; CONGO Lubumbashi Professor D. Ngoy Nkulu; Dr Nottingham Dr S.V.F. Wallace; Dr G. Malin; UNITED ARAB EMI-
D. Malamba Lez; Dr E. Ngoy Yolola; CZECH REPUBLIC Brno RATES Abu Dhabi Dr W.A.R. Almahmeed; Dr B. Saleh; Dr F.
Dr H. Poloczkova; DENMARK Copenhagen Dr F. Gustafsson; Dr Farook; Dr S. Wani; USA Mineola, NY Dr V. Paruchuri; Ms. D.
Patel; Dr K. Marzo.
A. Ersbll; EGYPT Alexandria Professor M. Hassanein; Alexan-
dria Professor Y. Elrakshy; Assiut Professor D.A. Fouad; Dr S.A.M.
Salman; Dr Z.E.A. Zareh; Cairo Dr R. Hanna; Dr B.S. Ibrahim; Dr
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